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  • 1. SECTION 1: CURRICULUM OVERVIEW FACILITIES FOR TRAINING 1.1 Sponsoring Institution: Name: Duke University Hospital Program Address: Duke University Medical Center Box 3951 Durham, North Carolina 27710 JACHO Approved: X Program director located at this site: X Number of inpatient beds: 1225 Number of Internal Medicine faculty: 13 Number of Endocrinology faculty: 12 Chair, Department of Internal Medicine: Name: Harvey Cohen, MD Title: Chair, Department of Medicine Address: Duke University Medical Center 1102 Duke North Hospital Durham, North Carolina 27710 Telephone: (919) 668-1755 Fax: (919) 681-5400 Email: cohen015@mc.duke.edu Chief, Division of Endocrinology and Metabolism: Name: Mark N. Feinglos, MD Title: Professor of Medicine and Chief Address: Duke University Medical Center Box 3921 Durham, North Carolina 27710 Telephone: (919) 684-4005 Fax: (919) 681-8477 Email: feing002@.mc.duke.edu Participating Hospitals: Name: Veterans Affairs Medical Center (Durham) Address: 508 Fulton Street Durham, North Carolina 27705 Distance from primary hospital: Across the street, less than two minute walk Are these rotations required: Yes, each week for 12 months Number of months assigned to this site: 12 (four full months, ½ clinic) JACHO Approved: X Program director located at this site: X Number of inpatient beds: 502 Number of Internal Medicine faculty: 17 Number of Endocrinology faculty: 2 Chair, Department of Internal Medicine: Name: William Yarger, MD Title: Chair, Department of Internal Medicine Address: 508 Fulton Street 1
  • 2. Durham, North Carolina 27705 Telephone: (919) 286-6941 Fax: (919) 286-6873 Email: yarge001@mc.duke.edu Chief, Division of Endocrinology and Metabolism: Name: Jennifer Green, MD Title: Chief, Division of Endocrinology and Metabolism Address: 508 Fulton Street Durham North Carolina 27705 Telephone: (919) 286-0411 ext 7196 Fax: (919) 286-6873 Email: green094@mc.duke.edu 1.2 Program Number: 1433621116 1.3 Program Director: Name: Mark Feinglos Title: Professor of Medicine, Chief Address: Duke University Medical Center Box 3921 Durham North Carolina 27705 Telephone: (919) 684-4005 Fax: (919) 681-8477 Email: feing002@mc.duke.edu 1.4 Other Key Faculty: Name: Ann Brown, MD Title: Assistant Professor of Medicine, Endocrinology Address: Duke University Medical Center Box 3611 Durham North Carolina 27710 Telephone: (919) 684-5002 Fax: (919) 681-7796 Email: brown006@mc.duke.edu Name: Thomas Weber, MD Title: Assistant Professor of Medicine, Endocrinology Address: Duke University Medical Center Box 3470 Durham, North Carolina 27710 Telephone: (919) 668-1367 Fax: (919) 668-1366 Email: weber004@mc.duke.edu Name: John Guyton, MD Title: Associate Professor of Medicine, Endocrinology Address: Duke University Medical Center Box 3510 Durham North Carolina 27710 Telephone: (919) 684-9036 Fax: (919) 681-7796 Email: john.guyton@duke.edu 2
  • 3. 1.5 Introduction: This subspecialty training program in endocrinology, diabetes and metabolism is designed to provide advanced training and experience at a level for the trainee to acquire the knowledge, skills, attitudes and experience required for all of the competencies needed by a consultant in this field. This program is designed to fulfill the needs of those trainees who anticipate their future activities to be solely the clinical practice of this specialty, those who expect to function as clinician-educators and those who intend to pursue careers in clinical and/or basic endocrine research. The program recognizes that some trainees may evolve into specialists whose activities encompass more than one of the above career paths. The teaching environment and educational experiences for trainees, detailed below, will equip them to become strong clinicians, educators, and investigators. 1.6 Goals: 1. To learn basic and advanced endocrine biochemistry, physiology and pathophysiology, which provide the basis for understanding endocrine disease. 2. To accumulate a critical mass of fundamental information and practical approaches for the diagnosis, management and prevention of endocrine disorders. 3. To acquire the technical and practical skills that are required by a consultant in endocrinology, diabetes and metabolism. 4. To acquire clinical skills in a progressive fashion and with increasing responsibility appropriate for a consultant in endocrinology, diabetes and metabolism. 5. To acquire knowledge and skills necessary for providing cost-effective, ethical and humanistic care of patients with diabetes and disorders of endocrinology and metabolism. 6. To acquire knowledge and skills necessary for critical analysis of the laboratory testing and the endocrine literature. 7. To acquire skills in design and performance of hypothesis-driven endocrine research, and to participate in such research or equivalent scholarly activity. This may include gaining extensive experience in grant writing and scientific presentation. 1.7 Objectives: The program will provide training in: 1. Endocrine biochemistry, physiology and pathophysiology. 2. Hormone action and inter-relationships. 3. Diagnosis and management of endocrine diseases including: (3.1) History and physical examination with emphasis on examination of the fundi, thyroid, breasts, penis, testes and female reproductive organs. (3.2) Selection and interpretation of endocrine biochemical tests. (3.3) Selection and interpretation of imaging procedures such as sonography, radionuclide scans, computerized axial tomography, magnetic resonance imaging, positron emission tomography, etc. (3.4) Fine needle aspiration of the thyroid. (3.5) Understanding pharmacotherapy for endocrine disorders and appropriate use of surgery, radiation therapy, treatment with radioisotopes, etc. 4. Professionalism, including peer interactions, communication with patients, their families and other health care providers, confidentiality and avoidance of conflict of interest. 5. Endocrine clinical and basic research. 6. Understanding of existing and emerging endocrine literature. 7. Personal scholarship and self-instruction. A summary of how these specific learning objectives apply to the major learning experiences of this program is indicated below: 3
  • 4. Objectives for the Major Learning Experiences Objectives 1 2 3 4 5 6 7 3.1 3.2 3.3 3.4 3.5 Ambulatory: Consultation X X X X X X X X X X Continuing Care X X X X X X X X X X Inpatient: Consultation X X X X X X X X X X Teaching: X X X X X X X X X X Conferences: Clinical X X X X X X X X X X X Basic Science X X X X X X Journal Club X X X X X X X X X Research X X X X X X ESAP X X X X X Procedures: X 1.8 Patient Care Experience Trainees are directly supervised and continually evaluated by attending physicians assigned to the inpatient and ambulatory settings. Inpatients are reviewed on a daily basis with the attending physician. Attending physicians who are physically in the ambulatory setting review the ambulatory care experience of the trainee on a case by case and real time basis. The continuing interaction between trainee and attending physician is the heart of the educational experience. The integration of endocrine disorders with other diseases of the patient is part of the interaction between attending physician and trainee. When relevant, health promotion and identification of risk factors for disease are emphasized. All patient interactions take into account cultural, socioeconomic, ethical occupational, environmental and behavioral issues. Our program provides a progressive learning experience. Trainees are given increasing responsibility as they progress through the program and demonstrate their expanding knowledge base and expertise in diagnosis and management of endocrine disease. They serve as leaders of the endocrine “team”, which is constituted by trainee, internal medicine residents and medical students, always under the supervision of the attending physician. Our program emphasizes a scholarly approach to diagnosis and management. Self-instruction is expected of the trainee along with critical analysis of the patient’s problems and appropriate decision analysis regarding further evaluation and/ or management. Professionalism and ethical behavior are hallmarks of this training program. Our faculty serves both as mentors and role model clinicians for the values of professionalism. These include placing the needs of the patient first, a commitment to scholarship, helping other colleagues, continuous quality improvement and humanistic behavior both in patient interactions and interactions with other health care providers. Issues concerning professional ethics and physician impairment are discussed as they relate to specific interactions with patients. When applicable, these issues will be discussed as part of the evaluation of specific patients. 1.8.1 General Duke University Medical Center and the Duke Medical School are nationally renowned institutions, being ranked consistently in the top ten according to US News and World Report. The division of Endocrinology, Metabolism and Nutrition at Duke is also ranked within the top 20 of all programs nationally. It is also home to a number of clinical, basic science and translational investigators who, through both NIH-sponsored and private research resources, direct studies in a variety of areas, including mechanisms of insulin action and insulin resistance, treatment of Type 2 diabetes mellitus, polycystic ovarian syndrome, osteoporosis and inherited and acquired hypophosphatemic bone disease. In addition to a strong research environment, clinical care in Endocrinology at Duke encompasses a wide spectrum of common and uncommon conditions. This is no doubt facilitated to 4
  • 5. a large extent by a rather large referral base and catchment area that includes a large portion of Southeastern United States. In addition, Duke also has an active International Medicine Program and provides consultation to patients from the Middle East as well as many other areas of the world. In addition to consultation on-site at Duke Hospital, Endocrine faculty members, in concert with Endocrine fellows, also provide consultation at a number of satellite outreach clinics, thereby facilitating a broader reach of endocrine expertise and care throughout North Carolina. In total, the Division of Endocrinology at Duke provided consultation to nearly 850 inpatients and 9,000 outpatients at Duke alone in 2003. 1.8.2 Ambulatory Care Since most endocrine care is delivered in an ambulatory setting, the ambulatory experience is emphasized throughout the entire duration of the program. We estimate that over 40% of the trainees time (based on an 80-hour work week) is spent in ambulatory care, averaged for the first and second years of the program. This includes 56% from the first year and 32% from the second year. Educational Purpose: To learn about a variety of diseases of endocrinology and metabolism, through consultation and provision of continuing care. Teaching Methods: Ambulatory care is both consultative and continuing. For each interaction, the trainee will spend sufficient time with the patient to carry out an appropriate history and physical examination and then to interact with and be directly supervised by the endocrine faculty assigned to that ambulatory activity. The learning experience surrounding a patient interaction evolves from review of history, physical examination and laboratory results with the faculty, taking direction from the faculty and being provided with references or other learning materials that can be used for self- instruction and subsequent review with the faculty. Disease Mix and Patient Characteristics: Patients are generally 18 years of age or older including adequate representation of geriatric patients. Trainees care for patients with a wide range of clinical problems in stages of illness appropriate to the ambulatory setting. In addition to clinics in which the trainee encounters the broad range of endocrine pathology, rotations through disease-specific clinics are an integral part of the training program. These clinical opportunities are required. They include pediatric endocrine, reproductive endocrine, thyroid/nuclear medicine and PCOS. Procedures and Services: Dynamic endocrine studies and fine needle aspiration biopsy of the thyroid is taught and performed by the trainees in the ambulatory setting. Appropriate laboratory testing, including imaging, is ordered and results reviewed as part of the doctor/patient/attending interaction. Cytological and pathological material is reviewed and analyzed when appropriate. Reading Lists and Educational Resources: These are listed below under the disease specific sections of the curriculum. There are also two binders containing core endocrine-related articles in addition to the reading list contained in the curriculum, located in the endocrine conference room. Evaluation: See section on evaluation below. Trainees are provided the opportunity to follow their ambulatory patients for the duration of the program. By means of the ambulatory experience provided in this program, the trainee has the opportunity to observe and learn the course of endocrine diseases and their treatments. 1.8.3 Inpatient Care Since endocrine specialists are frequently required to consult on and manage endocrine aspects of care in hospitalized patients, the training program also emphasizes training in the inpatient setting. 5
  • 6. Educational Purpose: To learn about a variety of diseases of endocrinology and metabolism as they occur in the hospitalized patient. Teaching Methods: Hospital care is mainly consultative. For each interaction, the trainee will spend sufficient time with the patient to carry out an appropriate history and physical examination and then to interact with and be directly supervised by the endocrine faculty assigned to that activity. The learning experience surrounding a patient interaction evolves from review of history, physical examination and laboratory results with the faculty, taking direction from the faculty and being provided with references or other learning materials that can be used for self-instruction and subsequent review with the faculty. Consultation is frequently requested to determine the impact of endocrine disease on coexisting illnesses that necessitated hospitalization. The trainee will also learn, under supervision, how to interact not only with the patient and family, but also with other physicians caring for the patient. Practice Setting______________ Number of consults/week 20 Number of fellows/team 1 Number of residents/team 1-2 Number students/team 1-2 Average duration of rounds (hrs) 3-4 hours Disease Mix and Patient Characteristics: On request, trainees provide consultation to the Internal Medicine service and other departments such as surgery, vascular surgery, obstetrics and gynecology, psychiatry, ophthalmology, neurosurgery, orthopedic surgery, etc. Patients will have a variety of diseases that impact on the endocrine system, diseases of other systems with coexisting endocrine disease, or manifestations of primary endocrine disease such as diabetes mellitus, thyroid or parathyroid disease that warrant hospitalization. Patients will be adults of all ages, including the geriatric age group and both sexes. The severity of illness will be much greater than in the ambulatory setting. Procedures and Services: Trainees will coordinate the evaluation and management of the endocrine aspects of the patient’s illness. After interaction with the endocrine-attending physician, the trainee may order or request (depending on the patient’s location) appropriate laboratory tests, biopsies, imaging and infusion studies, as dictated by the patient’s problem. Data will be reviewed and treatment recommended. Reading Lists and Educations Resources: These are listed below under the disease specific sections of the curriculum. There are also two binders containing core endocrine- related articles in addition to the reading list contained in the curriculum, located in the endocrine conference room. Evaluation: See section on evaluation below Trainees evaluate patients by history, physical examination, and review of available laboratory and other data. The trainee is encouraged to formulate a differential diagnosis, plan for further evaluation and management. These are reviewed with faculty assigned to teaching rounds. Learning occurs by an iterative process through continuing interaction with faculty, review of pertinent literature and further discussion as new data emerge or change in the patient’s condition occur as a consequence of recommended treatment. Experience in the inpatient setting will include preparation of appropriate patients with endocrine disease for surgery as well as postoperative management, radiation therapy and/or treatment with iodine I-131. Interaction with professionals from other departments is reviewed and evaluated. Inpatients who have surgery or biopsy, pathology and cytology are reviewed with appropriate specialists in those departments. 6
  • 7. 1.8.4 Patient Care Experiences (Year 1-2): Tabular Overview of Activities PATIENT CARE EXPERIENCE: YEAR 1 1) AMBULATORY CARE Clinical Patient Volume Location Duration Continuity Rotating Disease Mix Initial Visit F/U Visit Clinic 1 VA Clinic Half Day YES no *YES 3 per session 5 per session Durham, NC weekly during VA and ‘elective’ months Clinic 2 Outreach Clinic Whole day YES no *YES 3 per session 3 per session Various locations once a month Throughout NC for whole year Clinic 3 Specialty Clinics Full Day no YES **YES 2 per session 2 per session Duke Endocrine 4 days per week Clinics during ‘elective’ months Durham, NC See Appendix A Specialty Clinics: Lipid Clinic, Metabolic Bone Disease Clinic, Reproductive Endocrine Clinic, Polycystic Ovarian Disease Clinic, Thyroid Nodule Evaluation Clinic, Diabetes+General Endocrine Clinics, Pediatric Endocrine Clinic, Insulin Pump Education *Diabetes Mellitus, Bone, Thyroid, Pituitary Gland, Adrenal Glands, Lipids **Diabetes Mellitus, Bone, Thyroid, Pituitary Gland, Adrenal Glands, Lipids, PCOS, Pediatric Endocrinology, Reproductive Endocrinology 2) INPATIENT CARE The first-year endocrine fellow’s experience consists of a rotating set of inpatient and outpatient experiences which provides the fellow with exposure to a variety of disease states. The 12 months of the year are divided into 4 blocks of 3-month-cycling rotations: 1 month of the Duke Inpatient Consult Service, followed by 1 month of the VA Inpatient Consult Service, Outpatient Endocrine Clinic and 1 month of ‘elective’ Endocrine Specialty Clinics as described above. Duke Inpatient Consult Service During the Duke Inpatient Consult Service rotation, the fellow serves as the team leader and primary organizer for the Diabetes Management Service/Endocrine Consult Service and thus has the opportunity to manage complex inpatient diabetes cases as well as a broad array of general endocrine diseases. The fellow rounds with the Duke Endocrine Faculty on the entire service every day. The accessibility of the senior staff creates a fertile learning environment for the fellow on-service, who also gets additional training in mentoring and teaching the internal medicine residents and, occasionally, medical students who are an important component of the rounding team. Clinical Volume for the whole team generally consists of on average 4-5 new patient consults daily, in addition to follow-up of 10 to 15 patients of whom the service has previously been consulted and have ongoing endocrine issues. VA Inpatient Consult Service During the VA Inpatient Consult Service, the fellow also consults on inpatients with endocrine issues. Consults come from all departments of the hospital including post-surgical, medical, and psychiatric cases. The VA fellow has the opportunity to discuss cases with the VA Endocrine Chief and other VA Endocrine attendings. Clinical Volume is variable – it typically ranges from 4 to 8 consults weekly, for which the fellow is primarily responsible as this service does not include resident or student participation. 7
  • 8. PATIENT CARE EXPERIENCE: YEAR 2 1) AMBULATORY CARE Clinical Patient Volume Location Duration Continuity Rotating Disease Mix Initial Visit F/U Visit Clinic 1 VA Clinic Half Day YES no *YES 3 per session 5 per session Durham, NC Weekly, for the whole year Clinic 2 Duke Endocrine Clinic ½ day bimonthly YES no *YES 3 per session 3 per session Underserved Locales 8/12 months Clinic 3 Duke Outpatient Weekly for YES no **YES 2-4 per session 5-8 per session Clinic 4/12 months continuous The typical patient encounter is quite similar to the experience in year one with the main difference being an increased level of independence in the fellow’s care of the patient. The fellow now conducts the history and physical and formulates the treatment plan independently, without direct observation by the attending. However, the attendings are always on site during clinic and available for consultation, and they can directly participate if the fellow wishes. Attendings review written notes of the encounter for quality control as well. At the Duke Outpatient Clinic, the second year fellow runs the clinic with the supervision of two endocrine attending physicians. The second year fellow typically oversees one first year fellow, one medicine intern and one medical student. The second year fellow also has primary responsibility for patient follow-up. *Diabetes Mellitus, Bone, Thyroid, Pituitary Gland, Adrenal Glands, Lipids **Diabetes Mellitus, Bone, Thyroid, Pituitary Gland, Adrenal Glands, Lipids, PCOS, Reproductive Endocrinology 2) INPATIENT CARE Unlike the first year of training, there are no inpatient care experiences required this year. 1.9 Facilities and Resources The program has secretarial support to facilitate scheduling and referrals. Fellows have office space with computer facilities for email and internet services, including literature searches: this is particularly beneficial to the fellows in that the Duke Medical Center Library has electronic access to many publications as well. The faculty regularly receives a number of journals and books, all of which are available to the trainee. Trainees are encouraged to participate in local and national endocrine meetings. In general, each trainee attends at least one national meeting per year. 1.9.1 Teaching Sites Site 1 (a) Duke Inpatient Consult Service During the Duke Inpatient Consult Service rotation, the fellow serves as the team leader and primary organizer for the Diabetes Management Service/Endocrine Consult Service and thus has the opportunity to manage complex inpatient diabetes cases as well as a broad array of general endocrine diseases. The fellow rounds with the Duke Endocrine Faculty on the entire service every day. The accessibility of the senior staff creates a fertile learning environment for the fellow on-service, who also receives additional training in mentoring and teaching the internal medicine residents and, occasionally, medical students who are an important component of the rounding team. Clinical Volume for the whole team generally consists of, on average 4-5 new patient consults daily, in addition to follow-up of 10 8
  • 9. to 15 patients daily of whom the service has previously been consulted and have ongoing endocrine issues. (b) Duke PDC During four months of the initial fellowship year, fellows will attend a pre-specified block of Endocrine subspecialty clinics at Duke Clinic. These clinics are staffed by Adult Endocrine, Pediatric Endocrine and Reproductive Endocrine faculty members who have specific interests in a number of endocrine disease states, including but not limited to diabetes mellitus, lipid disorders, polycystic ovarian disease, thyroid disease, metabolic bone disease, pediatric endocrinology (including juvenile-onset diabetes mellitus and disorders of growth and development) and disorders of reproductive endocrinology, including infertility. In addition to the Duke site, fellows will also rotate through the Durham VA lipid and bone clinics while participating in this elective rotation. Fellows will also attend the Duke Outpatient Clinic on selected rotation blocks. In addition to direct patient interaction with faculty observation, the fellows will also be allotted one to two half-day sessions per week in order to facilitate self- directed education, well as initial identification and development of a mentored-research project, which will be pursued in earnest during the second year of fellowship training. Site 2 (a) Durham VA Inpatient Consult Service During the VA Inpatient Consult Service, the fellow consults on inpatients with endocrine issues. Consults come from all departments of the hospital including post-surgical, medical, and psychiatric cases. The VA fellow has the opportunity to discuss cases with the VA Endocrine Chief and other VA Endocrine attendings. Clinical Volume is variable – it typically ranges from 4 to 8 consults weekly, for which the fellow is primarily responsible as this service does not include resident or student participation. (b) Durham VA Endocrine Clinic The DVAMC Endocrine Clinic provides fellows with a wealth of general endocrine continuity experiences. Each fellow has a continuity clinic, which meets for half-a-day weekly, and the fellow is responsible not only for the patient encounter, which occurs during the visit, but also for all follow-up associated with that encounter. The VA Clinics include a General Endocrine clinic that takes place twice weekly, as well as a Bone/Calcium Disorder clinic and Lipid/Risk Reduction clinic that each occur weekly. These clinics provide exposure to a wide range of Endocrine disorders. These include, but are not limited to, conditions such as diabetes mellitus; a variety of thyroid conditions including thyroid cancer; adrenal and pituitary disorders; osteoporosis; hyperparathyroidism; and lipid disorders. As there are no other VA Endocrine clinics in North Carolina, a wide variety of patients are referred to the Durham Clinic for management. The consultation service provides experience in the management of these same conditions in the inpatient setting. Although the majority of patients seen at the VA are male, it is anticipated that the recent establishment of the Bone/Calcium disorder clinic will attract more female patients to the Endocrine service. In addition, the increasing presence of women in the armed forces will likely result in larger numbers of women seeking medical care through the VA system. Site 3 Duke Outpatient Clinic “DOC” Endocrine Clinic is a one-half day clinic per week. The clinic serves as an Endocrine continuity clinic for an Endocrine second-year fellow and is also attended by a first- year Endocrine fellow as well as an internal medicine intern. There is on-site supervision and teaching by faculty in the division of Endocrinology. The clinic serves as a referral site for the ambulatory clinics at DOC, Duke General Internal Medicine clinics, Lincoln clinics, and other clinics and hospitals in the area. Patients seen in this clinic have a variety of endocrine and other medical problems including, but not limited to, diabetes mellitus, hypertension, dyslipidemia, obesity, cardiovascular diseases, endocrine tumors, and diseases of the pituitary, thyroid, parathyroid, adrenals, reproductive system, electrolytes, and bone. In these clinics, trainees serve as the providers for a panel of patients and are fully responsible for the 9
  • 10. coordination of their care. Additionally, trainees have the opportunity to work with a multidisciplinary team of health professionals including pharmacists, psychologists, social workers, and diabetic educators. Site 4 Outreach Endocrine Clinic Underserved Locales throughout North Carolina Roxboro, NC The Outreach Endocrine Clinic provides fellows with further exposure to continuity of care, but with a particular ‘real-world’ experience in underserved areas of the state. Although there are numerous outreach locations throughout NC, each fellow is assigned to one specific clinic and returns to that clinic one-day per month, ensuring continuity. Typically, the fellow will see about 3 new-patient consultations (initial visits) and 3 to 4 return-patient visits in a single clinic session. The disease mix is again excellent as the population presents with issues from all areas of general endocrine. 1.9.2 Additional Facilities and Resources Our hospital has modern facilities and services, including in-patient, ambulatory care and laboratory resources and these are readily available to all trainees. In addition, complete biochemistry laboratories and hormone assays are available 24 hours daily. The hospital has facilities for karyotyping. The Department of Radiology provides MRI, CT, ultrasound, DEXA, PET, and other radiologic imaging services that can conduct studies for all types of endocrine diseases including petrosal sinus and adrenal vein sampling. The hospital supports a dietary/nutritional service. There is a fully staffed surgical pathology laboratory for the interpretation of surgical and cytologic specimens, including immunohistologic studies. Cytologic interpretation of thyroid aspirations is available within a few hours and fellows can review these specimens with the Department of Pathology staff. Nuclear Medicine provides all routine radionuclide-imaging methods including radioiodine thyroid scanning and ablation, adrenal and parathyroid scanning as well as MIBG and technetium pyrophosphate bone scans. Podiatry is available as needed. 1.9.3 Core Conferences Clinical Conferences: Endocrine Fellows Case Conference Educational Purpose: To discuss a variety of diseases of endocrinology, metabolism, and nutrition in considerably greater depth than what can usually be accomplished in the ambulatory care clinics or bedside setting. Correlation with endocrine biochemistry, physiology, and pathophysiology is an integral part of the conference. Teaching Method: This is a fellow-conducted conference: fellows have the responsibility of selecting appropriate cases and preparing presentations. Typically, one fellow will present 1-2 cases per conference in depth, followed by discussion and a presentation of teaching points or relevant literature as well. Disease Mix: All endocrine diseases are discussed. Cases reflecting disorders that may be less commonly encountered in a typical ward or clinic experience are highlighted during this conference. Procedures and Services: Appropriate use of biochemical testing, imaging, and biopsy, as well as review of techniques for the above studies, cytopathology, and pathology are discussed as relevant during conference. Reading Lists and Educational Resources: An integral part of most conference sessions includes hand-out materials summarizing important points, with lists and resources on specific groups of endocrine diseases. Evaluation: Fellows who present at conferences are evaluated by attending physicians who are present at conference. Their performance in this venue is part of the overall evaluation by attendings and the program director. Also see section on evaluation. Specific aspects of the clinical conference-case conference experience: Fellows Case Conference represents a major teaching opportunity for both the individual fellow presenter as well as all those in attendance at these sessions. This allows teaching of 10
  • 11. important points from clinical endocrinology, and, as appropriate, biochemistry and pathophysiology, in a format that also permits open discussion and assessment of appropriate clinical decision-making. Basic Science Conferences: Selected Endocrine Grand Round Sessions, Selected Endocrine Journal Club Sessions, Selected Fellows Didactic Course Sessions Educational Purpose: To instruct trainees in the basic biochemistry, physiology, and pathophysiology of the endocrine system. Subject areas have included molecular biology, immunology as related to endocrinology and metabolism, signal transduction pathways, biology of hormone receptors and principles of hormone action, biology of sexual development, reproductive endocrinology, endocrine aspects of sexual dysfunction, among other topics. [see topic lists below] Teaching Method: Faculty lead the conferences, which are usually in a seminar / open discussion format allowing interaction between the fellows and faculty speaker. Disease Mix: Not relevant Procedures and Services: Not relevant Evaluation: The faculty will evaluate fellows’ participation and interaction, while the fellows will also evaluate the effectiveness of the faculty in communicating the educational topics. Basic Science Conferences are held on a MINIMUM monthly basis, in that Grand Rounds Conferences generally includes at least one session monthly devoted to a basic science topic; this is also well-supplemented by journal clubs and fellows didactic course sessions which alternate basic science topics with clinical discussions. Additionally, many other basic science conferences take place within our institution on a daily basis in both basic science and clinical departments. Their schedules are posted throughout the medical center and its website and fellows are encouraged to attend as time allows. Aspects of the basic science conferences: Examples of recent topics: Fellows Course: Examples of Basic Science Topics: (As noted above, “Subject areas have included molecular biology, immunology as related to endocrinology and metabolism, signal transduction pathways, biology of hormone receptors and principles of hormone action, biology of sexual development, reproductive endocrinology, endocrine aspects of sexual dysfunction, among other topics.”)  -Hypogonadism / hormone receptors -Adrenal anatomy/physiology -Infertility and Contraception -Reproductive Physiology -Congenital Adrenal Hyperplasia and Intersex issues -Genetic Diabetes Syndromes (MODY) -G-Proteins, Receptors, and Endocrine Disease Journal Club Educational Purpose: To discuss a variety of both clinical and basic science aspects of endocrinology, metabolism, and nutrition in greater depth than at the bedside or ambulatory care setting, with an emphasis on emerging endocrine literature. Participation in the conference allows fellows additional training in critical appraisal of the literature, epidemiology, biostatistics, and clinical decision theory. Teaching Method: Fellows are expected to accurately summarize AND critically appraise a paper from the endocrine literature: they present analyses of experimental groups and design, methodology of measurements, and of statistical analysis. The topic is open for an interactive discussion between the presenting fellow, the other fellows who are all in attendance at this session, and attendings who attend as well. Disease Mix: Literature relating to all endocrine diseases are discussed. Procedures and Services: As research concerning endocrine procedures or services is published; those papers may come under discussion in Journal Club 11
  • 12. Reading Lists and Educational Resources: Most sessions include a handout with not only the journal article but also a summary and appraisal sheet. Evaluation: Fellows who present at conferences are evaluated by attending physicians who are present at conference. Their performance in this venue is part of the overall evaluation by attendings and the program director. Also see section on evaluation. Additionally, fellows may evaluate faculty as facilitators of Journal Club and active participants. Journal Club occurs on Thursdays of every other week; (the alternate Thursdays serve as teaching sessions during which Endocrine Board Review Questions are discussed among the fellows and attending educators). Specific aspects of the journal club experience Journal Club is unique in that it allows Endocrine Fellows to continue to develop and hone skills which are initially taught to them during residency: that of accurate and critical appraisal of the literature including attention to study design, methodology, and analyses. Further development of these skills develops physicians who not only can critically interpret the new endocrine literature but who also will focus this type of attention to detail in designing studies of their own. Research Conferences: Discussions of Research occur during Endocrine Grand Rounds and the Stedman Nutrition and Metabolism Center Forums Educational Purpose: To acquaint fellows with the status of current research carried out by the faculty, other fellows, members of other Divisions within the Department of Medicine, or other Departments at Duke Medical Center. Fellows can participate in interactive discussions during these sessions as well. Teaching Method: Interactive discussion of presented research in the areas of clinical and basic science endocrinology and metabolism including design, analysis, and interpretation of the data. Those fellows actively participating in either basic or clinical research will present their research project to the division at least annually: all upper level fellows give Endocrine Grand Rounds at least once per year, and first-year fellows present topics of potential research interest twice yearly. Disease Mix: Research may be presented that relates to any and all endocrine disease. Procedures and Services: .Not applicable Specific aspects: Research Conferences are available to fellows in the Division of Endocrinology, Metabolism, and Nutrition through a variety of venues, resulting in the realistic expectation that fellows attend Endocrine Research discussion sessions at least once monthly, and likely more often. Endocrine Grand Rounds occurs on a weekly basis in the division, and approximately at least twice monthly, Grand Rounds will be a presentation by either a fellow or division faculty in which the presenter’s on- going research is discussed in-depth. Additionally, the Sarah W. Stedman Nutrition and Metabolism Center provides weekly 60-90 minute presentation/discussion sessions wherein members of the endocrine division and experts from throughout the country present their research in the areas of nutrition and metabolism. 1.9.4 Procedures Fellows will obtain a comprehensive understanding of indications, contraindications, limitations, techniques, methods of interpretation, and potential complications of procedures that are required for the diagnosis and management of patients with disorders of endocrinology and metabolism, specifically thyroid fine-needle aspiration. This understanding includes informing the patient about the above aspects of specific procedures and obtaining informed consent. Procedures are taught and supervised by faculty in various patient care settings [settings as described above]. Fellows maintain password protected electronic logbooks to list each procedure and copies are kept. Entries include the name of the patients, identifying numbers, clinical problem, procedure, indication of complications if applicable, and results. All procedures are carried out in accordance with universal precautions and protection of healthcare workers, as defined by Occupational Safety and Health Administration (OSHA). Trainees, along with all other health care personnel at the institution, must participate in annual training sessions on precautions for health-care workers, as detailed by OSHA. 12
  • 13. Specific procedures will be detailed in the disease-specific sections of this curriculum. 1.9.5 Other Competencies Fellows who enter this program have universally been found to have sufficient computer skills to enable them to search the literature electronically and participate in computer-assisted instruction and use electronic information networks; however, there are multiple opportunities for fellows to further develop these skills through offerings at the Duke Medical Center Library and Office of Information Technology. Issues concerning quality assessment, quality improvement, risk management, and cost- effectiveness are discussed in all clinical and laboratory settings throughout the program. Similarly, ethics and professionalism are considered in all patient interactions and may be supplemented by materials provided by the American Board of Internal Medicine. Each fellow is provided materials on ethics and professional standards and is expected to carry out daily activities in accordance with the highest professional standards. Additionally, all fellows involved in clinical research at Duke are required to complete, and update yearly, on-line training modules on specific topics related to ethics in clinical research. Patient education, counseling, and end-of-life care are taught by example when appropriate in interactions with patients and their families. Other issues that concern palliative care for terminally ill patients are discussed when appropriate. Available supplementary teaching materials include publications as follows: 1) Care of the Dying and Promotion of Physician Competency-Educational Resource and Personal Narratives, published by the American Board of Internal Medicine (www.ABIM.org) and 2) EPEC (Education for Physicians on End-of-life Care), published jointly by the Robert Wood Johnson Foundation and the American Medical Association (www.ama- assn.org/ethic/epec). 1.9.6 Research and Other Scholarly Activities Trainees in this program are expected to carry out research and participate in other scholarly activity. During the first year, trainees are expected to learn about the research interests of the faculty members by attending Research Seminars, Journal clubs, or by direct interaction initiated by the faculty, trainee or program director. In general, trainees should reach an agreement to carry out research with a specific faculty member by the middle of the first year of the program. This allows the trainee to learn the literature concerning the research area and begin by repeated interaction with the faculty mentor, to formulate and design an experimental project. Thus, within 6-9 months, the trainee is ready to move into the research arena without delay. In our program, the allotment of time dedicated to research varies over the course of a training year as well as between years of training. In general, the annualized percentage effort for research is: Year 1 10% Year 2 80% The figure for year two is based, as per NIH Training Grant required, on a 60-hour workweek. The research experience in our training program is based on a mentor: trainee relationship that is meaningful, interactive at frequent intervals, and that leads to formulation of the research problem, determination of appropriate experimental design, use of appropriate research methodology, analysis of data, interpretation of results and, eventually, publication in peer-reviewed journals. This is supplemented by biannual research committee meetings with a research mentoring committee, comprised of the primary mentor and two additional faculty co-mentors. In our program, almost all trainees publish in peer-reviewed journals and present their work at national endocrine meetings. In addition to basic and clinical research, trainees will present at Clinical Conferences, Journal Club, and Research Seminars. They are encouraged to write up and publish interesting cases that they encounter during their training. Finally, faculty is encouraged to ask trainees to participate in the writing of invited Chapters or Reviews, with appropriate authorship designation. 13
  • 14. 1.10 Evaluation Evaluation in this program is an ongoing process and occurs in a 360-degree manner. During clinical rotations, the attending is the principal evaluator of the trainee. Trainees are evaluated in all aspects of clinical activities and patient care, including attributes of professionalism. Evaluation forms developed by the American Board of Internal Medicine are employed for this evaluation and the attending and trainee are expected to discuss the evaluation. Trainees are required to keep their own record of procedures indicating who supervised the procedure, and copies of the password procedure logbook or equivalent documents are provided to the program director for the trainee’s file annually. At semiannual intervals, the program director will review the evaluations with each trainee. Trainees will be advanced to a position of greater responsibility after they have demonstrated satisfactory scholarship and professional growth as demonstrated by the six competencies listed in MyEvaluations.Com. A written policy to ensure due process has been developed by the Department of Medicine and is used by all subspecialty divisions in our institution. To future determine the trainees’ factual knowledge, the program director, with the assistance of other faculty members, review questions from the Endocrine Self Assessment Program (ESAP), published by the Endocrine Society and Up-To-Date in a one hour session every second week. To complete the circle of evaluation, trainees will evaluate the faculty members who serve as Attendings and report those evaluations, using forms developed by the American Board of Internal Medicine, to the program director. Trainees, at annual intervals, also evaluate the program as a whole, using American Board of Internal Medicine forms. One faculty meeting each year, during the month following the completion of training, will be devoted, in part, to a review of these evaluations of the faculty and the program. The focus of this meeting will be to review the educational effectiveness of the curriculum. Plans to improve those parts of the program that may not be optimal will be developed at these meetings. Counseling and Remediation: In the unlikely event that a trainee requires remediation in one or more areas that impact on clinical competence, the program director will appoint an ad hoc committee of faculty to develop a plan of remediation, implement the plan and evaluate the trainee’s response. If a faculty member receives poor evaluations as an attending physician, those evaluations and plans for improving performance will be discussed in a meeting with the program director. The research mentor, using forms, will evaluate the research performance of each trainee. Those evaluations will be discussed with the trainee and then forwarded to the program director for review and inclusion in the trainee’s file. 14
  • 15. Section 2: Disorders of the Adrenal Cortex and Medulla 2.1 Introduction A complete understanding of the diseases affecting the adrenal gland is essential for the endocrinologist. Adrenal pathophysiology includes numerous life-threatening conditions ranging from electrolyte disturbances, alterations in blood pressure, and malignancy. Indeed, it is essential that the endocrinologist accurately recognize and promptly manage the patient with adrenal disease. An appropriate knowledge base for this area includes an understanding of the hormonal and neurological regulation of electrolytes and blood pressure, the biosynthesis of steroid hormones and their target tissues/actions, the genetic basis for inherited diseases of the adrenal gland, recognition of adrenal cortical hyper- and hypo-function as well as adrenal medullary hyperfunction, static and dynamic tests of adrenal gland function, adrenal imaging techniques and management of adrenal dysfunction. Many of these diseases affecting the adrenal gland are common, such as the incidental adrenal mass, and will be routinely encountered in most clinical training settings. In contrast, conditions such as a pheochromocytoma are more rare. As noted, however, the latter condition represents an extremely critical medical diagnosis. Thus, appropriate training in adrenal disease will likely reflect a combination of both hands-on clinical encounters and an array of additional learning experiences including both formal teaching and self-directed methods. 2.2 Discussion The training program provides opportunities for the endocrine trainee to develop competence in the clinical evaluation and management of patients with adrenal cortical and adrenal medullary disorders. This clinical experience includes opportunities to diagnose and manage adult outpatients and inpatients of both sexes. The Trainee is given opportunities throughout the training period to assume responsibility for and follow patients to observe the evolution and natural history of these disorders, as well as the efficacy of therapy. 2.2.1 Physiology The endocrine trainee should have a basic understanding of the normal physiology of the adrenal cortex and medulla. This knowledge base should include: (1) Adrenal Gland embryology, anatomy, and zonation (2) Adrenal steroid pathways of biosynthesis, specific enzymatic steps, and steroid hormone structures (3) Steroid metabolism (4) Hypothalamic-pituitary-adrenal axis and normal patterns of ACTH and cortisol secretion (5) Regulation of adrenal glucocorticoid, androgen, and estrogen secretion (6) Factors affecting measured levels of steroids in plasma and urine (7) Molecular and cellular mechanisms as well as physiologic effects of glucocorticoids, mineralocorticoids, androgens, and estrogens (8) Renin-angiotensin-aldosterone system and regular of mineralocorticoid secretion (9) Catecholamine biosynthetic pathway, physiological effects of catecholamines, excretion of catecholamines and catecholamine metabolites The method of education for adrenal physiology should include formal instruction and reading the chapters covering adrenal cortex and adrenal medulla from one of the major endocrine textbooks (1-5) and other resources. 2.2.2 Evaluation and Management of Adrenal Disorders Competency in the evaluation and management of the adrenal disorders required by the Residency Review Committee are listed in the Form at the end of the section (Disorders of the Adrenal). For each disorder listed, the trainee should have a thorough knowledge of: (1) Clinical Presentation (2) Pathophysiology (3) Physical examination findings 15
  • 16. (4) Differential diagnosis (5) Laboratory findings (6) Typical imaging findings (7) Clinical management The primary methods of education for these disorders should be direct clinical experiences and clinical case discussions. These case discussions would usually take place on hospital rounds or in the outpatient endocrine clinic setting, as well as clinical case conferences. The knowledge base of all of the adrenal disorders listed in the Form (Disorders of the Adrenal) should be enhanced with reading appropriate sections of an endocrine textbook (1-5), suggested supplemental articles, and Medline searches. 2.2.3 Rare Causes of Adrenal Disorders The trainee should also be familiar with rare causes of the adrenal disorders listed in the Form. For example, for the category of “Mineralocorticoid Excess,” in addition to primary aldosteronism, the trainee should be familiar with the spectrum of causes from rinin- dependent (eg, renovascular disease, coarctation of the aorta) to renin-independent (eg, 11- B-hydroxysteoid dehydrogenase deficiency, Liddle’s syndrome, hypercortisolism, congenital adrenal hyperplasia). The trainee should be knowledgeable of the special features of Cushing’s syndrome, adrenal insufficiency, aldosteronism, and pheochromocytoma in the hospitalized patient. 2.2.4 Adrenal Hyperplasia; 21-hydroxylase deficiency The trainee should have a thorough knowledge of the clinical presentation, pathophysiology, differential diagnosis, laboratory findings, and clinical management of 21- hydroxylase deficiency and should be familiar with other forms of congenital adrenal hyperplasia. 2.2.5 Hypertension With regard to hypertension, the trainee should know when to consider secondary (endocrine) causes of hypertension and how to manage essential hypertension in patients with endocrine disease (eg, diabetes mellitus). 2.2.6 Glucocorticoid Therapy Although not required by the RRC, a thorough understanding of glucocorticoid therapy should be achieved (see Form). This part of the curriculum includes: (1) Knowledge of the different glucocorticoid preparations (oral and Parenteral) (2) Chronic maintenance glucocorticoid dosing (3) Inpatient and outpatient “stress” coverage dosing (4) Management of glucocorticoid withdrawal including evaluation of hypothalamic pituitary-adrenal axis function (5) Recognition of the manifestations of excessive and insufficient glucocorticoid therapy. 2.2.7 Adrenal Studies and Procedures The endocrine trainee should understand the indications for and the interpretation of all of the tests and procedures listed in the tables below. The trainee should be proficient in identifying normal and abnormal adrenal glands on computerized imaging. Methods of education should include formal instruction, direct clinical experiences, clinical case discussions, and self-directed learning. Dynamic Endocrine Tests Cosyntropin stimulation test – 1 ug and 250 ug Corticotropin-releasing hormone (oCRH) stimulation test 16
  • 17. Dexamethasone suppression tests (DST) oCRH/DST protocol Insulin tolerance test Saline suppression test for aldosterone Clonidine suppression test for norepinephrine Imaging and Radiology Procedures Adrenal venous sampling for aldosterone Inferior petrosal sinus sampling for ACTH with oCRH stimulation Computerized adrenal imaging (CT, MRI) CT-guided adrenal FNA biopsy 123 I-metaiodobenzylguanidine (MIGB) scintigraphy Indium IN-111-labeled pentetreotide (OctreoScan) scintigraphy (6B-131-I)iodomethyl-19-norcholesterol (NP-59) scintigraphy 2.2.8 Evaluation Evaluation of competency should include discussions with faculty on a continuing basis and clinical presentations. Divisional ESAP Review Conferences also include adrenal questions. 2.3 Suggested Reading One of the following general endocrine textbooks The Adrenal Cortex and The Adrenal Medulla. In: A Grossman, ed., Clinical Endocrinology, 2nd ed. London: Blackwell Science Ltd: 1998. Adrenal Cortex. In: DeGroot LJ, Besser M, Burger HG,. James JL, Loriaux DL, Marshall JC, Odell WD, Potts JT, Jr, Rubenstien AH, eds. Endocrinology. 3rd ed. Philadelphia, PA: W.B. Saunders Co; 1995. Felig P, Baxter JD, Frohman LA, eds. Endocrinology and Metabolism, 3rd ed. New York, NY: McGraw-Hill Inc: 1995. Chapter 12 – The Adrenal Cortex, WL Miller, JB Tyrell Chapter 13 – Diseases of the Sympathochromaffin System, PE Cryer Chapter 14 – The Endocrinology of Hypertension, JD Baxter, D Perloff, W Hsueh, EG Biglieri Chapter 15 – Glucocorticoid Therapy, JB Tyrell The Adrenal Glands. In: Becker KL, Bilezikian JP, Bremner WJ, Hung W, Kahn CR, Loriaux DL, Nylen ES, Rebar RW, Roberson GL, Wartofsky L, eds. Principles and Practice of Endocrinology and Metabolism, 2nd ed. Philadelphia, Pa: J.B. Lippincott Co; 1995. Wilson JD, Foster DW, Kronenberg HM, Reed Larson P, eds. Williams Textbook of Endocrinology. 9th ed. Philadelphia, PA: W.B. Saunders Co; 1998. Chapter 12 – The Adrenal Cortex, DN Orth, WJ Kovacs Chapter 13 – Catecholamines and the Adrenal Medulla, JB Young, L Landsberg Chapter 14 – Endocrine Hypertension, R.B. Dluhy, GH Williams CD-ROM UpToDate in Endocrinology and Diabetes (CD ROM Series) (ISSN:190-3496). Available at http://www.uptodate.com. 17
  • 18. Journal Articles Cushing’s Syndrome Findling JW, Raff H. Newer diagnostic techniques and problems in Cushing’s disease. Endocrinol Metab Clin North Am. 1999; 28:191-210. Graham KE, Samuels MH, Nesbit GM, et al. Cavernous sinus sampling is highly accurate in distinguishing Cushing’s disease from ectopic adrenocorticotropin syndrome and in predicting intrapituitary tumor location. J Clinic Endocrinol Metab. 1999: 84:1602-1610. Newell-Price J, Trainer P, Besser M, Grossman A. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocr Rev. 1998: 19:647-672. Raff H. Raff JL, Findling JW. Late-night salivary cortisol as a screening test for Cushing’s syndrome. J Clinic Endocrinol Metab. 1998; 83:2681-2686. Adrenal Insufficiency Betterle C, Greggio NA, Volpato M. Clinical review 93: Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1998; 83:1049-55. Kleerekoper M, Schiebinger R, Gutai JP. Steroid therapy for adrenal disorders – getting the dose right. J Clni Endocrinol Metab. 1997; 82:3923-5. Pheochromocytoma and Mineralocorticoid Excess Dluhy RG, Lifton RP: Glucocorticoid-remediable aldosteronism. J Clinic Endocrinol Metab. 1999; 84:4341-4. Young, WF JR., Pheochromocytoma and primary aldosteronism: Diagnostic approaches. Endocrinol Metab Clin North Am. 1997; 26:801-827. White PC. Disorders of aldosterone biosynthesis and action. N. Engl J Med. 1994; 331:250-258. Nonfunctioning Adrenal Mass Angeli A, Osella G, Ali A, et al: Adrenal incidentaloma: An overview of clinical and epidemiological data from the National Italian Study Group. Horm Res. 1997; 47:279-283. Cook DM, Adrenal mass. Endocrinol Metab Clin North Am. 1997; 26:829-852. Kloos RT, Gross MD, Francis IR, Korobkin M, Shapiro B. Incidentally discovered adrenal masses. Endocr Rev. 1995: 16:460-484. Mantero F. Masini AM, Opocher G, et al. Adrenal incidentaloma: An overview of hormonal data from the National Italian Study Group. Horm Res. 1997; 47:284-289. Hirsutism, Virilization, and Congenital Adrenal Hyperplasia Derksen J. Nagesser SK, Meinders AE, Haak HR, van de Velde CJ. Identification of virilizing adrenal tumors in hirsute women. N Engl J Med. 1994; 331:968-973. Franks S. Polycystic ovary syndrome. N Engl J Med. 1995; 333:853-861. 18
  • 19. Gabrilove JL, Sharma DC, Wotiz HH, Dorfman RI. Feminizing adrenocortical tumors in the male – A review of 52 cases. Medicine. 1965; 44:37-44. Gabrilove JL, Seman AT, Sabet R, Mitty HA, Nicolis GL. Virilizing adrenal adenoma with studies on the steroid content of the adrenal venous effluent and a review of the literature. Endocr Rev. 1981;2:462-470. Pang S. Congenital adrenal hyperplasia. Endocrinol Metab Clin North Am. 1997; 26:853-891. Fluid and Electrolytes Gennari FJ. Hypokalemia. N Engl J Med. 1998; 339:451-458. Distrubances in Control of Body Fluid Volume and Composition. In: BM Brenner, ed. Brenner and Rector’s The Kidney. 5th ed. Philadelphia, PA: W.B. Saunders; 1996. Hypertension August P. Hypertension in men. J Clin Endocrinol Metab. 1999; 84:3451-3454. August P. Oparil S. Hypertension in women. J Clin Endocrinol Metab. 1999; 84:1862-1866. JNC-VI: The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Rockville, MD: National Institutes of Health; November 1997. NIH Publication 98-4080. Sibai BM. Treatment of hypertension in pregnant women. N Engl J Med. 1996; 335:257-265. Setaro JF, Black HR. Refractory hypertension. N Engl J Med. 1992; 327:543-547. Adrenal Studies and Procedures Aron DC, Raff H, Findling JW. Effectiveness versus efficacy: the limited value in clinical practice of high dose dexamethasone suppression testing in the differential diagnosis of adrenocorticotropin-dependent Cushing’s syndrome. J Clin Endocrinol Metab. 1997; 82:1780-1785. Doppman JL, Gill JR Jr. Hyperaldosteronism: Sampling the adrenal veins. Radiology. 1996; 198:309. Oldfield EH, Doppman JL, Nieman LK, et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Engl J Med. 1991; 325:897-905. Torpy DJ, Chenn CC, Mullen N, et al. Lack of utility of 111-In-pentetreotide scintigraphy in localizing ectopic ACTH producing tumors: follow-up of 18 patients. J Clinic Endocrinol Metab. 1999; 84:1186-1192. Yanovski JA, Cutler GB Jr, Chrousos GP, et al. The dexamethasone-suppressed corticotropin-releasing hormone stimulation test differentiates mild Cushing’s disease from normal physiology. J Clin Endocrinol Metab. 1998; 83:348-352. 19
  • 20. Self-Assessment Tests Endocrine Society’s Endocrine Self-Assessment Program (ESAP). Available at http://www.sales.uptodate@bdrinc.com/. American Association of Clinical Endocrinologists (AACE). Self-Assessment Profile (ASAP) for Endocrinology, Diabetes and Metabolism. Available at http://aace.com/asapindex.htm. 20
  • 21. Adrenal Disorders Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 1. Cushing’s syndrome a) Adrenal X X X X X X X X X b) Pituitary X X X X X X X X X c) Ectopic X X X X X X X X X d) Iatrogenic X X X X X X X X X 2. Adrenal Insufficiency a) Primary (including X X X X X X X X X polyglandular) b) Secondary X X X X X X X X X c) Adrenal crisis X X X X X X X X X d) Glucocorticoid therapy X X X X X X X X X 3. Pheochromocytoma X X X X X X X X X 4. Mineralocorticoid excess a) Aldosteronism X *X X X X X X X X 5. Nonfunctioning adrenal mass (including incidentaloma) a) Benign X *X X X X X X X X b) malignant X *X X X X X X X X 6. Hirsutism and virilization X *X X X X X X X X 7. Congenital adrenal hyperplasia X *X X X X X X X X 8. Fluid and electrolytes a) Hypernatremia and hyponatremia X X X X X X X X X b) Hypokalemia and hyperkalemia X X X X X X X X X c) Metabolic acidosis and alkalosis X X X X X X X X X 9. Hypertension a) Primary (essential) X X X X X X X X X b) Secondary (endocrine) X X X X X X X X X *Most often seen in outpatient setting 21
  • 22. Section 3: Bone and Mineral Disorders 3.1 Introduction A clear understanding of disorders of bone and mineral metabolism is a critical component of the fellowship in Endocrinology, Diabetes, and Metabolism. Osteoporosis is the major public health problem in this area. It is responsible for at least 1.3 million fractures and costs $13.8 billion in direct health care costs in the United States each year. The lifetime risk of a fracture of the vertebrae, wrist, or hip due to osteoporosis is nearly 40% for white women and increases to about 50% when other age-related fractures are included. Although osteoporosis is more common in women, men also incur substantial bone loss with aging, and elderly men have age-specific hip fracture rates and a prevalence of vertebral fractures that are at least half those in women. Given the widespread prevalence of osteoporosis, the endocrinology trainee needs to learn to work with the patient’s primary care and other physicians in providing appropriate consultative and management advice in the care of patients with osteoporosis. In addition to osteoporosis, a number of other disorders of bone and mineral metabolism are commonly referred to the practicing endocrinologist for evaluation and management. There include primary hyperparathyroidism, hypercalcemia of malignancy, Paget’s disease and nephrolithiasis. The remainder of the disorders in this area, while less common, clearly require the knowledge and experience of an endocrinologist to accurately diagnose and manage. These include hypoparathyroidism, other forms of hyper- and hypocalcemia, as well as disorders of other minerals (ie, magnesium and phosphorus), osteomalacia in its various forms, and developmental bone disorders. The overall competencies that an endocrinology trainee needs to acquire in this area begins with a solid understanding of the anatomy and biology of bone matrix and cellular elements. It is implied that trainees will have undertaken previous coursework in skeletal anatomy and physiology in their medical school training, which will be further enhanced throughout the course of their fellowship training. S/he will also be well versed in the physiology of calcium, magnesium, and phosphorus homeostasis, and understand the biochemistry of the calcium-regulating hormones. With this as a background, the trainee will become competent in the clinical evaluation of bone and mineral disorders, including obtaining a relevant, comprehensive history and performing the relevant physical examination, as well as ordering and interpreting the appropriate laboratory tests in a cost-effective manner. The specific disorders and the management skills needed for each are described below. Clinical experience will also include opportunities to diagnose and manage patients of both sexes in both the inpatient and outpatient setting. The trainee must also learn to function as a consultant for other physicians in these disorders. To truly understand the evolution and natural history of bone and calcium disorders, as well as the effectiveness of therapeutic interventions, the bone and mineral educational program will dedicate at least 30% of the experience in this area to the ambulatory care setting. Indeed, the majority of clinical training will occur in both bone and general endocrine outpatient clinics, complemented by inpatient consultation and management of acute and non-acute calcium and mineral disorders. The overall training program will facilitate the acquisition of these skills through a number of tools. These include, but are by no means limited to, didactic lectures, interactive computer programs and/or web based resources, oral case presentation and discussion, and most importantly, direct and close supervision by the faculty of trainee evaluation and management of patients with as wide a spectrum as possible of bone and calcium disorders. Evaluation. Clear mechanisms will be in place for the evaluation of the trainees and the provision of positive and negative feedback. Evaluation will occur in the form of faculty critiques of the trainee’s performance and informal Endocrine Self-Assessment Program (ESAP) question and answer sessions. Two self-assessment examinations are also available (ESAP and AACE). Feedback will be provided both orally on a biannual basis as well as using written evaluation sheets. In addition, trainees will have an opportunity and a mechanism for providing feedback to the faculty regarding the quality of teaching and mentoring they receive. 3.2 Discussion The section below summarizes the key learning areas for the clinical training program. 22
  • 23. 3.2.1 Biology of Bone The necessary basic background in this area includes an understanding of the fundamentals of bone biology. Specifically, the trainee will understand the macroscopic and microscopic structure of bone, as well as the fundamentals of bone remodeling and growth (ie, the processes of intramembranous and endochondral ossification). S/he will also have a knowledge of the cells in bone, specifically osteoblasts, osteocytes, and osteoclasts, as well as the composition and mineralization of the bone matrix. Finally, s/he will become familiar with the various systemic and local factors regulating bone development and remodeling. 3.2.2 Physiology of Calcium, Magnesium, and Phosphorus Homeostasis A basic understanding of mineral homeostasis will include knowledge of the factors regulating intestinal absorption, renal handling, and flux in and out of bone of these compounds. Included in this is the role of systemic hormones (1,25(OH)2D, PTH, growth hormone, estrogen, glucocorticoids, and others) as well as dietary factors (intake of these minerals, other factors such as sodium intake). The trainee will also have an understanding of alterations in calcium and phosphorus homeostasis during physiological states such as puberty, pregnancy, lactation, and aging. 3.2.3 Molecular Biology, Biochemistry, and Mechanism of Action of Calcitropic Hormones The trainee will have an understanding of the synthesis and secretion of PTH, its peripheral metabolism, and mechanism of action. S/he will have an understanding of the role of the calcium- sensing receptor in normal physiology. The trainee will understand the role of PTH-rP in malignancy. S/he will understand the synthesis, metabolism, and action of vitamin D and its key metabolite, 1,25(OH)2D. S/he should be aware of the potential normal skeletal and non-skeletal actions of PTH-rP and 1,25(OH)2D. Finally, s/he will have an understanding of the synthesis and secretion of calcitonin, as well as its action on bone resorption. 3.2.4 Clinical Evaluation of Bone and Mineral Disorders The trainee will learn to obtain a comprehensive but relevant history and perform the appropriate physical examination. This will include a detailed musculoskeletal examination, as well as other parts of a comprehensive examination (eg, gonadal exam) when appropriate. 3.2.5 Laboratory Methods The trainee will acquire an understanding of the methods, strengths, and limitations of the various measurements s/he will be requesting. S/he will understand issues of assay accuracy, variability (assay and biologic) and detection limits. S/he will be able to integrate a number of tests and recognize specific patterns of test abnormalities associated with various disease states. The trainee will have knowledge of abnormalities in protein binding that might affect serum calcium measurements, as well as possible artifacts/physiological alterations in the serum phosphorus and magnesium determinations. S/he will understand issues regarding the collection and interpretation of ionized calcium and urinary calcium measurements. S/he will have a full understanding of PTH assays, including the effects on the assay of changes in renal function, and the correct interpretation of the assay in light of the ambient serum calcium concentration. Similarly, s/he will have a basic knowledge of calcitonin assays. More recently, assays for PTH-rP have become available, and the trainee will have an understanding of when a PTH-rP level may be useful in the evaluation of the patient. S/he will have a knowledge of assays for 25-OHD and 1,25(OH)2D, and understand the situations warranting either the 25-OHD measurement (ie, in the evaluation of vitamin D deficiency or intoxication) or the 1,25(OH)2D measurement (as, for example, in the evaluation of possible granulomatous hypercalcemia). The trainee will also understand gonadal steroid and other hormonal measurements as they apply to the evaluation of bone and calcium disorders. The recent availability of biochemical markers of bone turnover has added another tool for the evaluation of osteoporosis and other metabolic bone diseases. The trainee will develop a working knowledge of markers of bone formation and resorption, and their potential uses. Finally, the trainee will have basic knowledge of molecular diagnostics, particularly as they apply to disorders of bone and calcium metabolism. This includes a basic understanding of the different 23
  • 24. techniques of molecular diagnostics (ie, mutation identification using single-strand conformational polymorphism, direct DNA sequencing, restriction endonuclease analysis, etc.). While general applicability of these techniques at this point is principally for the MEN syndromes, clearly they will be increasingly used in the future in the laboratory evaluation of bone and mineral disorders. 3.2.6 Imaging Techniques/Other Procedures The training program has a close working relationship with skeletal radiologists who can provide expert interpretation of bone radiographs of adults and children. The trainee will acquire the basic fundamental skills to recognize the radiographic appearance of at least common metabolic bone diseases (ie, osteoporosis, hyperparathyroidism, osteomalacia, Pagets, etc.). Similarly, s/he will have an understanding of bone scintigraphy and its appropriate use. Understanding bone mass measurements is a critical component in the evaluation of osteoporosis. The trainee will also have knowledge of the technical aspects of DEXA measurements, and understand issues of quality control, precision, and interpreting DEXA measurements, both in terms of diagnosing osteopenia and osteoporosis, as well as in interpreting longitudinal changes. S/he should also have a basic understanding of the use of DEXA for assessment of body composition. S/he should also be familiar with other available technologies, such as quantitative CT, ultrasound, and digital radiography. The trainee may, if possible, acquire the skills to perform and interpret bone biopsies. Bone histomorphometry is useful in the evaluation of difficult metabolic bone diseases, and still remains instrumental for the definitive diagnosis of osteomalacia and renal osteodystrophy. The trainee will learn the fundamentals of parathyroid imaging (scan and ultrasound), including the appropriate use of these tests in the cost-effective evaluation of the hyperparathyroid patient. S/he will also learn the appropriate use of CT and MR imaging in the evaluation of patients with persistent or recurrent hyperparathyroidism. 3.2.7 Postmenopausal and Age-Related Osteoporosis As noted in the introduction, osteoporosis is the major public health disorder in this area, and likely the most common referral diagnosis. As such, the trainee will develop a thorough understanding of the epidemiology and current concepts of the pathogenesis of postmenopausal and age-related osteoporosis. The trainee will also be familiar with the impact of physical activity and nutritional factors (in particular, calcium and vitamin D nutrition) on bone mass and of factors such as medications, impaired vision, and propensity to fall on fracture risk. S/he will be able to advise the patient on appropriate prevention measures, and learn to manage the woman going through the menopausal transition. S/he will be well versed in the diagnostic evaluation of osteoporosis, including the correct interpretation of BMD data within the context of the clinical setting of the particular patient. S/he will be able to exclude secondary causes of osteoporosis, including multiple myeloma, underlying malignancy, primary hyperparathyroidism, osteomalacia, and osteogenesis imperfecta. S/he will be comfortable with the use of both non-pharmacologic (ie, lifestyle changes, calcium supplementation, and, working with a physical therapist with a specific interest in exercise management of osteoporosis, prescription of appropriate physical therapy, exercise and alteration of body mechanics) and pharmacologic measures (HRT, SERMs, bisphosphonates, calcitonin, and PTH, when available) for the treatment of osteoporosis. S/he will be able to evaluate the patient who has sustained an osteoporotic fracture and institute measures to reduce the risk of subsequent fractures. The trainee will also be familiar with issues of pain management in patients with vertebral or other fractures. Finally, s/he should have the opportunity to work with the Orthopedist in the evaluation of patients with delayed healing of fractures. 3.2.8 Other Forms of Osteoporosis In addition to postmenopausal and age-related osteoporosis, the trainee will also be familiar with the evaluation and management of other forms of osteoporosis. Principal among these are glucocorticoid- and increasingly, transplant-associated osteoporosis. S/he should work closely with the primary physicians in the management of these difficult patients, since particularly the post- transplant patient often has multiple endocrine abnormalities (ie, hyperglycemia, hyperlipidemia) in addition to the metabolic bone disorder. Where appropriate, the trainee should advise on the 24
  • 25. management of all of the multiple endocrine/metabolic derangements in these patients. The trainee will also be familiar with other skeletal complications of glucocorticoid use, including a vascular necrosis. In addition, the trainee will also know how to evaluate and manage other forms of osteoporosis, including idiopathic (male and female) osteoporosis and various forms of secondary osteoporosis. 3.2.9 Rickets and Osteomalacia While less common than the various forms of osteoporosis, the trainee will learn to evaluate and treat the osteomalacic disorders and to distinguish these from osteoporosis. Nutritional vitamin D deficiency is particularly a problem in the elderly, and increases significantly the risk of hip fracture. In addition, recognition of vitamin D deficiency often uncovers a previously unsuspected diagnosis, such as non-tropical sprue, in an otherwise minimally symptomatic patient. The trainee will know the appropriate tests to order in this setting (ie, 25-hydroxyvitamin D level, PTH, urine calcium, anti-gliadin and anti-endomyseal antibodies), including possibly a bone biopsy when needed. Inherited disorders of vitamin D action or phosphate handling can be difficult to manage, and the trainee should have appropriate exposure to these if available. The evaluation of patients with tumor-induced osteomalacia is often extremely difficult, as the underlying tumor may be impossible to identify. As such, the trainee will also be familiar with the medical management of these patients. 3.2.10 Hypocalcemic Disorders The trainee will know how to manage acute hypocalcemia as, for example, in the post-operative setting. This includes the use of intravenous calcium preparations and when they are indicated. S/he will also be able to manage chronic hypocalcemia with oral calcium and vitamin D preparations and, if indicated, a thiazide diuretic. Working with a dietician, s/he should be able to advise the patient with hypoparathyroidism regarding dietary phosphate restriction, and use phosphate binders when indicated. S/he will also be able to assess the patient with various forms of hypocalcemia, including that due to acute pancreatitis, acute illnesses, and associated with the use of various medications. The trainee will also know the various types of parathyroid resistance syndromes and the appropriate testing necessary to establish a diagnosis of pseudohypoparathyroidism. S/he should be familiar with possible resistance to other hormones as well as the non-endocrine disorders in these patients. 3.2.11 Renal Osteodystrophy While primarily managed by the nephrologist, the endocrine trainee will have a clear understanding of renal osteodystrophy in its various forms, including secondary and tertiary hyperparathyroidism. The role of the endocrinologist may be most important during and following parathyroid surgery in these patients, and the trainee must be familiar with the post-operative management of these patients, particularly hungry bone syndrome. Use of bone biopsy and bone histomorphometry is particularly useful in the evaluation of renal osteodystrophy and if possible, the trainee may acquire appropriate training in these techniques. 3.2.12 Paget’s Disease The trainee will be familiar with current concepts of the pathogenesis, natural history, and treatment of Paget’s disease. The evaluation and management of Paget’s disease involves an understanding of the appropriate laboratory studies to identify the extent and severity of the disease (bone markers, scintigraphy, and radiographs), as well as combining this data with the patient’s symptoms, leading to a decision about appropriate therapy. The latter may include observation or pharmacologic therapy with calcitonin, oral, or intravenous bisphosphonates. 3.2.13 Hypercalcemic Disorders The trainee will have a full understanding of the evaluation and management of hypercalcemia. S/ he will be able to use the PTH assay to make a diagnosis of primary hyperparathyroidism versus non- parathyroid hypercalcemia (ie, hypercalcemia of malignancy, that due to granulomatous disorders, or other miscellaneous causes of hypercalcemia). S/he will be comfortable differentiating primary hyperparathyroidism from FHH, as well as pursuing, where appropriate, a diagnosis of familial 25
  • 26. hyperparathyroidism or an MEN syndrome. Included in this is an understanding of genetic testing for these syndromes. If a diagnosis of primary hyperparathyroidism is established, the trainee will know the necessary evaluation of these patients leading to a decision regarding surgical or medical management. If the patient goes for surgery, the trainee will be familiar with the peri- and post-operative management of these patients, including post-operative hypocalcemia. Specifically, the trainee will be able to distinguish hungry bone syndrome from post-operative hypoparathyroidism, and manage both appropriately. If a decision is made for medical therapy or observation, the trainee will be familiar with the follow-up of these patients and the endpoints that would result in a recommendation for surgery. Finally, s/he will be familiar with evolving approaches to the management of patients with primary hyperparathyroidism, both surgical (ie, minimal access parathyroidectomy, alcohol ablation) and medical (ie, bisphosphonates, calcium sensing receptor agonists). In addition to primary hyperparathyroidism, the trainee will know the evaluation and management of parathyroid cancer. S/he will be able to effectively evaluate and manage the patient with hypercalcemia in the setting of a suppressed PTH (ie, hypercalcemia of malignancy, that due to granulomatous disorders). 3.2.14 Other Mineral Abnormalities The trainee will be able to identify the possible causes of hypo- and hypermagnesemia in a patient, and to institute appropriate therapy. S/he will be able to identify situations in which hypomagnesemia is the cause or contributing to hypocalcemia. S/he will also be able to identify the etiology of hyper- or hypophosphatemia in a patient, and to treat these conditions. 3.2.15 Nephrolithiasis The trainee will be able to evaluate the patient with nephrolithiasis. Based on the type of stone and the evaluation (ie, identification of hypercalciuria, hyperoxaluria, hyperuricosuria, or low urinary citrate), the trainee will be able to identify any underlying disorders such as primary hyperparathyroidism or enteric hyperoxaluria. S/he will know the medical management of the patient based on this evaluation, and to work with a dietician in the appropriate dietary management of these patients. 3.2.16 Genetic, Developmental, and Dysplastic Skeletal Disorders The trainee should be familiar with these disorders, which can present both in children and in adults. These include various sclerosing bone disorders and skeletal dysplasias. The trainee should also be able to evaluate the patient referred because of an elevated bone density, in the absence of radiographic sclerosis. An experienced skeletal radiologist, which is available at Duke, is a great asset to the training program in the accurate diagnosis of these conditions based on the radiographic findingsThe trainee should have exposure to the evaluation and management of patients with osteogenesis imperfecta as well as appropriate medical management of both the skeletal aspects of fibrous dysplasia and, when present, the management of precocious puberty in these patients. 3.2.17 Skeletal Neoplasms/Infiltrative Disorders The trainee should be able to identify benign and malignant skeletal neoplasms on skeletal radiographs, and institute appropriate referrals to the orthopedic surgeon as well as the radiation and medical Oncologists. S/he should also be familiar with the various infiltrative disorders of bone, including mast cell disease and histiocytosis X. 3.2.18 Extraskeletal Calcification/Ossification These include relatively uncommon conditions such as tumoral calcinosis, dermatomyositis, and various ossification disorders. While the trainee may not necessarily have the opportunity to mange these relatively rare conditions, s/he should be familiar with these disorders and their treatment. 3.3 Suggested Reading Favus MJ, ed. Primer on Metabolic Bone Diseases and Disorders of Mineral Metabolism, Fourth Edition, Lippincott-Raven, Philadelphia, 1999. 26
  • 27. Disorders of Bone and Mineral Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 1. Biology of Bone a) Anatomy/ultrastructure X X X b) Osteoblasts/osteocytes/ X X osteoclasts X c) Bone matrix/mineralization X X X X X X d) Regulation of bone remodeling X X X X X X 2. Physiology of calcium, magnesium and phosphorous homeostasis a) Intestinal absorption X X X X X X X X X b) Renal handling X X X X X X X X X c) Calcium flux in/out of bone X X X X X X X X X d) Mineral balance & homeostasis X X X X X X X X X 3. Molecular biology, biochemistry, and mechanism of action of calcitropic hormones a) Synthesis & Metabolism of PTH X X X X X X X X X b) PTH – Mechanism of action X X X X X X X X X c) PTH – rP X X X X X X X X X d) Vitamin D and metabolites X X X X X X X X X e) Calcitonin X X X X X X X X X 4. Clinical Evaluation of Bone and Mineral Disorders a) Comprehensive, relevant history X X X X X X X X b) Physical examination X X X X X X X X 5. Laboratory Methods/Understanding assays for: a) Calcium, phosphorus, and X X X X X X X X X magnesium b) Ionized calcium X X X X X X X X X c) PTH X X X X X X X X X d) Calcitonin X X X X X X X X X e) PTH-rP X X X X X X X X X f) Vitamin D metabolites X X X X X X X X X g) Urinary calcium X X X X X X X X X h) Biochemical markers for bone X X X X X X X X X turnover i) Molecular diagnosis of bone and X X X X X X X X mineral disorders 27
  • 28. Disorders of Bone and Mineral (page 2) Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 6. Imaging techniques/other procedures a) Bone radiology in children and X X X X X X X X X adults b) Bone scintigraphy X X X X X X X X X c) Bone density and measurement X X X X X X X X X d) Bone biopsy X X X X X e) Bone histomorphometry X X X X X f) Parathyroid imaging X X X X X X X X X 7. Postmenopausal and Age-related osteoporosis a) Epidemiology X X X X X X X X b) Pathogenesis X X X X X X X X X c) Role of physical activity X X X X X X X X X d) Nutrition and osteoporosis X X X X X X X X X e) Prevention of osteoporosis X X X X X X X X X f) Evaluation and treatment of X X X X X X X X X osteoporosis 8. Other forms of Osteoporosis a) Juvenile osteoporosis X X X X X X X X X b) Idiopathic (male and female) X X X X X X X X X osteoporosis c) Glucocorticoid osteoporosis X X X X X X X X X d) Transplant related osteoporosis X X X X X X X X X e) Other forms of secondary X X X X X X X X X osteoporosis 9. Rickets and osteomalacia a) Nutritional rickets and X X X X X X X X osteomalacia b) Bone disease secondary to X X X X X X X X GI/Liver d/o c) Vitamin D Dependent rickets X X X d) Hypohosphatemic rickets X X X X X X X e) Tumor induced osteomalacia X X X X X X X f) Hypophosphatasia X X X X X X g) Fanconi syndrome and RTA X X X X X X h) Drug induced osteomalacia X X X X X X 28
  • 29. Disorders of Bone and Mineral (page 3) Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning with Patients Faculty Inpatient Outpatient Attd. Rd. Conferences 10. Hypocalcemic disorders a) Hypoparathyroidism X X X X X X X X X b) Parathyroid resistance X X X X X X X X X c) Misc causes of hypocalcemia X X X X X X X X X 11. Renal osteodystrophy X X X X X X X X X 12. Paget’s Disease X X X X X X X X 13. Hypercalcemic disorders a) Primary hyperparathyroidism X X X X X X X X X b) Familial hpt syndromes/MEN X X X X X X X X c) Familial hypocalciuric X X X X X X X X hypercalcemia d) Hypercalemia of malignancy X X X X X X X X X e) Hypercalcemia due to X X X X X X X X X granulomatous d/o f) Other, misc causes of X X X X X X X X X hypercalcemia 14. Other mineral abnormalities a) Magnesium depletion and X X X X X X X X hypermagnesemia b) Hyper- and hypophosphatemia X X X X X X X X X 15. Nephrolithiasis X X X X X X X X 16. Genetic, developmental, and X X X X X X X dysplastic d/o 17. Skeletal neoplasms/infiltrative d/o X X X X X X X 18.Extraskeletal X X X X X X X calcification/ossification 29
  • 30. Section 4: Diabetes 4.1 Introduction Diabetes is an increasingly common, potentially devastating, extraordinarily expensive, treatable, but incurable, chronic disease. It is by far the most common endocrine disorder that seriously impacts health and limits longevity in those affected. An estimated 16 million Americans, and 135 million people world wide, have diabetes. The World Health Organization projects the latter will grow to 300 million by the year 2025. Many more have impaired glucose tolerance or impaired fasting glucose and area at high risk for atherosclerotic disease and diabetes. People with diabetes are at 2- to 4-fold increased risk for a myocardial infarction or a stroke. Diabetes is the leading cause of blindness with its onset in working age adults and of non-traumatic amputations, and the most common single cause of end-stage renal disease requiring dialysis and transplantation. Medical care for people with diabetes costs approximately $100,000,000,000 per year in the United States. Much of this is for the care of long-term microvascular and macrovascular complications of diabetes that are now known to be in large part preventable. 4.2 Discussion 4.2.1 Sequelae of Treatment It is now well established that treatment makes a long-term difference for people with diabetes. Currently available treatments are far from ideal, but they are demonstrably effective. These treatments involve an integrated care team (eg, an endocrinologist, a diabetes educator, a nutritionist). Among the specific objectives of our training program is to teach our trainees (residents) in Endocrinology, Diabetes and Metabolism to know and understand the evidence that are in people with diabetes. (1) glycemic control reduces the risk of microvascular events (retinopathy, nephropathy and neuropathy( and may reduce macrovascular events: (2) treatment of dyslipidemia reduces the risk of macrovascular events: (3) treatment of hypertension and even early nephropathy reduces end-stage renal disease and other microvascular as well as macrovascular events; (4) aspirin reduces macrovascular events; (5) treatment of early retinopathy reduces blindness; (6) foot care reduces amputations; and (7) implementation of Standards of Care results in better glycemic control and reduces cost. 4.2.2. Treatment Goals and Minimum Outcome Measures Additional objective are to know, understand, and pursue the recommended treatment goals (updated by the ADA in each January issues of Diabetes Care) and minimum outcome measures shown in the following tables. Treatment Goals Goal Action Required* Hemoglobin A1C (%) <7 >8 Preprandial Glucose 80-120 <80,>140 (mg/dL) Bedtime Glucose (mg/dL) 100-140 <100,>160 LDL Cholesterol (mg/dL) <100 >130 Triglycerides (mg/dL) <200 >400 Blood Pressure (mm Hg) <130/85 >135/90 Urine Microalbumin Normal Elevated ____________________________________________________________________________ *Actions might include additional self management education, medical nutrition therapy, or both; increased SMGB, patient contact, or both; adjustments of meal plan, exercise, or pharmacological therapy; or co- management or referral to a diabetes specialist. In some individual patients it may be appropriate not to 30
  • 31. act, but the rationale for that decision should be made explicit. These goals need to be modified for children with diabetes. Minimum Outcome Measures Hemoglobin A1C Annually* Dilated Eye Exam Annually Foot Exam Annually Blood Pressure Annually Urine Microalbumin Annually Fasting Lipid Profile Annually Self Management Education Annually Medical Nutrition Therapy Annually Serum TSH Annually Self Blood Glucose Monitoring Yes Tobacco Counseling Yes ___________________________________________________________________________ *ADA Recommendation: Quarterly until glycemic control is achieved, then semiannually or annually. 4.2.3 Comprehensive Patient Evaluation Given this knowledge it is our objective to teach trainees to evaluate patients with diabetes comprehensively including assessments of: (1) glycemic control (long-term with HbA1c, short-term with the history and the SMBG log including identification of both hyper-and hypoglycemia); (2) blood pressure control; (3) lipid control (fasting lipid profile); (4) the status of microvascular complications (history, dilated eye examination, detailed foot examination including monofilament testing, urine albumin); (5) macrovascular complications (history, cardiovascular examination); (6) the need for addition self management education, medical nutrition therapy, or both; and (7) smoking status. The basic principles are emphasized throughout the trainee’s training experiences in our inpatient and outpatient care settings as well as in our didactic program and our clinical conferences. It is our premise that, while complications of diabetes must be detected and treated in their early stages, the prevention of complications through comprehensive diabetes care is the new paradigm in the management of diabetes. An additional objective of our program is to provide, through research experience and didactic instruction, insights into the basic and clinical scientific advances that will lead to improvements in the prevention and treatment of diabetes and its complications. 4.2.4 Clinical Experience Our training program provides opportunities for the trainee in Endocrinology, Diabetes, and Metabolism to develop clinical competence and expertise in the management of diabetes. Our educational program, including the mission of the Division of Endocrinology, Diabetes and Metabolism, the educational goals and objectives and the anticipated educational outcomes of the fellowship program, its methodologies for teaching, faculty, methods of evaluation and its educational settings (inpatient consultations, outpatient clinics and conferences including the formal didactic program), was detailed in Section I. Our facilities and resources were described in Section II. Its clinical experiences as they relate to diabetes are described in the paragraphs that follow. The clinical experiences of our trainees include opportunities to diagnose and manage inpatients and outpatients, representing adolescent and adult patients of both sexes and representing variable acuity, with both types 1 and 2 diabetes as well as the uncommon types of diabetes. It also includes opportunities for the trainee to function in the role of consultant for patients and other physicians and services in both inpatient and outpatient settings. Training in comprehensive diabetes care occurs repetitively in the setting of the trainee’s supervised inpatient and outpatient care of people with diabetes, and in the context of our didactic diabetes teaching 31
  • 32. program. The latter includes lectures (e.g. Patient Diabetes Education, Management of Diabetic Ketoacidosis, Insulin Pump Management, Nutritional Guidelines for Patients with Diabetes, pathophysiology of Diabetes, Diabetes in Pregnancy, Management of Patients with MODY and Other Less Common Forms of Diabetes, Management of Dyslipidemia – an Evidence Based Approach). Additionally, trainees spend 1/3 of the first year of training on the inpatient consult service for diabetes. During this time, they receive individualized, faculty-directed, patient-based instruction in diabetes management. Both faculty-directed and self-directed reading about diabetes, including both general and specific topics is encouraged. In this context trainees become competent and then expert in the comprehensive management of diabetes through supervised, progressive responsibility for the care of people with diabetes in their inpatient and outpatient activities throughout their fellowship training. This allows them to observe the natural history of diabetes and its complications, as well as the effectiveness of therapeutic interventions. Trainees have experience representing variable acuity and the full spectrum of diabetes. Patient Encounters, Trainee Supervision and Evaluation Patient encounters are supervised by a member of the Endocrinology, Diabetes and Metabolism faculty who reviews the historical, physical, and other information gathered by the trainee with that trainee at the bed side/examination table and provides immediate confirmatory or corrective feedback. That faculty member then reviews the trainee’s diagnostic and therapeutic plans, again providing immediate feedback. Learning is facilitated further by self-directed reading of the literature, reading suggested by the responsible faculty member or both, and by patient follow-up. The latter includes analysis of subsequent laboratory findings and of the patient’s course with refinement of the management plan over time, again in consultation with the responsible faculty member. Thus, learning is evaluated by direct observation of the trainee by the faculty member and discussions with that and other faculty and colleagues including presentations at rounds and case conferences as well as by assessment using ESAP questions. Biochemistry and Physiology Our curriculum emphasizes biochemistry and physiology, including cell and molecular biology as they relate to diabetes and its complications. These are fundamental to the management of diabetes. The appropriate utilization and interpretation of clinical laboratory, radionuclide and radiologic studies for the treatment of diabetes is stressed throughout the clinical and didactic program. Preventive Care Trainees have clinical experience in multidisciplinary diabetes education and treatment programs. As detailed earlier, our program emphasizes the training of fellows in the preventive aspects of diabetes care (i.e. glycemic control, lipid control, blood pressure control, aspirin, smoking cessation etc. and the identification and treatment of early microvascular and macrovascular complications) in the context of the Standards of Care and Outcome Measures recommended by the American Diabetes Association (updated each January in Diabetes Care) [or the Medical Guidelines for the Management of Diabetes Mellitus recommended by the American Association of Clinical Endocrinologists (Endocrine Practice 6:43, 2000).] Patient education by the physician, the diabetes educator, the nutritionist and other specialists is a fundamental component of diabetes care. Because diabetes is so common, patients with this disease are seen by trainees in virtually all of their inpatient and outpatient encounters and the team approach is also utilized in all of those settings. Multidisciplinary diabetes education and treatment is emphasized during the inpatient diabetes consult service. Trainees work closely with both diabetes educators and nutritionists to establish appropriate care plans for patients with diabetes. Likewise, trainees utilize the services of both diabetes educators and nutritionists in the outpatient setting as an adjunct to the management of their patients with diabetes. Accreditation Council for Graduate Medical Education Program Requirements The ACGME Program Requirements for Residency Education in Endocrinology, Diabetes, and Metabolism include a heavy emphasis on diabetes. Training in each of the proposed areas is provided in various formats during the fellowship curriculum. 32
  • 33. Inpatient Diabetes Management Service Trainees spend 1/3 of the first year on the inpatient Diabetes Management Service. During this time, trainees are under the direct supervision of endocrine faculty with expertise in diabetes. Trainees interact with patients, house staff, and a multidisciplinary diabetes team to facilitate the care of hospitalized patients with diabetes. During this rotation, trainees gain extensive experience in the management of both acute and chronic complication of both type 1 and type 2 diabetes, including diabetic ketoacidosis, hyperosmolar non-ketotic syndrome, hypoglycemia, and infections in the diabetic patient. Trainees are often primarily responsible for the management of surgical patients with diabetes and gain expertise in the utilization of intravenous insulin in acutely ill patients, chronic insulin administration (including use of all varieties of insulin and insulin delivery systems), and oral anti-diabetic therapy. While on the Diabetes Management Service, trainees work closely with a multidisciplinary team, including dieticians, a clinical diabetes educator, and a nurse practitioner certified in advanced diabetes management. Through their extensive contact with these specialists, trainees become expert in the provision of patient and family education, dietary principles, rationale for and calculation of diabetic diets, prescription of exercise programs, use of glucose monitoring devices and all forms of insulin delivery systems (including insulin pumps, insulin pens, etc), and foot care. The inpatient Diabetes Management Service also works with the obstetrics and gynecology services to assist in the management of both gestational diabetes and diabetes in the pregnant patient. Likewise, the service is frequently involved in the care of patients with cystic fibrosis related to diabetes. Again, trainees work closely with dieticians, diabetes educators, and social workers to address all aspects of diabetes care. Particular attention is given to the psychosocial effects of diabetes in this patient population. A major focus of the inpatient service is not only to provide excellent inpatient care of diabetes, but to ensure that patients will be able to continue that care on an outpatient basis. Trainees gain extensive experience, not only in the technical aspects of diabetes management, but also in the importance of psychological issues surrounding the care of diabetes and in the psychosocial effects of diabetes on both patients and families. Patient education, family education, and the empowerment of patients to direct their own care are frequent themes of training during this rotation. Outpatient Continuity Clinics Trainees have extensive experience in diabetes care as part of a multidisciplinary diabetes and education program via the outpatient continuity clinics. Patient monitoring and treatment objectives are taught repetitively under the supervision of responsible faculty. Trainees are required to know, understand, and pursue the recommended treatment goals and minimum outcome measures as stated in the recommendations updated each year by the ADA. In the outpatient setting, trainees have the opportunity to diagnose and manage all of the acute and chronic complications of type 1 and type 2 diabetes, including diabetic ketoacidosis, hyperosmolar non-ketotic syndromes, hypoglycemia, micro- and macrovascular disease, coronary heart disease, peripheral vascular disease, and cerebrovascular disease. Particular attention is given to the early diagnosis of diabetic retinopathy through training in the fundoscopic examination and appropriate referral of patients with eye disease. The proper technique for foot examination, including the use of a monofilament, is emphasized in order to emphasize the early detection of peripheral vascular disease and diabetic neuropathy. Consultation with diabetes educators, dieticians, podiatrists or nurses certified in foot care are encouraged to facilitate patient care. Outpatient Clinic Elective Rotation The elective rotation provides trainees the opportunity to participate in diabetes care under the supervision of a number of different faculty members. Trainees continue to gain expertise in the care of patients with type 1 and type 2 diabetes in the adult endocrine clinics. Additional experience in the care of adolescents and children with both type 1 and type 2 diabetes is obtained when trainees rotate through the pediatric endocrine clinics. During these rotations, trainees gain expertise in the psychological and psychosocial issues pertinent to the care of adolescents and children. Trainees also focus on the utilization and interpretation of autoimmune markers of type 1 diabetes in patient management and counseling as well as genetics and genetic counseling as it prelates to patients with endocrine and metabolic disorders. 33
  • 34. Didactic Teaching Program The didactic teaching program is intended not only to reinforce the training received in the clinical setting, but also to address endocrine issues, which may be clinically less common. Lectures in this curriculum pertaining to diabetes include: Patient Diabetes Education, Management of Diabetic Ketoacidosis, Insulin Pump Management, Nutritional Guidelines for Patients with Diabetes, Diabetes in Pregnancy, and Management of Dyslipidemia – an Evidence Based Approach. Other topics with in the core curriculum include pathophysiology and epidemiology of diabetes, the biochemistry and physiology of diabetes (including cell biology, molecular biology, and immunology), principles of hormone action (including signal transduction pathways and the biology of hormone receptors). The genetics of diabetes are addressed both generally and in a lecture on the diagnosis and management of patients with Maturity Onset Diabetes of the Young (MODY) and other less common forms of diabetes. Lectures given by the pediatric endocrinology faculty cover human growth, development, and pubertal maturation as it relates to diabetes. 4.2.5 Technical and Other Skills Trainees also develop technical and other skills relevant to diabetes. The issues of the performance of endocrine clinical laboratory and radionuclide studies and basic laboratory techniques – including quality control, quality assurance and proficiency standards – are addressed specifically in the trainee’s didactic program. In addition, trainees gain experience in these areas in their clinical and research activities. Provision is made for the trainees to acquire experience and skill in the interpretation of laboratory tests, including those based on immunoassays, radionuclide, ultrasound, radiologic and other imaging studies, and the effects of a variety of non-endocrine disorders on laboratory and imaging studies, and performance and interpretation of stimulation and suppression tests. This occurs in their inpatient and outpatient activities and in their patient-based conferences including the didactic program. Provision is also made for the trainees to acquire experience and skill in the management of adolescent and adult patients of all ages with diabetes mellitus, including the utilization and interpretation of autoimmune markers of type 1 diabetes in patient management and counseling, prescription of exercise programs, the rationale for and calculation of diabetic diets, oral anti-diabetic therapy, the use of intravenous insulin administration in acute decompensated diabetes, the use of all varieties of insulin delivery systems, glucose monitoring devices, funduscopic examination and recognition and appropriate referral of patients with diabetic retinopathy, foot care, psychosocial effects of diabetes on patients and their families, and patient and community education. They acquire experience and skill in each of these aspects of diabetes care through conferences and their inpatient and outpatient activities. 4.2.6 Formal Instruction The curriculum of our training program provides formal instruction in the pathogenesis and epidemiology of diabetes and genetics as it relates to diabetes. This occurs in lectures, clinical conferences and research seminars as well as in patient care settings. Indeed, discussion of issues such as the relative roles of insulin deficiency and insulin resistance in the pathogenesis of type 2 diabetes, the possible reasons for the increasing incidences of diabetes in developing, as well as developed countries, and the most recent insights into the molecular genetics of diabetes are recurring topics in the trainees’ clinical and research conferences. Thus, there is considerable informal as well as formal instruction these areas. Finally, trainees also receive formal instruction in developmental endocrinology – particularly growth, development and pubertal maturation – as it relates to diabetes in endocrine physiology and pathophysiology in diabetes and systemic diseases and principles of hormone action, in biochemistry and physiology, including cell and molecular biology and immunology, as they relate to endocrinology and metabolism in general and diabetes in particular, and signal transduction pathways and biology of hormone receptors. These are fundamental to the practice of modern endocrinology, diabetes and metabolism including clinical diabetology. 4.3 Suggested Reading 34
  • 35. Journal Articles The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med.1993; 329:977-986. The DCCT Research Group. Lifetime benefits and costs of intensive therapy as practiced in the Diabetes Control and Complications Trial. J Am Med Assoc. 1996; 276:1409-1415. The UKPDS Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. Lancet. 1998; 352:837-853. The UKPDS Group. Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes. Lancet. 1998;352: 854-865. The UKPDS Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes. Brit Med J. 1998; 317:703-713. The UKPDS Group. Efficacy of atenolol and captropril in reducing risk of macrovascular and microvascular complications in type 2 diabetes. Brit Med J. 1998; 317:713-720. The UKPDS Group. Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes. Brit Med J. 1998; 317:720-726. Pyorala K, Pederson TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study. Diabetes Care. 1997; 20:614-620. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without myocardial infarction. N Engl J Med. 1998; 339:229-234. Haffner SM, Alexander CM, Cook TJ, et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels. Arch Intern Med. 1999; 159:2661-2667. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993; 329:1456-1462. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting- enzyme inhibitor, Ramipril, on cardiovascular events in high-risk patients. N. Engl J Med. 2000; 342:145-153. The Heart Outcomes Prevention Evaluation Study Investigators. Effects of Ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000; 355:253-259. American Diabetes Association. Clinical Practical Recommendations 2000. Diabetes Care. 2000; 23(Suppl 1):S1-S116. 35
  • 36. Diabetes Mellitus Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discusions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 1. General a) Patient Monitoring X X X X X X X b) Treatment Objectives in adults X X X X X X X X X c) Objective in adolescents X X X X X X X X X 2. Acute and chronic complications a) Ketoacidosis X X X X X X X X b) Hyperosmolar non-ketotic coma X X X X X X X c) Hypoglycemia X X X X X X X X d) Retinopathy X X X e) Nephropathy X X X X X X f) Peripheral neuropathy X X X X X X g) Autonomic neuropathy X X X X X X h) Dermatologic X X X X X X X X i) Coronary heart disease X X X X X X j) Peripheral vascular disease X X X X X k) Cerebral Vascular disease X X X X 3. Gestational diabetes mellitus a) Screening X X X X X X b) Treatment X X X X X X X X 4. Surgical management a) Pre-operative preparation X X X X b) post-operative preparation X X X X 5. Patient education a) Home glucose monitoring X X X X X b) Psychosocial issues X X X X X X c) Genetics and counseling X X X X X X d) Nutrition X X X X X X X e) Hypoglycemia X X X X X X X f) Exercise X X X X X X g) Foot care X X X X X X 6. Therapy a) Oral agents X X X X X X b) Subcutaneous insulin X X X X X X X c) Insulin pump X X X X X X X X d) Intravenous insulin and DKA X X X X X X X 7. Other a) Pathogensis of diabetes mellitus X X X X X X b) Genetics as it relates to diabetes X X X X 8. Disease specific studies/procedures a) Fundoscopic examination X X X X b) Photocoagulation therapy X X X 9. Hypoglycemic Syndromes and Islet X X X X X X X Tumors 36
  • 37. Section 5: Gonadal Disorders 5.1 Introduction Endocrinology of the reproductive system encompasses normal pubertal development and adult male and female reproductive function and the effects of excesses or deficiencies of reproductive hormones on other body systems. Issues in reproductive endocrinology are extremely prevalent in the population, highlighting the importance of this area in an endocrine training program. Disorders of this system may arise at a hypothalamic, pituitary or gonadal level as a result of a primary abnormality or secondary to abnormalities in other endocrine or non-endocrine organs. These disorders may present as primary or acquired hypogonadism, infertility, or erectile dysfunction or with evidence of hyperandrogenism or hyperestrogenism. In addition, this area includes abnormalities of primary or secondary reproductive end organs such as skin, penis and accessory sex organs such as prostate, uterus, or breast. This is an extremely important area of endocrinology, not only due to the prevalence of primary abnormalities of the reproductive system per se, but also because of the profound impact of gonadal hormone abnormalities on other endocrine and non-endocrine systems including bone, thyroid, adrenal, metabolic, dermatologic, cardiovascular, muscle, neurologic and psychiatric. Disorders of non-reproductive systems may be hormone dependent and conversely non-reproductive disorders often affect the reproductive axis. 5.2 Discussion 5.2.1 Goals It is our intention that the trainee develops the following: 1. An understanding of the physiology of: (1) normal male and female adrenarche and puberty; (2) the normal menstrual cycle; (3) normal male reproductive physiology; (4) the physiology of the menopause and the physiology of reproductive aging in men and women; and (5) a basic understanding of the genetics of disorders of the reproductive system. 2. A basic understanding of the biochemistry, cell biology, and molecular biology of gonadotropin-releasing hormone, the gonadotropins, gonadal steroids and the inhibin/activin/follistatin family of proteins; an understanding of factors involved in growth and differentiation of the gonads (including germ cell development), internal genitalia and accessory sex organs, and autocrine/paracrine interactions in reproductive function; knowledge of the mechanism of gonadotropin and steroid hormone action. 3. Familiarity with the types of assays available for the measurement of gonadotropins, steroids, inhibins and insulin and the clinical utility of these assays in the diagnosis and management of patients with reproductive disorders; a basic familiarity with the evaluation and interpretation of semen analysis. 4. A basic understanding of how to perform, evaluate and determine, when applicable, the utility of dynamic provocative endocrine testing as it applies to the reproductive system. 5. An understanding of how to evaluate and determine the utility of and hypothalamic/pituitary, adrenal and testicular imaging, and bone densitometry. 6. A basic understanding of how to evaluate and manage disorders of sexual differentiation, disorders arising in the pediatric age group including congenital adrenal hyperplasias, chromosomal disorders such as Turner and Klinefelter syndromes, and precocious or delayed puberty. 7. An understanding of how to evaluate and manage female reproductive disorders including: (1) primary amenorrhea; (2) secondary amenorrhea or oligomenorrhea; (3) galactorrhea; (4) polycystic ovarian syndrome with/without hyperandrogenism; (5) dysfunctional uterine bleeding; (6) ovarian lesions; (7) premenstrual symptoms; (8) peri-menopausal and menopausal symptoms; and (9) infertility. The trainee may also receive training in ovulation induction. 37
  • 38. 8. An understanding of how to evaluate and manage male reproductive disorders including: (1) primary and acquired male hypogonadism; (2) gynecomastia; (3) erectile dysfunction; (4) testicular masses; and (6) prostatic disorders. The trainee may also receive training in fertility disorders including induction of spermatogenesis. 9. A basic understanding of the clinical presentation and prevalence of hormone producing neoplasms of the testis and ovary and of tumors that affect hypothalamic and pituitary function; familiarity with the treatment of hormone responsive tumors and disorders (breast, prostate, endometrium, pituitary). 10. An understanding of the effects of age on the reproductive axis in men and women and the subsequent effects of hypogonadism on other systems. 11. An understanding of the effects of acute and chronic disease on the reproductive system in men and women. 12. A basic understanding of the interaction of psychosocial disorders with the reproductive system including premenstrual dysphoric disorder, eating disorders, perimenopausal mood disorders, sexual dysfunction, decreased libido and substance abuse. 13. An understanding of the physiology and importance of the following drugs as they apply to the reproductive system: (1) GnRH, GnRH agonists/ antagonists, gonadotropins; (2) hormonal contraceptives; (3) selective androgen and estrogen receptor modulators (SARMS and SERMS); (4) hormone replacement therapy in men and women; (5) non-hormonal strategies for menopause management; and (6) non- prescription and environmental compounds. 14. A basic understanding of the emerging technologies and treatment and how they impact on the comprehensive management of reproductive endocrine disorders including assisted reproductive technologies and genetic testing. 5.2.2 Training 1. The training program will provide opportunities for the trainee to develop clinical competence in reproductive endocrinology. The opportunity to diagnose and manage male and female adolescent and adult patients with reproductive endocrine disorders will occur primarily in an outpatient setting due to the generally non-acute nature of these problems, but must also include attention to reproductive endocrine issues in inpatients with other endocrine and non-endocrine diagnoses. This training is likely to require interaction with pediatric endocrinology, gynecology, reproductive endocrinology and infertility and/or other subspecialties. 2. The trainee will be given the opportunity to assume responsibility for and follow patients with reproductive endocrine disorders throughout the training period. Due to the nature of these disorders, the majority of follow-up will be in outpatient settings, specifically the Durham VA Endocrine clinic and specific outreach Endocrine clinics. Appropriate experience with the spectrum of reproductive endocrine disorders in male and female adult patients may require that trainees see patients with a number of different attendings or in several different types of clinics. 3. In addition to mentored inpatient and outpatient diagnosis and management of patients with endocrine abnormalities pertaining to the reproductive system, trainees will be given the opportunity to gain experience with case presentation and critique in informal and formal settings to develop their own skills as teachers and consultants. 4. Due to the rarity of certain conditions and the need to cover a broad spectrum of reproductive endocrine disorders in males, females and adolescents, patient encounters will also be supplemented by an ordered series of sessions that will be either didactic or and clinical case discussion-based. 38
  • 39. 5. Formal instruction will be provided in the types of assays used for measurement of gonadotropins, steroids and inhibins and the concepts of standards, sensitivity and specificity as they pertain to these hormone assays. Individualized instruction will also be provided in examination of the pelvis, breast, testis and prostate. Other technologies, which have an impact on diagnosis and management of disorders of the reproductive system, may be included such as semen analysis, pelvic ultrasound and induction of ovulation. 6. Self-assessment tools including ESAP, MKSAP and AACE, will be available to assist the trainee in acquiring knowledge in reproductive endocrine areas. 5.2.3 Evaluation Trainees will be evaluated on their clinical skills in patient interactions, physical diagnosis, differential diagnosis and formulation of evaluation and treatment plans throughout the training period. Feedback will be given in an ongoing manner in the clinical setting and formal verbal and written evaluation on a biannual basis. 5.3 Suggested Reading Textbooks Sperling M. Pediatric Endocrinology. 1st ed. WB Saunders Co; 1996. Liftshitz F. Pediatric Endocrinology. 3rd ed.. Dekker; 1996. Tulchinsky B, Little AB, eds. Maternal-Fetal Endocrinology. 2nd ed. Philadelphia, Pa: WB Saunders Co; 1994. Martinez-Mora J. Textbook of Intersexual States. Doyma; 1994. Yee Wm, Rosen G, Cassidenti D. Transvaginal Sonography in Infertility. Lippincott-Raven; 1995. Azziz R, Nestler J, DeWailly D, eds. Androgen Excess Disorders in Women. Lippincott-Raven; 1997. Yen SSC, Jaffe RB, Barbieri RL, eds. Reproductive Endocrinology. 4th ed. Philadelphia, Pa: WB Saunders Co; 1999. CD-ROM Male and Female Reproductive Endocrinology Sections. Up-to-Date in Endocrinology & Diabetes [serial on CD-ROM]. The Endocrine Society, 2000. Internet sites National Center for Biotechnology Information. Online Mendelian Inheritance in Man. Available at http://www3.ncbi.nlm.nih.gov/Omim/. Accessed June 5, 2000. American Association for Clinical Endocrinologists. AACE Guidelines in Male Hypogonadism, Menopause and Sexual Dysfunction. Available at http://www.aace.com/indexjava.htm. Accessed June 5, 2000. Journal Articles Hulley S, Grady D, Bush T, et al for the Heart and Estrogen/progestin Replacement Study (HERS) Research Group. Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women. JAMA. 1998;280:605-613. 39
  • 40. Collaborative Group on Hormonal Factors in Breast Cancer. 1997 Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiologic studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet. 350:1047-1059. Hayes FJ, Seminara SB, Crowley WF, Jr. Hypogonadotropic Hypogonadism. Endocrinol Metab Clin North Amer. 1998; 4:739-763. Hayes FJ, Welt CK, Martin KA, Crowley WF, Jr. GnRH deficiency: Differential diagnosis and treatment. Endocrinologist. 1999;9:36-44. Adashi EY, Hennebold JD. Single-gene mutations resulting in reproductive dysfunction in women. N Engl J Med. 1999;340(9):709-718. Taylor AE. Polycystic ovary syndrome. Endocrinol Metab Clin North Am. 1998;27(4):877-902. Endocrine Reviews, Vol 20, No. 3, June 1999. Suggested Self-Evaluation Tools: Endocrine Self-Assessment Program 40
  • 41. Gonadal Disorders Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 1. Female a) Normal female reproductive X X X X X X X physiology including puberty b) Primary/secondary amenorrhea X X X X X X X X c) Dysfunctional uterine bleeding X X X X X X X X d) Hirsutism/virilization X X X X X X X X X e) Polycystic ovarian syndrome X X X X X X X X X f) Infertility X X X X X X X g) Menopause X X X X X X X X h) complementary/alternative X X X therapy 2. Male a) Normal male reproductive X X X X X X X physiology including puberty b) Hypogonadism X X X X X X X X X c) Gynecomastia X X X X X X X X d) Erectile dysfunction X X X X X X X e) Infertility X X X X X X f) Prostatic disorders X X X X X 3. Pediatric a) Intersex disorders X X X X X X b) Precocious puberty X X X X X X c) Delayed puberty X X X X X X d) Gonadal dysgenesis X X X X X X 4. Neoplasia a) Testicular tumors X X X b) Ovarian tumors X X X 5. Disease Specific Studies/Procedures a) GnRH/GnRH analogues X X X X b) Ovarian ultrasound X X X X c) Pelvic examination X X X X X d) Semen analysis X X X X e) Induction of spermatogenesis X X X X f) Male/Female hormone X X X X X X X X replacement g) Ovulation induction (suggestion) X X X 41
  • 42. Section 6: Hypothalamic-Pituitary Disorders 6.1 Introduction Growth, development and reproduction are regulated by the interactions of the endocrine and nervous systems. The pituitary regulates endocrine organs under the influence of the hypothalamus. Disorders of the pituitary and hypothalamus may therefore cause isolated or multisystem endocrine hypofunction and hyperfunction. Furthermore, expanding lesions of the pituitary/hypothalamic area may cause neurologic dysfunction. Goals: Trainees will acquire an understanding of (1) neuroendocrine physiology, specifically hypothalamic/pituitary anatomy and morphology, regulation of hormone secretion, cellular and molecular mechanisms of action (receptors, signal transduction pathways, gene interaction); (2) the pathophysiology, clinical manifestations, diagnostic approaches, and treatment of hypothalamic and pituitary dysfunction. By the end of their training, trainees will be competent in the evaluation and management of patients with hypothalamic-pituitary disorders (see below). Training and Evaluation: These objectives will be accomplished through a combination of interdisciplinary conferences, formal lectures, case discussions, direct clinical experience, and self-directed learning. Clinical training will include additional interactions with other related disciplines, including neurosurgery, neuroradiology, neurology, neuro-ophthalmology, pathology, and nuclear medicine. Trainees will receive regular evaluations through individual assessments from supervising faculty and semiannual evaluations by the Program Director and Clinical Director. 6.2 Discussion 6.2.1 Diagnostic Testing. The trainee will be able to understand the indications, performance and interpretation of the following tests. Basal Hormone levels (1) prolactin (PRL) (2) insulin-like growth factor-1 (IGF-1) (3) growth hormone (GH) (4) Free thyroxine (T4) (5) thyrotropin (TSH) (6) Cortisol (plasma and urine, including metabolites) (7) adrenocorticotropic hormone (ACTH) (8) luteinizing hormone (LH) (9) follicle stimulating hormone (FSH) (10) testosterone/estradiol (11) serum osmolality (12) urine osmolality. In addition, the trainee will be able to understand, when clinically applicable, the indication, performance and application of the following provocative and suppression tests: (1) Insulin-hypoglycemia stimulation (insulin tolerance test) (2) Thyrotropin Releasing Hormone (TRH) stimulation test (3) Gonadotropin Releasing Hormone (GnRH) stimulation test (4) Corticotropin Releasing Hormone (CRH) stimulation test (5) GH stimulation tests (L-dopa, arginine, clonidine, exercise, glucagon, GH Releasing Hormone [GHRH], insulin-hypoglycemia) (6) ACTH (cosyntropin) stimulation test (7) Metyrapone test (8) Dexamethasone suppression test (9) Oral glucose suppression test (10) Water deprivation test. 42
  • 43. 6.2.2 Neuroradiology The trainee will acquire an understanding of the indications for and interpretation of the following procedures. Magnetic Resonance Imaging (MRI) Computed Tomography (CT) Inferior Petrosal Sinus Sampling (when applicable) 6.2.3 Neuroophthalmology The trainee will acquire an understanding of the indications for and interpretation of formal visual field examinations 6.2.4 Other Tests (growth charts, radiologic bone age) 6.2.5 Treatment Modalities The trainee will acquire an understanding of the indications, advantages and adverse effects of surgical, medical and irradiation (conventional and stereo tactic) therapies for hypothalamic-pituitary disorders. 6.2.6 Specific Disorders The trainee will receive formal and/or informal instruction, and, when possible, clinical experience in the evaluation and management of the following disorders. Pituitary Adenomas Prolactinomas (1) Manifestations (galactorrhea, amenorrhea, infertility, erectile dysfunction, osteopenia, neurologic mass effects) (2) Diagnostic tests (basal PRL, assessment for hypopituitarism when indicated, exclusion of other causes of hyperprolactinemia, MRI) (3) Management options (dopamine agonists, surgery, irradiation) (4) Special considerations for pregnancy and MEN1 GH-secreting adenomas (1) Manifestations (acromegaly, gigantism, neurologic mass effects) (2) Diagnostic tests (IGF-1, glucose suppression test of GH, assessment for hypopituitarism when indicated, MRI) (3) Management options (surgery, somatostatin analogs, GH antagonists, dopamine agonists, irradiation) (4) Special considerations - ectopic GHRH syndrome, assessment for co-secretion of PRL, TSH, ACTH, association with MEN1 ACTH-secreting adenomas (1) Clinical manifestations - Cushing’s syndrome (2) Diagnostic tests (urinary free cortisol, ACTH, dexamethasone suppression testing, CRH testing, MRI, Inferior Petrosal Sinus Sampling, assessment for hypopituitarism when indicated) (3) Management options (surgery, irradiation, medical [ketoconazole, mitotane, metyrapone, and other agents]) (4) Special considerations - differential diagnosis from ectopic ACTH and ectopic CRH; Nelson’s syndrome TSH-secreting adenomas (1) Clinical manifestations - hyperthyroidism (2) Diagnostic tests (Free T4, TSH, alpha-subunit, consideration for TRH testing, MRI, assessment for hypopituitarism when indicated) (3) Management options (surgery, irradiation, somatostatin analogs) (4) Special consideration - differential diagnosis from thyroid hormone resistance. Gonadotropin cell adenomas (1) Clinical manifestations - mass effects (neurologic dysfunction, hypopituitarism) (2) Diagnostic tests (LH, FSH, glycoprotein subunits, TRH test, assessment for hypopituitarism, MRI, visual field assessment when indicated) 43
  • 44. (3) Management options (surgery, irradiation) Non-secreting tumors (1) Clinical manifestations - mass effects (neurologic dysfunction, hypopituitarism) (2) Diagnostic tests (assessment for hypopituitarism, MRI, visual field assessment when indicated) (3) Management options (surgery, irradiation) Space-occupying and Infiltrative Disorders of the Pituitary and Hypothalamic Region Space occupying lesions (Craniopharyngiomas, Rathke’s cleft cysts, meningiomas, arachnoid cysts, chordomas, dysgerminomas, hamartomas, gangliocytomas, abscess, metastases) Infiltrative/inflammatory disorders (sarcoidosis, tuberculosis, Langerhans cell histiocytosis, lymphoma, lymphocytic hypophysitis, hemochromatosis) Hypopituitarism Panhypopituitarism (1) Clinical manifestations (growth failure, fatigue, decreased strength, body hair loss, fine facial skin wrinkling, infertility, amenorrhea, erectile dysfunction, constipation, cold intolerance, bradycardia, orthostatic hypotension) (2) Etiology Congenital (gene, receptor, embryopathic) Acquired (tumors, infiltrative, trauma, apoplexy and Sheehan’s, irradiation, metabolic [weight loss, anorexia nervosa, malnutrition, hemochromatosis, critical illness], drug (corticosteroids, dopamine) Selective hormone deficiencies (1) Gonadotropins (Kallmann’s syndrome, weight loss, idiopathic) (2) ACTH (iatrogenic from glucocorticoid suppression, idiopathic very rare) (3) TSH (rare) (4) Growth Hormone Child onset (congenital or acquired) (i) Manifested as growth failure (ii) Differential diagnosis (hypothalamic vs pituitary, GH insensitivity syndrome, differentiate from non GH deficiency causes of short stature [systemic disease, dyschondroplasias, Turner’s syndrome, psychosocial, etc. ]) Adult onset is usually associated with other hormone deficiencies in panhypopituitarism. See above. Treatment (1) Growth hormone administration - dose adjusted by IGF-1 levels Special consideration - IGF-1 treatment for GH insensitivity (2) Thyroxine -dose adjusted clinically and by Free T4 levels (3) Glucocorticoids - dose adjusted clinically (4) Estrogen/Progestin - oral, transdermal (5) Testosterone - injection, transdermal (6) GnRH - possible utility with hypogonadotropic hypogonadism of hypothalamic etiology (7) HCG and HMG/FSH - for fertility in men and women Posterior Pituitary Disorders Diabetes Insipidus (1) Clinical Manifestations - polyuria, polydipsia, thirst, dehydration (2) Differential diagnosis Central vs. nephrogenic Congenital (familial) vs. acquired (see causes of hypopituitarism plus drug induced [cisplatin, carbamazepine, lithium, vincristine, etc.] plus metabolic [hypercalcemia, hypokalemia], sickle cell anemia) Psychogenic polydipsia 44
  • 45. Others causes of polyuria (3) Diagnostic testing Overnight water deprivation test Measurement of vasopressin Diagnostic trial of desmopressin MRI Assessment of anterior pituitary function (4) Treatment Desmopressin - nasal, oral, parenteral Chlorpropamide Thiazide diuretics (esp. nephrogenic) (5) Special considerations Coexistent thirst center damage Pregnancy - DI may be transient, may be associated with acute fatty liver of pregnancy Hyponatremia (1) Clinical manifestations (nausea, vomiting, headache, confusion, seizures, coma, death) - symptoms dependent upon degree and speed of onset (2) Differential diagnosis Hypovolemic - appropriate vasopressin (ADH) secretion Euvolemic - inappropriate ADH secretion (SIADH) {need to exclude hypothyroidism, hypoadrenalism} Hypervolemic - (intravascular hypovolemia, eg, cirrhosis, CHF) (3) Diagnostic tests Urine and serum osmolality and urine sodium Exclude other causes of hyponatremia (pseudohyponatremia- high triglycerides, glucose)(4) Treatment Mild - water restriction Severe - saline, hypertonic saline, furosemide, monitor closely to avoid central pontine myelinolysis Miscellaneous Hypothalamic Syndromes (1) Laurence-Moon-Biedl Bardet (2) Prader-Willi Syndrome (3) Sotosí Syndrome (cerebral gigantism) (4) Pineal region tumors (5) Empty sella syndrome 6.3 Suggested Reading Diagnostic Testing Abboud CF. Laboratory diagnosis of hypopituitarism. Mayo Clin Proc 1986; 61:35-48. Camanni F, Ghigo E, Arvat E: Growth hormone-releasing peptides and their analogs. Front Neuroendocrinol 19:47, 1998. Streeten DHP, Anderson GH, Bonaventura MM. The potential for serious consequences from misinterpreting normal responses to the rapid adrenocortiocotropin test. J Clin Endocrinol Metab 1996; 81:285-290. Cutler GB Jr. Corticotropin-releasing hormone (CRH): clinical studies and use. The Endocrinologist 1997; 7:10S-16S. Bevan JS, Burke CW, Esiri MM, Adams CBT. Misinterpretation of prolactin levels leading to management errors in patients with sellar enlargement. Am J Med 1987; 82:29-32. 45
  • 46. Barkan A, Chandler WF. Giant pituitary prolactinoma with falsely low serum prolactin: the pitfall of the "high-dose hook effect": case report. Neurosurgery 1998; 9:13-15. Neuroradiology Elster A. Modern imaging of the pituitary. Radiology 1993; 187:1-14. Donovan JL, Nesbit GM: Distinction of masses involving the sella and suprasellar space: Specificity of imaging features. AJR 1996; 167:597-503. Naidich MJ, Russell EJ. Current approaches to imaging of the sellar region and pituitary. Endocrinol Metab Clin N Amer 1999; 28:45-79. Hall WA, Luciano MG, Doppman JL et al. Pituitary magnetic resonance imaging in normal human volunteers: occult adenomas in the general population. Ann Intern Med 1994; 120:817-820. Neuroopthalmology Melen O. Neuro-ophthalmologic features of pituitary tumors. Endocrinol Metab Clin N Amer 1987; 16:585-608. Other Tests Greulich WW, Pyle SI: Radiographic Atlas of Skeletal Development of the Hand and Wrist, 2nd ed. Stanford, CA, Stanford University Press, 1959. Tanner JM, Whitehouse RH, Marshall WA et al. Assessment of Skeletal maturity and Prediction of Adult Height (TW2 Method). New York, Academic Press, 1975. Bayley N, Pinneau SR: Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr 1952; 40:423-441. Tanner JM, Whitehouse RH, Marshall WA et al. Prediction of adult height from height, bone age, and occurrence of menarche at ages 4-16, with allowance for midparent height. Arch Dis Child 1975; 50:14-26. Rosenfield RL. Essentials of growth diagnosis. Endocrinol Metab Clin N Amer 1996; 25:743-758. Treatment Modalities Laws ER Jr, Thapar K. Pituitary surgery. Endocrinol Metab Clin N Amer 1999; 28:119-131. Webb SM, Rigla M, Wagner A, Oliver B, Bartumeus F. Recovery of hypopituitarism after neurosurgical treatment of pituitary adenomas. J Clin Endocrinol Metab 1999; 84:3696-3700. Ciric I, Ragin A, Baumgartner C, Pierce D. Complications of transsphenoidal surgery: results of a national survery, review of the literature, and personal experience. Neurosurgery 1997; 40:225-237. Halberg FE, Sheline GE. Radiotherapy of pituitary tumors. Endocrinol Metab Clin N Amer 1987; 16:667-684. Brada M, Rajan B, Traish D et al. The long-term efficacy of conservative surgery and radiotherapy in the control of pituitary adenomas. Clin Endocrinol 1993; 38:571-578. Snyder PJ, Fowble BF, Schatz NJ, Savino PJ, Gennarelli TA. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med 1986; 81:457-462. Littley MD, Shalet SM, Beardwell CG et al. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Quart J Med 1989; 70:145-160. 46
  • 47. Brada M, Ford D, Ashley S, Bliss JM, Crowley S, Mason M, Rajan B, Traish D: Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. Brit Med J 1992; 304:1343. Jackson IMD, Noren G. Role of gamma knife therapy in the management of pituitary tumors. Endocrinol Metab Clin N Amer 1999; 28:133-142. Specific Disorders Pituitary Adenomas Melmed: Pathogenesis of pituitary tumors. Endocrinol Metab Clin N Amer 1999; 28:1-12. Asa SL, Ezzat S: The cytogenesis and pathogenesis of pituitary adenomas. Endocr Rev 1998; 19:798-727. Asa SL: The pathology of pituitary tumors. Endocrinol Metab Clin N Amer 1999; 28:13-43. Pernicone PJ, Scheithauer BW, Sebo TJ et al: Pituitary carcinoma: a clinicopathological tudy of 15 cases. Cancer 1997; 79:804-812. Burgess JR, Shepherd JJ, Parameswaran V, Hoffman L, Greenaway TM: Spectrum of pituitary disease in multiple endocrine neoplasia Type 1 (MEN 1): Clinical, biochemical, and radiological features of pituitary disease in a large MEN 1 kindred. J Clin Endocrinol Metab 1996; 81:2642-2646. Shimon I, Melmed S. Management of pituitary tumors. Ann Intern Med 1998; 129:472-483 Melmed S: The Pituitary. Cambridge, MA. Blackewell Science. 1995. Molitch ME (ed,). Advances in the Management of Pituitary Tumors. Endocrinol Metab Clin N Amer 1999 Vol. 28:1. Prolactinomas Molitch ME. Diagnosis and treatment of prolactinomas. Adv Intern Med 1999; 44:117-153. Klibanski A, Biller BMK, Rosenthal DI, Schoenfeld DA, Saxe V. Effects of prolactin and estrogen deficiency in amenorrheic bone loss. J Clin Endocrinol Metab 1988; 67:124-130. Molitch ME, Elton RL, Blackwell RE, et al. Bromocriptine as primary therapy for prolactin-secreting macroadenomas: results of a prospective multicenter study. J Clin Endocrinol Metab 1985; 60: 698-705. Webster J, Piscitelli G, Polli A, Ferrari CI, Ismail I, Scanlon MF for the Cabergoline Comparative Study Group. A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. N Engl J Med 1994; 331:904-909. Colao A, DeSarno A, Landi ML et al. Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage. J Clin Endocrinol Metab 1997; 82:3574-3579. Freda PU, Andreadis CI, Khandji G et al. Long-term treatment of prolactin-secreting macroadenomas with pergolide. J Clin Endocrinol Metab 2000; 85:8-13. Massoud F, Serri O, Hardy J, Somma M, Beauregard H. Transsphenoidal adenomectomy for microprolactinomas:10 to 20 years of follow-up. Surg Neurol 1996; 45:341-346. Feigenbaum SL, Downey DE, Wilson CB, Jaffe RB. Transsphenoidal pituitary resection for preoperative diagnosis of prolactin-secreting pituitary adenoma in women: long term follow-up. J Clin Endocrinol Metab 1996; 81:1711-1719. 47
  • 48. Molitch ME. Management of prolactinomas during pregnancy. J Reprod Med 1999; 44(Suppl):1121-1126. GH-secreting adenomas Melmed S: Acromegaly. N Engl J Med 1990; 322:966-972. Leiberman SA, Hoffman AR: Sequelae to acromegaly: reversibility with treatment of the primary disease. Horm Metab Res 1990; 22:313-318. Molitch ME: Clinical manifestations of acromegaly. Endocrine Metab Clin N. Amer. 1992; 21:597-614. Freda PU, Post KD, Powell JS, Wardlaw SL. Evaluation of disease status with sensitive measures of growth hormone secretion in 60 postoperative patients with acromegaly. J Clin Endocrinol Metab 1998; 83:3808-3816. Barkan AL, Beitins IZ, Kelch RP. Plasma insulin-like growth factor-I/Somatomedin-C in acromegaly: correlation with the degree of growth hormone hypersecretion. J Clin Endocrinol Metab 1988; 67:69-73. Dobrashian RD, O'Halloran DJ, Hunt A, Beardwell CG, Shalet SM. Relationships between insulin-like growth factor-1 levels and growth hormone concentrations during diurnal profiles and following oral glucose in acromegaly. Clin Endocrinol 1993; 38:589-593. Faglia G, Aorsio M, Bazzonei N: Ectopic acromegaly. Endocrinol Metab Clin N Amer 1992; 21:575-596. Melmed S, Jackson I, Kleinberg D, Klibanski A. Current treatment guidelines for acromegaly. J Clin Endocrinol Metab 1998; 83:2646-2652. Bates AS, van’t Hoff W, Jones JM, Clayton RN. An audit of outcome of treatment in acromegaly. Quart J Med 1993; 86:293-299. Abosch A, Tyrrell JB, Lamborn KR et al. Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas. Initial outcome and long-term results. J Clin Endocrinol Metab 1998; 83:3411-3416. Swearingen B, Barker FG II, Katznelson L et al. Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 1998; 83:3419-3426. Newman CB. Medical therapy for acromegaly. Endocrinol Metab Clin N Amer 1999; 28:171-190. Abs R, Verhelst J, Maiter D et al. Cabergoline in the treatment of acromegaly. A study in 64 patients. J Clin Endocrinol Metab 1998; 83:374-378. Newman CB, Melmed S, Snyder PJ et al. Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients. J Clin Endocrinol Metab 1995; 80:2768-2775. Flogstad Ak, Halse J, Barke S et al. Sandostatin LAR in acromegalic patients: long-term treatment. J Clin Endocrinol Metab 1997; 81:23-28. Turner HE, Vadivale A, Keenan J, Wass JAH: A comparison of lanreotide and octreotide LAR for treatment of acromegaly. Clin Endocrinol 1999; 51:275-280. Trainer PJ, Drake WM, Katnelson L et al: Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 2000; 342:1171-1177. Powell JS, Wardlaw SL, Post KD, Freda PU. Outcome of radiotherapy for acromegaly using normalization of insulin-like growth factor I to define cure. J Clin Endocrinol Metab 2000; 85:2068-2071. 48
  • 49. Landolt AM, Haller D, Lomax N et al. Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy. J Neurosurg 1998; 88:1002-1008. (9609294 ACTH-secreting adenomas Orth DN: Cushing's syndrome. N Engl J Med 1995; 332:791-803. Meier C, Biller BMK. Clinical and biochemical evaluation of Cushing’s syndrome. Endocrinol Metab Clin N Amer 1997; 26:741-762. Newell-Price J, Trainer P, Besser M et al. The diagnosis and differential diagnosis of Cushing’s syndrome and pseudo-Cushing’s states. Endocrine Revs 1998; 19:647-672. Findling JW, Raff H: Newer diagnostic techniques and problems in Cushing’s disease. Endocrinol Metab Clin N Amer 1999; 28:191-210. Oldfield EH, Doppman JL, Nieman LK et al. Petrosal sinus sampling with and without corticotropin- releasing hormone for the differential diagnosis of Cushing’s syndrome. N Engl J med 1991; 325:896-905. Invitti C et al: Diagnosis and management of Cushing’s syndrome: results of an Italian Multicentre Study. J Clin Endocrinol Metab 1999; 84:440-448. Mampalam TJ, Tyrrell JB, Wilson CB. Transsphenoidal microsurgery for Cushing’s disease. A report of 216 cases. Ann Intern Med 1988; 109:487-493. Swearingen B, Biller BMK, Barker FG et al. Long-term mortality after transsphenoidal surgery for Cushing disease. Ann Intern Med 1999; 130:821-824. Sonino N, Zielezny M, Fava GA et al: Risk factors and long-term outcome in pituitary-dependent Cushing’s disease. J Clin Endocrinol Metab 1996;81:2647-2652. Sonino N, Boscaro M. Medical therapy for Cushing’s disease. Endocrinol Metab Clin N Amer 1999; 28:211-222. Estrada J, Boronat M, Mielgo M et al: The long-term outcome of pituitary irradiation after unsuccessful surgery in Cushing’s diseaes. N Engl J Med 1997; 336:172-177. TSH-secreting adenomas Beck-Peccoz P, Brucker-Davis F, Persani L et al: Thyrotropin-secreting pituitary tumors. Endocrine Rev 1996; 17:610-638. (8969971) Brucker-Davis F, Oldfield EH, Skarulis MC, Doppman JL, Weintraub BD: Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the National Institutes of Health. J Clin Endocrinol Metab 1999; 84:476-486. Shomali ME, Katznelson L. Medical therapy for gonadotroph and thyrotroph tumors. Endocrinol Metab Clin N Amer 1999; 28:223-240. Chanson P, Weintraub BD, Harris AG. Octreotide therapy for thyroid-stimulating hormone-secreting pituitary adenomas: a follow-up of 52 patients. Ann Intern Med 1993; 119:236-240. Gonadotropin-cell adenomas Young WF, Scheithauer BW, Kovacs KT, et al. Gonadotroph adenoma of the pituitary gland: a clinicopathologic analysis of 100 cases. Mayo Clin Proc 1996; 71:649-656. 49
  • 50. Jameson JL, Klibanski A, Black PM, et al. Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas. J Clin Invest 1987; 80:1472-1478. Daneshdoost L, Gennarelli TA, Bashey HM, et al.. Recognition of gonadotroph adenomas in women. N Engl J Med 1991; 324:589-594. Shomali ME, Katznelson L. Medical therapy for gonadotroph and thyrotroph tumors. Endocrinol Metab Clin N Amer 1999; 28: 223-240. De Bruin TWA, Kwekkeboom DJ, Van’t Verlaat JW, et al. Clinically nonfunctioning pituitary adenoma and octreotide response to long term high dose treatment, and studies in vitro. J Clin Endocrinol Metab 1992; 75:1310-1317. Katznelson L, Oppenheim DS, Coughlin JF, et al. Chronic somatostatin analog administration in patients with ?-subunit-secreting pituitary tumors. J Clin Endocrinol Metab 1992; 75:1318-1325. Warnet A, Harris AG, Renard E, et al . A prospective multicenter trial of octreotide in 24 patients with visual defects caused by nonfunctioning and gonadotropin-secreting pituitary adenomas. Neurosurgery 1997; 41:786-796. Non-secreting tumors Arafah BM. Reversible hypopituitarism in patients with large nonfunctioning pituitary adenomas. J Clin Endocrinol Metab 1986; 62:1173-1179. Ebersold MJ, Quast LM, Laws ER, Scheithauer B, Randall RV. Long-term results in transsphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg 1986; 64:713-719. Comtois R, Beauregard H, Somma M, Serri O, Aris-Jilwan N, Hardy J. The clinical and endocrine outcome to transsphenoidal microsurgery of nonsecreting pituitary adenomas. Cancer 1991; 68:860-866. Tominaga A, Uozumi T, Arita K et al. Anterior pituitary function in patients with nonfunctioning pituitary adenoma: results of longitudinal follow-up. Endocrine J 1995; 42:421-427. Bradley KM, Adams CBT, Potter CPS, Wheeler DW, Anslow PJ, Burke CW. An audit of selected patients with non-functioning pituitary adenomas treated by transsphenoidal surgery without irradiation. Clin Endocrinol 1994; 41:655-659, 1994. Turner HE, Stratton IM, Byrne JV, Adams CBT, Wass JAH. Audit of selected patients with nonfunctioning pituitary adenomas treated without irradiation - a follow-up study. Clin Endocrinol 1999; 51:281-284. Hansen LK, Molitch ME. Postoperative radiotherapy for clinically nonfunctioning pituitary adenomas. The Endocrinologist 1998; 8:71-78. Donovan LE, Corenblum B The natural history of the pituitary incidentaloma. Arch Intern Med 1995; 153:181-183. Reincke M, Allolio B, Saeger W, et al, The 'incidentaloma' of the pituitary gland. Is neurosurgery required? JAMA 263:2772-2776, 1990. Molitch ME. Pituitary incidentalomas. Endocrinol Metab Clin N Amer 1997; 26:725-740. 50
  • 51. Space-occupying and infiltrative disorders Space-occupying lesions Freda PU, Wardlaw SL, Post KD. Unusual causes of sellar/parasellar masses in a large transsphenoidal surgical series. J Clin Endocrinol Metab 1996; 81:3455-3459. Rivarola MA, Mendilaharzu H, Warman M et al. Endocrine disorders in 66 suprasellar and pineal tumors of patients with prepubertal and pubertal ages. Horm Res 1992; 37:1-6. Shin JL, Asa SL, Woodhouse LJ, Smyth HS, Ezzat S. Cystic lesions of the pituitary: clinicopathological features distinguishing craniopharyngiomas, Rathke?s cleft cyst, and arachnoid cyst. J Clin Endocrinol Metab 1999; 84:3972-3982. Mukerjee JJ, Islam N, Kaltsas G, Lowe DG, Charlseworth M, Afshar F et al: Clinical, radiological and pathological features of patients with Rathke?s cleft cysts: tumors that may recur. J Clin Endocrinol Metab 82:2357, 1997. El-Mahdy W, Powell M. Transsphenoidal management of 28 symptomatic Rathke?s cleft cysts, with special reference to visual and hormonal recovery. Neurosurgery 1998; 42:7-17. DeVile CJ, Grant DB, Hayward RD, Stanhope R: Growth and endocrine sequelae of craniopharyngioma. Arch Dis Child 1996; 75:108. Morita A, Meyer FB, Laws ER Jr. Symptomatic pituitary metastases. J Neurosurg 1998; 89:69-73. Sklar CA, Grumbach MM, Kaplan SL, Conte FA. Hormonal and metabolic abnormalities associated with central nervous system germinoma in children and adolescents and the effect of therapy: report of 10 patients. J Clin Endocrinol Metab 1981; 52:9-16. Fernandez-Real JM, Fernancez-Castaner M, Villabona C et al: Giant intrasellar aneurysm presenting with panhypopituitarism and subarachnoid hemorrhage: a case report and literature review. Clin Investig 1994; 72:302-306. Infiltrative/Inflammatory disorders Stuart CA, Neelon FA, Lebovitz HE. Hypothalamic insufficiency: the cause of hypopituitarism in sarcoidosis. Ann Intern Med 1978; 88:589-594. Chapelon C, Ziza JM, Piette JC et al. Neurosarcoidosis: signs, course and treatment in 35 confirmred cases. Medicine 1990; 69:261-276. Kaltsas GA, Powles TB, Evanson J et al. Hypothalamo-pituitary abnormalities in adult patients with Langerhans cell histiocytosis: clinical, endocrinological, and radiological features, and response to treatment. J Clin Endocrinol Metab 2000:85; 1370-1376. Lam KSL, Sham MMK, Tam SCF, Ng MMT, Ma HTG. Hypopituitarism after tuberculous meningitis in childhood. Ann Intern Med 1993; 118:701-706. Wolansky LJ, Gallagher JD, Heary RF et al. MRI of pituitary abscess: two cases and review of the literature. Neuroradiology 1997; 39:499-503. Cosman F, Post KD, Holub DA, Wardlaw SL. Lymphocytic hypophysitis. Report of 3 cases and review of the literature. Medicine 1989; 68:240-256. 51
  • 52. Pressman EK, Zeidman SM, Reddy UM, Epstein JI, Brem H. Differentiating lymphocytic adenohypophysitis from pituitary adenoma in the peripartum patient. J Reprod Med 1995; 40:251-259. Hypopituitarism Panhypopituitarism Vance ML. Hypopituitarism. N Engl J Med 1994; 330:1651-1662. Lamberts SWJ, deHerder WW, van der Lely AJ. Pituitary insufficiency. Lancet 1998; 352:127-134. Treier M, Rosenfeld MG: The hypothalamic-pituitary axis: co-development of two organs. Curr Opin Cell Biol 8:833, 1996. Treier M, Gleiberman AS, O’Connell SM, et al: Multistep signaling requirements for pituitary organogenesis in vivo. Genes & Dev 12:1691, 1998. Radovick S, Nations M, Du Y, Berg LA, Weintraub BD, Wondisford FE: A mutation in the POU- homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. Science 257:1116, 1992. Pfäffle RW, DiMattia GE, Parks JS, Brown MR, Wit JM, Jansen M et al: Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia. Science 257:1118, 1992. Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O’Connell SM et al: Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 384:327, 1996. Wu W, Cogan JD, Pfäffle RW, Dasen J, Frisch H, O’Connell SM, Flynn SE et al: Mutations in PROP1 cause familial combined pituitary hormone deficiency. Nature Genetics 18:147, 1998. Cogan JD, Wu W, Phillips JA III, Arnhold IJP, Agapito A, Fofanova OV et al: The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. J Clin Endocrinol Metab 83:3346, 1998. Achermann JC, Jameson JL: Fertility and infertility: genetic contributions from the hypothalamic-pituitary- gonadal axis. Mol Endocrinol 1999; 13:812-818. Netchine I, Sobrier M-L, Krude H et al: Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency. Nature Genetics 2000; 25:182-186. Triulzi F, Scotti G, diNatale B, Pellini C, Lukezic M, Scognamiglio M et al: Evidence of a congenital midline brain anomaly in pituitary dwarfs: a magnetic resonance imaging study in 101 patients. Pediatrics 93:409, 1994. Bates AS, Van't Hoff W, Jones PJ et al: The effect of hypopituitarism on life expectancy. J Clin Endocrinol Metab 1996; 81:1169-1172. Edwards OM, Clark JDA. Post-traumatic hypopituitarism . Six cases and a review of the literature. Medicine 1986; 65:281-290. Benvenga S, Campenni A, Ruggeri RM, Trimarchi F. Hypopituitarism secondary to head trauma. J Clin Endocrinol Metab 2000; 85:1353-1361. Randeva HS, Schoebel J, Byrne J et al. Classical pituitary apoplexy: clinical featues, management and outcome. Clin Endocrinol 1999; 51:181-188. 52
  • 53. Sheehan HL. The recognition of chronic hypopituitarism resulting from postpartum pituitary necrosis. Am J Obstet Gynecol 1971; 111:852-854. Jialal I, Naidoo C, Norman RJ et al. Pituitary function in Sheehans’ syndrome. Obstet Gynecol 1984; 63:15-19. Snyder PJ, Fowble BF, Schatz NJ, Savino PJ, Gennarelli TA. Hypopituitarism following radiation therapy of pituitary adenomas. Am J Med 1986; 81:457-462. Littley MD, Shalet SM, Beardwell CG et al. Hypopituitarism following external radiotherapy for pituitary tumours in adults. Quart J Med 1989; 70:145-160. Constine LS, Woolf PD, Cann D, et al. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 1993; 328:87-94. Schwartz MW, Seeley RJ: Neuroendocrine responses to starvation and weight loss. N Engl J Med 336:1802, 1997. Björntorp P: Endocrine abnormalities in obesity. Diabetes Revs 5:52, 1997. Gama R, Smith MJ, Wright J, Marks V. Hypopituitarism in primary haemochromatosis: recovery after iron depletion. Postgrad Med J 1995; 71:297-298 Van den BergheG, de Zegher F, Bouillon R: Acute and prolonged critical illness as different neuroendocrine paradigms. J Clin Endocrinol Metab 83:1827, 1998. Molitch ME: Pituitary response to stress: Growth hormone and prolactin. In Endocrinology of Critical Disease. K.P. Ober (ed.), Humana Press, Totowa, NJ. 67-86, 1997. Turner HE, Wass JAH: Gonadal function in men with chronic illness. Clin Endocrinol 47:379, 1997. Bayraktar M, Van Thiel DH: Endocrine changes in liver disease. The Endocrinologist 5:403, 1995. Hou S: What are the clinically important consequences of ESRD-associated endocrine dysfunction? Sem Dialysis 1997; 10:11-13. Chrousos GP, Torpy DJ, Gold PW: Interactions between the hypothalamic-pituitary-adrenal axis and the female reproductive system: clinical implications. Ann Intern Med 129:229, 1998. Selective Hormone Deficiencies Yen SSC. Female hypogonadotropic hypogonadism. Endocrinol Metab Clin N Amer 1993;22;29-58. Whitcomb RW, Crowley WF Jr. Male hypogonadotropic hypogonadism. Endocrinol Metab Clin N Amer 1993;22:125-143. Waldstreicher J, Seminara SB, Jameson JL, Geyer A, Nachtigall LB, Boepple PA et al: The genetic and clinical heterogeneity of gonadotropin-releasing hormone deficiency in the human. J Clin Endocrinol Metab 81:4388, 1996. Conway GS: Clinical manifestations of genetic defects affecting gonadotrophins and their receptors. Clin Endocrinol 45:657, 1996. Nachtigall LB, Boepple PA, Pralong FP, Crowley WF Jr: Adult-onset idiopathic hypogonadotropic hypogonadism - a treatable form of male infertility. N Engl J Med 1996;336:410-415. 53
  • 54. Seminara SB, Hayes FJ, Crowley WF Jr: Gonadotropin-releasing hormone deficiency in the human (idiopathic hypogonadotropic hypogonadism and Kallmann?s syndrome): pathophysiological and genetic considerations. Endocrine Revs 19:521, 1998. Orme SM, Belchetz PE: Isolated ACTH deficiency. Clin Endocrinol 35:213, 1991. Yamamoto T, Fukuyama J, Hasegawa K, Sugiara M: Isolated corticotropin deficiency in adults. Report of 10 cases and review of literature. Arch Intern Med 1992; 152:1705-1712. Samuels MH, Ridgway EC. Central hypothyroidism. Endocrinol Metab Clin N Amer 1992; 21:903-919. Faglia G, Bitenski L, Pinchera A et al. Thyrotropin secretion in patients with central hypothyroidism: evidence for reduced biological activity of immunoreactive thyrotropin. J Clin Endocrinol Metab 1979; 48:989-998. Collu R, Tang J, Castagne J, Lagace G, Masson N, Hout C, Deal C, Delvin E, Faccenda E, Eidne KA, van Vliet G: A novel mechanism for isolated central hypothyroidism: inactivating mutations in the thyrotropin- releasing hormone receptor gene. J Clin Endocrinol Metab 1997; 82:1361-1365. Rosenfield RL. Essentials of growth diagnosis. Endocrinol Metab Clin N Amer 1996; 25:743-758. Phillips JA, Cogan JD: Genetic basis of endocrine disease. 6. Molecular basis of familial human growth hormone deficiency. J Clin Endocrinol Metab 78:11-6, 1994. Maheshwari HG, Silverman BL, DuPuis J, Baumann G: Phenotype and genetic analysis of a syndrome caused by an inactivating mutation in the growth hormone-releasing hormone receptor: Dwarfism of Sindh. J Clin Endocrinol Metab 83:4065, 1998. Rosenfeld RG, Rosenbloom AL, Guevara-Aguirre J: Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev 1994; 15:369-390. Carroll PV, Christ ER, Bengtsson BA et al: Growth hormone deficiency in adulthood and the effects of growth hormone replacement: a review. J Clin Endocrinol Metab 1998; 83:382-395. Hoffman DM, O?Sullivan AJ, Baxter RC, Ho KKY. Diagnosis of growth hormone deficiency in adults. Lancet 1994; 343:1065-1068. Anon: Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab 1998; 83:379-381. Vance ML, Mauras N: Growth hormone therapy in adults and children. N Engl J Med 1999;341:1206-1216. Tritos NA, Mantzoros CS. Recombinant human growth hormone: old and novel uses. Am J Med 1998;105:44-57. Bhasin S, Bremner WJ. Clinical Review 85: emerging issues in androgen replacement therapy therapy. J Clin Endocrinol Metab 1997;82:3-8. Bagatell CG, Bremner WJ: Androgens in men - uses and abuses. N Engl J Med 1996;334:707-714. Wang C, Berman N, Longstreth JA et al: Pharmacokinetics of transdermal testosterone gel in hypogonadal men: application of gel at one site versus four sites: a General Clinical Research Center Study. J Clin Endocrinol Metab 2000; 85:964-969. 54
  • 55. Snyder PJ, Peachey H, Berlin JA et al: Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 2000; 85:2670-2677. Posterior Pituitary Disorders Diabetes Insipidus Robertson GL: Diabetes insipidus. Endocrinol Metab Clin N Amer 1995; 24:549-572 Fujiwara TM, Morgan K, Bichet DG: Molecular biology of diabetes insipidus. Annu Rev Med 1995;46:331-343. Adrogue HJ, Madias NE: Hypernatremia. N Engl J Med 2000: 342:1493-1499. Ritting S, Robertson GL, Siggaard C et al: Identification of 13 new mutations in the vasopressin- neurophysin II gene in 17 kindred with familial autosomal dominant neurohypophyseal diabetes insipidus. Am J Hum Genet 1996; 48:107-117. Imura H, Nako K, Shimatsu A, Ogawa Y, Sando T, Fujisawa I et al: Lymphocytic infundibuloneurohypophysitis as a cause of central diabetes insipidus. N Engl J Med 329: 683, 1993. Barrett TG, Bundy SE, Macleod AF: Neurodegeneration and diabetes: UK Nationwide Study of Wolfram (DIDMOAD) syndrome. Lancet 1995; 346:1458-1463. Strom TM, Hortnagel K, Hofmann S, et al: Diabetes insipidus, diabetes mellitus, optic atrophy and deafness (DIDMOAD) caused by mutations in a novel gene (wolframin) coding for a predicted transmembrane protein. Hum Mol Genet 1998; 7:2021-2028. Bayliss PH: Investigation of suspected hypothalamic diabetes insipidus. Clin Endocrinol 1995; 43:507-510. Hensen J, Henig A, Fahlbusch R et al. Prevalence, predictors, and patterns of postoperative polyuria and hyponatremia in the immediate course after transsphenoidal surgery for pituitary adnoema. Clin Endocrinol 1999; 50:431-439. Richardson DW, Robinson AG. Desmopressin. Ann Intern Med 1985; 103:228-239 Lam KS, Wat MS, Choi KL et al: Pharmacokinetics, pharmacodynamics, long-term efficacy and safety of oral 1-deamino-8-D-arginine vasopressin in adult patients with central diabetes insipidus. Br J Clin Pharmacol 1996; 42:379-385. Durr JA: Diabetes insipidus in pregnancy. Am J Kidney Dis 1987; 9:276-283. Hyponatremia Bartter FC, Schwartz WB: The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967; 42:790-806. Adrogue HJ, Madias NE: Hyponatremia. N Engl J Med 2000;342:1581-1589. Verbalis JG: Hyponatremia: epidemiology, pathophysiology, and therapy. Curr Opin Nephrol Hyperten 1993; 2:635-652. DeVita MV, Gardenswartz MH, Konecky A, Zabetakis PM: Incidence and etiology of hyponatremia in an intensive care unit. Clin Nephrol 1990; 34:163-166. Ayus JC, Wheeler JM, Arieff AI: Postoperative hyponatremia encephalopathy in menstruant women. Ann Intern Med 1992; 117:891-897. 55
  • 56. Taylor SL, Tyrrell JB, Wilson CB: Delayed onset of hyponatremia after transsphenoidal surgery for pituitary adenomas. Neurosurgery 1995; 37:649-654. Harrigan MR. Cerebral salt wasting syndrome. A review. Neurosurgery 1996; 38:152-160. Sterns RH: Severe symptomatic hyponatremia: treatment and outcome. A study of 64 cases. Ann Intern Med 1987; 107:656-664. Sterns RH, Cappuccio JD, Silver SM, Cohen EP: Neurologic sequelae after treatment of severe hyponatremia: a multicenter perspective. J Am Soc Nephrol 1994; 4:1522-1530. Berl T: Treating hyponatremia: damned if we do and damned if we don’t. Kidney Int 1990;37:1006-1018. Ellis SJ. Severe hyponatremia. Complications and treatment. QJM 1995; 88:905-9. Gowrishankar M, Lin SH, Mallie JP et al. Acute hyponatremia in the perioperative period: insights into its pathophysiology and recommendations for management. Clinical Nephrol 1998; 50:352-359. Palm C, Gross P. V2-vasopressin receptor antagonists - Mechanism of effect and clinical implications in hyponatremia. Nephrol Dial Tranplant 1999; 14:2559-2563. Miscellaneous Hypothalamic Syndromes Cassidy SB, Schwartz S: Prader-Willi and Angelman syndromes. Disorders of genetic imprinting. Medicine 1998; 77:140-151. Couper RT, Couper JJ. Prader-Willi Syndrome. Lancet 2000; 356:673-675. Ruse R. Laurence-Moon-Biedl-Bardet Syndrome. Clinical, electrophysiological and genetic aspects. Acta Ophthalmol Scan Suppl 1998; 226:1-28. Poussaint TY, Barnes PD, Nichols K, Anthony DC, Cohen L, Tarbell NJ et al: Diencephalic syndrome: clinical features and imaging findings. Am J Neuroradiol 18:1499, 1997. Sotos JF, Dodge PR, Muirhead D, Crawford JD, Talbot NB: Cerebral gigantism in childhood: A syndrome of excessively rapid growth with acromegalic features and a nonprogressive neurologic disorder. N Engl J Med 271:109, 1964. Aoki N, Oikawa Akihiro, Sakai T: Serial neuroimaging studies in Sotos’ syndrome (cerebral gigantism syndrome). Neurol Res 20:149, 1998. Jennings MT, Gelman R, Hochberg F: Intracranial germ-cell tumors: Natural history and pathogenesis. J Neurosurg 63:155, 1985. Bruce JN, Stein BM: Surgical management of pineal region tumors. Acta Neurochir 134:130, 1995. Fauchon I, Jouvet A, Paquis P et al. Parenchymal pineal tumos: a clinicopathological study of 76 cases. Int J Radiat Oncol Biol Phys 2000; 46:959-968. Masera N, Grant DB, Stanhope R, Preece MA: Diabetes insipidus with impaired osmotic regulation in septo- optic dysplasia and agenesis of the corpus callosum. Arch Dis Child 70:51, 1994. Dattani MT, Martinez-Barbera J-P, Thomas PQ, Brickman JM, Gupta R, Mårtensson I-L et al: Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nature Genetics 19:125, 1998. 56
  • 57. Jordan RM, Kendall JW, Kerber CW. The primary empty sella syndrome. Analysis of the clinical characteristics, radiographic features, pituitary function and cerebrospinal fluid adenohypophysial hormone concentrations. Am J Med 1977; 62:569-580. Brismar K, Efendic S. Pituitary function in the empty sella syndrome. Neuroendocrinology 1981;32:70-77. 57
  • 58. Disorders of the Hypothalamus and Pituitary Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 1. Pituitary Tumors a) Cushing’s Disease X X X X X X X X X b) Acromegaly X X X X X X X X c) Prolactinoma X X X X X X X X d) Non-functioning adenomas X X X X X X X X 2. Space-Occupying/Infiltrative Disease a) Cranipharyngloma X X X X X X X X b) Hemochromatosis X X X X X X X X c) Histiocytosis X X X X X X X X X d) Sarcoid X X X X X X X X 3. Hypopituitarism a) Adrenal X X X X X X X X X b) Thyroid X X X X X X X X X c) Growth hormone X X X X X X X X X d) Gonadotropins X X X X X X X X X 4. Water Balance a) Diabetes insipidus X X X X X X X X X b) SIADH X X X X X X X X X 5. Disease Specific Studies/Procedures a) GnRH stimulation X X X X X X b) Insulin induced hypoglycemia X X X c) CRH stimulation X X X X X d) IPSS X X X e) Pituitary imaging MRI/CT X X X X X X X X f) Dexamethasone suppression X X X X X X X X 58
  • 59. Section 7: Lipid Disorders and Atherosclerosis 7.1. Introduction 7.1.1 Disease Area Dyslipidemia refers to abnormalities of plasma lipoproteins, including chylomicrons, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), lipoprotein(a), and other minor species. Hyperlipidemia signifies increased plasma cholesterol, triglyceride, or both, most often due to high LDL and/or VLDL. The terms “abnormal” and “increased” must take into account the fact that half of all adults in the U.S. have LDL cholesterol levels that warrant at least dietary intervention. Lipoprotein disorders include subtle abnormalities of composition, distribution, and lipid flux as well as obvious quantitative disorders of plasma cholesterol and triglyceride. The lipid section requires an understanding of the physiology and pathophysiology of lipoprotein metabolism, the clinical impact of disorders of lipoprotein metabolism, and their treatment. An understanding of dyslipidemia requires fundamental understanding of the various sites at which defects can occur in lipid metabolic pathways, the pathogenesis and diagnosis of both genetic disorders and secondary forms of dyslipidemia that result from the presence of several endocrine and other diseases, lifestyle and dietary variations, and/or the use of a variety of drugs. The metabolic syndrome involves disturbances of glucose, insulin, and fat metabolism, lipoproteins, inflammation, and blood pressure, all contributing to cardiovascular risk. The trainee should become familiar with the emerging understanding of the role of lipoproteins in the arterial wall, which is the most susceptible pathologic target for most lipid disorders. Lipidology also requires training in the therapy of these disorders, including dietary, lifestyle, and pharmacologic approaches. 7.1.2 Importance of Lipids Atherosclerosis, the key pathologic consequence of most lipid disorders, kills more than one third of all people in industrialized societies. Severe lipid disorders cause death and disability from myocardial infarction, stroke, and other vascular events as early as childhood and throughout adult life. Quantitative and qualitative disorders of LDL, VLDL (triglyceride), HDL, and lipoprotein(a) contribute to atherosclerotic risk. Epidemiologic studies of lipoprotein phenotypes and genetics continue to refine our understanding of and our ability to predict risk of cardiovascular morbidity and mortality. Clinical trials have shown that lipid treatment reduces major coronary and cerebrovascular events, achieving 25% to 40% event reductions in large trials and as much as 70% event reductions in smaller intensive trials. An understanding of the relationship between dyslipidemia and other cardiovascular risk factors in determining overall cardiovascular risk is important in treating premature, progressive, or persistent atherosclerosis. Very high plasma triglyceride levels are associated with the chylomicronemia syndrome that includes pancreatitis and other manifestations. An understanding of genetic and environmental/lifestyle factors that produce fasting chylomicronemia, and their appropriate management, is lifesaving in patients with this disorder. 7.2. Discussion 7.2.1. Goals By the completion of their fellowship, trainees should be competent in the diagnosis of common genetic and acquired forms of dyslipidemia and in the estimation of cardiovascular risk. They should understand the key points of physical examination (including corneal arcus, eruptive and tendinous xanthomas, femoral and other bruits), the various laboratory tests, and the strengths and limitations of these diagnostic findings and assays. Trainees should also develop expertise in the management of lipid disorders well beyond the level of the usual internist. This includes an understanding of the dietary principles and lifestyle issues involved in lipid treatment and atherosclerosis prevention. The valuable role of certain dietary supplements and over-the-counter drugs, and lack of value of others, should be understood, including aspirin, vitamins, fish oil, fiber, soy products, and stanol/sterol esters. The trainee should be well versed in prescribing drugs for treatment of dyslipidemia, singly and in combination, and in managing side effects. 59
  • 60. 7.2.2. Training These skills are acquired through various means including the following: (1) Didactic seminars as well as self-directed learning with reading material provided to learn physiology and pathophysiology. (2) Thorough familiarity with the latest guidelines for the diagnosis and management of dyslipidemia from the National Cholesterol Education Program. (3) Hands on evaluation and follow-up of outpatients with various genetic and acquired forms of dyslipidemia in both general endocrine continuity clinics and a weekly referral Lipid Clinic at the Durham VA Medical Center. (4) Emphasis through lectures, handouts, reading material, and face-to-face patient encounters on dietary, lifestyle, and supplement-based management of dyslipidemia and cardiovascular risk. (5) Formal lectures and suggested book chapters on pharmacologic management of dyslipidemia. (6) Appreciation of the role of non-physician health care providers in lipid management and cardiovascular risk reduction, via observation of a highly successful nurse-managed Risk Reduction Clinic integrated with the Durham VA Lipid Clinic. (7) Participation in ongoing basic and/or clinical research that includes molecular studies of the metabolic syndrome, drug trials with cardiovascular anatomic outcomes, clinical effectiveness studies in lipid treatment, and dietary studies aimed at triglyceride lowering. (8) Availability of participation in a one-day, repeated postgraduate education program, the Duke Lipid Clinic and Disease Management Preceptorship. 7.2.3. Specific Disorders of Lipid Metabolism and Cardiovascular Risk Reduction Strategies Triglyceride Chylomicronemia Polygenic/acquired (most adult cases) Lipoprotein lipase deficiency Apolipoprotein C-II deficiency VLDL Familial hypertriglyceridemia (FHTG) Familial combined hyperlipidemia (FCHL) Diabetic dyslipidemia Lipodystrophy Genetic Acquired (e.g., HIV, especially with protease inhibitor therapy) Dysbetalipoproteinemia (type III, or remnant hyperlipidemia) Cholesterol With increased triglyceride: FHTG, FCHL, diabetes, lipodystrophy, type III LDL Polygenic LDL receptor defect Familial defective apolipoprotein B Secondary Lipoprotein(a) HDL Low Hypoalphalipoproteinemia (multiple genes, most unknown) ABC-A1 transporter deficiency: homozygous and heterozygous ApoA-I milano High Familial hyperalphalipoproteinemia (multiple genes, most unknown) CETP deficiency Other Endocrine Dyslipidemia Hypothyroidism 60
  • 61. Hypercortisolism Acromegaly Estrogen, testosterone Nonlipid drugs, alcohol Management Atherosclerosis prevention and treatment LDL cholesterol HDL augmentation Lipoprotein(a) Triglyceride Lipoprotein size/density distribution Severe hypertriglyceridemia and pancreatitis 7.2.4. Special Considerations More than half of the morbidity/mortality risk associated with diabetes mellitus is due to accelerated atherosclerosis. Partly because LDL and non-HDL cholesterol levels can be reduced by medications and diet to levels far lower than the average population levels, lipid treatment targeting these parameters is known to powerfully prevent and ameliorate diabetic atherogenesis. Emerging evidence suggests that treatment targeting HDL may also benefit diabetic patients. High triglyceride is a stronger risk factor for atherosclerotic events in diabetic, compared to non-diabetic patients. Special emphasis on the management of diabetic cardiovascular risk, diabetic dyslipidemia, and the dyslipidemia accompanying the insulin resistance/metabolic syndrome is included in the curriculum. This includes knowledge of the pathophysiology of disordered lipid metabolism accompanying the dysfunctional energy metabolism of these states, and the interactions with management of body weight and hyperglycemia. A global approach to cardiovascular risk management in diabetes and insulin resistance is taught. The management of severe hypertriglyceridemia and pancreatitis risk receives special emphasis. Fasting chylomicronemia is difficult to treat and often receives less than adequate management in general medical practice. Trainees gain an understanding of the interaction of genetic and acquired hypertriglyceridemia leading to the chylomicronemia syndrome. At the completion of the fellowship, trainees are expected to be competent in the management of this condition. The LDL receptor defect occurs in 1 in 500 persons worldwide. These patients require early and intensive treatment with medication as well as diet. Usual care of these patients is often inadequate. The practicing endocrinologist in every community should be equipped to accept multiple referrals of these patients with monogenic familial hypercholesterolemia. Among adults, especially those with coronary disease, three or more medications used concomitantly may markedly reduce atherosclerosis progression and risk, even when standard goals of therapy are not met. Dysbetalipoproteinemia (type III hyperlipoproteinemia) occurs in approximately 1 in 5000 persons in the population worldwide. It is extremely atherogenic, but usually responds dramatically to appropriate treatment. Therapy with a statin alone, commonly offered in general medical practice, fails to control dysbetalipoproteinemia. Duke trainees should achieve competence in understanding the pathophysiology, diagnostic clues, laboratory confirmation, and the multifaceted treatment required for successful management of dysbetalipoproteinemia. Combinations of drugs that improve lipid metabolism are being used much more frequently, as clinical trials suggest improved cardiovascular outcomes. Some combinations, however, have potentially dangerous side effects - particularly rhabdomyolysis. Trainees will develop an understanding of the benefit and relative risk of combination therapy. In rare instances with high LDL and/or lipoprotein(a) resistant to therapy, particularly when associated with advancing clinical atherosclerotic disease, apheresis becomes a consideration. A number of rare disorders of lipid and lipoprotein metabolism have provided considerable insight into our understanding of basic biochemistry and pathophysiology. These include lecithin cholesterol acyltransferase deficiency, hepatic lipase deficiency and genetic polymorphisms, cholesteryl ester transfer protein deficiency, apolipoprotein CII deficiency, abetalipoproteinemia, and Tangier disease. Most practicing endocrinologists are unlikely to see any of these conditions in their lifetime. The role of these pathway defects is taught to illustrate lipoprotein physiology, but a detailed working knowledge of the 61
  • 62. diseases is not a requirement of the curriculum. A less rare condition is hypobetalipoproteinemia, sometimes associated with fatty liver, but otherwise a favorable prognosis. Trainees are taught the recognition, diagnosis, and implications of hypobetalipoproteinemia. 7.2.5. Evaluation The attending faculty in continuity and subspecialty clinics evaluate trainees on a regular basis. Evaluations include comments regarding clinical judgment, medical knowledge, clinical skills, humanistic qualities, professionalism, medical care, and continuing scholarship. 7.3. Suggested Reading and Internet Resources Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). J Am Med Assoc 285:2486-2497, 2001. Guyton JR. Dietary and pharmacologic management of atherosclerosis. In: Sellke and del Nido, eds. Sabiston and Spencer’s Surgery of the Chest. Saunders, Boston, 2004. Lipid-lipoprotein chapters in Scriver et al., eds., The Metabolic & Molecular Bases of Inherited Disease. McGraw-Hill, New York, 2000. Current Opinion in Lipidology: Journal published six times per year with in-depth reviews. National Cholesterol Education Program at www.nhlbi.nih.gov/guidelines/cholesterol. Download ATP III guidelines, summary or entire document. Download regular computer or handheld Framingham risk calculator. National Lipid Association at www.lipid.org. See especially Patient Information articles on atherogenesis and type III hyperlipidemia. Consider joining this organization for $50/year with reduced rates for regional annual symposia. National Lipid Association Self-Assessment Program. Volume 1. Diagnosis and management of dyslipidemia. CME program similar to MKSAP, from the National Lipid Association, www.lipid.org. Future miniprograms on specific dyslipidemias and full programs on the metabolic syndrome and cardiovascular risk reduction. National Lipid Education Council at www.lipidhealth.org. Slides, news, case studies. Lipids Online (Baylor College of Medicine website), www.lipidsonline.org. Extensive slides and commentary. 62
  • 63. Evaluation: Lipid Disorders and Atherosclerosis (1) Cholesterol Polygenic LDL receptor defect HDL Management (2) Triglyceride Chylomicrons VLDL Lipodystrophy Dysbetalipoproteinemia Management (3) Combined hyperlipidemia Management (4) Secondary dyslipidemia Diabetes mellitus Hypothyroidism (5) Metabolism/atherosclerosis Atherogenesis Combination drug rx Global risk reduction (6) Other Lipoprotein metabolism Genetic disorders Lipoprotein(a) 63
  • 64. Disorders of Lipid Metabolism Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 1. Cholesterol a) Polygenic X X X X X X X X X b) LDL receptor defect X X X X X X X X X c) HDL X X X X X X X X X d) Management X X X X X X X X X 2. Triglyceride a) Chylomicrons X X X X X X X X X b) VLDL X X X X X X X X X c) Lipodystrophy X X X X X X X X X d) Management X X X X X X X X X 3. Combine hyperlipidemia a) Dysbetalipoproteinemia X X X X X X X X X b) Management X X X X X X X X X 4. Secondary dyslipidemia a) Diabetes mellitus X X X X X X X X X b) Hypothyroidism X X X X X X X X X 5. Metabolism/atherosclerosis a) Atherogenesis X X X X X X b) Combination Drug Rx X X X X X X X X X c) Global risk reduction X X X X X X X X X 6. Other a) Lipoprotein metabolism X X X X X X b) Genetic disorders X X X X X X X X X c) Lipoprotein(a) X X X X X X X X X 64
  • 65. Section 8: Nutrition and Obesity 8.1 Introduction Endocrinology is concerned with the actions of hormones and the organs and tissues in which the hormones are formed. A number of hormones are particularly involved with fuel, vitamin, and mineral metabolism. They are profoundly involved in substrate flux and the utilization of food for energy production and storage. Their importance in nutrition is therefore great. A practicing endocrinologist must have a basic knowledge of nutrition to understand the endocrine interactions that occur. At a minimum, there much be in an endocrinology subspecialty training curriculum a core knowledge in nutrition (including nutrition support), and an understanding of eating disorders (including obesity, anorexia nervosa and bulimia). The goals for the training of Endocrine trainees in nutrition are to have a working knowledge of the above conditions, both basic pathophysiology and treatment modalities. 8.2 Discussion 8.2.1 Core Knowledge in Nutrition Fuel Metabolism Fellows’ Lecture Series Lillian Lien, MD and Susan Spratt, MD: Basic Concepts of Fuel Metabolism Stedman Nutrition Metabolism Forum Sheila Collins Ph.D.: Fat Cell Beta-adrenergic receptors: signaling mechanisms controlling metabolism and thermogenesis Deborah Muoio, Ph.D.: Fatty acid regulated gene expression and metabolic plasticity in skeletal muscle Jeff Rathmell, Ph.D. Cell Metabolism; A key regulator of cell fate? David Okar: Molecular Mechanisms in Metabolic Control AMWA Obesity Curriculum Section on pathophysiology of obesity Role of hormones and peptides and the CNS in the regulation of fuel metabolism Fellows’ Lecture Series Susan Spratt, MD and Lillian Lien, MD: Basic Concepts in Fuel Metabolism Stedman Nutrition Metabolism Forum Andrea M. Haqq: Characterization of the molecular role of the melanocortin-4 receptor and translational patient oriented research: serum ghrelin in normal children and children with Prader-Willi Syndrome Michael Freemark, MD: An Experimental model of beta cell dysfunction, insulin resistance, and glucose intolerance: the prolactin receptor-deficient/GH deficient mouse AMWA Obesity Curriculum Section on pathophysiology of obesity 65
  • 66. Micronutrient requirements Fellows’ Lecture Series Vitamins A S. Spratt, MD: Basics of Vitamin and Mineral Sources in Diet Metabolism Bioavailability T. Weber, MD: Osteoporosis Absorption T. Hayward, MD: TPN Parenteral Preparations Endocrine Grand Rounds Metabolism R. Liebowitz, MD: Vitamin Supplements Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Fellows’ Lecture Series Dietary Supplements T. Weber, MD: Vitamin D Deficiency D T. Weber, MD: Osteoporosis Sources in Diet T. Hayward, MD: TPN Lecture Bioavailability Clinic with Spratt, Weber, and Gesty-Palmer Absorption Patient Handouts by Marilyn Sparling, RD Parenteral Preparations Metabolism Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Dietary Supplements Fellows’ Lecture Series S. Spratt, MD: Basics of Vitamin and Mineral E Metabolism Sources in Diet T. Hayward, MD: TPN Bioavailability Endocrine Grand Rounds Absorption R. Liebowitz, MD: Vitamin Supplements Parenteral Preparations Metabolism Antagonists Drug/Nutrient Interactions Deficiency Syndromes Fellows’ Lecture Series Excess Syndromes S. Spratt, MD: Basics of Vitamin and Mineral DRIs Metabolism Dietary Supplements T. Hayward, MD: TPN K Endocrine Grand Rounds Sources in Diet R. Liebowitz, MD: Vitamin Supplements Bioavailability Absorption Parenteral Preparations Metabolism Fellows’ Lecture Series Antagonists S. Spratt, MD: Basics of Vitamin and Mineral Drug/Nutrient Interactions Metabolism Deficiency Syndromes T. Hayward, MD: TPN Excess Syndromes D. McNeill, MD: DM and Pregnancy DRIs Endocrine Grand Rounds Dietary Supplements R. Liebowitz, MD: Vitamin Supplements Folate 66
  • 67. Sources in Diet Bioavailability Absorption Parenteral Preparations Metabolism Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Dietary Supplements Vitamin C Fellows’ Lecture Series Sources in Diet S. Spratt, MD: Basics of Vitamin and Mineral Bioavailability Metabolism Absorption T. Hayward, MD: TPN Parenteral Preparations Endocrine Grand Rounds Metabolism R. Liebowitz, MD: Vitamin Supplements Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Dietary Supplements Thiamine Fellows’ Lecture Series Sources in Diet S. Spratt, MD: Basics of Vitamin and Mineral Bioavailability Metabolism Absorption T. Hayward, MD: TPN Parenteral Preparations Endocrine Grand Rounds Metabolism R. Liebowitz, MD: Vitamin Supplements Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Fellows’ Lecture Series Dietary Supplements S. Spratt, MD: Basics of Vitamin and Mineral Metabolism Riboflavin T. Hayward, MD: TPN Sources in Diet Endocrine Grand Rounds Bioavailability R. Liebowitz, MD: Vitamin Supplements Absorption Parenteral Preparations Metabolism Antagonists Fellows’ Lecture Series Drug/Nutrient Interactions Deficiency Syndromes S. Spratt, MD: Basics of Vitamin and Mineral Excess Syndromes Metabolism DRIs J. Guyton, MD: Treatment of Lipid Disorders Dietary Supplements T. Hayward, MD: TPN Endocrine Grand Rounds Niacin R. Liebowitz, MD: Vitamin Supplements Sources in Diet Clinic with Dr. John Guyton and patient handouts Bioavailability prepared by him Absorption 67
  • 68. Parenteral Preparations Metabolism Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Dietary Supplements Fellows’ Lecture Series S. Spratt, MD: Basics of Vitamin and Mineral B12 Metabolism Sources in Diet T. Hayward, MD: TPN Bioavailability Endocrine Grand Rounds Absorption R. Liebowitz, MD: Vitamin Supplements Parenteral Preparations VAMC clinical experience Metabolism Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Fellows’ Lecture Series Dietary Supplements S. Spratt, MD: Basics of Vitamin and Mineral Metabolism Biotin T. Hayward, MD: TPN Sources in Diet Endocrine Grand Rounds Bioavailability R. Liebowitz, MD: Vitamin Supplements Absorption Parenteral Preparations Metabolism Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Dietary Supplements Pantothenic acid Fellows’ Lecture Series Sources in Diet S. Spratt, MD: Basics of Vitamin and Mineral Bioavailability Metabolism Absorption T. Hayward, MD: TPN Parenteral Preparations Metabolism Endocrine Grand Rounds Antagonists R. Liebowitz, MD: Vitamin Supplements Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Dietary Supplements Pyridoxine Antioxidants Inositol/ Choline/ Carnitine MINERALS Calcium 68
  • 69. Sources in Diet Clinic with Tom Weber, MD and Susan Spratt, MD Bioavailability Absorption Patient Handouts by Marilyn Sparling, RD Fellows’ Lecture Series Parenteral Preparations Metabolism M.A. Bethel, MD: Hypercalcemia Antagonists S. Spratt, MD: PHPT Drug/Nutrient Interactions T. Hayward, MD: TPN lecture Deficiency SyndromesEndocrine Grand Rounds Excess Syndromes R Liebowitz, MD on Vitamin and Dietary DRIs Supplements Dietary Supplements Phosphorus Clinic with Tom Weber, MD Sources in Diet Bioavailability Fellows’ Lecture Series Absorption S. Spratt, MD: Basics of Vitamin and Mineral Metabolism Parenteral Preparations Metabolism T. Hayward, MD: TPN Antagonists Endocrine Grand Rounds Drug/Nutrient Interactions R. Liebowitz, MD: Vitamin and Dietary Deficiency SyndromesSupplements Excess Syndromes T. Weber, MD: XLH, TIO, ADHR, and FGF-23: DRIs New Insights into the Pathogenesis of Dietary Supplements Hypophosphatemic osteomalacia Magnesium Sources in Diet Bioavailability Fellows’ Lecture Series Absorption S. Spratt, MD: Basics of Vitamin and Mineral Metabolism Parenteral Preparations Metabolism T. Hayward, MD: TPN Antagonists MA Bethel, MD: Hypocalcemia Drug/Nutrient Interactions Endocrine Grand Rounds Deficiency Syndromes R. Liebowitz, MD: Vitamin and Dietary Excess Syndromes Supplements DRIs ESAP Dietary Supplements Manganese Sources in Diet Bioavailability Absorption Fellows’ Lecture Series Parenteral Preparations S. Spratt, MD: Basics of Vitamin and Mineral Metabolism Metabolism Antagonists T. Hayward, MD: TPN Drug/Nutrient Interactions Endocrine Grand Rounds Deficiency Syndromes R. Liebowitz, MD: Vitamin and Dietary Excess Syndromes Supplements DRIs Dietary Supplements Clinical Experience with consideration to celiac sprue and type 1 DM Iron ESAP Sources in Diet Bioavailability Absorption 69
  • 70. Parenteral Preparations Metabolism Antagonists Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Dietary Supplements Zinc Sources in Diet Fellows’ Lecture Series Bioavailability S. Spratt, MD: Basics of Vitamin and Mineral Absorption Metabolism Parenteral Preparations T. Hayward, MD: TPN Metabolism Endocrine Grand Rounds Antagonists R. Liebowitz, MD: Vitamin and Dietary Drug/Nutrient Interactions Supplements Deficiency Syndromes ESAP Excess Syndromes DRIs Dietary Supplements Copper Fellows’ Lecture Series Sources in Diet Bioavailability S. Spratt, MD: Basics of Vitamin and Mineral Absorption Metabolism Parenteral Preparations T. Hayward, MD: TPN Metabolism Endocrine Grand Rounds Antagonists R. Liebowitz, MD: Vitamin and Dietary Supplements Drug/Nutrient Interactions Deficiency Syndromes ESAP Excess Syndromes DRIs Dietary Supplements Selenium Fellows’ Lecture Series Sources in Diet S. Spratt, MD: Basics of Vitamin and Mineral Bioavailability Metabolism Absorption T. Hayward, MD: TPN Parenteral Preparations Metabolism Endocrine Grand Rounds Antagonists R. Liebowitz, MD: Vitamin and Dietary Supplements Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Fellows Lecture Series Dietary Supplements W. Burch: Lecture on Thyroid Anatomy S. Spratt: Lecture on Amiodarone Iodine Hyperthyroidism Sources in Diet Bioavailability T. Hayward: TPN lecture Absorption Endocrine Grand Rounds Parenteral Preparations R. Leibowitz: Dietary Supplements Metabolism Lecture Antagonists 70
  • 71. Drug/Nutrient Interactions Deficiency Syndromes Excess Syndromes DRIs Dietary Supplements Macronutrient Utilization Marilyn Sparling, RD Diabetes Mellitus Nutrition Marilyn Sparking, RD and Susan Spratt, MD Basic Nutrition Lecture Modulation of Disease Processes By nutrients in food and by dietary supplements (carcinogenesis, diabetes mellitus, cardiovascular disease, pregnancy, metabolic bone disease) Diabetes Mellitus Fellow Lecture Series Marilyn Sparling, RD: DM Nutrition Stedman Metabolism Forum Ann Brown, MD: Exercise, Insulin Resistance, and PCOS William Kraus, MD: STRIDE: Effects of exercise on visceral body fat, insulin responsiveness and fibronolysis Lynis Dohn, PhD: Mechanisms of Insulin resistance in human skeletal muscle Francis Neelon, MD: Kinetic of HbA1c Formation and degradation: observations during rice diet treatment of type 2 diabetes CVD Fellow Lecture Series John Guyton, MD: Lipid Biochemistry and Treatment John Guyton, MD: Lipid trial data and inherited disorders Stedman Metabolism Forum John Guyton, MD: Atherosclerosis: pathologic focus for metabolic disorders Robert Waterland, PhD: Early Origins of Adult Chronic Disease: Metabolic imprinting and epigenetic Laura Svetky, MD: Diet and Blood Pressure (DASH) Metabolic Bone Disease Fellow Lecture Series Tom Weber, MD: Vitamin D Deficiency Stedman Metabolism Forum Pao-Hwa Lin: Impact of the DASH diet on bone and calcium metabolism Carcinogenesis Stedman Metabolism Forum Wendy DeMark-Wahnefried, PhD, RD: Nutrition-based translational initiatives in breast and prostate cancer Wendy DeMark-Wahnefried, PhD, RD: Diet-Exercise Intervention to prevent sarcopenic obesity among women receiving adjuvant chemotherapy for breast cancer Bruce Kristal, PhD: Serum metabolome of dietary restriction: markers for cancer risk? 71
  • 72. Connie W bales, PhD, RD: Life-extending enhancing effects of caloric restriction 8.2.2 Eating Disorders OBESITY Definition Fellows’ Lecture Series Susan Spratt, MD: Basic Concepts in Obesity AMWA Curriculum Epidemiology Fellows’ Lecture Series Susan Spratt, MD: Basic Concepts in Obesity AMWA Curriculum CDC.GOV website Etiology Fellows’ Lecture Series Susan Spratt, MD: Basic Concepts in Obesity AMWA Curriculum Co-Morbidities Metabolic Syndrome Clinical Experience: inpatient, outpatient attendings’ and fellows’ clinics AMWA Curriculum Endocrine Grand Rounds Phillippa Miranda, MD: Metabolic Syndrome Ann Brown: Exercise, PCOS and Diabetes Prevention Stedman Nutrition Metabolism Forum See previously listed lectures Clinical Evaluation Fellows’ Lecture Series Susan Spratt, MD: Basic Concepts in Obesity Stedman Nutrition Metabolism Forum Dean Sherry, PhD: Application of Biophysical Methods for Metabolic Analysis Jeffrey MacDonald: Metabolomic Using NMR AMWA Curriculum Treatment Lifestyle Modification Stedman Nutrition Metabolism Forum William Kraus, MD: STRIDE Diet Treatment High Protein, high Fat, Low Carb Eric Westman, MD and William Yancy, MD in talks to Endocrine Grand Rounds, Medicine Grand Rounds and Stedman Nutrition Metabolism Forum Clinic with Dr. John Guyton Protein supplemental modified fast, liquid diets AMWA Obesity Curriculum Low fat, high carbohydrate diets Francis Neelon, MD: Rice Diet Perspective at Endocrine Grand Rounds and Stedman Nutrition Metabolism Forum Speaker on: Structure House at Stedman Nutrition Metabolism Forum Marilyn Sparling, RD 72
  • 73. Traditional ADA AHA Endocrine Grand Rounds Marilyn Sparling, RD: ADA Diet Clinical experience on inpatient and outpatient rounds Meal Replacements AMWA Obesity Curriculum Physical Activity/Exercise AMWA Obesity Curriculum Stedman Nutrition Metabolism Forum William Kraus, MD: STRIDE Ann Brown., MD: Exercise and PCOS Pharmacologic Treatment Stedman Nutrition Metabolism Forum Kishore Gadde, MD: New Pharmaceutical Interventions for Obesity AMWA Obesity Curriculum Surgery Stedman Nutrition Metabolism Forum Jarol B. Knowles, MD: Bariatric Surgery Medicine Grand Rounds John Grant, MD: Bariatric Surgery Complications of Treatment Obesity Clinical Trials Stedman Nutrition Metabolism Forum Howard Eisenson and Eric Westman: Obesity Research at Duke DFC Anorexia/Bulimia Patients diagnosed with eating disorders such as anorexia nervosa or bulimia nervosa often poses challenges for the medical community. Such challenges include but are not limited to: the severe medical complications associated with these disorders, difficulties with patient regimen adherence, and minimization of symptom severely by the patient. To establish an effective working relationship with this patient group, it is imperative that physicians understand not only the medical sequelae of these disorders but also the phenomenological experience of the disorder from the patient’s perspective. In this manner, the physician is in a better position to join with the patient to create a collaborative team. Such knowledge and understanding may also help to minimize the physician’s experience of frustration. This aspect of the curriculum will address specific issues regarding physician behavior and clinical management of these disorders. Dr. Nancy Zucker, a clinical psychologist who specializes in the treatment of eating disorders and the director of the Duke Eating Disorders Program wrote this aspect of the curriculum. Dr. Susan Spratt, who is the endocrinologist affiliated with the eating disorders program at Duke, addresses the medical management of this population. Clinical Syndrome, Psychological Characteristics and Treatment Fellows’ Lecture Series Nancy Zucker, PhD: Clinical Syndrome, Psychological Characteristics and Treatment Neuro-endocrine Abnormalities and Clinical Sequelae of Anorexia/Bulimia Fellows’ Lecture Series Susan E. Spratt, MD: Neuro-endocrine Abnormalities and Clinical Sequelae of Anorexia/Bulimia The lectures will include the gonadotropin abnormalities hypo metabolic manifestation and hormones involved in the pituitary-hypothalamus axis problem that occur with anorexia nervosa and bulimia. 73
  • 74. In addition, emergency and long-term complications such as osteoporosis, amenorrhea, cardia arrhythmia, dentition problems, sepsis, hypothermia, hypoglycemia, and electrolyte abnormalities will be discussed. Other Resources Available: Weekly Eating Disorders Forum 8.2.3 Nutrition Support Protein Calories Malnutrition (marasmus) Head and neck cancer, malabsorption, CNS disease, anorexia and bulimia, GI obstruction, iatrogenic, drug induced, senescence Protein Malnutrition (Adult Kwashiorkor-Like Syndrome) Critical illness acute vs sustained/chronic, trauma, burn, protein-losing enteropathy, HIV, cancer, nephritic syndrome Nutritional Assessment History, physical exams, including anthropometrics, laboratory assessment, body composition; metabolic cart Treatment (1) Enteral: oral and tube feeding (2) Parenteral (3) Pharmacological (anabolics) (4) Combined modalities (5) Monitoring treatment Interpretation of Clinical Trials in Nutrition Support 8.2.4 Specific Technical Procedures Metabolic Cart – Energy Expenditure Basic Nutrition Lecture AMWA Curriculum Dexa for Body Composition Thomas J. Weber, MD How to read bone mineral densities Will include section on body composition Total Parenteral Nutrition Formulation/Management Endocrine Grand Rounds Thomas Hayward, MD: Total Parenteral Nutrition 8.3 Suggested Reading Biochemical and Physiological Aspects of Human Nutrition. Martha Stipanuk, editor. W.B. Saunders Company George Bray. Contemporary Diagnosis and Management of Obesity. Newtown, Pa: Handbooks in Health Care Co. Jeffrey S. Flier, Daniel W. Foster, Eating Disorders: Obesity, Anorexia Nervosa, and Bulimia Nervosa. In: Williams Textbook of Endocrinology. Disorder of Fuel Metabolism. In: Kenneth L. Becker, ed. Principles and Practice of Endocrinology, 2nd ed. Philadelphia, Pa: J.B. Lippincott Company. Physicians Desk Reference: Dietary Supplements. 74
  • 75. C-D ROMS Nutrition in Medicine (NIM) Series. Steven Zeisel, MD, Ph.D., editor. Website: www.med.unc.edu/nutr/nim Commerical: www.medeorinteractive.com Shils ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th edition, Williams and Wilkins. 75
  • 76. Nutrition and Obesity Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 1. Obesity a) Pathophysiology X X X X X b) Diagnosis X X X X X X X X c) Management X x X X X X X X 2. Starvation a) Anorexia nervosa X X X b) Bulimia X X X 3. Vitamin Deficiency a) Water soluble X X X X X X X X b) Fat soluble X X X X X X X X 4. Total Parenteral Nutrition a) Management X X X 76
  • 77. Section 9: Thyroid Disorders 9.1 Introduction Thyroid specific disorders include both anatomical defects of the thyroid gland as well as disorders due to the effects of thyroid hormones on extrathyroidal tissues. Thyroid disorders are among the most common diseases encountered by the endocrine consultant. They occur in the population with prevalence greater than 10% in some studies. Furthermore the incidence of thyroid disorders is rising in part because our diagnostic tools are more sensitive and sophisticated. Thyroid disorders account for a significant amount of morbidity in our society and the trainee should be competent in their diagnosis and treatment. 9.2 Discussion 9.2.1 Program Requirements 1. The training program provides opportunities for the trainee to develop clinical competence in the area of thyroid disease. Clinical experience includes opportunities to diagnose and manage adolescent and adult inpatients and outpatients of both sexes with a variety of thyroid diseases of varying acuity. The program also includes opportunities to function in the role of an endocrinology consultant for patients and other physicians and services in both inpatient and outpatient settings. 2. The trainees are given opportunities to assume responsibility for and follow patients throughout the training period in both inpatient and outpatient settings to observe the evolution and natural history of thyroid disorders, as well as the effectiveness of therapeutic interventions. Residents will have experience representing variable acuity in a wide spectrum of thyroid related diseases. 3. The curriculum also emphasizes biochemistry and physiology, including cell and molecular biology, as they relate to thyroid disease. The appropriate utilization and interpretation of clinical laboratory, radionuclide, and radiological studies for the diagnosis and treatment of thyroid disease is stressed. 4. Residents have formal instruction, clinical experience, or opportunities to acquire expertise in the evaluation and management of the disorders listed below as well as aspects of those disorders that relate to: (1) psychiatric disease (2) aging, with particular emphasis on the care of geriatric patients and thyroid related changes associated with aging (3) adaptations and maladaptations to systemic diseases with respect to affects on the hypothalamic-pituitary-thyroid axis. 5. In relation to the diseases listed below there is instruction in: (1) thyroid physiology and pathophysiology in systemic diseases and principals of hormone action (2) biochemistry and physiology, including cell and molecular biology and immunology, as they relate to thyroid disease (3) signal transduction pathways and biology of thyroid hormone receptor and their interaction with other hormone receptor pathways. 6. In relation to the diseases listed below, residents have experience in the performance of endocrine clinical laboratory and radionuclide studies and basic laboratory techniques, provision is made for the trainee to acquire experience and skill in the following areas: (4) The interpretation of laboratory tests, immunoassays, and radionuclide, ultrasound radiologic, and other imaging studies for the diagnosis and treatment of thyroid diseases; (5) The effects of a variety of non-endocrine disorders on laboratory and imaging studies and performance and interpretation of stimulation and suppression tests are related to thyroid disease; 77
  • 78. (3) Thyroid related emergencies, including: (a) Severe hypo- and hyperthyroidism (thyroid storm and myxedema coma) (b) Severe thyroid dysfunction during and after pregnancy (c) Tracheal compression from a goiter or from the treatment of thyroid disease (d) Agranulocythosis secondary to anti-thyroid drug therapy 9.2.2 Specific Disease Disorders The methods of education and methods of evaluation for the disorders of the thyroid are provided in the subsequent table and listed in six board areas. 1. The trainee should develop a comprehensive understanding of all causes of thyrotoxicosis. The major method of education will be by direct clinical experiences in the outpatient clinic, by clinical case discussions on attending rounds and in conferences, and by self-directed learning for Graves' disease, thyroiditis, and toxic nodular goiters. For these disorders the trainee will be evaluated by direct observations and discussions with the faculty, as well as by clinical preparations. For other causes of thyrotoxicosis, the trainee may use self-directed learning, clinical case discussions, or obtain formal instruction to assure adequate understanding of the other causes of thyrotoxicosis. 2. The trainee should develop a comprehensive understanding of all causes of hypothyroidism. Autoimmune and post-ablative hypothyroidism should be learned by direct clinical experience in the outpatient setting, as well as by clinical case discussions and self-directed learning. Teaching of the other causes of hypothyroidism may also utilize formal instruction, clinical case discussions, and other self- directed learning to meet this objective. 3. The trainee should develop a comprehensive understanding of thyroid cancer. The differentiated epithelial thyroid cancer should be learned by direct clinical experience in the outpatient setting and supplemented by experience in the inpatient setting. Further teaching by clinical case discussion and self- directed learning is encouraged. Medullary thyroid cancer should also be learned by direct clinical experience in either the outpatient or inpatient setting with supplementation by formal instruction, clinical case discussion, and self-directed learning. Other cases of thyroid cancer may be taught by clinical case discussions or self-directed learning. 4. The trainee should develop a comprehensive understanding of the causes of nodules and goiters. The single nodule, multinodular goiter, and a diffuse goiter should be learned by direct clinical experience in the outpatient setting with supplementation by clinical case discussions and self-directed learning. Other causes of nodules and goiters may be taught by self-directed learning in direct addition to direct clinical experience and clinical case discussion. 5. The trainee should become familiar with other causes of thyroid dysfunction. These include pregnancy-related thyroid dysfunction, polyglandular autoimmune syndrome, and thyroid dysfunction in non-thyroidal disease. These diseases should be learned by direct clinical experience in the inpatient or outpatient setting. They may be supplemented by clinical case discussions and self-directed learning. Other causes of thyroid dysfunction may be taught by self-directed learning in addition to clinical case discussions and direct clinical experience. 6. The trainee should have significant experience to become competent in the following procedures: (1) Fine-needle aspiration biopsies of a thyroid nodule (2) Interpretation of thyroid ultrasound and nuclear imaging studies 9.2.3 Evaluation The evaluation of the trainees in all areas should include direct observations with a patient and discussions with the faculty. Additional evaluations can occur following clinical presentations by the trainee. 9.2.4 Suggested Reading "Papillary and Follicular Thyroid Cancer", Schlumberger, NEJM 338: 297-305, 1998 78
  • 79. "AACE/AAES Med/Gung Guidelines for Clinical Practice: Management of Thyroid Cancer" Thyroid Carcinoma Task Force, Endocrine Practice 7 (3), May/June 2001 "Thyroid Hormone and the CV System" Klein NEJM 344(f): 501-509, 2001 "Postpartum Thyroiditis" Stagnaro-Green JCEM 87(9): 4042-4047, 2002 "Management of Hyper- and Hypothyroidism in the Pregnant Women" Roti JCEM 81(5): 1679-1682, 1996 "Thyroiditis" Pearce NEJM 348 (26): 2646-2544, 2003 "Subclinical Hypothyroidism" Toft NEJM 345 (7): 512-516, 2001 "Clinical and Laboratory Diagnosis of Thyrotoxicosis" Lyda, Endocrine and Metabolism Clinics of North America 27 (1): 25-35, 1998 "Oral Cholecystographic Agents of the Thyroid", Braga JCEM 86(5): 1853-1860, 2001 "Drug Therapy: The Management of Hyperthyroidism", Franklyn NEJM 330(24): 1731-1738, 1994 "Antithyroid Drugs in the Management of Patients with Graves' Disease: An Evidence-Based Approach to Therapeutic Controversies" Cooper JCEM 88(8): 3474-3482, 2003 "Current Concepts: Management of a Solitary Thyroid Nodule" Mazzafemi NEJM 328 (8): 553-559, 1993 "Life Threatening Thyrotoxicosis" Burch, Endocrine and Metabolism Clinics of North America, 22 (2): 263-277, June 1993 "Graves' Disease" Weetinan NEJM 343 (17): 1236-1248, 2000 79
  • 80. Disorders of the Thyroid Method of Education Method of Evaluation Formal Direct Clinical Clinical Case Self- Direct Discussions Clinical Instructions Experience Discussions Directed Observations With Presentations Learning With Patients Faculty Inpatient Outpatient Attd. Rds. Conferences 1. Hyperthyroidism a) Graves’ disease X X X X X X X X X b) Thyroiditis X X X X X X X X X c) Toxic nodule X X X X X X X X X d) Toxic multinodular goiter X X X X X X X X e) Struma Ovarii X X X f) Thyrotoxicosis factitia X X X X X g) Other 2. Hypothroidism a) Thyroiditis X X X X X X X X X b) Post-ablative X X X X X X X X X c) Other 3. Thyroid Cancer a) Papillary thyroid cancer X X X X X X X X X b) Follicular thyroid cancer X X X X X X X X X c) Medullary Thyroid cancer X X X X X X X d) Anaplastic thyroid cancer X X X e) Other 4. Nodules a) Simple nodule X X X X X X X X X b) Multinodular goiter X X X X X X X X X c) Diffuse goiter X X X X X X X X X d) Other 5. Other a) Polyglandular autoimmune X X X X X X X Syndrome b) Pregnancy-related thyroid disease X X X X X c) Non-thyroidal illness X X X X X X X X 6. Disease Specific Studies/Procedures a) Fine needle aspiration X X X X X X b) Thyroid ultrasound X X X X X X c) Thyroid scan-iodine X X X X X X X X X d) Thyroid scan-Tc X X X X X X X X X 80
  • 81. APPENDICES 81
  • 82. Appendix A Elective Rotation Schedule Gen Endo MON TUES WED THURS FRI AM Burch Peds Jelesoff 2/4 Wed Nuc Med Spratt Green 1/3 Wed (8:30-12:00) PM Burch Peds DOC Optional VA Endo Bone MON TUES WED THURS FRI AM Optional Peds Weber Spratt Optional PM Lyles Peds Weber Bone Radiology VA Endo Lipids/PCO MON TUES WED THURS FRI AM Peds Brown REI Guyton (Duke) Optional PM Peds Guyton (VA) DOC Optional VA Endo Diabetes MON TUES WED THURS FRI AM McNeill Peds Jelesoff Green Brown PM Sparling/Nicollerat Peds DOC Optional VA Endo 82
  • 83. Appendix B Gonadal Disorders – Learning Opportunities Formal Instruction Direct Clinical Experience Clinical Case Discussions Self-Directed Learning Inpatient Outpatient Attending Rounds Conferences Female Normal female Fellow’s Lecture Pediatric Endo Elective Fellow’s Case Confernce, reproductive physiology Series Reproductive Endo WHSS including puberty Elective Attending Clinics Primary/secondary Fellow’s Lecture Attending Clinic Fellow’s Case Conference, amenorrhea Series Fellow’s Clinic WHSS Reproductive Endocrine Elective Dysfunctional uterine Fellow’s Lecture Attending Clinics WHSS, WH website bleeding Series Fellow’s Clinic Hirsutism/virilization Fellow’s Lecture Endocrine Attending Clinics Fellow’s Case Conference, Series Service Fellow’s Clinic WHSS, website Polycystic ovarian Fellow’s Lecture Endocrine Attending Clinics Endocrine Grand Rounds, syndrome Series Service PCOS Clinic (Brown) WHSS, WH website Fellow’s Clinic Reproductive Endocrine Elective Pediatric Endocrine Elective Infertility Reproductive Endocrine Endocrine Grand Rounds, Elective WHSS PCOS Clinic (Brown) Menopause Fellow’s Lecture Endocrine Attending Clinic Endocrine Grand Rounds, Series Service Fellow’s Clinic WHSS, WH website Complementary and WHSS, website Alternative Approaches to Women’s health issues Psychosocial disorders Attending Clinics WHSS associated with Fellow’s Clinic reproductive system, including pre-menstrual dysphoric disorder, perimenopausal mood disorders, eating disorders, sexual dysfunction and decreased libido 83
  • 84. Formal Instruction Direct Clinical Experience Clinical Case Discussions Self-Directed Learning Inpatient Outpatient Attending Rounds Conferences Male Normal male reproductive Pediatric Endocrine Elective physiology including puberty Hypogonadism Male Hypogonadism Clinic (Weber), VAMC Endocrine Clinic, Attending Clinics Gynecomastia VAMC Endocrine Clinic Erectile dysfunction Male Hypogonadism Clinic (Weber), Attending Clinics Infertility Reproductive Endocrine Elective Prostatic disorders X, also covered under “erectile dysfunction” Male/Female Osteoporosis, including Fellow’s Lecture Endocrine Osteoporosis Clinic (Weber, Endocrine Grand Rounds, assessment with bone Series Service Spratt) WHSS density testing, and Fellow’s Clinic therapy with sex steroids, SERMS/SARMS and physical therapy Effects of chronic illness Endocrine Attending Clinics (McNeill, Fellow’s Case on reproductive system Consult Burch, Spratt, Jelesoff) Conference and DMS VA Endocrine Clinic Pediatric Intersex disorders Pediatric Endo Elective Fellow’s Case Conference Precocious Puberty Pediatric Endo Elective Delayed Puberty Pediatric Endo Elective Gonadal Dysgenesis Pediatric Endo Elective Attending Clinics Neoplasia Testicular Tumors VAMC Endocrine Clinic Ovarian Tumors 84
  • 85. Formal Instruction Direct Clinical Experience Clinical Case Discussions Self-Directed Learning Inpatient Outpatient Attending Rounds Conferences Disease Specific Studies/ Procedures GnRH/GnRH Analogues Fellow’s Conference Ovarian Ultrasound Attending Clinics Endocrine Grand Rounds, Reproductive Endocrine WHSS Elective PCOS Clinic (Brown) Pelvic Examination Fellow’s Clinic Reproductive Endocrine Elective Semen Analysis (note: Reproductive Endocrine procedure is not routinely Elective taught in fellowship. Focus is on interpretation) Induction of Fellow’s Endocrine Grand Rounds spermatogenesis (note: Conference fellows not exposed to performance of this procedure) Male/Female Hormone Fellow’s Endocrine Attending Clinics WHSS Replacement Lecture Series Service Fellow’s Clinic Endocrine Grand Rounds VAMC Endocrine Clinic Oral Contraceptive Fellow’s Endocrine Attending Clinics WHSS Management Lecture Series Service PCOS Clinic (Brown) Oral Glucose Tolerance Attending Clinics WHSS Test PCOS Clinic (Brown) Evaluation: Evaluation of fellow’s performance occurs during Fellow’s Case Conference as they present cases and relevant literature. It also occurs during regular sessions in which Endocrine Self Assessment Program (ESAP), and other similar questions are discussed. Fellow’s also present at Endocrine Grand Rounds, and are observed in patient interactions by the supervising attending in Attending Clinics, VAMC Endocrine Clinic, and Fellow’s Clinic. 85
  • 86. Appendix C Ambulatory Settings Practice Setting # of # Faculty/ # Fellow/ # Hours/ RN/ CDE Nutrition Computer w/ Textbooks Rooms/Clinic Session Session Session LPN Net Access (reference) VA Endocrine 6 1 1-3 4 Y Y Y Y Y(on line) Clinic (Green) VA Lipid Clinic 4 1 1 4 Y Y Y Y Y (Guyton) VA Bone Clinic 3 1 1 4 Y N N Y Y(on line) (Gesty-Palmer) DOC Endo 3 3 2 6 Y Ref to Duke Ref to Dur Regional Y (online w/MD Consult) Clinic (Kourany) Duke Endo 2-3 1 1 4 Y Y Y Y Y (online w/MD Consult) Electives (Weber) 3 1 1 7 Y Y Y Y Y (online w/MD Consult) Outreach Laurinburg (Weber) Outreach Roxboro 3 1 1 7 Y N N Y Y(on line) (Gesty-Palmer) Outreach 3 1 1 7 Y Y Y Y Y Fayetteville (Tan) 86