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ENDOCRINOLOGY BOARD REVIEW Presented by Med/Peds PGY III Class
ENDOCRINOLOGY   Disorders of the Hypothalamic – Pituitary Axis K. Dionne Posey, MD, MPH
ENDOCRINOLOGY <ul><li>Pituitary Disorders </li></ul><ul><li>Thyroid Disorders </li></ul><ul><li>Adrenal Disorders </li></u...
 
Hypothalamic–Pituitary Axis
Pituitary Gland <ul><li>Located within the sella tursica  </li></ul><ul><li>Contiguous to vascular and neurologic structur...
 
Pituitary Gland <ul><li>Anterior pituitary gland </li></ul><ul><ul><li>Secrete various trophic hormones </li></ul></ul><ul...
Anterior Pituitary Gland <ul><li>Anterior Pituitary  “ Master gland” </li></ul><ul><ul><li>Major blood source: hypothalami...
 
Anterior Pituitary Gland <ul><li>Anterior Pituitary  “ Master gland” </li></ul><ul><ul><li>Secreted in a  pulsatile  manne...
 
Hypopituitarism
Gonadotropin Deficiency <ul><li>Women </li></ul><ul><li>Oligomenorrhea or amenorrhea </li></ul><ul><li>Loss of libido </li...
ACTH Deficiency <ul><li>Results in hypocortisolism </li></ul><ul><ul><li>Malaise </li></ul></ul><ul><ul><li>Anorexia </li>...
TSH Deficiency <ul><li>Hypothyroidism </li></ul><ul><li>Atrophic thyroid gland  </li></ul>
Prolactin Deficiency <ul><li>Inability to lactate postpartum </li></ul><ul><li>Often 1 st  manifestation of Sheehan syndro...
Growth Hormone Deficiency <ul><li>Adults </li></ul><ul><ul><li>Often asymptomatic </li></ul></ul><ul><ul><li>May complain ...
 
Hypopituitarism <ul><li>Etiology </li></ul><ul><li>Anterior pituitary diseases  </li></ul><ul><ul><li>Deficiency one or mo...
Hypopituitarism <ul><ul><li>Primary pituitary disease </li></ul></ul><ul><ul><ul><li>Tumors </li></ul></ul></ul><ul><ul><u...
Hypopituitarism
Hypopituitarism <ul><li>Developmental and genetic causes </li></ul><ul><ul><li>Dysplasia </li></ul></ul><ul><ul><ul><li>Se...
Hypopituitarism: Developmental and Genetic causes <ul><ul><ul><li>Septo-Optic dysplasia </li></ul></ul></ul><ul><ul><ul><l...
Hypopituitarism: Genetic <ul><ul><li>Septo-Optic dysplasia </li></ul></ul><ul><ul><ul><ul><li>Hypothalamic dysfunction and...
Hypopituitarism: Developmental <ul><li>Kallman Syndrome </li></ul><ul><ul><ul><li>Defective hypothalamic gonadotropin-rele...
Hypopituitarism: Developmental <ul><li>Kallman Syndrome </li></ul><ul><ul><ul><li>Males patients </li></ul></ul></ul><ul><...
Hypopituitarism: Developmental <ul><li>Laurence-Moon-Bardet-Biedl Syndrome </li></ul><ul><ul><ul><li>Rare autosomal recess...
Hypopituitarism: Developmental <ul><li>Frohlich Syndrome (Adipose Genital Dystrophy) </li></ul><ul><ul><ul><li>A broad spe...
Hypopituitarism <ul><li>Acquired causes: </li></ul><ul><ul><li>Infiltrative disorders </li></ul></ul><ul><ul><li>Cranial i...
Hypopituitarism: Acquired <ul><li>Lymphocytic Hypophysitis </li></ul><ul><ul><li>Etiology </li></ul></ul><ul><ul><ul><li>P...
 
Hypopituitarism: Acquired <ul><li>Pituitary Apoplexy </li></ul><ul><ul><li>  Hemorrhagic infarction of a pituitary adenoma...
Hypopituitarism: Acquired <ul><li>Pituitary Apoplexy </li></ul><ul><ul><li>Risk factors: </li></ul></ul><ul><ul><ul><li>Di...
Quick  Quiz!!! <ul><li>When should you suspect pituitary apoplexy? </li></ul>
Answer <ul><li>Suspect in patient presenting with </li></ul><ul><ul><ul><li>Variable onset of severe headache </li></ul></...
Hypopituitarism: Acquired <ul><li>Empty Sella Syndrome </li></ul><ul><ul><li>Often an incidental MRI finding   </li></ul><...
Hypopituitarism <ul><li>Clinical Presentation </li></ul><ul><li>Can present with features of deficiency of one or more ant...
Hypopituitarism <ul><li>Diagnosis </li></ul><ul><li>Biochemical diagnosis of pituitary insufficiency  </li></ul><ul><ul><l...
Hypopituitarism <ul><li>Treatment   </li></ul><ul><li>Hormone replacement therapy  </li></ul><ul><ul><li>usually free of c...
Hormone Replacement Intranasal desmopressin (5-20 ug twice daily) Oral 300-600 ug qd Vasopressin Adults: Somatotropin (0.3...
Take home points: <ul><li>Remember that the cause may be functional  </li></ul><ul><ul><li>Treatment should be aimed at th...
Pituitary Tumors
 
Pituitary Tumors <ul><li>Microadenoma < 1 cm </li></ul><ul><li>Macroadenoma > 1 cm </li></ul><ul><li>Is the tumor causing ...
Pituitary Tumors <ul><li>Diagnosis </li></ul><ul><ul><li>Check levels of all hormones produced </li></ul></ul><ul><ul><li>...
 
 
 
 
Craniopharyngioma <ul><ul><li>Derived from Rathke's pouch.  </li></ul></ul><ul><ul><li>Arise near the pituitary stalk  </l...
Craniopharyngioma <ul><li>Associated symptoms include: </li></ul><ul><ul><li>visual field abnormalities, personality chang...
Craniopharyngioma <ul><li>Anterior pituitary dysfunction and diabetes insipidus are common </li></ul><ul><li>Treatment  </...
 
 
Quick  Quiz!!! <ul><li>How does prolactin differ from LH/FSH in regard to hypothalamic control? </li></ul>
Answer <ul><li>Tonic hypothalamic inhibition by Dopamine </li></ul>
Prolactinoma <ul><li>Most common functional pituitary tumor </li></ul><ul><li>Usually a  micro adenoma </li></ul><ul><li>C...
Prolactinoma <ul><li>Women </li></ul><ul><ul><li>Amenorrhea – this symptom causes women to present earlier </li></ul></ul>...
Prolactinoma <ul><li>Essential to rule out secondary causes!! </li></ul><ul><ul><li>Drugs which decrease dopamine stores <...
Prolactinoma <ul><li>Diagnosis </li></ul><ul><ul><li>Assess hypersecretion </li></ul></ul><ul><ul><ul><li>Basal, fasting m...
Prolactinoma <ul><li>Treatment </li></ul><ul><ul><li>Medical  </li></ul></ul><ul><ul><ul><li>Cabergoline – dopamine recept...
 
 
Quick  Quiz!!! <ul><li>What type of tumors are most prolactinomas? </li></ul><ul><li>Prolactin levels >200 almost always i...
Answer <ul><li>What type of tumors are most prolactinomas?  Microadenomas </li></ul><ul><li>Prolactin levels >200 almost a...
 
Growth Hormone Tumors <ul><li>Gigantism </li></ul><ul><ul><li>GH excess before closure of epipheseal growth plates of long...
Growth Hormone Tumors <ul><li>May have DM or glucose intolerance </li></ul><ul><li>Hypogonadism </li></ul><ul><li>Large ha...
Growth Hormone Tumors <ul><li>Diagnosis </li></ul><ul><ul><li>Screen: </li></ul></ul><ul><ul><ul><li>Check for high IGF-I ...
 
 
Quick  Quiz!!! <ul><li>How do you screen for acromegaly? </li></ul>
Answer <ul><li>Check for high IGF-I levels (>3 U/ml) </li></ul>
Pituitary Gland <ul><li>Anterior pituitary gland </li></ul><ul><ul><li>Secrete various trophic hormones </li></ul></ul><ul...
Posterior Pituitary Gland <ul><li>The Neurohypophysis </li></ul><ul><li>Major blood source: the inferior hypophyseal arter...
Posterior Pituitary Gland <ul><li>Production of  </li></ul><ul><ul><li>Vasopressin (antidiuretic hormone;  ADH; AVP ) </li...
Posterior Pituitary Gland <ul><li>Vasopressin (Anti Diuretic Hormone) </li></ul><ul><ul><li>Some control via anterior hypo...
Posterior Pituitary Gland <ul><li>Rapidly secreted in direct proportion to serum osmolality </li></ul><ul><ul><li>Increase...
 
Diabetes Insipdus <ul><li>Etiology </li></ul><ul><ul><li>Deficient AVP can be primary or secondary </li></ul></ul><ul><ul>...
Diabetes Insipdus <ul><li>Gestational DI </li></ul><ul><ul><ul><ul><li>Primary deficiency of plasma AVP  </li></ul></ul></...
Diabetes Insipdus <ul><li>Secondary deficiencies of AVP </li></ul><ul><ul><li>Results from  inhibition of secretion  by  e...
Diabetes Insipdus <ul><li>Secondary deficiencies of AVP </li></ul><ul><ul><li>Antidiuretic response to AVP   </li></ul></u...
Diabetes Insipdus <ul><li>Pathophysiology </li></ul><ul><ul><li>When secretion or action of AVP is reduced to   80 to 85%...
Diabetes Insipdus <ul><li>Pathophysiology </li></ul><ul><ul><li>Primary polydipsia </li></ul></ul><ul><ul><ul><li>Pathogen...
Diabetes Insipdus <ul><li>Clinical Presentation </li></ul><ul><ul><li>Production of abnormally large volumes of dilute uri...
Diabetes Insipdus <ul><li>Diagnosis </li></ul><ul><ul><li>Verify polyuria </li></ul></ul><ul><ul><ul><li>a 24-h urine outp...
Diabetes Insipdus <ul><li>Diagnosis </li></ul><ul><ul><li>Water deprivation test </li></ul></ul><ul><ul><ul><li>If does no...
Diabetes Insipdus <ul><li>Diagnosis: Neurogenic vs Nephrogenic </li></ul><ul><li>Administer Desmopressin (DDAVP)  </li></u...
Diabetes Insipdus <ul><li>Treatment </li></ul><ul><ul><li>Neurogenic DI  </li></ul></ul><ul><ul><ul><li>DDAVP  </li></ul><...
 
Syndrome of Inappropriate ADH secretion <ul><li>Etiology </li></ul><ul><ul><li>CNS </li></ul></ul><ul><ul><ul><li>Lesions,...
Syndrome of Inappropriate ADH secretion <ul><li>Pathophysiology </li></ul><ul><ul><li>Excessive AVP production resulting i...
Syndrome of Inappropriate ADH secretion <ul><li>Clinical Presentation </li></ul><ul><ul><li>Acute </li></ul></ul><ul><ul><...
Syndrome of Inappropriate ADH secretion <ul><li>Diagnosis </li></ul><ul><ul><li>Diagnosis of exclusion </li></ul></ul><ul>...
Syndrome of Inappropriate ADH secretion <ul><li>Treatment </li></ul><ul><ul><li>Acute </li></ul></ul><ul><ul><ul><li>Fluid...
Treatment Guidelines <ul><li>See Handout </li></ul>
References <ul><li>Harrison's Principles of Internal Medicine - 16th Ed. (2005)  </li></ul><ul><li>Up to Date </li></ul><u...
Questions
True or False <ul><li>The pituitary: </li></ul><ul><li>Pituitary tumors are usually macroadenomas. </li></ul><ul><li>Lack ...
Answers <ul><li>The pituitary: </li></ul><ul><li>Pituitary tumors are usually macroadenomas.  –  True </li></ul><ul><li>La...
<ul><li>A 24 year old woman complains of fatigue and malaise.  She gave birth to a healthy infant 4 months before presenta...
<ul><li>A) Start thyroxine replacement therapy </li></ul><ul><li>B) Request a neurosurgeon to perform a biopsy of the pitu...
<ul><li>A) Start thyroxine replacement therapy </li></ul><ul><li>B) Request a neurosurgeon to perform a biopsy of the pitu...
<ul><li>A 38-year-old woman is referred to you by her gynecologist. She first presented to her gynecologist 4.5 years ago ...
<ul><li>Her prolactin level is now 60.5 ng/mL, and a visual field examination shows a small superotemporal field cut in th...
<ul><li>What is the most likely diagnosis? </li></ul><ul><li>  </li></ul><ul><li>(A) Prolactinoma </li></ul><ul><li>(B) Cl...
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  • Stimulate production of IGFs Suppressed by hyperglycemia Stimulated by hypoglycemia GH bone age &lt; chron age CGD
  • Pituitary adenoma Lymphocytic hypophysitis
  • Pituitary adenoma. Coronal T1-weighted postcontrast MR image shows a homogeneously enhancing mass ( arrowheads ) in the sella turcica and suprasellar region compatible with a pituitary adenoma; the small arrows outline the carotid arteries.
  • Adenoma Craniopharyngioma
  • Craniophayrngioma
  • Prolactin
  • Insensible losses ~500ml/day; so intake should be ~500 less than UO Quadraparesis, ataxia, abn extraocc movements 3% saline &lt;/= 0.05ml/kg/min; stat check NA q 2hr Stop once inreases by 12mmol or to 130mmol/L Watch UO
  • Lymphocytic Hypophysitis
  • Transcript of "ENDOCRINOLOGY"

    1. 1. ENDOCRINOLOGY BOARD REVIEW Presented by Med/Peds PGY III Class
    2. 2. ENDOCRINOLOGY Disorders of the Hypothalamic – Pituitary Axis K. Dionne Posey, MD, MPH
    3. 3. ENDOCRINOLOGY <ul><li>Pituitary Disorders </li></ul><ul><li>Thyroid Disorders </li></ul><ul><li>Adrenal Disorders </li></ul><ul><li>Gonadal Disorders </li></ul><ul><li>Calcium Disorders </li></ul><ul><li>Lipid Disorders </li></ul>
    4. 5. Hypothalamic–Pituitary Axis
    5. 6. Pituitary Gland <ul><li>Located within the sella tursica </li></ul><ul><li>Contiguous to vascular and neurologic structures </li></ul><ul><ul><li>Cavernous sinuses </li></ul></ul><ul><ul><li>Cranial nerves </li></ul></ul><ul><ul><li>Optic chiasm </li></ul></ul><ul><li>Hypothalamic neural cells synthesize specific releasing and inhibiting hormones </li></ul><ul><ul><li>Secreted directly into the portal vessels of the pituitary stalk </li></ul></ul><ul><li>Blood supply derived from the superior and inferior hypophyseal arteries </li></ul>
    6. 8. Pituitary Gland <ul><li>Anterior pituitary gland </li></ul><ul><ul><li>Secrete various trophic hormones </li></ul></ul><ul><ul><li>Disease in this region may result in syndromes of hormone excess or deficiency </li></ul></ul><ul><li>Posterior pituitary gland </li></ul><ul><ul><li>More of a terminus of axons of neurons in the supraoptic and paraventricular nuclei of the hypothalamus </li></ul></ul><ul><ul><li>Storehouse for the hormones </li></ul></ul><ul><ul><li>The main consequence of disease in this area is disordered water homeostasis </li></ul></ul>
    7. 9. Anterior Pituitary Gland <ul><li>Anterior Pituitary “ Master gland” </li></ul><ul><ul><li>Major blood source: hypothalamic-pituitary portal plexus </li></ul></ul><ul><ul><ul><li>Allows transmission of hypothalamic peptide pulses without significant systemic dilution </li></ul></ul></ul><ul><ul><ul><li>Consequently, pituitary cells are exposed to sharp spikes of releasing factors and in turn release their hormones as discrete pulses </li></ul></ul></ul><ul><ul><li>Production of six major hormones: </li></ul></ul><ul><ul><ul><li>Prolactin (PRL) </li></ul></ul></ul><ul><ul><ul><li>Growth hormone (GH) </li></ul></ul></ul><ul><ul><ul><li>Adrenocorticotropin hormone (ACTH) </li></ul></ul></ul><ul><ul><ul><li>Luteinizing hormone (LH) </li></ul></ul></ul><ul><ul><ul><li>Follicle-stimulating hormone (FSH) </li></ul></ul></ul><ul><ul><ul><li>Thyroid-stimulating hormone (TSH) </li></ul></ul></ul>
    8. 11. Anterior Pituitary Gland <ul><li>Anterior Pituitary “ Master gland” </li></ul><ul><ul><li>Secreted in a pulsatile manner </li></ul></ul><ul><ul><li>Elicits specific responses in peripheral target tissues </li></ul></ul><ul><ul><li>Feedback control at the level of the hypothalamus and pituitary to modulate pituitary function exerted by the hormonal products of the peripheral target glands </li></ul></ul><ul><ul><li>Tumors cause characteristic hormone excess syndromes </li></ul></ul><ul><ul><li>Hormone deficiency </li></ul></ul><ul><ul><ul><li>may be inherited or acquired </li></ul></ul></ul>
    9. 13. Hypopituitarism
    10. 14. Gonadotropin Deficiency <ul><li>Women </li></ul><ul><li>Oligomenorrhea or amenorrhea </li></ul><ul><li>Loss of libido </li></ul><ul><li>Vaginal dryness or dyspareunia </li></ul><ul><li>Loss of secondary sex characteristics (estrogen deficiency) </li></ul><ul><li>Men </li></ul><ul><li>Loss of libido </li></ul><ul><li>Erectile dysfunction </li></ul><ul><li>Infertility </li></ul><ul><li>Loss of secondary sex characteristics (testosterone deficiency) </li></ul><ul><li>Atrophy of the testes </li></ul><ul><li>Gynecomastia (testosterone deficiency) </li></ul>
    11. 15. ACTH Deficiency <ul><li>Results in hypocortisolism </li></ul><ul><ul><li>Malaise </li></ul></ul><ul><ul><li>Anorexia </li></ul></ul><ul><ul><li>Weight-loss </li></ul></ul><ul><ul><li>Gastrointestinal disturbances </li></ul></ul><ul><ul><li>Hyponatremia </li></ul></ul><ul><li>Pale complexion </li></ul><ul><ul><li>Unable to tan or maintain a tan </li></ul></ul><ul><li>No features of mineralocorticoid deficiency </li></ul><ul><ul><li>Aldosterone secretion unaffected </li></ul></ul>
    12. 16. TSH Deficiency <ul><li>Hypothyroidism </li></ul><ul><li>Atrophic thyroid gland </li></ul>
    13. 17. Prolactin Deficiency <ul><li>Inability to lactate postpartum </li></ul><ul><li>Often 1 st manifestation of Sheehan syndrome </li></ul>
    14. 18. Growth Hormone Deficiency <ul><li>Adults </li></ul><ul><ul><li>Often asymptomatic </li></ul></ul><ul><ul><li>May complain of </li></ul></ul><ul><ul><li>Fatigue </li></ul></ul><ul><ul><li>Degrees exercise tolerance </li></ul></ul><ul><ul><li>Abdominal obesity </li></ul></ul><ul><ul><li>Loss of muscle mass </li></ul></ul><ul><li>Children </li></ul><ul><ul><li>GH Deficiency </li></ul></ul><ul><ul><li>Constitutional growth delay </li></ul></ul>
    15. 20. Hypopituitarism <ul><li>Etiology </li></ul><ul><li>Anterior pituitary diseases </li></ul><ul><ul><li>Deficiency one or more or all anterior pituitary hormones </li></ul></ul><ul><li>Common causes: </li></ul><ul><ul><li>Primary pituitary disease </li></ul></ul><ul><ul><li>Hypothalamic disease </li></ul></ul><ul><ul><li>Interruption of the pituitary stalk </li></ul></ul><ul><ul><li>Extrasellar disorders </li></ul></ul>
    16. 21. Hypopituitarism <ul><ul><li>Primary pituitary disease </li></ul></ul><ul><ul><ul><li>Tumors </li></ul></ul></ul><ul><ul><ul><li>Pituitary surgery </li></ul></ul></ul><ul><ul><ul><li>Radiation treatment </li></ul></ul></ul><ul><ul><li>Hypothalamic disease </li></ul></ul><ul><ul><ul><li>Functional suppression of axis </li></ul></ul></ul><ul><ul><ul><ul><li>Exogenous steroid use </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Extreme weight loss </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Exercise </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Systemic Illness </li></ul></ul></ul></ul><ul><ul><li>Interruption of the pituitary stalk </li></ul></ul><ul><ul><li>Extrasellar disorders </li></ul></ul><ul><ul><ul><li>Craniopharyngioma </li></ul></ul></ul><ul><ul><ul><li>Rathke pouch </li></ul></ul></ul>
    17. 22. Hypopituitarism
    18. 23. Hypopituitarism <ul><li>Developmental and genetic causes </li></ul><ul><ul><li>Dysplasia </li></ul></ul><ul><ul><ul><li>Septo-Optic dysplasia </li></ul></ul></ul><ul><ul><li>Developmental hypothalamic dysfunction </li></ul></ul><ul><ul><ul><li>Kallman Syndrome </li></ul></ul></ul><ul><ul><ul><li>Laurence-Moon-Bardet-Biedl Syndrome </li></ul></ul></ul><ul><ul><ul><li>Frohlich Syndrome (Adipose Genital Dystrophy) </li></ul></ul></ul><ul><li>Acquired causes: </li></ul><ul><ul><li>Infiltrative disorders </li></ul></ul><ul><ul><li>Cranial irradiation </li></ul></ul><ul><ul><li>Lymphocytic hypophysitis </li></ul></ul><ul><ul><li>Pituitary Apoplexy </li></ul></ul><ul><ul><li>Empty Sella syndrome </li></ul></ul>
    19. 24. Hypopituitarism: Developmental and Genetic causes <ul><ul><ul><li>Septo-Optic dysplasia </li></ul></ul></ul><ul><ul><ul><li>Kallman Syndrome </li></ul></ul></ul><ul><ul><ul><li>Laurence-Moon-Bardet-Biedl Syndrome </li></ul></ul></ul><ul><ul><ul><li>Frohlich Syndrome (Adipose Genital Dystrophy) </li></ul></ul></ul>
    20. 25. Hypopituitarism: Genetic <ul><ul><li>Septo-Optic dysplasia </li></ul></ul><ul><ul><ul><ul><li>Hypothalamic dysfunction and hypopituitarism </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>may result from dysgenesis of the septum pellucidum or corpus callosum </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Affected children have mutations in the HESX1 gene </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>involved in early development of the ventral prosencephalon </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>These children exhibit variable combinations of: </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>cleft palate </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>syndactyly </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>ear deformities </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>hypertelorism </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>optic atrophy </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>micropenis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>anosmia </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Pituitary dysfunction </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Diabetes insipidus </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>GH deficiency and short stature </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Occasionally TSH deficiency </li></ul></ul></ul></ul></ul>
    21. 26. Hypopituitarism: Developmental <ul><li>Kallman Syndrome </li></ul><ul><ul><ul><li>Defective hypothalamic gonadotropin-releasing hormone (GnRH) synthesis </li></ul></ul></ul><ul><ul><ul><li>Associated with anosmia or hyposmia due to olfactory bulb agenesis or hypoplasia </li></ul></ul></ul><ul><ul><ul><li>May also be associated with: color blindness, optic atrophy, nerve deafness, cleft palate, renal abnormalities, cryptorchidism, and neurologic abnormalities such as mirror movements </li></ul></ul></ul><ul><ul><ul><li>GnRH deficiency prevents progression through puberty </li></ul></ul></ul><ul><ul><ul><li>characterized by </li></ul></ul></ul><ul><ul><ul><ul><li>low LH and FSH levels </li></ul></ul></ul></ul><ul><ul><ul><ul><li>low concentrations of sex steroids </li></ul></ul></ul></ul>
    22. 27. Hypopituitarism: Developmental <ul><li>Kallman Syndrome </li></ul><ul><ul><ul><li>Males patients </li></ul></ul></ul><ul><ul><ul><ul><li>Delayed puberty and hypogonadism, including micropenis </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>result of low testosterone levels during infancy </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Long-term treatment: </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>human chorionic gonadotropin (hCG) or testosterone </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Female patients </li></ul></ul></ul><ul><ul><ul><ul><li>Primary amenorrhea and failure of secondary sexual development </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Long-term treatment: </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>cyclic estrogen and progestin </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Diagnosis of exclusion </li></ul></ul></ul><ul><ul><ul><li>Repetitive GnRH administration restores normal pituitary </li></ul></ul></ul><ul><ul><ul><li>Fertility may also be restored by the administration of gonadotropins or by using a portable infusion pump to deliver subcutaneous, pulsatile GnRH </li></ul></ul></ul>
    23. 28. Hypopituitarism: Developmental <ul><li>Laurence-Moon-Bardet-Biedl Syndrome </li></ul><ul><ul><ul><li>Rare autosomal recessive disorder </li></ul></ul></ul><ul><ul><ul><li>Characterized by mental retardation; obesity; and hexadactyly, brachydactyly, or syndactyly </li></ul></ul></ul><ul><ul><ul><li>Central diabetes insipidus may or may not be associated </li></ul></ul></ul><ul><ul><ul><li>GnRH deficiency occurs in 75% of males and half of affected females </li></ul></ul></ul><ul><ul><ul><li>Retinal degeneration begins in early childhood </li></ul></ul></ul><ul><ul><ul><ul><li>most patients are blind by age 30 </li></ul></ul></ul></ul>
    24. 29. Hypopituitarism: Developmental <ul><li>Frohlich Syndrome (Adipose Genital Dystrophy) </li></ul><ul><ul><ul><li>A broad spectrum of hypothalamic lesions </li></ul></ul></ul><ul><ul><ul><ul><li>hyperphagia, obesity, and central hypogonadism </li></ul></ul></ul></ul><ul><ul><ul><li>Decreased GnRH production in these patients results in </li></ul></ul></ul><ul><ul><ul><ul><li>attenuated pituitary FSH and LH synthesis and release </li></ul></ul></ul></ul><ul><ul><ul><li>Deficiencies of leptin, or its receptor, cause these clinical features </li></ul></ul></ul>
    25. 30. Hypopituitarism <ul><li>Acquired causes: </li></ul><ul><ul><li>Infiltrative disorders </li></ul></ul><ul><ul><li>Cranial irradiation </li></ul></ul><ul><ul><li>Lymphocytic hypophysitis </li></ul></ul><ul><ul><li>Pituitary Apoplexy </li></ul></ul><ul><ul><li>Empty Sella syndrome </li></ul></ul>
    26. 31. Hypopituitarism: Acquired <ul><li>Lymphocytic Hypophysitis </li></ul><ul><ul><li>Etiology </li></ul></ul><ul><ul><ul><li>Presumed to be autoimmune </li></ul></ul></ul><ul><ul><li>Clinical Presentation </li></ul></ul><ul><ul><ul><li>Women, during postpartum period </li></ul></ul></ul><ul><ul><ul><li>Mass effect (sellar mass) </li></ul></ul></ul><ul><ul><ul><li>Deficiency of one or more anterior pituitary hormones </li></ul></ul></ul><ul><ul><ul><ul><li>ACTH deficiency is the most common </li></ul></ul></ul></ul><ul><ul><li>Diagnosis </li></ul></ul><ul><ul><ul><li>MRI - may be indistinguishable from pituitary adenoma </li></ul></ul></ul><ul><ul><li>Treatment </li></ul></ul><ul><ul><ul><li>Corticosteroids – often not effective </li></ul></ul></ul><ul><ul><ul><li>Hormone replacement </li></ul></ul></ul>
    27. 33. Hypopituitarism: Acquired <ul><li>Pituitary Apoplexy </li></ul><ul><ul><li>  Hemorrhagic infarction of a pituitary adenoma/tumor </li></ul></ul><ul><ul><li>Considered a neurosurgical emergency </li></ul></ul><ul><ul><li>Presentation: </li></ul></ul><ul><ul><ul><li>Variable onset of severe headache </li></ul></ul></ul><ul><ul><ul><li>Nausea and vomiting </li></ul></ul></ul><ul><ul><ul><li>Meningismus </li></ul></ul></ul><ul><ul><ul><li>Vertigo </li></ul></ul></ul><ul><ul><ul><li>+/ - Visual defects </li></ul></ul></ul><ul><ul><ul><li>+/ - Altered consciousness </li></ul></ul></ul><ul><ul><li>Symptoms may occur immediately or may develop over 1-2 days </li></ul></ul>
    28. 34. Hypopituitarism: Acquired <ul><li>Pituitary Apoplexy </li></ul><ul><ul><li>Risk factors: </li></ul></ul><ul><ul><ul><li>Diabetes </li></ul></ul></ul><ul><ul><ul><li>Radiation treatment </li></ul></ul></ul><ul><ul><ul><li>Warfarin use </li></ul></ul></ul><ul><ul><li>Usually resolve completely </li></ul></ul><ul><ul><li>Transient or permanent hypopituitarism is possible </li></ul></ul><ul><ul><ul><li>undiagnosed acute adrenal insufficiency </li></ul></ul></ul><ul><ul><li>Diagnose with CT/MRI </li></ul></ul><ul><ul><li>Differentiate from leaking aneurysm </li></ul></ul><ul><ul><li>Treatment: </li></ul></ul><ul><ul><ul><li>Surgical - Transsphenoid decompression </li></ul></ul></ul><ul><ul><ul><ul><li>Visual defects and altered consciousness </li></ul></ul></ul></ul><ul><ul><li>Medical therapy – if symptoms are mild </li></ul></ul><ul><ul><ul><li>Corticosteroids </li></ul></ul></ul>
    29. 35. Quick Quiz!!! <ul><li>When should you suspect pituitary apoplexy? </li></ul>
    30. 36. Answer <ul><li>Suspect in patient presenting with </li></ul><ul><ul><ul><li>Variable onset of severe headache </li></ul></ul></ul><ul><ul><ul><li>Nausea and vomiting </li></ul></ul></ul><ul><ul><ul><li>Meningismus </li></ul></ul></ul><ul><ul><ul><li>Vertigo </li></ul></ul></ul><ul><ul><ul><li>+/ - Visual defects </li></ul></ul></ul><ul><ul><ul><li>+/ - Altered consciousness </li></ul></ul></ul>
    31. 37. Hypopituitarism: Acquired <ul><li>Empty Sella Syndrome </li></ul><ul><ul><li>Often an incidental MRI finding </li></ul></ul><ul><ul><li>  Usually have normal pituitary function </li></ul></ul><ul><ul><ul><li>Implying that the surrounding rim of pituitary tissue is fully functional </li></ul></ul></ul><ul><ul><li>Hypopituitarism may develop insidiously </li></ul></ul><ul><ul><li>Pituitary masses may undergo clinically silent infarction with development of a partial or totally empty sella by cerebrospinal fluid (CSF) filling the dural herniation. </li></ul></ul><ul><ul><li>Rarely, functional pituitary adenomas may arise within the rim of pituitary tissue, and these are not always visible on MRI </li></ul></ul>
    32. 38. Hypopituitarism <ul><li>Clinical Presentation </li></ul><ul><li>Can present with features of deficiency of one or more anterior pituitary hormones </li></ul><ul><li>Clinical presentation depends on: </li></ul><ul><ul><li>Age at onset </li></ul></ul><ul><ul><li>Hormone effected, extent </li></ul></ul><ul><ul><li>Speed of onset </li></ul></ul><ul><ul><li>Duration of the deficiency </li></ul></ul>
    33. 39. Hypopituitarism <ul><li>Diagnosis </li></ul><ul><li>Biochemical diagnosis of pituitary insufficiency </li></ul><ul><ul><li>Demonstrating low levels of trophic hormones in the setting of low target hormone levels </li></ul></ul><ul><li>Provocative tests may be required to assess pituitary reserve </li></ul>
    34. 40. Hypopituitarism <ul><li>Treatment </li></ul><ul><li>Hormone replacement therapy </li></ul><ul><ul><li>usually free of complications </li></ul></ul><ul><li>Treatment regimens that mimic physiologic hormone production </li></ul><ul><ul><li>allow for maintenance of satisfactory clinical homeostasis </li></ul></ul>
    35. 41. Hormone Replacement Intranasal desmopressin (5-20 ug twice daily) Oral 300-600 ug qd Vasopressin Adults: Somatotropin (0.3-1.0 mg SC qd) Children: Somatotropin [0.02-0.05 (mg/kg per day)] GH Males Testosterone enanthate (200 mg IM every 2 wks) Testosterone skin patch (5 mg/d) Females Conjugated estrogen (0.65-1.25 mg qd for 25days) Progesterone (5-10 mg qd) on days 16-25 Estradiol skin patch (0.5 mg, every other day) For fertility: Menopausal gonadotropins, human chorionic gonadotropins FSH/LH L-Thyroxine (0.075-0.15 mg daily) TSH Hydrocortisone (10-20 mg A.M.; 10 mg P.M.) Cortisone acetate (25 mg A.M.; 12.5 mg P.M.) Prednisone (5 mg A.M.; 2.5 mg P.M.) ACTH Hormone Replacement Trophic Hormone Deficit
    36. 42. Take home points: <ul><li>Remember that the cause may be functional </li></ul><ul><ul><li>Treatment should be aimed at the underlying cause </li></ul></ul><ul><li>  Hypopituitarism may present </li></ul><ul><ul><li>Acutely with cortisol deficiency </li></ul></ul><ul><ul><li>After withdrawal of prolonged glucocorticoid therapy that has caused suppression of the HPA axis. </li></ul></ul><ul><ul><li>Post surgical procedure </li></ul></ul><ul><ul><li>Post trauma </li></ul></ul><ul><ul><ul><li>Hemorrhage </li></ul></ul></ul><ul><li>Exacerbation of cortisol deficiency in a patient with unrecognized ACTH deficiency </li></ul><ul><ul><li>Medical/surgical illness </li></ul></ul><ul><ul><li>Thyroid hormone replacement therapy </li></ul></ul>
    37. 43. Pituitary Tumors
    38. 45. Pituitary Tumors <ul><li>Microadenoma < 1 cm </li></ul><ul><li>Macroadenoma > 1 cm </li></ul><ul><li>Is the tumor causing local mass effect? </li></ul><ul><li>Is hypopituitarism present? </li></ul><ul><li>Is there evidence of hormone excess? </li></ul><ul><li>Clinical presentation: </li></ul><ul><ul><li>Mass effect </li></ul></ul><ul><ul><ul><li>Superior extension </li></ul></ul></ul><ul><ul><ul><ul><li>May compromise optic pathways – leading to impaired visual acuity and visual field defects </li></ul></ul></ul></ul><ul><ul><ul><ul><li>May produce hypothalamic syndrome – disturbed thirst, satiety, sleep, and temperature regulation </li></ul></ul></ul></ul><ul><ul><ul><li>Lateral extension </li></ul></ul></ul><ul><ul><ul><ul><li>May compress cranial nerves III, IV, V, and VI – leaning to diplopia </li></ul></ul></ul></ul><ul><ul><ul><li>Inferior extension </li></ul></ul></ul><ul><ul><ul><ul><li>May lead to cerebrospinal fluid rhinorrhea </li></ul></ul></ul></ul>
    39. 46. Pituitary Tumors <ul><li>Diagnosis </li></ul><ul><ul><li>Check levels of all hormones produced </li></ul></ul><ul><ul><li>Check levels of target organ products </li></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Surgical excision, radiation, or medical therapy </li></ul></ul><ul><ul><li>Generally, first-line treatment surgical excision </li></ul></ul><ul><ul><li>Drug therapy available for some functional tumors </li></ul></ul><ul><ul><li>Simple observation </li></ul></ul><ul><ul><ul><li>Option if the tumor is small, does not have local mass effect, and is nonfunctional </li></ul></ul></ul><ul><ul><ul><li>Not associated with clinical features that affect quality of life </li></ul></ul></ul>
    40. 51. Craniopharyngioma <ul><ul><li>Derived from Rathke's pouch. </li></ul></ul><ul><ul><li>Arise near the pituitary stalk </li></ul></ul><ul><ul><ul><li>extension into the suprasellar cistern common </li></ul></ul></ul><ul><ul><li>These tumors are often large, cystic, and locally invasive </li></ul></ul><ul><ul><li>Many are partially calcified </li></ul></ul><ul><ul><ul><li>characteristic appearance on skull x-ray and CT images </li></ul></ul></ul><ul><ul><li>Majority of patients present before 20yr </li></ul></ul><ul><ul><ul><li>usually with signs of increased intracranial pressure, including headache, vomiting, papilledema, and hydrocephalus </li></ul></ul></ul>
    41. 52. Craniopharyngioma <ul><li>Associated symptoms include: </li></ul><ul><ul><li>visual field abnormalities, personality changes and cognitive deterioration, cranial nerve damage, sleep difficulties, and weight gain. </li></ul></ul><ul><li>Children </li></ul><ul><ul><li>growth failure associated with either hypothyroidism or growth hormone deficiency is the most common presentation </li></ul></ul><ul><li>Adults </li></ul><ul><ul><li>sexual dysfunction is the most common problem </li></ul></ul><ul><ul><li>erectile dysfunction </li></ul></ul><ul><ul><li>amenorrhea </li></ul></ul>
    42. 53. Craniopharyngioma <ul><li>Anterior pituitary dysfunction and diabetes insipidus are common </li></ul><ul><li>Treatment </li></ul><ul><ul><li>Transcranial or transsphenoidal surgical resection </li></ul></ul><ul><ul><ul><li>followed by postoperative radiation of residual tumor </li></ul></ul></ul><ul><ul><ul><li>This approach can result in long-term survival and ultimate cure </li></ul></ul></ul><ul><ul><ul><li>most patients require lifelong pituitary hormone replacement. </li></ul></ul></ul><ul><li>If the pituitary stalk is uninvolved and can be preserved at the time of surgery </li></ul><ul><ul><li>Incidence of subsequent anterior pituitary dysfunction is significantly diminished. </li></ul></ul>
    43. 56. Quick Quiz!!! <ul><li>How does prolactin differ from LH/FSH in regard to hypothalamic control? </li></ul>
    44. 57. Answer <ul><li>Tonic hypothalamic inhibition by Dopamine </li></ul>
    45. 58. Prolactinoma <ul><li>Most common functional pituitary tumor </li></ul><ul><li>Usually a micro adenoma </li></ul><ul><li>Can be a space occupying macroadenoma – often with visual field defects </li></ul><ul><li>Although many women with hyperprolactinemia will have galactorrhea and/ or amenorrhea </li></ul><ul><ul><li>The absence these the two signs do not excluded the diagnosis </li></ul></ul><ul><li>GnRH release is decreased in direct response to elevated prolactin, leading to decreased production of LH and FSH </li></ul>
    46. 59. Prolactinoma <ul><li>Women </li></ul><ul><ul><li>Amenorrhea – this symptom causes women to present earlier </li></ul></ul><ul><ul><li>Hirsutism </li></ul></ul><ul><li>Men </li></ul><ul><ul><li>Impotence – often ignored </li></ul></ul><ul><ul><li>Tend to present later </li></ul></ul><ul><ul><li>Larger tumors </li></ul></ul><ul><ul><li>Signs of mass effect </li></ul></ul>
    47. 60. Prolactinoma <ul><li>Essential to rule out secondary causes!! </li></ul><ul><ul><li>Drugs which decrease dopamine stores </li></ul></ul><ul><ul><ul><li>Phenothiazines </li></ul></ul></ul><ul><ul><ul><li>Amitriptyline </li></ul></ul></ul><ul><ul><ul><li>Metoclopramide </li></ul></ul></ul><ul><ul><li>Factors inhibiting dopamine outflow </li></ul></ul><ul><ul><ul><li>Estrogen </li></ul></ul></ul><ul><ul><ul><li>Pregnancy </li></ul></ul></ul><ul><ul><ul><li>Exogenous sources </li></ul></ul></ul><ul><ul><li>Hypothyroidism </li></ul></ul><ul><li>If prolactin level > 200, almost always a prolactinoma (even in a nursing mom) </li></ul><ul><li>Prolactin levels correlate with tumor size in the macroadenomas </li></ul><ul><ul><li>Suspect another tumor if prolactin low with a large tumor </li></ul></ul>
    48. 61. Prolactinoma <ul><li>Diagnosis </li></ul><ul><ul><li>Assess hypersecretion </li></ul></ul><ul><ul><ul><li>Basal, fasting morning PRL levels (normally <20 ug/L) </li></ul></ul></ul><ul><ul><li>Multiple measurements may be necessary </li></ul></ul><ul><ul><ul><li>Pulsatile hormone secretion </li></ul></ul></ul><ul><ul><ul><li>levels vary widely in some individuals with hyperprolactinemia </li></ul></ul></ul><ul><ul><li>Both false-positive and false-negative results may be encountered </li></ul></ul><ul><ul><ul><li>May be falsely lowered with markedly elevated PRL levels (>1000 ug/L) </li></ul></ul></ul><ul><ul><ul><ul><li>assay artifacts; sample dilution is required to measure these high values accurately </li></ul></ul></ul></ul><ul><ul><ul><li>May be falsely elevated by aggregated forms of circulating PRL, which are biologically inactive (macroprolactinemia) </li></ul></ul></ul><ul><ul><li>Hypothyroidism should be excluded by measuring TSH and T4 levels </li></ul></ul>
    49. 62. Prolactinoma <ul><li>Treatment </li></ul><ul><ul><li>Medical </li></ul></ul><ul><ul><ul><li>Cabergoline – dopamine receptor agonist </li></ul></ul></ul><ul><ul><ul><li>Bromocriptine - dopamine agonist </li></ul></ul></ul><ul><ul><ul><ul><li>Safe in pregnancy </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Will restore menses </li></ul></ul></ul></ul><ul><ul><ul><li>Decreases both prolactin and tumor size (80%) </li></ul></ul></ul><ul><ul><li>Surgical </li></ul></ul><ul><ul><ul><li>Transsphenoidal surgery – irridation (if pt cannot tolerate rx) </li></ul></ul></ul>
    50. 65. Quick Quiz!!! <ul><li>What type of tumors are most prolactinomas? </li></ul><ul><li>Prolactin levels >200 almost always indicate what? </li></ul><ul><li>Do prolactin levels correlate with tumor size? </li></ul>
    51. 66. Answer <ul><li>What type of tumors are most prolactinomas? Microadenomas </li></ul><ul><li>Prolactin levels >200 almost always indicate what? Almost always indicates prolactinoma </li></ul><ul><li>Do prolactin levels correlate with tumor size? Yes, in macroadenomas </li></ul>
    52. 68. Growth Hormone Tumors <ul><li>Gigantism </li></ul><ul><ul><li>GH excess before closure of epipheseal growth plates of long bones </li></ul></ul><ul><li>Acromegaly </li></ul><ul><ul><li>GH excess after closure of epipheseal growth plates of long bones </li></ul></ul><ul><ul><li>Insidious onset </li></ul></ul><ul><ul><ul><li>Usually diagnosed late </li></ul></ul></ul>
    53. 69. Growth Hormone Tumors <ul><li>May have DM or glucose intolerance </li></ul><ul><li>Hypogonadism </li></ul><ul><li>Large hands and feet </li></ul><ul><li>Large head with a lowering brow and coarsening features </li></ul><ul><li>Hypertensive – 25% </li></ul><ul><li>Colon polyps </li></ul><ul><ul><li>3-6 more likely than general population </li></ul></ul><ul><li>Multiple skin tags </li></ul>
    54. 70. Growth Hormone Tumors <ul><li>Diagnosis </li></ul><ul><ul><li>Screen: </li></ul></ul><ul><ul><ul><li>Check for high IGF-I levels (>3 U/ml) </li></ul></ul></ul><ul><ul><ul><li>Remember, levels very high during puberty </li></ul></ul></ul><ul><ul><li>Confirm: </li></ul></ul><ul><ul><ul><li>100gm glucose load </li></ul></ul></ul><ul><ul><ul><li>Positive: GH levels do not increase to <5ng/ml </li></ul></ul></ul><ul><li>Treatment </li></ul><ul><ul><li>Surgical </li></ul></ul><ul><ul><li>Radiation </li></ul></ul><ul><ul><li>Bromocriptine - temporizing measure </li></ul></ul><ul><ul><ul><li>May decrease GH by 50% </li></ul></ul></ul><ul><ul><li>Octreotide </li></ul></ul><ul><ul><ul><li>For suboptimal response to other treatment </li></ul></ul></ul>
    55. 73. Quick Quiz!!! <ul><li>How do you screen for acromegaly? </li></ul>
    56. 74. Answer <ul><li>Check for high IGF-I levels (>3 U/ml) </li></ul>
    57. 75. Pituitary Gland <ul><li>Anterior pituitary gland </li></ul><ul><ul><li>Secrete various trophic hormones </li></ul></ul><ul><ul><li>Disease in this region may result in syndromes of hormone excess or deficiency </li></ul></ul><ul><li>Posterior pituitary gland </li></ul><ul><ul><li>More of a terminus of axons of neurons in the supraoptic and paraventricular nuclei of the hypothalamus </li></ul></ul><ul><ul><li>Storehouse for the hormones </li></ul></ul><ul><ul><li>The main consequence of disease in this area is disordered water homeostasis </li></ul></ul>
    58. 76. Posterior Pituitary Gland <ul><li>The Neurohypophysis </li></ul><ul><li>Major blood source: the inferior hypophyseal arteries </li></ul><ul><li>Directly innervated by hypothalamic neurons </li></ul><ul><ul><li>(supraopticohypophyseal and tuberohypophyseal nerve tracts) via the pituitary stalk </li></ul></ul><ul><li>Sensitive to neuronal damage by lesions that affect the pituitary stalk or hypothalamus </li></ul>
    59. 77. Posterior Pituitary Gland <ul><li>Production of </li></ul><ul><ul><li>Vasopressin (antidiuretic hormone; ADH; AVP ) </li></ul></ul><ul><ul><li>Oxytocin </li></ul></ul><ul><li>Vasopressin (antidiuretic hormone; ADH; AVP ) </li></ul><ul><ul><li>Acts on the renal tubules to reduce water loss by concentrating the urine </li></ul></ul><ul><ul><li>Deficiency causes diabetes insipidus (DI), characterized by the production of large amounts of dilute urine </li></ul></ul><ul><ul><li>Excessive or inappropriate production predisposes to hyponatremia if water intake is not reduced in parallel with urine output </li></ul></ul><ul><li>Oxytocin </li></ul><ul><ul><li>Stimulates postpartum milk letdown in response to suckling </li></ul></ul>
    60. 78. Posterior Pituitary Gland <ul><li>Vasopressin (Anti Diuretic Hormone) </li></ul><ul><ul><li>Some control via anterior hypothalamus </li></ul></ul><ul><ul><ul><li>Contains separate osmoreceptors which aid in ADH release and thirst regulation </li></ul></ul></ul><ul><ul><li>Osmotic stimulus </li></ul></ul><ul><ul><ul><li>Sodium </li></ul></ul></ul><ul><ul><ul><li>Mannitol </li></ul></ul></ul><ul><ul><li>Non osmotic factors </li></ul></ul><ul><ul><ul><li>Blood pressure and volume at extremes </li></ul></ul></ul><ul><ul><ul><li>Nausea </li></ul></ul></ul><ul><ul><ul><li>Angiotensin II </li></ul></ul></ul><ul><ul><ul><li>Insulin induced hypoglycemia </li></ul></ul></ul><ul><ul><ul><li>Acute hypoxia </li></ul></ul></ul><ul><ul><ul><li>Acute hypercapnia </li></ul></ul></ul>
    61. 79. Posterior Pituitary Gland <ul><li>Rapidly secreted in direct proportion to serum osmolality </li></ul><ul><ul><li>Increased with </li></ul></ul><ul><ul><ul><li>Aging </li></ul></ul></ul><ul><ul><ul><li>Hypercalcemia </li></ul></ul></ul><ul><ul><ul><li>Hypoglycemia </li></ul></ul></ul><ul><ul><ul><li>Lithium treatment </li></ul></ul></ul><ul><ul><ul><li>Volume contraction </li></ul></ul></ul><ul><ul><li>Decreased with </li></ul></ul><ul><ul><ul><li>Hypokalemia </li></ul></ul></ul><ul><li>Threshold set point </li></ul><ul><ul><li>Increased </li></ul></ul><ul><ul><ul><li>Hypervolemia, Acute hypertension, Corticosteroids </li></ul></ul></ul><ul><ul><li>Decreased </li></ul></ul><ul><ul><ul><li>Pregnancy, Pre-menses, Volume contraction </li></ul></ul></ul>
    62. 81. Diabetes Insipdus <ul><li>Etiology </li></ul><ul><ul><li>Deficient AVP can be primary or secondary </li></ul></ul><ul><ul><ul><li>The primary form </li></ul></ul></ul><ul><ul><ul><ul><li>Deficiency in secretion </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Agenesis or irreversible destruction of the neurohypophysis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Malformation or destruction of the neurohypophysis by a variety of diseases or toxins </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Neurohypophyseal DI , Pituitary DI , or Central DI </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Deficiency in action </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Can be genetic, acquired, or caused by exposure to various drugs </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Nephrogenic DI </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>It can be caused by a variety of congenital, acquired, or genetic disorders </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>50% idiopathic </li></ul></ul></ul></ul></ul>
    63. 82. Diabetes Insipdus <ul><li>Gestational DI </li></ul><ul><ul><ul><ul><li>Primary deficiency of plasma AVP </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Result from increased metabolism by an N-terminal aminopeptidase produced by the placenta </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Signs and symptoms manifest during pregnancy and usually remit several weeks after delivery </li></ul></ul></ul></ul>
    64. 83. Diabetes Insipdus <ul><li>Secondary deficiencies of AVP </li></ul><ul><ul><li>Results from inhibition of secretion by excessive intake of fluids </li></ul></ul><ul><ul><ul><li>Primary polydipsia </li></ul></ul></ul><ul><ul><ul><ul><li>Dipsogenic DI </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>characterized by an inappropriate increase in thirst </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>caused by a reduction in the &quot;set&quot; of the osmoregulatory mechanism. </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>association with multifocal diseases of the brain such as neurosarcoid, tuberculous meningitis, or multiple sclerosis but is often idiopathic. </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Psychogenic polydipsia </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>is not associated with thirst </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>polydipsia seems to be a feature of psychosis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Iatrogenic polydipsia </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>results from recommendations of health professionals or the popular media to increase fluid intake for its presumed preventive or therapeutic benefits for other disorders </li></ul></ul></ul></ul></ul>
    65. 84. Diabetes Insipdus <ul><li>Secondary deficiencies of AVP </li></ul><ul><ul><li>Antidiuretic response to AVP </li></ul></ul><ul><ul><ul><li>Results from polyuria </li></ul></ul></ul><ul><ul><ul><li>Caused by washout of the medullary concentration gradient and/or suppression of aquaporin function. </li></ul></ul></ul><ul><ul><ul><li>Usually resolves 24 to 48 h after the polyuria is corrected </li></ul></ul></ul><ul><ul><ul><ul><li>Often complicate interpretation of tests commonly used for differential diagnosis </li></ul></ul></ul></ul>
    66. 85. Diabetes Insipdus <ul><li>Pathophysiology </li></ul><ul><ul><li>When secretion or action of AVP is reduced to  80 to 85% of normal </li></ul></ul><ul><ul><ul><li>urine concentration ceases and the rate of output increases to symptomatic levels </li></ul></ul></ul><ul><ul><li>Primary defect (pituitary, gestational, or nephrogenic DI) </li></ul></ul><ul><ul><ul><li>Polyuria results in a small (1 to 2%) decrease in body water and a commensurate increase in plasma osmolarity and sodium concentration that stimulate thirst and a compensatory increase in water intake </li></ul></ul></ul><ul><ul><ul><li>Overt signs of dehydration do not develop unless the patient also has a defect in thirst or fails to drink for some other reason </li></ul></ul></ul>
    67. 86. Diabetes Insipdus <ul><li>Pathophysiology </li></ul><ul><ul><li>Primary polydipsia </li></ul></ul><ul><ul><ul><li>Pathogenesis of the polydipsia and polyuria is the reverse of that in pituitary, nephrogenic, and gestational DI </li></ul></ul></ul><ul><ul><ul><ul><li>Excessive intake of fluids slightly increases body water, thereby reducing plasma osmolarity, AVP secretion, and urinary concentration. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Results in a compensatory increase in urinary free-water excretion that varies in direct proportion to intake </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Clinically appreciable overhydration uncommon </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>unless the compensatory water diuresis is impaired by a drug or disease that stimulates or mimics endogenous AVP </li></ul></ul></ul></ul></ul>
    68. 87. Diabetes Insipdus <ul><li>Clinical Presentation </li></ul><ul><ul><li>Production of abnormally large volumes of dilute urine </li></ul></ul><ul><ul><ul><li>The 24-h urine volume is >50 mL/kg body weight and the osmolarity is <300 mosmol/L. </li></ul></ul></ul><ul><ul><li>The polyuria produces symptoms of urinary frequency, enuresis, and/or nocturia, which may disturb sleep and cause mild daytime fatigue or somnolence. </li></ul></ul><ul><ul><li>It is also associated with thirst and a commensurate increase in fluid intake (polydipsia). </li></ul></ul><ul><ul><li>Clinical signs of dehydration are uncommon unless fluid intake is impaired. </li></ul></ul>
    69. 88. Diabetes Insipdus <ul><li>Diagnosis </li></ul><ul><ul><li>Verify polyuria </li></ul></ul><ul><ul><ul><li>a 24-h urine output collection </li></ul></ul></ul><ul><ul><ul><li>> 50 mL/kg per day (>3500 mL in a 70-kg man). </li></ul></ul></ul><ul><ul><li>Check osmolarity </li></ul></ul><ul><ul><ul><li>>300 mosmol/L </li></ul></ul></ul><ul><ul><ul><ul><li>due to a solute diuresis and the patient should be evaluated for uncontrolled diabetes mellitus or other less common causes of excessive solute excretion </li></ul></ul></ul></ul><ul><ul><ul><li><300 mosmol/L </li></ul></ul></ul><ul><ul><ul><ul><li>Due to water diuresis and should be evaluated further to determine which type of DI is present </li></ul></ul></ul></ul>
    70. 89. Diabetes Insipdus <ul><li>Diagnosis </li></ul><ul><ul><li>Water deprivation test </li></ul></ul><ul><ul><ul><li>If does not result in urine concentration before body weight decreases by 5% or plasma osmolarity/sodium exceed the upper limit of normal </li></ul></ul></ul><ul><ul><ul><ul><li>(osmolarity  300 mosmol/L, specific gravity  1.010) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Primary polydipsia or a partial defect in AVP secretion or action are largely excluded </li></ul></ul></ul></ul><ul><ul><li>Severe pituitary or nephrogenic DI are the only remaining possibilities </li></ul></ul>
    71. 90. Diabetes Insipdus <ul><li>Diagnosis: Neurogenic vs Nephrogenic </li></ul><ul><li>Administer Desmopressin (DDAVP) </li></ul><ul><ul><ul><li>1  g </li></ul></ul></ul><ul><ul><ul><li>0.03 ug/kg </li></ul></ul></ul><ul><ul><ul><li>subcutaneously or intravenously </li></ul></ul></ul><ul><li>Measure urine osmolality </li></ul><ul><ul><li>(30,60,120 min) </li></ul></ul><ul><ul><li>1 to 2 h later </li></ul></ul><ul><li>An increase of >50% indicates severe pituitary DI </li></ul><ul><li>Smaller or absent response is strongly suggestive of nephrogenic DI </li></ul>
    72. 91. Diabetes Insipdus <ul><li>Treatment </li></ul><ul><ul><li>Neurogenic DI </li></ul></ul><ul><ul><ul><li>DDAVP </li></ul></ul></ul><ul><ul><ul><li>Chlorpropamide (Diabinese) </li></ul></ul></ul><ul><ul><ul><ul><li>Antidiuretic effect can be enhanced by cotreatment with a thiazide diuretic </li></ul></ul></ul></ul><ul><ul><ul><ul><li>SE: hypoglycemia, disulfiram like reaction to ethanol </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Contraindicated in Gestional DI </li></ul></ul></ul></ul><ul><ul><li>Nephrogenic DI </li></ul></ul><ul><ul><ul><li>Not affected by treatment with DDAVP or chlorpropamide </li></ul></ul></ul><ul><ul><ul><li>May be reduced by treatment with a thiazide diuretic and/or amiloride in conjunction with a low-sodium diet </li></ul></ul></ul><ul><ul><ul><li>Inhibitors of prostaglandin synthesis (e.g., indomethacin) are also effective in some patients </li></ul></ul></ul><ul><ul><li>Psychogenic or dipsogenic DI </li></ul></ul><ul><ul><ul><li>there is no effective treatment </li></ul></ul></ul>
    73. 93. Syndrome of Inappropriate ADH secretion <ul><li>Etiology </li></ul><ul><ul><li>CNS </li></ul></ul><ul><ul><ul><li>Lesions, Inflammatory disease </li></ul></ul></ul><ul><ul><ul><li>Trauma, psychosis </li></ul></ul></ul><ul><ul><li>Drugs </li></ul></ul><ul><ul><ul><li>Stimulate AVP release </li></ul></ul></ul><ul><ul><ul><ul><li>Nicotine, phenothiazines, TCAs, SSRIs </li></ul></ul></ul></ul><ul><ul><ul><li>Chlorpropamide, clofibrate, carbamazepine, cyclophosphamide, vincristine </li></ul></ul></ul><ul><ul><li>Pulmonary </li></ul></ul><ul><ul><ul><li>Infection </li></ul></ul></ul><ul><ul><ul><li>Mechanical/ventilatory issue </li></ul></ul></ul>
    74. 94. Syndrome of Inappropriate ADH secretion <ul><li>Pathophysiology </li></ul><ul><ul><li>Excessive AVP production resulting in decreased volume of highly concentrated urine </li></ul></ul><ul><ul><li>Water retention </li></ul></ul><ul><ul><li>Decreased plasma osmolarity </li></ul></ul><ul><ul><li>Decreased plasma Na </li></ul></ul>
    75. 95. Syndrome of Inappropriate ADH secretion <ul><li>Clinical Presentation </li></ul><ul><ul><li>Acute </li></ul></ul><ul><ul><ul><li>Water intoxication </li></ul></ul></ul><ul><ul><ul><li>Headache, confusion </li></ul></ul></ul><ul><ul><ul><li>Nausea, vomiting </li></ul></ul></ul><ul><ul><ul><li>Anorexia </li></ul></ul></ul><ul><ul><ul><li>Coma, convulsions </li></ul></ul></ul><ul><ul><li>Chronic </li></ul></ul><ul><ul><ul><li>May be asymptomatic </li></ul></ul></ul>
    76. 96. Syndrome of Inappropriate ADH secretion <ul><li>Diagnosis </li></ul><ul><ul><li>Diagnosis of exclusion </li></ul></ul><ul><ul><li>AVP level inappropriately elevated relative to plasma osmolality </li></ul></ul>
    77. 97. Syndrome of Inappropriate ADH secretion <ul><li>Treatment </li></ul><ul><ul><li>Acute </li></ul></ul><ul><ul><ul><li>Fluid restriction </li></ul></ul></ul><ul><ul><ul><li>Hypertonic saline </li></ul></ul></ul><ul><ul><ul><ul><li>Central myelinolysis </li></ul></ul></ul></ul><ul><ul><li>Chronic </li></ul></ul><ul><ul><ul><li>Demeclocyline 150-300mg PO TID-QID </li></ul></ul></ul><ul><ul><ul><ul><li>Reversible Nephrogenic DI </li></ul></ul></ul></ul>
    78. 98. Treatment Guidelines <ul><li>See Handout </li></ul>
    79. 99. References <ul><li>Harrison's Principles of Internal Medicine - 16th Ed. (2005) </li></ul><ul><li>Up to Date </li></ul><ul><li>Med Study – Endocrine </li></ul><ul><li>Mayo Clinic Board Review </li></ul>
    80. 100. Questions
    81. 101. True or False <ul><li>The pituitary: </li></ul><ul><li>Pituitary tumors are usually macroadenomas. </li></ul><ul><li>Lack of galactorrhea essentially rules out a prolactinoma. </li></ul><ul><li>Prolactin levels correlate with the size of a prolactinoma </li></ul><ul><li>Prolactin level of 230 in a nursing woman is probably due to a prolactinoma </li></ul><ul><li>An enlarged sella tursica can be seen in a hypothyroid patient. </li></ul>
    82. 102. Answers <ul><li>The pituitary: </li></ul><ul><li>Pituitary tumors are usually macroadenomas. – True </li></ul><ul><li>Lack of galactorrhea essentially rules out a prolactinoma. – False </li></ul><ul><li>Prolactin levels correlate with the size of a prolactinoma – True </li></ul><ul><li>Prolactin level of 230 in a nursing woman is probably due to a prolactinoma – True </li></ul><ul><li>An enlarged sella tursica can be seen in a hypothyroid patient. – True </li></ul>
    83. 103. <ul><li>A 24 year old woman complains of fatigue and malaise. She gave birth to a healthy infant 4 months before presentation. She did not breastfeed. Menses have subsequently been irregular and infrequent, representing a change from before pregnancy. The family history is notable for a sister who has Hashimoto thyroiditis. The pregnancy test is negative, and the serum level of prolactin is normal. Of interest, TSH is 0.9mIU/L (normal, 0.3-5.0) and free thyroxine is 0.8ng/dL (normal, 0.8-1.4). The results of MRI of the pituitary are reported as normal. The next step would be to: </li></ul>
    84. 104. <ul><li>A) Start thyroxine replacement therapy </li></ul><ul><li>B) Request a neurosurgeon to perform a biopsy of the pituitary </li></ul><ul><li>Perform a water deprivation test </li></ul><ul><li>Perform a 1 µg corticotropin (ACTH) stimulation test </li></ul><ul><li>Measure IGF-1 </li></ul>
    85. 105. <ul><li>A) Start thyroxine replacement therapy </li></ul><ul><li>B) Request a neurosurgeon to perform a biopsy of the pituitary </li></ul><ul><li>C) Perform a water deprivation test </li></ul><ul><li>D) Perform a 1 µg corticotropin (ACTH) stimulation test </li></ul><ul><li>E) Measure IGF-1 </li></ul>
    86. 106. <ul><li>A 38-year-old woman is referred to you by her gynecologist. She first presented to her gynecologist 4.5 years ago with amenorrhea of 3 years’ duration and galactorrhea of 1 year’s duration. She had been taking no medications, and her initial physical examination was unremarkable except for expressible galactorrhea bilaterally. A routine chemistry screen was normal; her T4 level was 7.8 µg/dL, serum TSH was 1.4 µU/mL, and prolactin level was 48.2 ng/mL. </li></ul><ul><li>After taking bromocriptine for 2 months, her prolactin level was 19 ng/mL, at which point her galactorrhea ceased and she had her first menstrual period in 3 years. She continued to take bromocriptine over the next 4 years; her prolactin level remained less than 20 ng/mL, and she continued to have regular periods. However, she stopped taking her bromocriptine 6 months ago and is now having progressively worse headaches. </li></ul>
    87. 107. <ul><li>Her prolactin level is now 60.5 ng/mL, and a visual field examination shows a small superotemporal field cut in the right eye. A computed tomographic (CT) scan shows a 2.4-cm ´ 1.6-cm sellar mass with considerable suprasellar extension. She is now referred to you for further management. </li></ul><ul><li>  </li></ul><ul><li>What is the most likely diagnosis? </li></ul><ul><li>  </li></ul><ul><li>(A) Prolactinoma </li></ul><ul><li>(B) Clinically nonfunctioning pituitary adenoma </li></ul><ul><li>(C) Metastatic cancer to the sella </li></ul><ul><li>(D) Craniopharyngioma </li></ul>
    88. 108. <ul><li>What is the most likely diagnosis? </li></ul><ul><li>  </li></ul><ul><li>(A) Prolactinoma </li></ul><ul><li>(B) Clinically nonfunctioning pituitary adenoma </li></ul><ul><li>(C) Metastatic cancer to the sella </li></ul><ul><li>(D) Craniopharyngioma </li></ul>
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