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Endocrine Diseases

                            Hypercorticism                  Gigantism               Acromegaly
                   (Amenorrhea-Galactorrhea Syndrome)               Sim...
Sheehan’s Syndrome             Diabetes Insipidus            Inappropriate ADH
                    (Post-partum Pituitary ...
Cretinism                  Myxedema                  Hashimoto’s Thyroiditis
Subacute                     Post Partum Thyroiditis   Subclinical Hypothyroidism
                   Granulomatous Thyroid...
Graves’ Disease            Diffuse Nontoxic Goiter
                      Multinodular Goiter         (Toxic Diffuse Goiter...
Subclinical       Primary Hyperparathyroidism
                      Hyperthyroidism                                       ...
Hypoparathyroidism                          Thyroid Cancer

                                **VERY RARE***

 Type of Disea...
                                                                              Conn’s Syndrome

                       Glucocorticoid                 Adrenogenital Syndrome                Secondary
                                 Addison’s Disease                                 Pheochromocytoma
             Ganglioneuroma/ Neuroblastoma              Type I Diabetes Mellitus    Type II Diabetes Mellitus


                         Insulinoma                Gastrinoma
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[ ] Endocrine Final.doc

  1. 1. Endocrine Diseases Hypercorticism Gigantism Acromegaly (Cushing’s Disease) Type of Disease Hyperpituitarism Pathology Overproduction of ACTH from Over production of Overproduction of GH pituitary GH in a child in an adult Cause Pituitary: Tumor or hyperplasia Functioning adenoma of anterior pituitary Signs & Symptoms Hirtuism, Eunuchoid habitus, Course facial features, masculinization/virilization elongated arms and prominent eyebrow, (indicative of adrenal tumor legs, deficient genital massive scalloped due to androgens), striae, and secondary sex tongue, myopathy, central obesity, round face, characteristics nerve entrapment, hyperpigmentation (indicative prognathism, spade- of pit or ectopic production of shaped hands and ACTH), severe proximal feet, osteoporosis, HTN, myopathy, psychological hypertrophied viscera disturbances, osteoporosis, buffalo hump, DM, HTN, facial plethora, acne, menstrual disorders Diagnosis Hypokalemia, alkalosis, CRH assay (differentiate Cushing Ds GH Level GH level from ectopic ACTH) ↑ cortisol Treatment Surgical removal of producing tumor **Octreotide High doses of hydrocortisone 1 (Sandostatin) day prior to surgery and 300mg Bromocriptine continuous IV on the day of (Parlodel) surgery Iatrogenic Cushing’s Disease: Hydrocortisone 100mg QD, metyrapone (Metopirone), Aminogluthemide (Cytadren) in combination w/ Ketoconazole
  2. 2. Disease Prolactinoma (Amenorrhea-Galactorrhea Syndrome) Simmond’s Disease Craniopharyngioma (Pituitary Cachexia) **most common functional pituitary tumor** Type of Disease Hyperpituitarism Hypopituitarism Pathology Overproduction of prolactin Underproduction of pituitary Pressure on pituitary thus tropic hormones decreasing output of tropic hormones Cause Functioning adenoma of anterior pituitary Destruction of pituitary gland Vestigial remnants of from: Rathke’s pouch form slow Non-secretory adenoma growing cystic tumors Metastases to pituitary along craniopharyngeal Adjacent tumor placing canal pressure on pituitary Infarction after delivery Inflammatory Granulomatous Ds Autoimmune pituitary destruction Irradiation Empty Sella Tursica Sx Infiltration: sarcoidosis, histocytosis, hemachromatosis Lesions of Hypothalamus from: Craniopharyngioma, Glioma Germinoma Signs & Symptoms Women Males Pressure on pituitary – erosion of Galactorrhea Visual defects surrounding bones, Amenorrhea Impotence hypothalamus – hydrocephalus, Oligomenorrhea Headaches optic nerves – bitemporal Infertility EOM paralysis hemianopia Early manifestations Late manifestations Diagnosis ↑ prolactin level ↓ tropic hormones ↓ tropic hormones Treatment Bromocriptine (Parlodel)
  3. 3. Sheehan’s Syndrome Diabetes Insipidus Inappropriate ADH (Post-partum Pituitary Secretion Necrosis) (SIADH) Type of Disease Hypopituitarism Hypopituitarism of posterior Hyperpituitarism of pituitary posterior pituitary Pathology Enlargement of pituitary Underproduction of ADH Overproduction of ADH during pregnancy followed by sudden hypotension precipitates necrosis leading to decreased pituitary secretion OR DIC, cavernous sinus thrombosis, DM Cause Sudden infarction of Acquired: **Cranial: Intracranial trauma anterior lobe due to Compression familial (hemorrhage), infection hemorrhage or shock or destruction (meningitis), cytotoxic during delivery or of drugs traumatic abortion hypothalamus OR OR posterior Ectopic ADH secretion pituitary by inflammatory and infiltrative lesions, tumors, radiation, trauma or surgery Signs & Symptoms Failure of lactation, Large volumes of dilute gonadotropic urine (polyuria), excessive deficiency, ACTH, TSH, thirst (polydipsia), and MSH deficiency hypernaturemia, prefer ice cold water Empty sella turcica Diagnosis Water Depravation Test Treatment Vasopressin Lypressin (Diapid) Desmopressin Acetate (DDAVP, concentraid)
  4. 4. Cretinism Myxedema Hashimoto’s Thyroiditis (Autoimmune Thyroiditis) Type of Disease Hypothyroidism Pathology Underproduction of Underproduction of Circulating thyroid hormones during thyroid hormones in older autoantibodies to infancy children or adults thyroglobulin, follicular cell membranes and Usually due to iodine surface receptors. deficiency Cause 1. Deficiency of thyroid tissue: agenesis or 1. Autoimmune hypoplasia, surgery, radiation disease of 2. Goiter: iodine deficiency, goitrogenic humoral and agents, Hashimoto’s Thyroiditis CMI 3. Hypothalamic lesions and hypopituitarism 2. Familial 4. Peripheral resistance to thyroid hormones 3. HLA DR5 **Most common form of hypothyroidism** Signs & Symptoms Failure of normal mental Cold, lethargic, mentally Features of and bodily development, dull, coarse features, hypothyroidism, short stature, wide-set puffy skin, hair loss, progressive painless eyes, protuberant tongue, accumulation of moderate enlargement dry skin, coarse facial mucinous ground of thyroid features substance within dermis (myxedema) Increased incidence of Neurologic: spasticity lymphoma deafness, severe mental CVS: cardiomegaly, retardation bradycardia Often associated with other autoimmune CNS: mental slowing, disorders (SLE, RA, Graves stupor, coma Ds) Diagnosis ↓ fT3 and fT4, ↑ sTSH >5 (except hypothalamic lesions Test for Ab and hypopituitarism) TSH, T4 ESR Treatment Levothyroxine (T4) Levothyroxine (T4) (Synthroid) (Synthroid) Infants (1-6mo) 1-1.5mg Tx must start w/in 2-3mo Adult .017mg to reverse sx Recheck after 6-8 weeks
  5. 5. Subacute Post Partum Thyroiditis Subclinical Hypothyroidism Granulomatous Thyroiditis (PPT) (DeQuervain’s Thyroiditis) (Silent Thyroiditis) Type of Disease Hypothyroidism Pathology Granulomas develop in thyroid gland resulting in enlargement Cause Uncertain, viral infection Uncertain, response to Hashimotos, Tx Grave’s Ds, suggested pregnancy Lithium, inadequate thyroid replacement, Iodine-containing rx, pulsatile TSH, Adrenal insufficiency, drugs, TSH producing tumor Signs & Symptoms Painful enlargement of NONPainful enlargement some asymptomatic, thyroid, self limited ds, of thyroid, self limited ds Some symptomatic: recovery in about 3-6 Phase I: hyperthyroid, ↓ cardiac, lipid, months to nl TSH, ↑ fT3&T4, ↓RAIU neurobehavior (esp. Phase I: hyperthyroid, ↓ Phase II: ↓ T3&T4, ↑ TSH, ↑ depression) to nl TSH, ↑ fT3&T4, ↓RAIU RAIU Phase II: ↓ T3&T4, ↑ TSH, ↑ Phase III : TSH, T3, T4 wnl RAIU Can mimic pp depression Phase III : TSH, T3, T4 wnl Diagnosis TSH ↑ TSH, nl T4, fT4 T4 RAIU Treatment Hyperthyroid state: sx:beta-blockers Tx symptomatic as well as Asx: monitor asymptomatic w/ Hypothyroid state: Levothyroxine Sx: Levothyroxine for 6 – 12 mo. Recheck 6 weeks Asx: monitor
  6. 6. Graves’ Disease Diffuse Nontoxic Goiter Multinodular Goiter (Toxic Diffuse Goiter) (Simple Goiter) (Plummer’s Ds) **Most common form of hyperthyroidism** Type of Disease Hyperthyroidism Pathology Irregular nodular Excessive stimulation by Diffuse enlargement of enlargement of thyroid thyroid stimulating thyroid due to distended follicles immunoglobulins with marked colloid accumulation, fibrosis, hemorrhage Cause Transformation from long- Uncertain, probably Iodine deficiency due to: standing Simple Goiter caused by immunologic 1. Deficiency in food mechanism and defect and water in Ag-specific suppressor 2. Goitrogens T-cells 3. Physiologic demand Associated w/ HLA-DR3 and autoimmune Ds (SLE, Hashimoto’s Disease) Signs & Symptoms Might be sx-free Features of Diffuse enlarged thyroid hyperthyroidism: Complication include: nervousness, restlessness, pressure on trachea, emotional lability, esophagus occasional tachycardia, Obstruction of SVC w/ palpitations, arrythmias, retrosternal extension of dyspnea, heat goiter. intolerance, sweating, fatigue, tremor, hair loss, lid lag and stare, atrial fibrillation, thyromegaly, exophthalmos Thyroid Storm Self limited in 30% Diagnosis ↑ fT3 & fT4, ↓ sTSH ↑T3RIA, Thyroid Ab ↑ fT3 & fT4, ↓ TSH Treatment Propylthiouracil Propylthiouracil Methimazole Methimazole *Radioactive iodide *Radioactive iodide Surgery: Subtotal Thyroidectomy
  7. 7. Subclinical Primary Hyperparathyroidism Hyperthyroidism Secondary **most common cause of Hyperparathyroidism hypercalcemia Type of Disease Hyperthyroidism Hyperparathyroidism Pathology Compensatory hyperplasia in response to hypocalemic state Cause Euthyroid Graves, Parathyroid adenoma autonomous Carcinoma **Chronic renal failure adenoma, Excessive hyperplasia Malabsorption Sx THR Tx, Thyroid Vit D deficiency Hormone suppressive therapy Signs & Symptoms Asymptomatic or symptomatic: atrial Osteitis Fibrosa Cystica (cysts fibrillation, formed from resorption of Ca osteoporosis – leads to pathologic fx and “Brown tumors”) BONES Nephrolithiasis, gallstones – STONES Pancreatitis – GRONES Peptic Ulcers – MONES Assoc. w/ MEN Diagnosis Nl fT4, FTI, T3RIA ↑serum Ca (3 consec. ↓ serum Ca ↓ TSH Tests;unless >12) ↑ serum phosphate ↓ serum phosphate ↑PTH ↑PTH ↑ALP ↑urinary Ca in 24hr urine ↑ALP ↑cAMP in serum or urine radiograph (find brown turmors) Treatment If on suppression CA or adenoma: surgery therapy: ↓ Rx Acute Ds: ↑ excretion w/ saline & furosemide, Asx: repeat TSH Mithramycin, Calcitonin, Diphosphates, Hydrocortisone, 3-6mo, Gallium Nitrate 24hr RAIU – if ↑ use Moderate Ds : hydration, diuresis, phosphates, calcitonin, beta blocker or indocin, ASA, Disodium Etdronate antithyroid rx Crisis: hopitlization, hydration Mithramycin, Disodium Etidronate
  8. 8. Hypoparathyroidism Thyroid Cancer **VERY RARE*** Type of Disease Hypoparathyroidism Papillary (most commom), Follicular, mixed, anaplastic, medullary (can be assoc w/ MEN) Pathology Inadequate secretion of PTH or end- organ resistance Cause Idiopathic, post surgical, radiation Recurrent thyroid CA, hx of radiation therapy, autoimmune ds, parathyroid exposure aplasia associated w/ DiGeorge’s Signs & Symptoms Severe cases: cardiac arrhythmias, Vary tetany, ↑ intracranial pressure w/ Dysphagia, hoarseness, firm and immobile papilledema, cataracts, diarrhea, nodules, cervical lymphadenopathy epilepsy, Trousseau’s Sign, numbness, tingling, Chvestek sign Suspect nodules in males >40 and females >50 and ALL nodules in children Diagnosis ↓ Serum Ca sTSH, Ab, Tg (+ in malignancy) ↑phosphate levels Thyroid scan (cold nodules), ↓PTH Calcitonin level U/S FNA biopsy Treatment Thyroidectomy (suspect CA, compression, cosmetic) RIA(inoperable, residual ds in neck, invasion, metastasis) Chemotherapy T4 suppressive therapy of TSH
  9. 9. Disease Conn’s Syndrome Cushing Syndrome (Primary Hyperaldosteronism) Type of Disease Hyperadrenalism Pathology **Pituitary: Tumor or hyperplasia (Cushing Disease) Hypersecretion of aldosterone Adrenal: Tumor Ectopic production of ACTH or CRH (usually carcinoid tumor of lung or pancreas) Iatrogenic Cause Overproduction of ACTH from pituitary(Cushing Ds) **Adrenocortical OR overproduction of CRF from hypothalamus OR adenoma ectopic ACTH production OR Adrenal tumor Hyperplasia producing cortisol Carcinoma (rarely) Signs & Symptoms Hirtuism, masculinization/virilization (indicative of Polyuria, polydypsia, adrenal tumor due to androgens), striae, central muscle weakness, renal K obesity, round face, hyperpigmentation (indicative of loss pit or ectopic production of ACTH), severe proximal myopathy, psychological disturbances, osteoporosis, HTN but hyporeninemia buffalo hump, DM, HTN, facial plethora, acne, (due to feedback from menstrual disorders, bruising, CHF, edema, polyuria, aldosterone) polydipsia Diagnosis Hypokalemia, alkalosis, CRH assay (differentiate ↑ Aldosterone level Cushing Ds from ectopic ACTH) ↓ Renin Level ↑ (pituitary or ectopic) or ↓ (adrenal adenoma) ACTH Metabolic alkalosis depending on cause, ↑ or ↓ MSH depending on Exessive K in urine cause, ↓ serum K ↑serum and 24° urine cortisol, ↑ serum glucose Saline Suppression Test Dexamethasone Suppression Test CT , then Venous/Arterial Pituitary MRI to confirm sampling Treatment Spironolactone Surgical removal of producing tumor, irradiation or (Aldactone) resection of hyperplastic adrenals Or Diuretics High doses of hydrocortisone 1 day prior to surgery and 300mg continuous IV on the day of surgery Iatrogenic Cushing’s Disease: Hydrocortisone 100mg QD, metyrapone (Metopirone), Aminogluthemide (Cytadren) in combination w/ Ketoconazole
  10. 10. Disease Glucocorticoid Adrenogenital Syndrome Secondary Remediable Aldosteronism Adrenal (GRA) Insufficiency Type of Disease Hyperadrenalism Hypoadrenalism Pathology Hypersecretion of Congenital Adrenal Decreased aldosterone/glucocorticoid Adrenal Virilization: production of suppression Hyperplasia Tumor or ACTH (CAH): inborn hyperplasia enzyme defect resulting in an which inhibits overproduction cortisol thus ↑ of androgens ACTH causing adrenal hyperplasia and overproduction of androgens Cause Abnl hybrid gene results in Congenital Adrenocortical, Destructive stimulation of aldosterone hyperplasia, pituitary or lesions by ACTH adenoma or of the carcinoma hypothalamus Signs & Symptoms HTN Present @ brith Virilization of w/ virilization of female female Salt wasting Diagnosis ↑ aldosterone level ↑ ACTH ↓ ACTH ↓ cortisol level ↓ cortisol level ↓ cortisol level ↑androgens nl aldosterone Treatment Dexamethasone given to Corticotropin predisposed mother to prevent (only parenteral) fetus from genital deformation Hydrocortisone (oral) IV Hydrocortisone Mineralcorticoids
  11. 11. Disease Addison’s Disease Pheochromocytoma (Primary Adrenocortical Insufficiency) Type of Disease Hypoadrenalism Ds of Hypersecretion of the Adrenal Medulla Pathology Destruction of adrenal cortex resulting in ↓ Tumor arising from chromaffin cells cortisol production and aldosterone of adrenal medulla secreting catecholamines (outside the adrenals: paragangliomas) Cause ***Idiopathic adrenalitis (autoimmune) Sporatic *TB Familial *Histoplasmosis Amyloidosis, metastatic carcinoma, Some associated w/ MEN II, MEN III hemochromatosis (all resulting in damage to the pituitary or hypothalamus) Signs & Symptoms Acute: rapid Chronic: insidious Paroxysmal or sustained HTN, progression, shock, onset, malaise, weight angina, cardiac arrhythmias septicemia, loss, hypotension, loss leading to CHF, flushing, Waterhouse- of body hair, diaphoresis, palpitations, N/V Friderichsen, DIC w/ menstrual irregularities, tachycardia, widespread skin hemorrhage in skin hyperpigmentation, and organs, weakness, fatigue, Episodic HA, sweating, anxiety, dehydration, anorexia, GI sx, tremor, visual disturbances, ringing hypotension, saltcravings, postural in ears, papilledema, heart weakness, hypotension murmurs, cardiomegaly hypothermia, abd pain, N/V Idiopathic often assoc. w/ other autoimmune diseases Diagnosis ↓ cortisol ↑ catecholamines in serum and ↓ Na+ urine ↓ glucose Presence of VMA (Vanillylmandelic ↑ K+ acid)in 24° urine **pathnomonic ↑ ACTH MRI to confirm Treatment Acute: Chronic: Alpha adrenergic blockers w/ Beta Cortisol 100mg IV Q Hydrocortisone Blockers 6-8° until stable 20-30mg QD Reduce over 5d to 2/3 given in am Surgery maintenance dose of 1/3 given in afternoon 50mg/d IV saline Fludrocortisone Glucose
  12. 12. Disease Ganglioneuroma/ Neuroblastoma Type I Diabetes Mellitus Type II Diabetes Mellitus Type of Disease Ds of Hypersecretion of the Adrenal Metabolic Disorder of the Pancreas Medulla Pathology Ganglioneuroma Neuroblastoma Ab against beta cells Target tissue develops Benign tumor of Highly destroy islet cells resulting insulin resistance ganglion cells malignant in a decreased production tumor from of insulin neural crest Cause Tumor Immune Overeating, Obesity, Viral (Cacksackie Virus – Genetics (large molecular mimecry) predisposition) Genetic (linked to HLA Risk factors: aging, DR3&4 on sedentary lifestyle Chromosome 6) Signs & Symptoms Onset early in life, but can Onset usually >30, but is Neuroblastoma: common in occur at any time, Wt loss, becoming more childhood, abdominal mass, anemia, dry skin, weakness, Insulitis, common in younger, fever, wt loss DKA, Hyperglycemia upper segment obesity, resulting in AGES & sorbitol polyuria, abnl insulin Commonly metastasizes to bone of depositions, eventually secretion, insulin skull and orbit (Hutchison-type) coma if untx, insulinopenia, resistance, ↑ glucose To liver (Pepper Syndrome) infections, polyuria, production from liver, polyphagia, polydipsia ↑triglycerides d/t inability to activate Chronic Complications: lipoprotein lipase, CAD, MI, stroke, gangrene, hyperlipidemia cataracts, artherosclerosis, indicates poor control retinopathy, nephropathy, neuropathy, vascular Chronic Complications: disease CAD, MI, stroke, gangrene, cataracts, artherosclerosis, retinopathy, nephropathy, neuropathy, vascular Ds Diagnosis ↓ insulin ↓ insulin ↑ HbA1c ↑ HbA1c Ab to islet cells or insulin Fasting glucose Fasting glucose >126mg/dL >126mg/dL Random glucose Random glucose >200mg/dL >200mg/dL Treatment 1. NPH BID w/ premeal Diet, exercise, wt loss Lispro Sulfonylureas 2. Glargine Q HS w/ Glucophage premeal Lispro Insulin (occas.) Pt education Goal: HbA1C 7% or lower Tx hyperlipidemia Pt education DKA tx: hydration, insulin
  13. 13. Disease Insulinoma Gastrinoma (Zollinger-Ellison Syndrome) Type of Disease Pancreatic Tumor Pancreatic Tumor Pathology Insulin producing Gastrin Producing tumor of the islet cells tumor of islet cells Cause Tumor Tumor Signs & Symptoms Dizziness, confusion, Triad: gastrinoma, bizarre behavior, gastric acid seizure, coma hypersecretion, peptic ulcer disease 10% malignant Diarrhea, fluid Assoc. w/ MEN I electrolyte imbalance 60% malignant Assoc w/ MEN I Diagnosis ↑ insulin ↓ glucose Treatment