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BR-Endocrinology
5/22/06
| Question | Answer |
|---|---|
| Hypothalamus | diencephalon; forms from embryologic forebrain |
| Pituitary gland: Anterior versus Posterior | Rathke's pouch (ectoderm from mouth); Versus Invagination from hypothalamus |
| Thyroid gland | pharyngeal endoderm; migrates caudally; follicular cells - endoderm; C-cells (calcitonin) - 4th pharyngeal pouch |
| Parathyroid gland: Inferior versus Superior | 3rd versus 4th pharyngeal pouch; dorsal migration onto thyroid |
| Adrenals | mesodermal; enclosed in renal fascia; 4g each; Zona glomerulosa and fasciculata present at birth (reticularis at 3yo) |
| Adrenal medulla | neural crest cells develop chromaffin cells |
| Pancreas | ventral and dorsal bud of endoderm from foregut; ventral = uncunate process/part of head |
| Exocrine pancreas | acinar cells and ducts form from endoderm surrounded by mesoderm |
| Endocrine pancreas | mesodermal cells aggregate into islet cells |
| Craniopharyngioma | cystic tumor pituitary from remnants of Rathke's pouch |
| Thyroglossal duct cysts | midline remnant of migration of thryoid (in contrast to lateral branchial cysts along SCM); persists into adult life |
| Absence of parathyroid glands | ocurs in DiGeorge Syndrome; no PTH = hypoparathyroidism |
| Congenital adrenal hyperplasia | 21-hydroxylase deficiency (mc); 17- and 11- deficiencies also |
| Annular pancreas | duodenal obstruction; ventral/dorsal buds constrict duodenum |
| Accessory pancreatic tissue | usu found in stomach; this is the most common type of "choristroma" - misplaced nml tissue w/in another organ |
| GnRH | secreted by hypothalamus, effects LH/FSH secretion, stimulated by puberty; inhibited by progesterone and testosterone |
| FSH | secreted by anterior pituitary; affects follicular growth & estrogen secretion (granulosa cells) OR sperm maturation (sertoli cells); stimulated by pulsatile GnRH release; Inhibited by constant GnRH release & inhibin |
| LH | secreted by basophils of ant pituitary; effects ovulation, corpus leuteum, E/P synth (theca cells) OR testosterone synth (Leydig cells); Stimulated by pusatile GnRH; Inhibited by constant GnRH, Progesterone or Testosterone |
| Estrogen | secreted by ovary (granulosa cells); effects proliferative phase of cycle, development of female repro organs; Stimulated by FSH; Inhibited by estrogen |
| Progesterone | secreted by ovary (theca cells); effects breast development, secretory activity in luteal phase; Stimulated by LH; Inhibited by Progesterone |
| Testosterone | secreted by Testes (Leydig cells); effects Spermatogenesis, converts testosterone to DHT via 5-a-reductase (2* sex traits); Stimulated by LH; Inhibited by testosterone |
| Finasteride | 5-a-reductase inhibitor; treatment for BPH |
| Flutamide | competitive androgen receptor blocker; treatment for prostatic carcinoma |
| hCG | secreted by Placenta (syncytiotrophoblast); increases P/E synthesis; |
| elevation of hCG | normal pregnancy, hydatiform mole, choriocarcinomas, gestational tumors, ectopic pregnancy, pseudocyesis |
| ACTH | secreted by ant pituitary; effects synth/secretion of adrenal cortical hormones; Stimulated by CRH and stress; Inhibited by Cortisol |
| Cortisol (glucocorticoids) | secreted by adrenal cortex (zona fasciculata); anti-inflammatory (inhibits phospholipase A2); immune suppression; stimulates GNG; increases blood glucose; Stimulated by ACTH; Inhibited by Cortisol |
| Lipocortin | mediates the anti-inflammatory effect of cortisol by inhibiting phospholipase A2 and prostaglandin synthesis; cortisol also inhibits production of IL-2 |
| Aldosterone | secreted by adrenal cortex (zona glomerulosa); increases renal Na reabsorption and K secretion; increases blood volume; Stimulated by hypovolemia, angiotensin II, hyperkalemia, hyponatremia; Inhibited by hyperNa, hypoK, fluid overload |
| TSH | secreted by ant pituitary; effects synth/secretion of T4/T3; Stimulated by TRH; Inhibited by T4, T3 |
| T4, T3 | secreted by thyroid; effects growth, CNS maturation, inc BMR, CO, & nutrient utilization; Stimulated by TSH & estrogen; Inhibited by Somatostatin & Dopamine |
| Somatostatin | secreted by hypothalamus; inhibits secretion of growth hormone; Stimulated by growth hormone & somatomedins (IGF) |
| non-brain sources of somatostatin | GI tract, delta cells of pancreas; fxns to systemically decrease secretion of insulin, glucagon and gastrin |
| Growth Hormone | ant pituitary acidophils; Dec glucose uptake, inc ptn synth, bone growth, organ size, lean body mass; Stim by GHRH, exercise, puberty, hypoglycemia, estrogen, stress, endogenous opiates; Inhibited by IGF, somatostatin, obesity, pregnancy, hyperglycemia |
| Prolactin | secreted by ant pituitary acidophils; stimulates milk production/secretion, breast development; inhibits ovulation; Stimulated by prolactin stimulating hormone, TRH; Inhibited by Dopamine |
| Oxytocin | secreted by hypothalamus via posterior pituitary; stimulates milk letdown/ejection & uterine contraction; Stimulated by suckling, dilation of cervix; Inhibited by alcohol, stress |
| PTH | secreted by parathyroid chief cells; increases serum Ca, renal Ca absorption, inhibits phosphate reab; activates VitD to inc intestinal Ca absorption; Stim by dec serum Ca or mild dec Mg; Inhibited by severe dec in Mg |
| Vitamin D (1,25 dihydrocholecalciferol) | secreted by kidney (active form produced by 1a-12-hydroxylase) & sun exposed skin; Inc intestinal & renal Ca/phosphorus absorption; Inc bone Ca resorption; Stimulated by dec serum Ca, inc PTH, dec serum phosphate |
| ADH (vasopressin) | secreted by hypothalamus via post pituitary; Inc water absorption thru distal tubules/collecting duct (V2 receptor); vasoconstriction (V1 receptor); Stim by hypvolemia, nicotine, opiates, inc serum osmolarity; Inhib by ethanol, ANF, dec osmolarity |
| Glucagon | stimulated by alpha cells of pancreatic islets; Inc blood glucose, inc glycogenolysis/GNG in liver, inc lypolysis & ketone synth; Stim by dec blood glucose, inc AAs, ACh; Inhib by hyperglycemia, insulin, somatostatin |
| Insulin | secreted by beta cells of pancreas; Dec blood glucose via uptake into muscle/fat; dec glycogenolysis/GNG; inc ptn synthesis; inc fat deposition/inhibits lipolysis; Stim by hyperglycemia, AA, glucagon, ACh; Inhib by hypoglycemia, somatostatin |
| Glucose enters cells via | facilitated transporters: GLUT-1 thru GLUT-5 |
| GLUT-4 | abundant in skeletal muscle |
| GLUT-1 | found on erythrocytes |
| T4 to T3 conversion | occurs in periphery b/c T4 has longer half-life (5-7days) and T3 is more potent (1day) |
| Hormone second messenger systems | bioactive chemicals bind membrane receptors resulting in phosphorylation of intracellular ptns or changes in ion channel conductivity and subsequent cellular modulation |
| G protein mechanism | hormone binds, GTP replaces GDP on Gptn; the GTP-alpha subunit dissociates from beta-gamma complex and converts ATP to cAMP; Hormone is released and complex returns to inactive state when GTPase cleaves GTP to GDP |
| Insulin receptor | is tyrosine kinase linked; binding to the alpha subunit causes phosphorylation of the tyrosine kinase connected to beta subunit; this recruits GLUTs to cell membrane and inc uptake of glucose |
| Insulin | secreted in a pre-pro form; loses a C-peptide by golgi modification to 2 polypeptides linked by disulfide bridges; stimulates glucose absorption and triacylglycerol synth |
| Glucagon | single polypeptide secreted in response to low glucose, inc AA, and epi; activating GNG/glycogenolysis; forms ketone bodies and inc AA uptake by liver |
| Whipple's triad is required for hypoglycemia diagnosis | low blood glucose, hypoglycemic symptoms (sweating, palpitations, anxiety, tremor); improvement of symptoms with glucose administration; diabetics may not exhibit same symptoms |
| Causes of hypoglycemia | excess insulin administration, sulfonylurias (glucose lowering drug), alcohol, insulinoma, factitious hyperinsulinism |
| Tx of hypoglycemia | measure blood glucose levels; give glucose or IV dextrose; administer glucagon or epinephrine |
| Causes of Hyperglycemia | DM, chronic pancreatitis, acromegaly, cushings, drugs (furosemide, glucocorticoids, growth hormone, OCPs, thiazides) |
| Acute symptoms of hyperglycemia | ketoacidosis or hyperosmolar nonketotic coma; polyuria, polydipsia, polyphagia, wt loss, encephalopathy (tremor, convulsion or coma) |
| Diabetes mellitus - insulin deficiency | inc lypolysis (inc FFAs, ketones); Inc ptn catabolism (inc AAs, nitrogen loss in urine); Dec glucose uptake (hyperglycemia, - uria, osmotic diuresis, electrolyte depletion) ==> dehydration, acidosis, coma, death |
| Acute manifestations of diabetes mellitus | polydipsia, polyuria, polyphagia, wt loss, DKA, hyperosmolar coma, unopposed GH/epi secretion (exacerbates hyperglycemia) |
| Chronic manifestations of diabetes mellitus: Non-enzymatic glycosylation | Small vessel dz (thick BM: retina, glaucoma, nephropathy); Large vessel atherosclerosis (CAD, gangrene, CVA); Neuropathy (motor/sensory/ANS degen); Cataracts (sorbitol) |
| Diabetic retinopathy | small vessel dz w/hemorrhage, exudates, microaneurysms, vessel proliferation |
| Diabetic nephropathy | nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to HTN |
| Tests for diabetes | fasting serum glucose, glucose tolerance test, HbA1c |
| HLA-DR3 and 4 | a/w type I diabetes; insulin dependent |
| Diabetic ketoacidosis | complication of type I DM; d/t inc insulin requirement d/t stress or infxn; Excess fat breakdown = ketogenesis from FFAs |
| Kussmaul respirations | rapid/deep breathing a/w diabetic ketoacidosis; pt should have fruity breath |
| Signs/symptoms/complications of Diabetic ketoacidosis | Kussmaul respirations, hyperthermia, N/V, abd pain, psychosis/dementia, dehydration, fruity breath; fatal Rhizopus infxn, cerebral edema, arrhythmias/HF |
| Labs and treatment for diabetic ketoacidosis | Hyperglycemia, inc H, low HCO3 (anion gap metabolic acidosis); inc ketones; leukocytosis, hyperkalemia (but depleted intracellular K); Tx = Fluids, insulin, K |
| Diabetes Insipidus | Intense thirst and polyuria and inability to concentrate urine d/t lack of ADH (central) or lack of renal response to ADH (nephrogenic) |
| Causes of central diabetes insipidus | pituitary tumor, trauma, surgery, histiocytosis X |
| Causes of nephrogenic diabetes insipidus | hereditary, 2* to hypercalcemia, lithium, demeclocycline |
| Findings and Treatment for Diabetes Insipidus | Urine specific gravity <1.006; Serum osmolality >290mOsm/L; Adequate fluid intake |
| Treatment specific to central DI | intranasal desmopressin (ADH analog) |
| Treatment specific to nephrogenic DI | hydrochlorothiazide, indomethacin, or amiloride |
| Syndrome of Inappropriate ADH Secretion | excess water retention, hyponatremia, urine osmolarity > serum osmolarity (pretty much opposite of DI); low Na levels can cause seizures |
| Causes of SIADH | ectopic ADH (small cell carcinoma); CNS disorder/head trauma; Pulmonary dz; Drugs (cyclophosphamide) |
| Cushing's Syndrome Etiologies | increased cortisol d/t one of the following: Cushing's dz, Primary adrenal hyper/neoplasia; Ectopic ACTH; Iatrogenic |
| Cushing's Disease | primary pituitary adenoma; Elevated ACTH levels; Elevated Cortisol |
| Primary adrenal hyper-/neoplasia | Decreased ACTH; Elevated Cortisol |
| Iatrogenic Cushings | decreasd levels of ACTH; Elevated cortisol |
| Cushing's syndrome clinical picture | hypertension, wt gain, moon facies, truncal obesity, buffalo hump, hyperglycemia (insulin resistance), skin thinning/striae, osteoporosis, amenorrhea, immune suppression |
| Primary Hyperaldosteronism (Conn's Syndrome) | d/t aldosterone-secreting tumor resulting in HTN, hypokalemia, metabolic ALKALOSIS, LOW plasma RENIN; Tx = Spironolactone (aldosterone antagonist) |
| Secondary Hyperaldosteronism | d/t Renal a. stenosis, CRF, CHF, Cirrhosis, or Nephrotic Syndrome; The kidney's perception of hypovolemia causes RAAS overactivity; a/w HIGH plasma RENIN; Tx = Spironolactone |
| Addison's Disease | 1* deficiency of Aldosterone and Cortisol d/t ADRENAL ATROPHY (all 3 layers); causes Hypotension, skin HYPERPIGMENTATION (d/t MSH byproduct of ACTH from POMC); |
| Secondary adrenal insufficiency | no skin hyperpigmentation; dz is d/t decreased pituitary ACTH |
| Pheochromocytoma | mc tumor of adrenal medulla in adults; derived from neural crest chromaffin cells; a/w Neurofibromatosis, MEN types II and III; 10% malignant, bilateral, extra-adrenal, calcified, kids, familial |
| Neuroblastoma | mc tumor of adrenal medulla in KIDS; but can occur anywhere along sympathetic chain; malignant |
| Pheochromocytoma specifics | secrete combo of NE/E (urinary VMA and plasma catecholamines elevated); Episodic hyperadrenergic Sx: (inc BP, HA, sweat, palpitation, pallor) |
| Treatment for pheochromocytoma | alpha-antagonists: PHENOXYBENZAMINE a non-selective irreversible alpha-blocker |
| Multiple Endocrine Neoplasia Type I: Wermer's | AD; 3 Ps: Pituitary, Parathyroid, Pancreas (Zollinger-Ellison gastrin/HCl syndrome, insulinomas, VIPomas); Presents w/kidney stones and stomach ulcers |
| MEN Type II: Sipple's Syndrome | AD (a/w ret gene); Medullary thyroid carcinoma; PHEO; PARATHYROID tumor or adenoma (palpitations) |
| MEN Type III | AD (a/w ret gene); medullary thyroid carcinoma, PHEO, ORAL/GI mucosal NEUROMAS (ganglioneuromatosis) |
| Hypothyroidism | cold intolerance, hypoactivity, wt gain, fatigue, lethargy, dec appetite, constipation, weakness, dec reflexes, MYXEDEMA (face/periorbital), dry skin/hair |
| TSH test is sensitive for primary hypothyroidism | High TSH = low total T4, freeT4, and T3 uptake; VERSUS Low TSH = inc total T4, free T4 and T3 uptake |
| Hyperthyroidism | heat intolerance, hyperactivity, wt loss, chest pain/palpitations, arrhythmias, diarrhea, inc reflexes, warm/moist skin, fine hair |
| Riedel's Thyroiditis | hypothyroidism d/t replacement of thyroid tissue with fibrous tissue |
| Grave's Disease | autoimmune HYPERTHYROIDISM; type II hypersensitivity d/t TSI & TSH-receptor ANTIBODIES; pts have proptosis, EOM swelling, PRETIBIAL myxedema, DIFFUSE GOITER; presents during stress (ex: childbirth); HLA-DR3, B8 |
| Hashimoto's thyroiditis = mc hypothyroidism w/adequate iodine intake | Autoimmune HYPOTHYROIDISM; anti-MICROSOMAL (thyroglobulin, thyroid peroxidase) antibodies; slow course, enlarged non-tender thyroid; lymphocytic infiltrate w/germinal ctrs; Females; a/w DM, pernicious anemia, Sjogren's (other AI dzs) |
| Subacute (de Quervain's) Thyroiditis | self-limited HYPOTHYROIDISM a/w viral illness; Elevated ESR, jaw pain, early inflammation, PAINFUL THYROID (may first present as hyperthryroid); a/w HLA-B35 |
| Hypothyroidism and goiter d/t autoimmune Abs (Grave's) | increased Total T4 and T3; Decreased TSH; Increased radioactive T3 uptake; Increased uptake of radioactive iodine |
| Treatment of Hyperthyroidism (Grave's) | antithyroid drugs: Propylthiouracil, Methimazole; a b-blocker to dec cardiac effects; Radioactive iodine, Surgery |
| Thyrotoxicosis factitia | a Munchausen's syndrome; pt intentionally administers excess thyroid hormone (levothyroxine) to simulate Sx of hyperthyroidism |
| Caution with surgery on thyroid or parathyroid | must preserve recurrent laryngeal nerve (which runs posterior to these glands); cutting it will cause paralysis of mm speech (except cricothyroid) and hoarseness on affected side |
| Cretinism | hypothyroidism in MR, pot-bellied, pale, puffy-faced child w/protruding umbilicus and tongue; can be endemic (d/t lack of dietary iodine) or sporadic (defect in T4 or thyroid formation, or maternal Abs); common in China |
| Thyroid levels are routinely checked | at birth, along with PKU and galactosemia screens |
| Causes of Hypercalcemia: CHIMPANZEES | Calcium ingestion (milk-alkali syndrome), Hyperparathyroid (2* to bone turnover); Iatrogenic (thiozides), Multiple Myeloma, Paget's disease, Addison's disease, Neoplasms, Zollinger-Ellison, Excess vit D, Excess vit A, Sarcoidosis |
| Primary Hyperparathyroidism | usu an adenoma; inc Ca in blood/urine; hypophosphatemia; Elevated PTH; Weakness, Constipation |
| Secondary Hyperparathyroidism | hyperplasia 2* to low serum Ca; usu Chronic Renal Disease; low Ca, hi phosphate, hi PTH |
| Osteitis Fibrosa Cystica (Von Recklinghausen's syndrome) | cystic bone spaces fill with brown fibrous tissue |
| Renal osteodystrophy | bone lesions 2* to hyperparathyroidism d/t renal disease |
| Hypoparathyroidism | Low Ca and TETANY; d/t accidental excision of glands OR DiGeorge Syndrome; Latent tetany can be induced w/Chvostek's sign (facial nerve tap) or Trousseau's sign (carpal spasm) |
| Pseudohypoparathyroidism | AR kidney with no response to PTH; pt has hypocalcemia, short 4th/5th digits and short stature |
| Carcinoid Syndrome | d/t neuroendocrine tumors (mc = appendix; small bowel) that secrete 5-HT (serotonin); Mets produce symptoms b/c GI 5HT has 1st pass liver metabolism; Flushing, Diarrhea, wheezing, R-sided vavlular dz; Inc 5-HIAA in urine; Tx = OCTREOTIDE |
| Rule of 1/3s in Carcinoid Syndrome | 1/3 metastasize, present with 2nd malignancy, are multiple |
| Zollinger-Ellison Syndrome | Gastrin-secreting tumor of pancreas or duodenum; Causes recurrent ulcers; May be a/w MEN-I |
| Most common cause of hypocalcemia | hypoalbuminemia and alkalosis (low H+, albumin becomes more negatively charged and binds more Ca; low free Ca causes tetany d/t lowered threshold for muscular APs); Tx with BISPHOSPHONATES or PULSATILE PTH for severe cases |
| Osteoporosis | reduction of bone mass in spite of normal bone mineralization |
| Type I Osteoporosis | Postmenopausal; inc resorption d/t low estrogen level; a/w vertebral compression fxs (acute back pain, loss of height, kyphosis) |
| Type II Osteoporosis | Senile; affects both men and women >70yo; Distal radius (Colle's fractures) and vetebral wedge fxs |
| Insulin therapy | binds receptor/tyrosine kinase; inc liver glycogen storage, muslce glycogen/ptn synth and K uptake, TG storage; used for diabetes or life-threatening hyperkalemia/stress-induced hyperglycemia |
| Tolbutamide, Chlorpropamide, Glyburide, Glipizide | Sulfonylureas treat Type 2 DM only; stimulates release of endogenous insulin; Disulfiram-like effects |
| Metformin | inhibits GNG and increases glycolysis; lowers serum glucose levels; may cause lactic acidosis; treats Type 1 or 2 |
| Pioglitazone, Rosiglitazone | increase target cell response to insulin in Type 2; mono or combo therapy |
| Acarbose, Miglitol | alpha-glucosidase inhibitor; used as mono or combo therapy inType2; inhibits brush border enzyme; delayed hydrolysis/absorption of sugars lowers postprandial hyperglycemia |
| Leuprolide | GnRH analog when pulsatile (Tx Infertility); Antagonist when continuous (Tx prostate cancer w/flutamide; or fibroids) |
| Propylthiouracil, Methimazole | Treats Hyperthyroidism by inhibiting coupling of thyroid hormones; decreses peripheral conversion of T4 to T3 (propylthiouracil) |
| Finesteride | Treates BPH; 5a-reductase inhibitor prevents conversion of testosterone to DHT; can also stimulate hair growth |
| Flutamide | Treats prostate carcinoma; competes w/androgens at testosterone receptor; use with leuprolide to inhibit LH/FSH |
| Ketoconazole, Spironolactone | Treats polycystic ovarian syndrome to prevent hirsutism by inhibiting steroid synthesis |
| Hydrocortisone, Prednisone, Triamcinolone, Dexamethasone, Beclomethasone | Treat Addison's disease, inflammation, immune suppression, asthma; glucocorticoids; dec synth of prostaglandins/leukotrienes via inhibition of phospholipid A2 and COX2 expression; can cause iatrogenic Cushings and peptic ulcers |
| Sildenafil, Vardenafil, Tadalafil | inhibit cGMP phosphodiesterase (inc cGMP) relaxes smooth muscle in corpus cavernosum, inc blood flow (NO) and penile erection; "fills the penis" for erectile dysfunction; LIFE-THREATENING hypotension w/Nitrates |
| Clomiphene | Treats infertility; partial estrogen agonist inc LH/FSH release & stimulates ovulation; "momiphene"; possible multiple births, hot flashes, ovarian hypertrophy |
| Mifepristone | RU-486; inhibits progestins at their receptors; abortifacent; can cause bleeding, GI N/V/A/pain |
| OCPs | synthetic estrogen/progestin; dec risk for ovarian/endometrial cancer, dec ectopic pregnancy, dec pelvic infxn, regulates menses; inc TGs, depression, wt gain, N, HTN, hypercoaguable state; daily po |
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bscaryp