3rdexcc.docx

Three parts of the pituitary Anterior (adenohyophysis) Intermediate lobe (pars intermedialis) Posterior (neurohypophysis) Major products of the posterior/neurohypophysis Oxytocin Vasopressin/ADH HPT axis Hyothalamus∙TRH→ Pituitary∙TSH→ Thyroid∙T3,T4→ T3 suppresses H/P activity External inhibition of HPT axis glucocorticoids cytokines Anterior pituitary hormones ACTH TSH LH FSH PRL GH MSH Hormones which stimulate male gonadal function w/ a 55 minute interval pulse LH FSH Regulatory hypothalamic hormone for gonadal function GnRH (gonadotropin-releasing hormone) Diurnal variation of ACTH nadir 11pm-3am peak 6am-9am Effect of TRH Stimulates TSH and prolactin secretion Effect of GnRH Stimulates LH and FSH Effect of Somatostatin (SS) Inhibits GH and TSH release from pituitary Effects of vasopressin (ADH) controls water metabolism stimulates ACTH secretion Layers of the adrenal gland G - Salt F - Sugar R - Sex Zona Glomerulosa (adrenal) produces ... Mineralocorticoids (Aldosterone) Zona Fasciculta produces.... glucocorticoids (cortisol) Zonda Reticularis produces... Androgens DHEA Androstendione Cholesterol enters steroidogenic pathways in response to .... ACTH (adrenocorticotropic hormone) produced by the anterior pituitary Angiotensin II Rate limiting step in steroid synthesis Conversion of cholesterol to pregnenolone

Adrenal medulla produces.... Nor/epinephrine (catecholamines) Aldosterone synthesis Adrenal cortex (G zone) Progesterone→deoxycorticosterone→→aldosterone Cortisol synthesis Adrenal cortex Progesterone→→11-Deoxycortisone→cortisol Regulation of aldosterone RAAS system Response to high extracellular K, low Na, low blood volume Effects of aldosterone Increases excretion of K+ Increases Na+ retention Increases water retention Conn's disease (primary aldosteronism) Benign adenoma PA/PRA>25 Low renin High aldo that fails to decrease w/ saline inhibition Congenital adrenal hyperplasia Decreased aldo and cortisol enzyme disorder elevated testosterone most common cause of adrenogenital disorder Isolated hypoaldosteronism adrenal gland destruction chronic heparin therapy adrenalectomy g-layer enzyme deficiency CAH effects Na wasting (hypoaldosterone) ↑K,acid Hypoglycemia, ↑ACTH virilization CAH diagnosis ↑17-OH progesterone CYP21A2 gene mutation ambiguous genitalia in newborn female Hyperaldosteronism metabolic aklalosis hypertension hypokalemia Signs of Addison's Postural hypotension hyponatremia hyperkalemia increased ACTH blunted cortisol response to ACTH Low ACTH with blunted cortisol response Secondary adrenal insufficiency (steroid therapy) High ACTH with blunted cortisol response Addison's Cortisol secretion primary glucocorticoid F-zone (zona fasciculata) Regulation of cortisol is controlled by ... ACTH from anterior pituitary Effects of cortisol ↑ lipolysis ↑ gluconeogenesis

↑blood glucose by inhibition of glucose uptake by cells ↑ heart rate ↑water retention Cushing's syndrome (hypercortisolism) cause excess glucocorticoid production ↑ cortisol ↑glucose #1 - exogenous steroids (bilateral adrenal atrophy ↓ACTH) #2 - Adrenal adenoma Cushings symptoms Increased fat storage (moon face, buffalo hump) Spindly appendages Immune (IL2) suppression Hypertension Cushing's test Non-suppressible ACTH secretion to high-dose dexamethasone ↑cortisol Cushing's diagnosis steps ↑urine free cortisol ↑baseline AM cortisol loss of diurnal variation loss of dexamethasone suppression Determining ACTH-dependency in CUshings CRH stim test CRH is injected, ACTH measured Low ACTH: independent (Adrenal cause) High ACTH: dependent (pituitary cause) Most common cause of ectopic ACTH-dependent Cushing's small cell lung carcinomas Addison's disease (adrenal insufficiency) cause primary adrenal failure ACTH deficiency Addison's symptoms fatigue anorexia nausea diarrhea abdominal pain Diagnosis of Addison's ↓base cortisol w/ ACTH>200 Parent of testosterone and estrone Androstenedione Primary precursor of estrogens DHEA Diagnosis of hyperandrogenism DHEAS/DHEA/17-ketosteroid levels ↑DHEA/S →adrenal ↑testosterone→gonadal 3 methods of catecholamine degradation 1. reuptake to secretory vesicles 2. uptake to liver 3. degradation COMT and MAO produce metabolites from free catecholamines MAO converts to VMA (in neurons) Measurements of catecholamines urine LC/MS/MS 24hr specimen

Drugs causing sympathetic hyperactivity (+catecholamines) decongestants stimulants bronchodilators MAOIs TSH Foods causing +catecholamines Contain tyramine Some beers, red wines smoked/aged meats fermented foods soy Pheochromocytoma catecholamine-producing tumor Pheochromocytoma diagnosis 24-hour urine values: ↑NE (>170) ↑EPI (>35) ↑Dopa (>700) ↑Metanephrine (>400) Clonidine suppression test ↓ in pheochromocytoma Second messengers cAMP (PTH)° cGMP DAG inositol triphosphate Feedback loops in HPT axis TRH stimulates TSH stimulates thyroxine thyroxine inhibits TSH/TRH Tropic effectors FLAT (FSH,LH,ACTH,TSH) act on other glands Growth hormone antagonizes the effect of ____ on glucose metabolism insulin Stimulatory effects of GH ↑hepatic gluconeogenesis ↑lipolysis ↑protein synthesis Testing for growth hormone productions relies on ____ suppressibilty of GH by oral glucose loading IGF/IGFBP levels Growth hormone can be stimulated by these methods GHRH infusion + l-arginine L-arginine+L-dopa Acromegaly (excess GH) results from pituitary tumor Symptoms: gigantism arthritis diabetes hypertension sleep apnea Prolactin Inhibited by dopamine Causes lactation (direct effector) Excess causes hpogonadism Prolactinoma most common functional pituitary tumor Effects of prolactinoma

amenorrhea infertility galactorrhea headaches Production of vitamin D 1. 7-dehydrocholesterol→D3 (skin) 2. D3→25(OH)D3(liver) 3.25(OH)D3→1,25(OH)2D3 (kidney) Kidneys and calcium Diseased kidney impairs calcium metabolism PHPT, calcium kidney stones Primary form of bone in long bones cortical Primary form of bone in axial skeleton, elastic trabecular Calcium and albumin Low albumin leads to low total calcium, normal ionized calcium Mot common cause of hyprcalcemia primary hyperparathyroidism (PHPT) Causes of PHPT Adenoma paratyroid hyperplasia PHPT lab results ↑Ca2+ ↓K+ (phosphaturia) ↑PTH ↑Hyperchloremic acidosis Diagnostic test for hypercalcemia PTHrP (Parathyroid Hormone-Related Peptide) eleated result indicates malignancy Familial hypocalciuric hypercalcemia benign germline mutation of CSR Endocrine diseases leading to hypercalcemia adenoma hyperthyroidism Addison's (lower ACTH, low cortisol) Milk-alkali/Burnett's syndrome very low PTH results from excess Ca intake+alkali Renal failure and calcium Hypercalcemia due to impaired excretion PTH elevated limited Vit D production Drugs that cause hypercalcemia thiazide diuretics lithium Vitamin A (↑bone resorption) Most accurate test for hypocalcemia serum ionized calcium Hypocalcemia symptms tetany Chvostek's sign tingling extremities seizures QT prolongation Secondary hyperparathyroidism Increased PTH secretion due to hypocalcemia Rickets childhood disease caused by Vit D deficiency, abnormal mineralization bony deformities

Most prevalent metabolic bone disease osteoporosis Thryoid hormone regulates metabolism T3 and T4 99%+ is bound to protein Calcitonin regulates calcium homeostasis secreted by parafollicular C cells Major thyroxine binding proteins Thyroxine-binding globulin (TBG) Thyroxine-binding prealbumin (TBPA) Albumin Most useful biomarker for thyroid function TSH Ideal tumor marker for thyroid cancer thyroglobulin Fine Needle Aspirate (FNA) first thyroid nodule test IDs malignancies Hypothyroidism analytes ↓ FT4 ↑TSH ↑lipids ↓Na Most common cause of hypothyroidism chronic lymphocytic thryoiditis (Hashimoto) Hashimoto's thyroiditis definition autoimmune thyroid damage low thyroxine TPO antibodies Most common cause of thyrotoxicosis Graves' Disease Symptoms of thyrotoxicosis tremor palpitations perspiration heat intolerance emotional lability Graves' Disease lab resuts ↑FT4/T3 Undetectable TSH TSHr antibodies Graves' symptoms Orbital soft tissue swelling double vision corneal disease thyrotoxicosis dermopathy goiter Treatment of Graves' beta blockers radioactive iodine thyroidectomy Addisonian crisis ↓ACTH ↑K, Ca ↓Cortisol Effects of CRH releases ACTH Effects of dopamine inhibits prolactin release

Precursor of all catecholamines Dopamine (from L-dopa) Lactotroph hyperplasia enlargement of pituitary during pregnancy Rate limiting step (conversion to pregnenalone) of steroids takes place ..... in the mitchondrial membrane performed by CYP450 Primary feedback inhibitor of ACTH glucocorticoids (ie cortisol) Chronic angiotensin II stimulation or Na restriction can cause.... aldosterone hypersecrection G-zone hypertrophy Effects of elevated aldosterone Metabolic alkalosis Hypokalemia volume expansion Aldosterone inhibitors progesterone dopamine ANP Drugs which suppress aldosterone ACE inhibitors NSAIDS heparin Types of hyperaldosteronism primary - low renin secondary - high renin pseudo - renal tubular disease Cosyntropin synthetic cortisol stimulant used to differentiate Addison's from secondary adrenal insufficiency HPA Axis Hypothalamus releases CRH→ Pituitary releases ACTH→ Adrenal F-zone releases cortisol Feedback inhibition of HPA axis Cortisol inhibits CRH/ACTH release Mechanism of testosterone Converts to DHT by 5α-reductase Production of testosterone in the gonads takes place in ___ cells in response to ____ Leydig cells in response to LH Klinefelter's syndrome 47,XXY karyotype feminization of males elevated LH, low test Monitoring of testosterone therapy PSA blood counts lipid levels Primary analyte for thyroid disease screening TSH T/F: PTH and 1,25(OH)2D [Vitamin D] are the principal hormones involved in the normal physiologic regulation of calcium homeostasis. True The primary organs involved in the maintenance of calcium homeostasis are the investing, ___, and kidney. Bone

Skin, ___, and kidney are involved in the production of the active metabolite of vitamin D. Liver T/F: Cod liver oil is a source of vitamin D. True T/F: 1,25 (OH)2D is the best blood test for determining adequacy of vitamin D stores in the body. False T/F: PTHrP is produced by some cancers and often leads to cancer-associated hypercalcemia. True T/F: 1,25 (OH)2D due to 1-hydroxylase activity in macrophages, may be produced to excess in granulomatous diseases and lymphoid disorders, leading to hypercalcemia. False In PHPT, the defect primarily lies in ___. In secondary hyperparathyroidism, the defect primarily lies with the threat of ___ to the body. parathyroid, hypocalcemia Development of __ __ is the primary compilation of hypercalciuria (increased urinary exception of calcium) kidney stones __ __ is the most common cause of hypoparathyroidism. neck surgery __ is a type of bone most rapidly lost in response to hypogonadism and glucocorticoid therapy. trabecular bone __ cells in bone are responsible of bone resorption, and __ cells are responsible for bone formation. osteoclasts, osteoblasts __ is the most prevalent metabolic bone disease in the united states. osteoporosis T/F: Hormone replacement does not inhibit bone resorption in osteoporotic patients. False T/F: Triparatide is the only drug currently approved by the FDA for the treatment of osteoporosis that directly stimulates bone formation (i.e. it is not an antiresorptive drug). True