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256 Cards in this Set
- Front
- Back
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What two lipid lowering drug classes predispose the patient to the formation of gallstones?
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Bile acid-binding resins (e.g., cholestyramine) and Fibrates
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Will you have a low or high urinary calcium in primary hyperparathyroidism?
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high
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WHat is the first intervention that should be done in an 8yo with 42 degree celsius fever and seizures?
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COOLING - use cold blankets, move to cool environment, remove clothes, etc.
Use antipyretics (acetaminophen is first line) but the cooling should be started IMMEDIATELY to prevent permanent neurological damage |
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With Conn's syndrome - what two drugs can be used for non-surgical treatment?
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Spironolactone has been used for years and is very effective.
Eplerenone, a new drug, is just as effective as spironolactone but has fewer side effects. It is now commonly used in patients who can not tolerate spironolactone. The most commonly cited side effect of these drugs is gynecomastia (9% in spironolactone, 1% in eplerenone). |
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2yo female has ambiguous genitalia, high blood pressure, and mildly low potassium - what does she have?
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11-hydroxylase deficiency - causes increased synthesis of adrenal androgens bc of low cortisol --> increased ACTH --> androgen synthesis --> ambiguous genitalia
Also causes low renin HTN with mild hypokalemia bc buildup of aldosterone precursor (11-deoxycorticosterone) has mineralocorticoid properties. |
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Adrenal cortex and medulla - Anatomy
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Zona Glomerulosa - regulated by Renin-angiotensin; secretes aldosterone
Zona Fasciculata - regulated by ACTH, hypothalamic CRH; secretes cortisol, sex hormones Zona Reticularis - regulated by ACTH, hypothalamic CRH; secretes sex hormones (e.g., androgens) Medulla - regulated by preganglionic sympathetic fibers; secretes catecholamines (Epi, NE) |
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Adrenal medulla - Pheochromocytoma vs. neuroblastoma
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Pheochromocytoma - most common tumor of the adrenal medulla in adults
Neuroblastoma - most common in children Pheochromocytoma causes episodic hypertension; neuroblastoma does not. |
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Fetal adrenal gland
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Consists of an outer adult zone and inner active fetal zone. Adult zone is dormant during early fetal life but begins to secrete cortisol late in gestation. Cortisol secretion is controlled by ACTH and CRH from fetal pituitary and placenta. Responsible for fetal lung maturation and surfactant production.
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Adrenal gland drainage
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Left adrenal --> left adrenal vein --> left renal vein --> IVC
Right adrenal --> right adrenal vein --> IVC Same as left and right gonadal vein. |
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Pituitary gland - details?
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Posterior pituitary (neurohypophysis) --> vasopressin (ADH) and oxytocin, made in they hypothalamus and shipped to pituitary. Neurophysins carry ADH and oxytocin from the hypothalamus to the posterior pituitary. Derived from neuroectoderm.
Anterior pituitary (adenohypophysis) --> FSH, LH, ACTH, TSH, prolactin, GH, melanotropin (MSH). Derived from oral ectoderm (Rathke's pouch). alpha subunit - common subunit to TSH, LH, FSH, and hCG. Beta subunit - determines hormone specificity Acidophils - GH, prolactin Basophils - FSH, LH, ACTH, TSH |
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How to remember which pituitary hormones are held in acidophils and which are in basophils?
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B-FLAT
FSH LH ACTH TSH Acidophils are the other anterior pituitary hormones, GH and prolactin |
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What protein carries ADH and oxytocin from hypothalamus to the posterior pituitary?
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Neurophysins
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What four hormones have the Alpha and Beta subunit?
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hCG, FSH, LH, TSH
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Endocrine pancreas cell types
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Islets of Langerhans are collections of alpha, beta, and delta endocrine cells (most numerous in tail of pancreas). Islets arise from pancreatic buds. alpha = glucagon (peripheral), Beta = insulin (central), delta = somatostatin (interspersed)
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Insulin - details?
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Released in Beta cells of pancreas in response to ATP from glucose metabolism closing K+ channels and depolarizing cells. Required for adipose and skeletal muscle uptake of glucose. Insulin does not cross the placenta.
Inhibits glucagon release by alpha cells of pancreas. |
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Insulin - regulation?
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Hyperglycemia, GH, and Beta-2 agonists increase insulin
Hypoglycemia, alpha2 agonists, and somatostatin decrease insulin. Alpha agonists inhibit insulin secretion in general, beta-agonists stimulate insulin release in general Serum C-peptide is not present with exogenous insulin intake (proinsulin --> insulin + C-peptide) |
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Anabolic effects of insulin
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1. increased glucose transport in skeletal mm. and adipose
2. Increased glycogen synthesis and storage 3. Increased triglyceride synthesis and storage 4. Increased Na+ retention (kidneys) 5. Increased protein synthesis (muscles) 6. Increased cellular uptake of K+ and amino acids |
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Glucose transport proteins - GLUT 1, GLUT 2, GLUT 4
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GLUT 1 - RBCs, brain
GLUT 2 (Bidirectional): Beta islet cells, liver, kidney, small intestine GLUT 4 (insulin responsive): adipose tissue, skeletal muscle |
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Glucose uptake - mechanism?
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Insulin binds to insulin receptors --> tyrosine phosphorylation which causes PI3k pathway and RAS/MAP kinase pathway to activate
PI3k pathway --> glycogen, lipid, protein synthesis; Vesicles containing GLUT4 are exocytosed (thus allowing glucose to be transported into the cell) RAS/MAP kinase pathway --> cell growth, DNA synthesis |
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Insulin secretion - pancreatic Beta cells - mechanism?
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Glucose enters cells via GLUT 2 (may be GLUT 1, controversial). Glycolysis --> ATP production.
ATP --> closed ATP-sensitive K+ channels --> depolarization of cell --> open voltage-gated Ca2+ channels --> Increased intracellular calcium --> Exocytosis of insulin granules |
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Insulin secretion - how does glucagon inhibit insulin release from pancreatic Beta cells?
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Adenylate cyclase can be activated via G-protein pathway which is activated by Glucagon, inhibited by epi/norepi. This takes ATP out of the cell (converts it to cAMP) which leads to reduction of intracellular calcium and inhibits release of Insulin
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Insulin-dependent organs
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Skeletal muscle and adipose tissue depend on insulin for increased glucose uptake (GLUT-4)
Brain and RBCs take up glucose independent of insulin levels (GLUT-1). Brain depends on glucose for metabolism under normal circumstances and uses ketone bodies in starvation. RBCs always depend on glucose because they have no mitochondria for aerobic metabolism. |
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Glucagon
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made by alpha cells of pancreas. Secreted in reponse to hypoglycemia. Inhibited by insulin, hyperglycemia, and somatostatin.
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Effects of glucagon
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1. Glycogenolysis, gluconeogenesis
2. Lipolysis and ketone production 3. Inhibition of insulin and further glucagon release |
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Hypothalamic-pituitary hormone regulation - Effects of TRH?
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Induces TSH, prolactin release
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Hypothalamic-pituitary hormone regulation - Effects of dopamine?
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Inhibits prolactin release.
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Hypothalamic-pituitary hormone regulation - Effects of Corticotropin Releasing-hormone (CRH)?
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Promotes ACTH release.
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Hypothalamic-pituitary hormone regulation - Effects of GHRH?
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Promotes GH release.
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Hypothalamic-pituitary hormone regulation - Effects of somatostatin?
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Inhibits GH, TSH release.
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Hypothalamic-pituitary hormone regulation - Effects of GnRH?
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Promotes FSH, LH release.
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Hypothalamic-pituitary hormone regulation - Effects of Prolactin?
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Inhibits GnRH release.
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Prolactin - Regulation?
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Prolactin secretion from anterior pituitary is tonically inhibited by dopamine from hypothalamus. Prolactin in turn inhibits its own secretion by increasing dopamine synthesis and secretion from hypothalamus. TRH increases prolactin secretion.
Dopamine agonists (bromocriptine) inhibit prolactin secretion and can be used in treatment of prolactinoma. Dopamine antagonists (most antipsychotics) and estrogens (OCPs, pregnancy) stimulate prolactin secretion. |
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Prolactin - Function?
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Stimulates milk production in breast; inhibits ovulation (in females) and spermatogenesis (in males) by inhibiting GnRH synthesis and release.
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Growth hormone (somatotropin) - regulation?
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Released in pulses in response to GHRH. Secretion increases during exercise and sleep. Secretion inhibited by glucose and somatostatin.
Excess secretion of GH (e.g., pituitary adenoma) may cause acromegaly or gigantism. |
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Growth hormone (somatotropin) - function?
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Stimulates linear growth and muscle mass through somatomedin secretion. Increases insulin resistance (diabetogenic).
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Adrenal Steroid - synthesis pathway?
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Congenital bilateral adrenal hyperplasias - 17alpha-hydroxylase deficiency
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Mineralocorticoids - increased
Cortisol - decreased Sex hormones - decreased HYPERtension, hypokalemia XY: Decreased DHT --> pseudohermaphroditism (variable ambiguous genitalia, undescended testes) XX: externally phenotypic female with normal internal sex organs, lacks secondary sex characteristics |
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Congenital bilateral adrenal hyperplasias - 21-hydroxylase deficiency
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Mineralocorticoids - decreased
Cortisol - decreased Sex hormones - increased Most common form. HYPOtension, hyperkalemia, increased renin activity, volume depletion. Masculinization, female pseudohermaphroditism. |
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Congenital bilateral adrenal hyperplasias - 11Beta-hydroxylase deficiency
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Mineralocorticoids - decreased aldosterone, increased 11-hydroxycorticosterone
Cortisol - decreased Sex hormones - increased HYPERtension (11-deoxycorticosterone is a mineralocorticoid and secreted in excess). Masculinization. |
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Cortisol - source? function?
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Source - Adrenal zona fasciculata
Function - Cortisol is BBIIG: 1. Maintains Blood pressure (upregulates alpha1 receptors on arterioles) 2. Decreased Bone formation 3. Anti-Inflammatory/Immunosuppressive: Inhibits production of leukotrienes and prostaglandins, inhibits leukocyte adhesion leading to neutrophilia (PMNs pool in the blood), blocks histamine release from mast cells, reduces eosinophils, blocks IL-2 production 4. Increased insulin resistance (diabetogenic) 5. Increased Gluconeogenesis, lipolysis, proteolysis Bound to corticosteroid-binding globulin (CBG). Chronic stress induces prolonged secretion. |
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Cortisol - Regulation?
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CRH (hypothalamus) stimulates ACTH release (pituitary), causing cortisol production in adrenal zona fasciculata. Excess cortisol decreases CRH, ACTH, and cortisol secretion.
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What portion of the nephron does PTH act on?
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Distal convoluted tubule
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PTH - Source?
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Chief cells of parathyroid.
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PTH - Functions?
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1. Increased bone resorption of calcium and phosphate.
2. Increased kidney reabsorption of calcium in distal convoluted tubule. 3. Decreased kidney reabsorption of phosphate. 4. Increased 1,25-(OH)2 Vitamin D (calcitriol) PTH increases serum Ca2+, decreases serum (PO4)3-, increases urine (PO4)3- Increases production of M-CSF and RANK-L in osteoBLASTS, stimulating osteoCLASTS. |
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PTH - Regulation?
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Decreased free serum Ca2+ increases PTH secretion.
Decreased Mg2+ increases PTH secretion, but greatly decreased Mg2+ decreases PTH secretion. |
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Calcium homeostasis
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Note: Vitamin D (calcitriol0 directly feeds back to inhibit PTH synthesis.
Increased serum calcium feeds back to inhibit PTH secretion. |
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Phosphate homeostasis
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Low serum phosphorus --> induces conversion of 25-OH vitamin D to 1,25(OH) vitamin D
Calcitriol induces release of phosphate from bone matrix, increases phosphate reabsorption in intestines. |
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What enzyme does PTH induce to convert 25-OH vitamin D into calcitriol?
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1alpha-hydroxylase
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Vitamin D (cholecalciferol) - Source
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Vitamin D3 from sun exposure in skin. D2 ingested from plants. both converted to 25-OH vitamin D in liver and to 1,25-(OH)2 vitamin D (active form) in kidney.
Vitamin D deficiency causes rickets in kids and osteomalacia in adults. 24,25-(OH)2 vitamin D is an inactive form of vitamin D. |
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Vitamin D (cholecalciferol) - Function
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1. Increases absorption of dietary calcium and phosphate.
2. Increases bone resorption of Ca2+ and (PO4)3- PTH increases calcium reabsorption and decreases phosphate reabsorption, while 1,25-(OH)2 vitamin D increases absorption of BOTH calcium and phosphate. |
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Vitamin D (cholecalciferol) - Regulation
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Increased PTh, decreased [Ca2+], decreased phosphate cause increased 1,25 (OH)2 vitamin D production.
1,25-(OH)2 vitamin D feedback inhibits its own production. |
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Calcitonin - Source? Function? Regulation?
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Source - Parafollicular cells (C cells) of thyroid
Function - Decreased bone resorption of calcium Regulation - Increased serum Ca2+ causes calcitonin secretion Calcitonin opposes actions of PTH. Not important in normal calcium homeostasis. |
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Signaling pathways of endocrine hormones - cyclic AMP
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FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2 receptor), MSH, PTH, calcitonin, GHRH, glucagon
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How to remember what hormones use cAMP?
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FLAT CHAMP
FSH LH ACTH TSH CRH hCG ADH (V2 receptor) MSH PTH Also calcitonin, GHRH, glucagon |
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Signaling pathways of endocrine hormones - cyclic GMP
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ANP, NO (EDRF)
(Think vasodilators) |
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Signaling pathways of endocrine hormones - IP3
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GnRH, Oxytocin, ADH (V1 receptor), TRH, histamine (H1), angiotensin II, gastrin
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How to remember which hormones use IP3 pathway?
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GOAT
GnRH Oxytocin ADH (V1 receptors) TRH also histamine (H1), angiotensin II, gastrin |
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Signaling pathways of endocrine hormones - Steroid receptors (cytoplasmic? nuclear?)
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Cytoplasmic - Vitamin D, Estrogen, Testosterone, Cortisol, Aldosterone, Progesterone
Nuclear - T3/T4 |
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Signaling pathways of endocrine hormones - Intrinsic tyrosine kinase (MAP kinase pathway)
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Insulin, IGF-1, FGF, PDGF
(Think growth factors.) |
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Signaling pathways of endocrine hormones - Receptor-associated tyrosine kinase (JAK/STAT pathway)
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Prolactin, GH, cytokines (e.g., IL-2, IL-6, IL-8)
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Steroid/thyroid hormone mechanism
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Transport - steroid hormones are lipophilic and therefore must circulate bound to specific binding globulins, which increase their solubility.
In men, increased sex hormone-binding globulin lowers free testosterone --> gynecomastia. In women, decreased SHBG raises free testosterone --> hirsutism; SHBG levels increase during pregnancy. |
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Thyroid-hormones (T3/T4) - basics?
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Iodine-containing hormones that control the body's metabolic rate.
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Thyroid-hormones (T3/T4) - Source?
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Follicles of thyroid. Most T3 formed in target tissues.
Thyroxine-binding globulin (TBG) binds most T3/T4 in blood; only free hormone is active. Decreased TBG in hepatic failure; increased TBG in pregnancy or OCP use (estrogen increases TBG). T4 is major product; converted to T3 in peripheral tissue by 5'-deiodinase. |
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Thyroid-hormones (T3/T4) - Functions?
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1. Bone growth (synergism with GH)
2. CNS maturation 3. Increased Beta1 receptors in heart = increased CO, HR, SV, contractility 4. Increased basal metabolic rate via increased Na+/K+-ATPase activity = increased O2 consumption, RR, body temperature 5. Increased glycogenolysis, gluconeogenesis, lipolysis |
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How to remember functions of T3?
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4 B's:
Brain maturation Bone growth Beta-adrenergic effects Basic Metabolic Rate elevation |
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Thyroid-hormones (T3/T4) - Regulation
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TRH (hypothalamus) stimulates TSH (pituitary), which stimulates follicular cells.
Negative feedback by free T3 to anterior pituitary decreases sensitivity to TRH. Thyroid-stimulating immunoglobulin, like TSH, stimulates follicular cells (Graves disease). |
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Thyroid-hormones (T3/T4) - Synthesis
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T3 binds receptors with greater affinity than T4.
Peroxidase is enzyme responsible for oxidation and organification of iodide as well as coupling of MIT and DIT. Propylthiouracil inhibits both peroxidase and 5'-deiodinase. Methimazole inhibits peroxidase only. |
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Wolff-Chaikoff effect
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Excess iodine temporarily inhbits thyroid peroxidase --> decreased iodine organification --> decreased T3/T4 production.
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Cushing's syndrome - basics?
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Increased cortisol due to a variety of causes.
Exogenous (iatrogenic) steroids - #1 cause; decreased ACTH. Endogenous cuases: 1. Cushing's disease (70%) - due to ACTH secretion from pituitary adenoma; increased ACTH. 2. Ectopic ACTH (15%) - from nonpituitary tissue making ACTH (e.g., small cell lung cancer, bronchial carcinoids); increased ACTH. 3. Adrenal (15%) - adenoma, carcinoma, nodular adrenal hyperplasia; decreased ACTH. |
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Cushing's syndrome - findings?
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Hypertension, weight gain, moon facies, truncal obesity, buffalo hump, hyperglycemia (insulin resistance), skin changes (thinning, striae), osteoporosis, amenorrhea, and immune suppression.
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Effect of dexamethasone test on cortisol - Normal person?
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Low dose suppresses cortisol
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Effect of dexamethasone test on cortisol - ACTH-pituitary tumor?
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Low-dose does not suppress.
High-dose suppresses cortisol. |
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Effect of dexamethasone test on cortisol - Ectopic ACTH-producing tumor
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Cortisol remains high with both low and high dose.
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Effect of dexamethasone test on cortisol - Cortisol-producing tumor
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Cortisol remains high with both low and high dose.
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Hyperaldosteronism - Primary
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Caused by adrenal hyperplasia or an aldosterone-secreting adrenal adenoma (Conn's syndrome), resulting in hypertension, hypokalemia, metabolic alkalosis, and LOW plasma renin. May be bilateral or unilateral.
Treatment: surgery to remove the tumor and/or spironolactone, a K+-sparing diuretic that works by acting as an aldosterone antagonist |
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Hyperaldosteronism - Secondary
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Kidney perception of low intravascular volume results in an overactive renin-angiotensin system. Due to renal artery stenosis, chronic renal failure, CHF, cirrhosis, or nephrotic syndrome. Associated with HIGH plasma renin.
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Addison's disease - details?
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Chronic primary adrenal insufficiency due to adrenal atrophy or destruction by disease (e.g., autoimmune, TB, metastasis). Deficiency of aldosterone and cortisol, causing hypotension (hyponatremic volume contraction), hyperkalemia, acidosis, and skin hyperpigmentation (due to MSH, a by-product of increased ACTH production from POMC).
Characterized by Adrenal Atrophy and Absence of hormone production; involves All 3 cortical divisions (spares medulla). Distinguish from secondary adrenal insufficiency (decreased pituitary ACTH production), which has no skin hyperpigmentation and no hyperkalemia. |
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Waterhouse-Friderichsen syndrome
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Acute primary adrenal insufficiency due to adrenal hemorrhage associated with N. meningitidis septicemia, DIC, and endotoxin shock.
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Pheochromocytoma - details?
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Most common tumor of the adrenal medulla in adults. Derived from chromaffin cells (arise from neural crest).
Most tumors secrete epinephrine, NE, and dopamine and can cause episodic hypertension. Urinary VMA (a breakdown product of norepinephrine) and plasma catecholamines are elevated. Associated with neurofibromatosis, MEN types 2A and 2B. |
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Pheochromocytoma - treatment?
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Alpha-antagonists, especially phenoxybenazime, a non-selective, irreversible alpha-blocker, followed by surgery to remove the tumor.
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Pheochromocytoma - episodic hyperadrenergic symptoms (5 P's)
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Pressure (elevated BP)
Pain (headache) Perspiration Palpitations (tachycardia) Pallor |
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Pheochromocytoma - Rule of 10's
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10% malignant
10% bilateral 10% extra-adrenal 10% calcify 10% kids 10% familial |
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Neuroblastoma - details?
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The most common tumor of the adrenal medulla in children. Can occur anywhere along the sympathetic chain. Homovanillic acid (HVA), a breakdown product of dopamine, elevated in urine. Less likely to develop hypertension.
Overexpression of N-myc oncogene associated with rapid tumor progression. |
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What substance can be elevated in the urine that may suggest a neuroblastoma in a kid?
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Homovanillic acid (HVA) - a breakdown product of dopamine
NOT VMA |
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Hypothyroidism vs. Hyperthyroidism - Sign/symptoms
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Hypothyroidism:
Cold intolerance (dec. heat production) Weight gain, decreased appetite Hypoactivity, lethargy, fatigue, weakness Constipation Decreased reflexes Myxedema (facial/periorbital) Dry, cool skin; coarse, brittle hair Bradycardia, dyspnea on exertion Hyperthyroidism: Heat intolerance (inc. heat production) Weight loss, increased appetite Hyperactivity Diarrhea Increased reflexes Pretibial myxedema (Graves' disease) Warm, moist skin; fine hair Chest pain, palpitations, arrhythmias, increased Beta-adrenergic receptors |
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Hypothyroidism vs. Hyperthyroidism - Lab Findings
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Hypothyroidism:
Increased TSH (sensitive test for primary hypothyroidism) Decreased total T4 Decreased free T4 Decreased T3 uptake Hyperthyroidism: Decreased TSH (if primary) Increased total T4 Increased free T4 Increased T3 uptake |
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Hypothyroidism - Hashimoto's thyroiditis
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Most common cause of hypothyroidism; an autoimmune disorder (antimicrosomal, antithyroglobulin antibodies). Associated with HLA-DR5. Increased risk of non-Hodgkin's lymphoma.
Histology: Hurthle cells (see picture), lymphocytic infiltrate with germinal centers. Findings: moderately enlarged, nontender thyroid May be hyperthyroid early in course (thyrotoxicosis during follicular rupture). |
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Hypothyroidism - Cretinism
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Due to severe fetal hypothyroidism. Endemic cretinism occurs wherever endemic goiter is prevalent (lack of dietary iodine); sporadic cretinism is caused by defect in T4 formation or developmental failure in thyroid formation.
Findings: pot-bellied, pale, puffy-faced child with protruding umbilicus and protuberant tongue |
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Hypothyroidism - Subacute thyroiditis (de Quervian's)
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Self-limited hypothyroidism often following a flulike illness. May be hyperthyroid early in course.
Histology: granulomatous inflammation Findings: Elevated ESR, jaw pain, early inflammation, very tender thyroid |
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Hypothyroidism - Riedel's thyroiditis
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Thyroid replaced by fibrous tissue (hypothyroid)
Findings: fixed, hard (rock-like), and painless goiter |
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Hypothyroidism - Other Causes
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Iodine deficiency, thyroglossal duct cyst, goitrogens, Wolff-Chaikoff effect
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Hyperthyroidism - Graves' disease
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An autoimmune hyperthyroidism with thyroid-stimulating/TSH receptor antibodies. Ophthalmopathy (proptosis, EOM swelling), pretibial myxedema (see picture), increase in connective tissue deposition, diffuse goiter. Often presents during stress (e.g., childbirth).
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Hyperthyroidism - Thyroid storm
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Stress-induced catecholamine surge leading to death by arrhythmia. Seen as a serious complication of Grave's and other hyperthyroid disorders. May see increased alk phos due to increased bone turnover.
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Hyperthyroidism - Toxic multinodular goiter
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Focal patches of hyperfunctioning follicular cells working independently of TSH due to mutation in TSH receptor. Increased release of T3 and T4. Hot nodules are rarely malignant.
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Hyperthyroidism - Jod-Basedow phenomenon
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Thyrotoxicosis if a patient with iodine deficiency goiter is made iodine replete.
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Thyroid Cancer - Papillary Carcinoma
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Most common, excellent prognosis, "ground-glass" nuclei (Orphan Annie, see picture), psammoma bodies, nuclear grooves. Increased risk with childhood irradiation.
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Thyroid Cancer - Follicular carcinoma
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Good prognosis, uniform follicles
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Thyroid Cancer - Medullary carcinoma
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From parafollicular "C cells"; produces calcitonin, sheets of cells in amyloid stroma. Associated with MEN types 2A and 2B.
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Thyroid Cancer - Undifferentiated/anaplastic
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Older patients; very poor prognosis.
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Thyroid Cancer - Lymphoma
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Associated with Hashimoto's thyroiditis.
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Hyperparathyroidism - Primary
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Usually an adenoma. Hypercalcemia, hypercalciuria (renal stones), hypophosphatemia, elevated PTH, elevated alk phos, elevated cAMP in urine. Often asymptomatic, or may present with weakness and constipation ("groans").
"Stones, bones, and groans." |
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Osteitis fibrosa cystica
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Associated with primary hyperparathyroidism. Cystic bone spaces filled with brown fibrous tissue (bone pain).
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Hyperparathyroidism - Secondary
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Secondary hyperplasia due to decreased gut Ca2+ absorption and elevated serum phosphate, most often in chronic renal disease (causes hypovitaminosis D --> decreased Ca2+ absorption). Hypocalcemia, hyperphosphatemia, elevated alk phos, elevated PTH.
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Renal osteodystrophy
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Bone lesions due to secondary or tertiary hyperparathyroidism due in turn to renal disease.
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Hyperparathyroidism - tertiary
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Refractory (autonomous) hyperparathyroidism resulting from chronic renal disease. Massively elevated PTH and elevated [Ca2+].
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Hypoparathyroidism - details?
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Due to accidental surgical excision (thyroid surgery), autoimmune destruction, or DiGeorge syndrome.
Findings: hypocalcemia, tetany |
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Chvostek's sign
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Tapping facial nerve --> contraction of facial muscles.
Seen in hypoparathyroidism, hypocalcemia. |
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Trousseau's sign
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Occlusion of brachial artery with BP cuff --> carpal spasm.
Seen in hypoparathyroidism, hypocalcemia. |
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Pseudohypoparathyroidism
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a.k.a. Albright's hereditary osteodystrophy
Autosomal-dominant kidney unresponsiveness to PTH. Hypocalcemia, shortened 4th/5th digits, short stature. |
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Pituitary adenoma - details?
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Most commonly prolactinoma. Findings: amenorrhea, galactorrhea, low libido, infertility (decreased GnRH). bromocriptine or cabergoline (dopamine agonists) causes shrinkage of prolactinomas.
Can impinge on optic chiasm --> bitemporal hemianopia |
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Acromegaly - details
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Excess GH in adults. (Elevated GH is normal in stress, exercise, and hypoglycemia).
Findings: large tongue with deep furrows, deep voice, large hands and feet, coarse facial features, impaired glucose tolerance (insulin resistance). Increased Gh in children --> gigantism (increased linear bone growth). Diagnosis: elevated serum IGF-1; failure to suppress serum GH following oral glucose tolerance test Treatment: pituitary adenoma resection followed by octreotide administration |
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Diabetes insipidus - details?
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Characterized by intense thirst and polyuria together with an inability to concentrate urine owing to lack of ADH (central DI - pituitary tumor, trauma, surgery, histiocytosis X) or to a lack of renal response to ADH (nephrogenic DI - hereditary or secondary to hypercalcemia, lithium, demeclocycline [ADH antagonist]).
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Diabetes Insipidus - Diagnosis?
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Water deprivation test - urine osmolality doesn't increase. Response to desmopressin distinguishes between central and nephrogenic.
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Diabetes Insipidus - Findings?
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Urine specific gravity < 1.006; serum osmolality > 290 mOsm/L.
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Diabetes Insipidus - Treatment?
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Adequate fluid intake.
For central DI - intranasal desmopressin (ADH analog). For nephrogenic DI - hydrochlorothiazide, indomethacin, or amiloride. |
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SIADH - details?
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Syndrome of Inappropriate Antidiuretic Hormone secretion:
1. Excessive water retention 2. Hyponatremia 3. Urine osmolarity > serum osmolarity Body responds with depressed aldosterone (hyponatremia) to maintain near-normal volume status. Very low serum sodium levels can lead to seizures (correct slowly). Treatment: demeclocycline or H2O restriction |
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SIADH - common causes (4)
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1. Ectopic ADH (small cell lung cancer)
2. CNS disorders/head trauma 3. Pulmonary disease 4. Drugs (e.g., cyclophosphamiade and carbamazepine) |
|
|
Hypopituitarism - details?
|
Undersecretion of pituitary hormones due to:
1. Nonsecreting pituitary adenoma, craniopharyngioma 2. Sheehan's syndrome (hemorrhagic or ischemic infarct of pituitary following postpartum bleeding; usually presents with failure to lactate) 3. Empty sella syndrome (unexplained atrophy of pituitary; common in obese women) 4. Brain injury, hemorrhage 5. Radiation |
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|
Diabetes Mellitus - Acute Manifestations
|
Polydipsia, polyuria, polyphagia, weight loss, DKA (type I), hyperosmolar coma (type 2), unopposed secretion of GH and epinephrine (exacerbating hyperglycemia)
|
|
|
Diabetes Mellitus - Effects of insulin deficiency (and glucagon excess)
|
Decreased glucose uptake --> hyperglycemia, glycosuria, osmotic diuresis, electrolyte depletion --> dehydration, acidosis --> coma, death
Increased protein catabolism --> increased plasma amino acids, nitrogen loss in urine --> hyperglycemia, glycosuria, ostmotic diuresis, electrolyte depletion --> dehydration, acidosis --> coma, death Increased lipolysis --> increased plasma FFAs, ketogenesis, ketonuria, ketonemia --> dehydration, acidosis --> coma, death |
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|
Diabetes Mellitus - Chronic manifestations - Nonenzymatic glycosylation
|
1. Small vessel disease (diffuse thickening of basement membrane) --> retinopathy (hemorrhage, exudates, microaneurysms, vessel proliferation), glaucoma, nephropathy (nodular sclerosis, progressive proteinuria, chronic renal failure, arteriosclerosis leading to hypertension, Kimmelstiel-Wilson nodules [see picture])
2. Large vessel atherosclerosis, CAD, peripheral vascular occlusive disease, and gangrene --> limb loss, cerebrovascular disease |
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|
Diabetes Mellitus - Chronic Manifestations - Osmotic Damage
|
1. Neuropathy (motor, sensory, and autonomic degeneration)
2. Cataracts (sorbitol accumulation) |
|
|
Diabetes Mellitus - Tests
|
Fasting serum glucose, glucose tolerance test, HbA1c (measures long-term diabetic control)
|
|
|
Type 1 vs. type 2 diabetes mellitus - Primary defect
|
Type 1 - autoimmune destruction of Beta cells after infection
Type 2 - Increased resistance to insulin |
|
|
Type 1 vs. type 2 diabetes mellitus - Insulin necessary to treatment
|
Type 1 - always
Type 2 - sometimes |
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|
Type 1 vs. type 2 diabetes mellitus - Age (exceptions commonly occur)
|
Type 1 - < 30
Type 2 - > 40 |
|
|
Type 1 vs. type 2 diabetes mellitus - Association with obesity
|
Type 1 - No
Type 2 - Yes |
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|
Type 1 vs. type 2 diabetes mellitus - Genetic predisposition
|
Type 1 - Relatively weak (50% concordance in identical twins), polygenic
Type 2 - Relatively strong (90% concordance in identical twins), polygenic |
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|
Type 1 vs. type 2 diabetes mellitus - Associated with HLA system
|
Type 1 - Yes (HLA DR3 and DR4)
Type 2 - No |
|
|
Type 1 vs. type 2 diabetes mellitus - Glucose intolerance
|
Type 1 - severe
Type 2 - Mild to moderate |
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|
Type 1 vs. type 2 diabetes mellitus - Insulin Sensitivity
|
Type 1 - High
Type 2 - Low |
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|
Type 1 vs. type 2 diabetes mellitus - Ketoacidosis
|
Type 1 - Common
Type 2 - Rare |
|
|
Type 1 vs. type 2 diabetes mellitus - Beta-cell numbers in the islets
|
Type 1 - Decreased
Type 2 - Variable (with amyloid deposits) |
|
|
Type 1 vs. type 2 diabetes mellitus - Serum insulin level
|
Type 1 - decreased
Type 2 - Variable |
|
|
Type 1 vs. type 2 diabetes mellitus - Classic symptoms of polyuria, polydipsia, polyphagia, weight loss
|
Type 1 - common'
Type 2 - sometimes |
|
|
Type 1 vs. type 2 diabetes mellitus - Histology
|
Type 1 - Islet leukocytic infiltrate
Type 2 - Islet amyloid deposit |
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|
Diabetic Ketoacidosis - details?
|
One of the most important complications of type I diabetes. Usually due to elevated insulin requirements from increased stress (e.g., infection). Excess fat breakdown and increased ketogenesis from elevated FFAs, which are then made into ketone bodies (Beta-hydroxybutyrate > acetoacetate).
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|
|
Diabetic Ketoacidosis - Signs/Symptoms
|
Kussmaul respirations (rapid/deep breathing), nausea/vomiting, abdominal pain, psychosis/ delirium, dehydration. Fruity breath odor (due to exhale acetone).
|
|
|
Diabetic Ketoacidosis - Labs
|
Hyperglycemia, elevated H+, decreased HCO3- (anion gap metabolic acidosis), elevated blood ketone levels, leukocytosis.
Hyperkalemia, but depleted intracellular K+ due to transcellular shift from decreased insulin. |
|
|
Diabetic Ketoacidosis - Complications
|
Life-threatening mucormycosis, Rhizopus infection, cerebral edema, cardiac arrhythmias, heart failure.
|
|
|
Diabetic Ketoacidosis - Treatment
|
IV fluids, IV insulin, and K+ (to replete intracellular stores); glucose if necessary to prevent hypoglycemia.
|
|
|
Carcinoid syndrome
|
Rare syndrome caused by carcinoid tumors (neuroendocrine cells from GI tract), especially metastatic small bowel tumors, which secrete high levels of serotonin (5-HT). Not seen if tumor is limited to GI tract (5-Ht undergoes first-pass metabolism in liver).
Results in recurrent diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease. Most common tumor of appendix. Elevated 5-HIAA in urine. Treatment: octreotide |
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|
Carcinoid syndrome - rule of 1/3s
|
1/3 metastasize
1/3 present with 2nd malignancy 1/3 multiple |
|
|
Zollinger-Ellison Syndrome
|
Gastrin-secreting tumor of pancreas or duodenum. Stomach shows rugal thickening with acid hypersecretion. Causes recurrent ulcers. May be associated with MEN type 1.
|
|
|
What can be measured in the urine to help diagnose carcinoid syndrome?
|
5-HIAA
|
|
|
Multiple endocrine neoplasias (MEN) - MEN 1 (Wermer's syndrome)
|
Parathyroid tumors.
Pituitary tumors (prolactin or GH) Pancreatic endocrine tumors -- Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas (rare) commonly presents with kidney stones and stomach ulcers |
|
|
Multiple endocrine neoplasias (MEN) - MEN 2A (Sipple's syndrome)
|
Medullary thyroid carcinoma (secretes calcitonin), Pheochromocytoma,
Parathyroid tumors |
|
|
Multiple endocrine neoplasias (MEN) - MEN 2B
|
Medullary Thyroid Carcinoma (secretes calcitonin)
Pheochromocytoma Oral/intestinal ganglioneuromatosis (associated with marfinoid habitus) |
|
|
Multiple endocrine neoplasias (MEN) - Rule of P's, and other notes
|
MEN 1 = 3 P's (from cephalid to caudad: Pituitary, Parathyroid, and Pancreas)
MEN 2A = 2 P's (Parathyroids and Pheochromocytoma) also Medullary Thyroid Carcinoma MEN 2B = 1 P (Pheochromocytoma) also Medullary Thyroid Carcionoma and Oral/Intestinal Ganglioneuromatosis (associated with marfanoid habitus) All MEN syndromes have autosomal-dominant inheritance. Associated with RET gene in MEN types 2A and 2B. |
|
|
Diabetes drugs - basics
|
Treatment strategy for type 1 DM - low-sugar diet, insulin replacement
Treatment strategy for type 2 DM - dietary modification and exercise for weight loss; oral hypoglycemics and insulin replacement. |
|
|
Diabetes Drugs - Insulin - Examples? Action? Clinical Use? Toxicities?
|
Lispro (rapid-acting), Aspart (rapid-acting), Regular (short-acting), NPH (intermediate), Glargine (long-acting), Detemir (long-acting)
Action: Bind insulin receptor (tyrosine kinase activity). Liver - increase glucose storage as glycogen Muscle - Increase glycogen and protein synthesis, K+ uptake. Fat: aids TG storage Clinical Use: Type 1 DM, type 2 DM, gestational diabetes, life-threatening hyperkalemia, and stress-induced hyperglycemia Toxicities - Hypoglycemia, hypersensitivity reaction (very rare) |
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|
Diabetes Drugs - Sulfonylureas - Examples? Action? Clinical Use? Toxicities?
|
First Generation: Tolbutamide, Chlorpropamide
Second Generation: Glyburide, Glimepiride, Glipizide Action: Close K+ channel in Beta-cell membrane, so cell depolarizes --> triggering of insulin release via Ca2+ influx. Clinical Use: Stimulate release of endogenous insulin in type 2 DM. Require some islet function, so useless in type 1 DM. Toxicities: First generation - disulfiram-like effects Second Generation - hypoglycemia |
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|
Diabetes Drugs - Biguanides - Examples? Action? Clinical Use? Toxicities?
|
Metformin.
Action: Exact mechanism unknown. Decreases gluconeogenesis, increases glycolysis, increases peripheral glucose uptake (insulin sensitivity). Clinical use: Oral. First line therapy in type 2 DM. Can be used in patients without islet function. Toxicities: Most grave adverse effect is lactic acidosis (contraindicated in renal failure). |
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|
Diabetes Drugs - Glitazones/thiazolidinediones - Examples? Action? Clinical Use? Toxicities?
|
Pioglitazone, Rosiglitazone
Action: Increases insulin sensitivity in peripheral tissues. binds to PPAR-gamma nuclear transcription regulator. Genes activated by PPAR-gamma regulate fatty acid storage and glucose metabolism. Activation of PPAR-gamma increases insulin sensitivity and levels of adiponectin. Clinical use: Used as monotherapy in type 2 DM or combined with above agents. Toxicities: Weight gain, edema. hepatotoxicity, heart failure |
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|
Diabetes Drugs - Alpha-glucosidase inhibitors - Examples? Action? Clinical Use? Toxicities?
|
Acarbose, Miglitol
Action: Inhibit intestinal brush-border alpha-glucosidases. Delayed sugar hydrolysis and glucose absorption --> decreased postprandial hyperglycemia. Clinical use: Used as monotherapy in type 2 DM or in combination with above agents. Toxicities: GI disturbances |
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|
Diabetes Drugs - Mimetics - Examples? Action? Clinical Use? Toxicities?
|
Pramlintide
Action: decreases glucagon Clinical use: Type 2 DM Toxicity: Hypoglycemia, nausea, diarrhea |
|
|
Diabetes Drugs - GLP-1 analogs - Examples? Action? Clinical Use? Toxicities?
|
Exenatide
Action: Increases insulin, decreases glucagon release. Clinical Use: Type 2 DM Toxicities: Nausea, vomiting, pancreatitis. |
|
|
Propylthiouracil, Methimazole - Mechanism? Clinical Use? Toxicity?
|
Mechanism - Block peroxidase thereby inhibiting organification of iodide and coupling of thyroid hormone synthesis. Propylthiouracil also blocks 5'-deiodinase, which decreases peripheral conversion of T4 to T3.
Clinical use: Hyperthyroidism Toxicity: Skin rash, agranulocytosis (rare), aplastic anemia, hepatotoxicity (propylthiouracil). Methimazole is a possible teratogen. |
|
|
Levothyroxine, triiodothyronine - Mechanism? Clinical Use? Toxicity?
|
Mechanism - Thyroxine replacement
Clinical use - Hypothyroidism, myxedema Toxicity - Tachycardia, heat intolerance, tremors, arrhythmias |
|
|
Hypothalamic/pituitary drugs - GH - clinical use?
|
GH deficiency, Turner syndrome
|
|
|
Hypothalamic/pituitary drugs - Somatostatin (octreotide) - Clinical use?
|
Acromegaly, carcinoid, gastrinoma, glucagonoma
|
|
|
Hypothalamic/pituitary drugs - Oxytocin - Clinical use?
|
stimulates labor, uterine contractions, milk let-down; controls uterine hemorrhage.
|
|
|
Hypothalamic/pituitary drugs - ADH (desmopressin) - Clinical Use?
|
Pituitary (central, not nephrogenic) Diabetes Insipidus
|
|
|
Demeclocycline - Mechanism? Clinical use? Toxicity?
|
Mechanism - ADH antagonist (member of the tetracycline family)
Clinical use - SIADH Toxicity - Nephrogenic DI, photosensitivity, abnormalities of bone and teeth |
|
|
Glucocorticoids - Examples? Mechanism? Clinical Use? Toxicity?
|
Hydrocortisone, prednisone, triamcinolone, dexamethasone, beclomethasone
Mechanism: Decreases the production of leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX-2. Clinical use: Addison's disease, inflammation, immune suppression, asthma Toxicity: Iatrogenic Cushing's syndrome - buffalo hump, moon facies, truncal obesity, muscle wasting, thin skin, easy bruisability, osteoporosis, adrenocortical atrophy, peptic ulcers, diabetes (if chronic). Adrenal insufficiency when drug stopped after chronic use. |
|
|
What does flutamide do?
|
non-steroid antiandrogen - competes with testosterone and DHT in their target cells
Can be used to treat effects of prostate cancer by reducing androgen induced growth of primary tumor and metastases. |
|
|
What blood level can be checked to diagnose menopause?
|
FSH - will be elevated due to lack of negative feedback from estrogen
|
|
|
What type of proteins are synthesized by Rough Endoplasmic Reticulum?
|
Secretory, membrane-bound, and lysosomal proteins
|
|
|
A patient with a testicular mass has elevated T3/T4 and signs/symptoms of hyperthyroidism. Explain.
|
May be a teratoma that is secreting hCG --> the beta subunit is the same as in FSH, LH, and TSH. Has stimulatory effect on thyroid gland at TSH receptor site.
|
|
|
Why should you check a TSH before starting Amiodarone?
|
Amiodarone is 40% iodine by weight, and therefore a common side-effect is thyroid dysfunction --> hypothyroidism.
Patients with pre-existing autoimmune thyroid disease are at increased risk of this side-effect. Amiodarone-induced hypothyroidism is treated with levothyroxine and amiodarone is CONTINUED. |
|
|
How to remember that Amiodarone has a thyroid side effect?
|
amIODarone - it is 40% iodine by weight
|
|
|
What type of insulin is used in patients with DKA?
|
Regular (short-acting) insulin - it is given intravenously
|
|
|
How will serum levels of calcium, phosphate, and PTH be affected by a celiac disease patient?
|
Poor absorption of vitamin D --> hypocalcemia and hypophosphatemia, and increased secretion of PTH.
|
|
|
What is the calcium level in primary hyperparathyroidism? Secondary? Tertiary?
|
Primary - Hypercalcemia
Secondary - Hypocalcemia Tertiary - Hypercalcemia |
|
|
25 yo man with infertility, bilateral gynecomastia, small firm testes, and abnormally long arms. What disease?
|
Klinefelter's syndrome - Seminiferous tubules are progressively destroyed and hyalinized, causing the testes to be small and firm. Serum inhibin levels are decreased as a result of the damage to the seminiferous tubules. Interstitial Leydig cells are damaged leading to low levels of testosterone and erectile dysfunction. Because of the low levels of Testosterone and Inhibin, serum LH and FSH are elevated.
The hypogonadism causes a delay in the fusion of the epiphyseal growth plates, leading to abnormally long arms and legs. Most patients with Klinefelter's syndrome are infertile. |
|
|
A patient has low LH, normal FSH, elevated testosterone, and low sperm count. What do they have?
|
Treatment with androgens or anabolic steroids
|
|
|
If a patient has polydipsia and polyuria, with a low serum sodium concentration, what does she have?
|
Psychogenic polydipsia - If she had diabetes insipidus, her serum sodium should be high (> 142 mEq/L) due to water loss
|
|
|
What is the first line treatment for gastrinomas?
|
Proton pump inhibitors
|
|
|
What is the important negative side-effect of Tamoxifen?
|
Endometrial hyperplasia (remember that both Tamoxifen and Raloxifene increase bone density)
|
|
|
Do patients with SIADH have peripheral edema?
|
No - initially they may have a mild hypervolemia, but the elevated intravascular volume inhibits the RAAS system and so you have a EUVOLEMIC HYPONATREMIA. This is stressed on Qbank.
|
|
|
Propranolol and other beta blockers treat thyrotoxicosis by TWO mechanisms. What are they?
|
There is a thyroid-mediated upregulation of Beta receptors on peripheral tissues which leads to hypersensitivity to catecholamines and the common excitability symptoms seen with hyperthyroidism. Beta blockers obviously prevent this.
By an unknown mechanism, however, Beta blockers ALSO inhibit the conversion of T4 to T3 in peripheral tissues. |
|
|
What will be the effect on Testosterone and DHT with initiation of Leuprolide for prostate cancer?
|
Concordant increase (due to initial increase in GnRH release), followed by concordant decrease to castrate levels (GnRH suppression)
|
|
|
What does inhibin do in men?
|
Inhibits FSH release from anterior pituitary, has NO effect on hypothalamus.
|
|
|
With a pituitary adenoma that secretes ACTH, what cellular effect on the Zona Fasciculate will there be?
|
Hyperplasia (NOT hypertrophy)
|
|
|
What is the common symptom associated with VIPoma?
|
Massive diarrhea
|
|
|
Why is the symptomotology of pheochromocytoma intermittent?
|
Not known.
|
|
|
If a patient is hypoglycemic and has a high CRP, how can you distinguish overdose of a secretogogue (e.g., sulfonylureas) vs. an insulinoma?
|
Check the urine for the presence of the drug
|
|
|
What enzyme is absent in renal failure that causes calcitriol levels to be low?
|
1-alpha-hydroxylase
|
|
|
Delayed puberty + anosmia = ?
|
Kallman's syndrome - hypogonadrotropic hypogonadism
|
|
|
In a patient with hypertension treated medically and hypercalcemia with low PTH, what is going on?
|
Hydrochlorothiazide --> induces increased absorption of Ca2+ in the DCT, and PTH is suppressed
|
|
|
What is one of the most important gene products that is regulated by Pioglitazone through PPAR-gamma activity?
|
Adiponectin
|
|
|
What is the medication of choice for treating gestational diabetes?
|
Insulin
|
|
|
What is the inheritence pattern for the Congenital Adrenal Hyperplasias?
|
All are inherited in an autosomal recessive fashion
|
|
|
Of LDL, HDL, and free fatty acids, which one would lead to insulin resistance if abnormal?
|
Free fatty acids
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|
|
Explain how hyperglycemia can cause cataracts.
|
The lens is not insulin dependent, and has constitutively open GLUT transporters. Therefore, with hyperglycemia, you get an increase in intracellular glucose. This is converted to sorbitol and then to fructose, all of which causes osmotic water influx and osmotic cellular injury. This leads to rupture of these cells and subsequent opacification and cataract formation.
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|
Patient with signs of meningitis has hyponatremia, hyperkalemia, and hypoglycemia. What is it?
|
Waterhouse-Friderichsen Syndrome - N. meningitis --> adrenal hemorrhage and insufficiency
|
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|
Post-viral syndrome with signs of hyperthyroid and a tender thyroid, what should you think?
|
Subacute thyroiditis (de Quervain's) - shows granulomatous inflammation on histology and notably can be hyperthyroid at beginning
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|
If you are considering a thyroid disease and histology shows mononuclear, parenchymal infiltration with well-developed germinal centers, what disease should you consider?
|
Hashimoto's thyroiditis - shows Hurthle cells, lymphocytic infiltrate with germinal centers on histology
|
|
|
What is a major risk for hypoglycemia in a well-controlled type 1 diabetic?
|
Exercise - strengthens response to insulin in target cells, and also increases insulin-independent uptake of glucose
In a normal person, hypoglycemia will inhibit insulin release from beta cells. In type 1 diabetics, this does not occur and the inject insulin remains high. |
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|
What are the main side effects of TZDs like pioglitazone?
|
Weight gain, edema, congestive heart failure 2/2 fluid retention
|
|
|
An untreated prolactinoma will lead to what effect on bones?
|
Suppressses GnRH release, thus lowering estorgen levels --> bone resorption and loss of bone density (osteoporosis)
|
|
|
What is a treatment for mild von Willebrand's disease?
|
DDAVP --> induces vWF release from endothelial cells and can help stop bleeding during minor surgical procedures
|
|
|
What is pituitary apoplexy?
|
Pituitary hemorrhage into a pre-existing pituitary adenoma - this is a medical emergency
Signs of meningeal irritation can be seen, thus mimicking a SAH These patients will die of massive cardiovascular collapse from ACTH insufficiency. Give glucocorticoids and an emergency neurosurgical consult. |
|
|
how can you distinguish pituitary apoplexy from subarachnoid hemorrhage?
|
If they have bitemporal hemianopia, then it is pituitary
|
|
|
What is the histology pattern of medullary thyroid cancer?
|
uniform polygonal or spindle-shaped cells with extracellular amyloid deposits. Amyloid stains with Congo red.
|
|
|
If a thyroid biopsy shows branching structures with calcifications, what is it?
|
Papillary carcinoma - psammoma bodies
|
|
|
45yo man with chronic fatigue and mild weight gain, and elevated creatine kinase - what test to order?
|
TSH - may be hypothyroid myopathy
any patient with hypothyroid can have myopathy -- shows pale muscle fibers with decreased striations and deposition of a mucinous material. Atrophy of the type II muscle fibers may be present too. These patients will show elevated creatine kinase. |
|
|
If you see calcified lesions on a thyroid biopsy, what do you HAVE to think?
|
These are Psammoma bodies - only seen in papillary thyroid cancer
|
|
|
what test is diagnostic of Type 1 Diabetes?
|
Fasting blood glucose - if it is above 126 on 2 separate occasions that is diagnostic
|
|
|
What is the only use of the oral glucose tolerance test?
|
Screening pregnant women for gestational diabetes
|
|
|
If someone has a hypoglycemic episode with type I diabetes, how does glucagon injection act to rapidly improve their blood sugar?
|
increases production of glucose from the liver --> increases glycogenolysis and increases gluconeogenesis
|
|
|
If a thyroid cancer produces calcitonin - what cancer is it, and what mutation has probably occurred?
|
Medullary thyroid cancer - tumors of parafollicular calcitonin-secreting C-cells.
If inherited, germline mutations of the RET proto-oncogene are present in more than 95% of patients. (this mutation is also commonly found in sporadic MTC) |
|
|
What clinical finding is MOST specific for hyperthyroidism?
|
Pretibial myxedema - a late finding of Graves disease (also occasionally seen in hashimoto's thyroiditis)
Exophthalmos, pretibial myxedema, periorbital and conjunctival edema, and eye-movement limitations from hyperthyroidism are only seen in Grave's disease. |
|
|
What is the difference between myxedema and pretibial myxedema?
|
Myxedema refers to the decreased mental status seen in severe hypothyroidism.
Pretibial myxedema is the characteristic skin abnormality seen in Grave's disease. |
|
|
What is the effect of sex steroids on bone growth?
|
Initially they increase linear growth, but they also encourage closure of epiphyseal growth plates.
|
|
|
What should always be monitored in patients on Thiazolidinediones (TZDs)?
|
LFTs - they put you at risk for hepatotoxicity
Note - ejection fraction is not regularly monitored - TZDs are contraindicated in class III or IV heart failure though because they can aggravate it |
|
|
How can you differentiate partial from complete central diabetes insipidus?
|
Response to vasopressin - if urine osmolality increases by >50%, then it is complete
if only increases 10-50%, then it is partial (some endogenous vasopressin present but not enough for normal kidney function) |
|
|
How to treat idiopathic hirsutism?
|
Inhibition of testosterone synthesis or its efffect on skin.
Spironolactone - blocks androgen receptors at the hair follicles, and decreases testosteron ptroduction. Other drugs: flutamide (testosterone receptor antagonist) and finasteride (5-alpha-reductase inhibitor) |
|
|
By what mechanism does anastrazole work to reduce the size of breast cancer primary tumor and metastases?
|
Aromatase inhibitor - prevents conversion of testosterone --> estrogen in peripheral tissues
Others include letrozole and exemestane |
|
|
Somatostatin secreted from pancreatic delta cells inhibits the secretion of what other hormones?
|
Secretin, cholecystikinin, glucagon, insulin, and gastrin
|
|
|
What is better acutely for a patient who passes out in the supermarket due to hypoglycemia - intramuscular glucose or intramuscular glucagon
|
Intramuscular glucagon --> if hypoglycemia becomes severe enough to induce unconsciousness, parenteral teratment is required
IM glucagon induces liver gluconeogenesis and glycogenolysis and returns the patient to consciousness within ten to fifteen minutes In the public, parenteral glucose is impractical bc it would need to be IV and through a slow IV push at 3cc/min of 50% dextrose |
|
|
Type II DM patient on long-acting SQ insulin qd has high postprandial glucose levels. What type of insulin should be added?
|
A rapid-acting such as Insulin Aspart - their onset of action is under 15 minutes and peaks between 45-75 minutes, a pattern that closely mimics the endogenous postprandial insulin response of normal individuals.
|
|
|
Why does regular Insulin take 30 minutes to start acting?
|
Dimer and hexamer formation occurs and takes time to dissociate after injection --> rapid-acting insulins like Insulin Aspart are monomers and do not have this problem.
|
|
|
What is a serious side effect of PTU and methimazole that needs to be monitored
|
Agranulocytosis
Any patient on one of these meds who has signs of an infection needs to have a CBC w/ differential drawn. Patients typically present with fever and a sore throat. |
|
|
Glucocorticoids increase protein synthesis in what organ?
|
Liver --> induce gluconeogenesis, specifically by stimulating the formation of phosphoenolpyruvate carboxykinase and glucose-6 phosphatase.
They also increase glycogen synthetase. Thus, glucocorticoids promote an increase in liver protein synthesis secondary to their upregulating effects on the enzymes involved in gluconeogenesis and glycogenesis. |
|
|
Primary mineralocorticoid excess would have what effect on Serum Sodium, Potassium, and Bicarbonate?
|
Sodium - no change --> "aldosterone escape" occurs where increased sodium and chloride absorption leads to intravascular hypervolemia which in turn promotes the release of atrial natriuretic peptide causing diuresis and eventual compensatory sodium loss.
Potassium - Decrease Bicarbonate - Increase - you get a metabolic alkalosis with elevated aldosterone levels |
|
|
What is metyrapone testing?
|
Tests the HPA axis by inhibiting 11-Beta-hydroxylase, which converts 11-beta-deoxycortisol to cortisol. Thus, with metyrapone administration, serum cortisol levels are reduced, stimulating pituitary secretion of ACTH.
In normal HPA axis, administration of metyrapone will cause a significant increase in 11-deoxycortisol in serum and 17-hydroxy-corticosteroids (urine marker for 11-deoxycortisol) in the urine. |
|
|
How do post-menopausal women present with prolactinomas?
|
Headaches, visual field cuts
|
|
|
What is the most sensitive marker for the development of hypothyroidism?
|
Serum TSH
|
|
|
What is the diagnosis of Hashimoto's thyroiditis based on?
|
Clinical examination, presence of hypothyroidism (elevated TSH and low T4/T3) and elevated antithyroid peroxidase antibody.
A biopsy is typically not required. |
|
|
What is the histologic finding with Hashimoto's thyroiditis?
|
Mononuclear, perenchymal infiltration with well-developed germinal centers and large, oxyphilic cells with granular cytoplasm ("Hurthle cells")
|
|
|
If workers are exposed to a radioactive material waste that contains heavy isotopes, what should be administered to prevent tissue damage?
|
Potassium iodide - all types of chemicals (inorganic iodide, perchlorate/pertechnetate ions, and radioactive iodine) are all taken up by the thyroid gland using the same Sodium Iodide Symporter (NIS), each competitively inhibits the others.
Potassium iodide administration will thus inhibit the uptake of the radioactive chemicals. |
|
|
How would treating a patient with Hashimoto's thyroiditis with exogenous T3 affect TSH, total T3, Reverse T3 and T4 levels?
|
TSH - decrease
T3 - increase Reverse T3 - Decrease T4 - Decrease Exogenous T3 supplementation would reduce circulating levels of TSH, and thus cause decreased secretion of T4 from the thyroid gland (which would also lead to decreased peripheral rT3 conversion). T3 is not typically prescribed to hypothyroid patients because its short half-life and rapid gastrointestinal absorption can lead to wide fluctuations in plasma levels throughout the day. |
|
|
What is the difference between synergism and permissivity?
|
Synergism is when the effect of two drugs together is larger than the sum of their individual effects.
Permissivity occurs when the effect of one drug is increased by the addition of a second drug, that does not produce the same effect on its own. |
|
|
Why can C-reactive peptide be used as a marker for total Beta cell function while insulin can not?
|
Insulin is degraded by first pass hepatic metabolism, while CRP is not.
|
|
|
What type of target does pioglitazone act on?
|
PPAR-gamma, an intracellular nuclear receptor
|
|
|
What test should you order before putting someone on metformin? Why?
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Creatinine -- metformin's most grave side effect is lactic acidosis (contraindicated in renal failure)
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There is a common risk factor among many of the oral diabetes drugs that is characteristically NOT a risk factor of taking metformin. What is it?
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Metformin can not cause hypoglycemia
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Why does metformin sometimes cause lactic acidosis?
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Increases the intestinal production of lactate by anaerobic glycolysis. This lactate is normally absorbed in the liver by gluconeogenesis, but metformin also inhibits this, leading to lactate levels in the blood.
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What effect does estrogen supplementation have on thyroid hormone?
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Elevated total T4 levels, but asymptomatic. This is because estrogen increases levels of Thyroid Binding Globulin in the blood. The free T4 and free T3 remains normal so patients are euthyroid.
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Why should non-selective beta blockers be avoided in diabetic patients?
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Beta 2 receptor blocking prevents gluconeogenesis and peripheral glycogenolysis and lipolysis. For that reason, selective Beta 1 blockers are preferred in diabetics.
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Why would Propranolol diminish the symptoms of hypoglycemia?
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With hypoglycemia there is release of epinephrine, norepinephrine, and glucagon into the blood stream. Adrenergic side effects of hypoglycemia include sweating, tremor, palpitations, hunger, and nervousness.
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Patients with type I diabetes are at risk for developing what adrenal pathology?
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Autoimmune adrenalitis which manifests as primary adrenal insufficiency. Patients will have hyponatremia, hyperkalemia, hypochloremia, and metabolic acidosis. ACTH stimulation fails to promote cortisol release.
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46yo female with rash over lower extremities --> biopsy shows superficial necrolysis. On physical exam, erythematous indurated lesions with crusting and scaling. Patient diagnosed with diabetes 6 months ago and anemia 1 month ago. What disease?
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Glucagonoma --> patients get necrolytic migratory erythema, especially in the groin region
Other clinical features may include: hyperglycemia, stomatitis, cheilosis, and abdominal pain |
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What type of protein deposit occurs in Beta cells in type II diabetes?
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Amylin type amyloid
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What is the most common cause of death in patients with Type II diabetes?
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Myocardial Infarction
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What are the LH, FSH, and estradiol levels in a patient with anorexia nervosa?
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Decreased LH, decreased FSH, decreased Estradiol.
Decreased total body fat leads to a loss of estradiol and the LH surge leading to amenorrhea. FSH levels are abnormal due to low caloric intake leading to leptin abnormalities and the ventromedial nucleus acting up...mechanism not clear but it suppresses GnRH. |
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What potassium levels are seen in DKA intracellularly? Extracellularly?
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Intracellularly - low potassium (acidosis, low insulin levels)
Extracellularly - Normal to high (diuresis does not pull enough out of the body for the extracellular compartment to also be low |
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What type of glucose transporter, and in what cells, is responsive (expression is regulated by) to insulin levels?
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GLUT4 - in skeletal muscle and adipose tissue
ONLY type of transporter that responds to insulin levels |
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What two cell types are the ONLY cell types in which glucose transporter expression is responsive to changes in insulin levels?
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Skeletal muscle and adipose tissue
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What is the mainstay of therapy for congenital adrenal hyperplasia (21 hydroxylase deficiency)?
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Physiologic doses of cortisol --> used to inhibit ACTH secretion (which will then lower the rates of DHEA and androstenedione secretion which is the cause of many of the symptoms).
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What type of leukocyte increases in the blood following stress dose glucocorticoid administration?
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Neutrophils - they also decrease lymphocyte counts
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By conservative measures, what is the lower cut off for weight in gestational diabetes related neonatal macrosomia?
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> 4.0 kg
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What does menotropin and exogenous hCG do to treat infertility?
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Menotropin acts like FSH to induce a dominant follicle, then a single large dose of hCG is injected to simulate the LH surge
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How does ACTH affect aldosterone secretion?
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It doesn't --> need to have angiotensin II in order to convert corticosterone to aldosterone at the end of the pathway which effectively means that ACTH does not induce aldosterone secretion.
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Why specifically are renin levels low in Conn's syndrome?
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High blood pressure inhibits renin release (NOT aldosterone inhibition of renin release)
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