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step 1 - endocrine
Terms in this set (80)
hormones produced in diff layers of adrenal cortex
zona glomeruloa: aldosterone (salt)
zona fascicularis: cortisol (sugar)
zona reticularis: androgens (sex)
how does insulin secretion occur?
glu -> ATP generation -> close K+ ch and depolarize pancreatic B cell membrane -> open voltage-gated Ca ch -> Ca influx -> exocytosis of insulin granules
insulin independent: RBC, brain
B islet cells, liver, kidney, small intestine
insulin dependent: adipose, skeletal m.
how does insulin inc sk m uptake of glu?
insulin -> insulin rec on sk m membrane -> tyrosine phosphorylation -> PI3 kinase -> exocytosis of GLUT4 containing vesicles -> inc GLUT4 expression, glu transport
what are the sx/lab findings of 17-alpha hydroxyls def?
can't make cortisol or androgens, so inc mineralocorticoids, dec cortisol, sex hormones.
in XY -> pseudohermaphroditism with ambiguous genitalia
XX -> nl internal organs, no secondary sex characteristics.
what are the sx/labs in 21 hydroxyls def?
block step in aldosterone and cortisol prod -> inc sex hormone, dec aldo and cortisol.
HYPOtension, masculinization (pseudohermaphroditism in females)
sx/labs in 11 beta-hydroxylase def?
can't make aldo or cortisol, but inc 11-deoxycorticosterone (mineralocorticoid) --> HTN, masculinization (inc androgens)
what enz does ACTH inc the activity of?
desmolase (cholesterol -> prognenolone)
what enz does angiotensin II inc the activity of?
aldosterone synthase (corticosterone -> aldosterone)
what are the effects of cortisol?
B: maintain BP -> inc alpha1 rec on arterioles
B: dec Bone formation
I: anti-Inflammatory/Immunosuppressive: inhib leukocyte adhesion, inhib leukotriene, prostaglandins, block histamine release, dec eos, block IL2 prod.
I: Insulin resistance
G: inc gluconeogenesis, lipolysis, proteolysis
what does calcitonin do? where is it produced?
made in parafollicular cells (C cells) of thyroid. dec bone resorption of Ca.
what does propylthiouracil inhibit? methimazole?
propyl - inhib peroxidase (oxidize and organify iodide) and 5'-deiodinase (T4 -> T3)
methimazole inhib only peroxidase.
what is wolff-chaikoff effect?
excess iodine inhib thyroid peroxidase -> dec iodine organification -> dec T3/T4 production.
what are some exogenous and endogenous causes of cushing syndrome? how do you distinguish?
exogenous: steroid use most common. dec ACTH
1) Cushing's disease - pituitary adenoma -> inc ACTH
2) ectopic ACTH e.g. from small cell lung ca -> inc ACTH
3) adrenal adenoma, carcinoma, nodular adr hyperplasia -> dec ACTH
what are sx of cushing syndrome?
truncal obesity, wt gain, moon facies, buffalo hump, hyperglycemia, skin changes (thinning, striae - inhib collagen synth), osteoporosis, amenorrhea, immune suppression, m weakness (breakdown m), HTN (upregulate alpha1 rec in vessels).
what is the effect of low and high dose dexamethasone on cortisol in pituitary adenoma?
remains elevated w/ low dose, but suppressed with high dose.
what is addisons dz?
chronic primary adrenal insufficiency due to autoimmune/TB/other cause of adrenal atrophy. dec aldosterone, cortisol --> hypotension, hyperK, acidosis, inc ACTH and resultant inc MSH -> skin hyperpigmentation
what is secondary adrenal insufficiency?
dec pituitary ACTH production.
ACUTE primary adrenal insuff due to adr hemorrhage caused by N meningitides sepsis
how do you dx pheo?
inc urine vanillylmandelic acid (breakdown product of NE and epi), plasma catecholamines
rule of 10's for pheo
10% extraadrenal (e.g. wall of bladder)
sx of cretinism (fetal hypothyroidism)
what causes graves' dz?
what are the types of thyroid cancer?
1) papillary - most common, best prognosis. ionizing radiation inc risk. orphan annie eyes (nuclei), nuc groove, psammoma bodies (calcifications).
2) follicular ca - uniform follicles surr by dense capsule. good prognosis.
3) medullary ca - from parafollicular cells -> make calcitonin -> hypocalcemia. malignant cells in amyloid stroma. assoc with MEN 2A, 2B
4) undifferentiated/anaplastic - worst prognosis.
5) lymphoma - assoc with hashimoto's thyroiditis
sx of primary hyperparathyroid
inc PTH -> inc bone resorption -> hypercalcemia, inc alk phos
hypercalciuria -> renal stones (Ca oxalate)
metastatic calcification (e.g. nephrocalcinosis)
acute pancreatitis (Ca activates enz)
osteitis fibrosis cystica
pathogenesis of secondary hyperparathyroid
chronic renal dz -> dec active vitD -> dec Ca abs in gut -> hypocalcemia, hyperphosphatemia -> inc PTH -> inc bone resorption, inc alk phos
high phosphate also dec free Ca by binding it.
what is tertiary hyperparathyroid?
CKD --> refractory hyperparathyroid (inc PTH even when Ca nl)
what is pseudohypoparathyroidism?
also called Albright's hereditary osteodystrophy. AD kidney unresponsiveness to PTH (mut in Gs prot) -> hypocalcemia. short stature, short 4th & 5th digits.
inc PTH, dec Ca.
how do you dx acromegaly?
inc serum IGF-1, failure to suppress serum GH after oral flu tolerance test
what is zollinger ellison synd?
gastrin-secreting tumor of pancreas or duodenum -> acid hyper secretion. assoc with MEN 1
MEN1 (Wermer's synd)
Pituitary tumor (prolactin or GH)
Pancreas endocrine tumor- zollinger-ellison, insulinoma, VIPoma, glucagonoma
- often present with kidney stones (inc PTH-> Ca) and stomach ulcers (zollinger ellison)
medullary thyroid (calcitonin)
2 MEN in Black deal with martians (marfanoid) gang (ganglioneuroma) with chrome (pheo) medals around their neck (medullary thyroid)
what gene mut is assoc with MEN 2A and B?
how do sulfonylureas work?
(e.g. glipizide, glyburide) close K ch on B cell men -> depolarize -> inc Ca -> insulin release
what are some se of sulfonylureas?
1st gen (tolbutamide, chlorpropamide): disulfiram-like run.
2nd gen: hypoglycemia
what are se of metformin?
GI upset. lactic acidosis -> contraindicated in renal dailure
how do thiazolidinediones work?
bind PPAR-gamma nuc transcription regulator -> inc insuln sensitivity in peripheral tissue.
how do alpha glucosidase inhib work?
e.g. acarbose, miglitol. inhib intestinal brush border alpha-glucosidases -> delayed sugar abs -> dec postprandial hyperglycemia.
how does exenatide / liraglutide work?
GLP-1 analogs - GLP1 is an anti hyperglycemic hormone prod by intestine. inc insulin and dec glucagon secretion from pancreas.
how do linagliptin, sitagliptin work?
DPP4 inhibitors - inhib breakdown of GLP1 -> inc insulin and dec glucagon release from pancreas.
weight gain, edema, hepatotoxicity, HF.
how does demeclocycline work?
inhibit collecting tubule response to ADH. tx SIADH.
dx of GH adenoma
inc GH, IGF-1 (from liver)
non-suppression of GH with oral glucose
tx of GH adenoma
octreotide (somatostain analog) - block ant pit response to GHRH -> no GH.
GH rec antagonist
tx of prolactinoma
bromocriptine - dopamine agonist. dopamine suppresses prolactin.
causes of hypopituitarism
1) pituitary adenoma
3) sheehan synd - pituitary infarction due to intrapartum hemorrhage (pit enlarges during pregnancy but vasc supply same, so susceptible to damage). loss of pubic hair.
4) empty sella - congenital: herniation of arachnoid CSF -> compress pituitary
central diabetes insipidus
dec ADH -> polyuria, poludipsia, hypernatremia, high serum osmolality, low urine osm.
tx of central DI
drug that can cause nephrogenic DI
1) ectopic prod - eg small cell lung ca
2) CNS trauma
3) pulm inf
4) drugs - cyclophosphamide
demeclocycline - block effect of ADH
free water restriction
thyroglossal duct cyst sx
anterior neck mass
how does TSH inc basal metabolic rate?
inc Na/K ATPase
why does exophthalmos and pretibial myxedema occur?
anti-TSH rec Ab --> excess glucosamonoglycans
labs in graves dz
inc total and free T4
block thyroid peroxidase -> oxidation, organification, and coupling necessary for thryoid hormone synth.
HLA assoc in hashimoto thyroiditis
path of hashimoto thyroiditis
germinal centers --> can get marginal cell (B cell) lymphoma
subacute (dequervain) granulomatous thyroiditis
transient hyperthyroidism after viral inf.
sx - tender thyroid.
reidel fibrosing thyroiditis
chronic inflammation with extensive fibrosis of thyroid
sx - "hard as wood" thyroid, nontender. can extend to local structure. present in young female.
follicular adenoma vs. carcinoma
both have follicular cells surr by dense capsule - but carcinoma invades beyond the capsule.
FNA can't distinguish betw the 2.
how does follicular carcinoma metastasize?
what should you do if you find a pt has +ret oncogene?
prophylactic thyroidectomy. ret assoc with MEN 2A, 2B.
labs in primary hyperparathyroid
inc urinary cAMP b/c PTH binds Gs-coupled prot -> AC -> cAMP -> inc in urine b/c of inc cAMP in tubular cells
inc serum alk phos (alkaline environment necessary to lay down bone - sign of osteoblastic activity)
where do pancreatic beta cells sit?
in the center of the islet.
HLA assoc with T1DM
HLA DR3, DR4
inc gluconeogenesis, glycogenolysis, fatty acid breakdown
path findings in T2DM
amyloid in islets
pathogenesis of small vessel injury in T2DM
hyaline arteriosclerosis (pink m in vessel wall) -> can create sclerosis in glomeruli, chronic renal failure.
osmotic damage in T2DM
high glucose -> (aldose reductase) -> sorbitol -> osmotic damage.
cause schwann cell damage -> neuropathy
retinal blood vessel perixytes -> aneurysm -> hemorrhage -> blindness
lens -> cataracts
endocrine tumor of pancreas. episodic hypoglycemia with MS changes. dec glu, inc insulin, inc c-peptide (indicates you're making insulin)
excess production of gastrin by parietal cells. zollinger ellison.
achlorhydria (inhib gastrin)
cholelithiasis and steatorrhea due to dec GB contraction
excess vasoactive intestinal peptide. watery diarrhea, hypokalemia, achlorhydria (VIP inhibits gastric acid secretion).
mechanism of immunosuppression in cushing synd
inhib phospholipase A2 -> can't make TXA
inhib histamine release
most common mut in congenital adrenal hyperplasia and sx
21 hydroxylase def -> inc sex steroids (precocious puberty in males and clitoral enlargement in females)
no cortisol - life threatening hypotension.
inc ACTH -> adrenal hyperplasia
no aldosterone - salt wasting with hyponatremia, hyperkalemia, hypovolemia
syndromes assoc with pheo
MEN2A (medullary thyroid, parathyroid) and 2B (medullary thyroid, ganglioneuroma)
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