Endocrine total

pidetiki's version from 2016-03-30 17:13


Question Answer
2 amine hormone groupsthyroid + catechol
catecholamines polarityhydrophilic
catecholamine hormones (3)DA, Epi, NorEpi
thyroid hormones polarityhydrophobic
glycoprotein family (4) - polarityLH, FSH, TSH, hCG - hydrophillic
proopiomelanocortin(POMC)→ACTh→MSH + CLIP
propressophysin→ ADH (+neurophysin)
Prothyrotropin releasing hormone→ TRH
steroid hormones 2 adrenal 3 gonadadrenal: cortisol, aldosterone
gonad: testosterone, estradiol, progesterone
steroid hormones polarityhydrophobic
effector for Giα, Gsαadenylate cyclase (→cAMP)
cAMP effect on PKAcAMP binds the regulator subunit→ the catalytic subunit dissociates→ catalytic subunit catalyzes the phosphorylation of a substrate
phospholipase pathwayhormone binds receptor→Gp binds PLC→ PLC releases DAG(activates PKC) + IP3(releases intracellular Ca2+)
Tyrosine kinase pathwayligand binds receptor→ complex binds to TK causing dimerization→TKs autophosphorylate each other→ intracellular signaling molecules are phosphorylated by TK dimer
catecholamine/peptide hormone releaseexocytosis (hydrophilic) (Cell receives stimulus→stimulate cAMP, Ca2+→cause peptide hormone to line up (due to microfilament/microtubule)→bind to cell membranefuse and release peptides)
thyroid hormone storage / releasestored as hydrophilic peptide prohormone outside of the cell (TG)→ endocytosed→broken down by proteolysis to T3, T4
steroid hormone storage / releasestored in lipid droplet, released by diffusion
water soluble hormone transportcatechol / peptides circulate unbound
H-P-A axishypothalamus→CRH→(AP)ACTH→Adrenal cortex→DHEA, Aldosterone, Cortisol(-sl)
stimulates CRH (4)ADH, ATII, neural inputs, stress
inhibits CRH (2)cortisol, oxytocin
cortisol- neg. feedback of (2)ant. pit. and hypothal.
POMC→ACTH(adrenal steroids), MSH(melanocytes-skin pigment)
consequence of high ACTH↑ release of POMC→ ↑ ACTH, MSH→ ↑skin pigment
stimulate/suppress ACTH↑ = CRH(evaluate w/ adrenal gland hormones), ↓ = glucocorticoids
H-P-Gn axishypothalamus→GnRH→(AP)FSH+LH→(sex organs) inhibin(-s) + testosterone(-sl), estrogen, progesterone
inhibits GnRHsex hormones + prolactin
pulsatile secretion vs. continuous secretion of GnRHpulsatile= LH/FSH release, continuous= no LH/FSH release
have same α subunits (4)LH, FSH, TSH, hCG
stimulate/suppress (AP) LH/FSH↑ = GnRH(puberty?), ↓ = not done
suppress LSH/FSH (tx precocious puberty)long-acting GnRH (continuous)
H-P-T axishypothalamus→TRH→(AP) TSH + prolactin→(thyroid) T3(-s) + T4
stimulate/suppress TSH↑ = just test TSH + free T4
↓ = T3 (tumor)
H-P-GH axishypothalmus→GHRH + somatostatin(-AP+H)→(AP) GH→(liver) IGF-1(-H,AP)
inhibited by somatostatinGH and TSH
GH stimulation / inhibitionhypoglycemia/hyperglycemia, IGF-1, somatostatin
stimulate / suppress GHGHRH, exercise, L-DOPA, Arg, hypoglycemia, stress, IV-insulin(not well tolerated but gold standard) / glucose
H-P-PRLHypothalamus → (AP) DOPA (inhibits PRL)
DA antagonists →↑ PRL
test for ADH insufficiencydon't drink 8 hours, urine concentrated?
dx nonfunctioning adenomalab for hyper/hyposecretion, pituitary MRI, visual field testing (if abuts CNII)
tumor secreting ___ hormone does NOT require surgeryPRL
severe headache + visual disturbances + hypotensionpossible pituitary apoplexy (MRI / CT + steroids)
dx hypercortisolism (cushing's) (3)24 hr urine cortisol, dexamethasone suppression, midnight salivary cortisol→ serum ACTH→ adrenal CT (if<5) / pituitary MRI (if >10)
tx cushing'strans-sphenoidal microsurgery→radiation→bilateral adrenalectomy
acromegaly clinicallarge jaw, hands, feet, tongue, nose, articular overgrowth, sleep apnea, weight gain, HTN, HA
dx acromegalyIGF-1→(if ↑)GH suppression test (OGTT→GH not reduced)→pituitary MRI (after dx)
tx acromegaly1. transphenoidal surgery 2. somatostatin/dopamine agonists/ GH rec. antagonist 3. radiation
hyperprolactinemia sxpremenopausal- hypogonadism/amenorrhea/galactorrhea
postmenopausal-rare sx (mass effect maybe)
tx hyperprolactinemia1. dopamine agonists (cabergoline, bromocriptine)
??ACTH def. primary adrenal insufficiency sx, may have bad hypotension, fatigue
Gn def. sxwomen- amenorrhea, vag. dryness / men- infertile dec libido
Gn def. dx↓ LH, FSH + ↓ estradiol/testosterone
tx Gn defsex steroid replacement (unless it is from ↑ PRL)
enzyme that adds I to TG and couples iodinated tyrosinesthyroid peroxidase
3 causes of hypothyroidism1. iodine def. 2. hashimoto's 3. drugs
thyroid replacement drugslevothyroxine(T4), liothyronin(T3), liotrix (T4, T3)
s.e. thyroxin replacement↑ cardiac activity
sx. of thyrotoxicosis↑ symp. activity, exopthalmos, tremor, tachycardia, insomnia, weight loss, ↑ BMR, ↑ body temp
inhibit thyroid peroxidasethionamides (propylthioruacil, methimazole)
s.e. methimazoleteratogenic
t1/2 methimazole4-6 hours (longer)
s.e. propylthiouracil (+ methimazole)agranulocytosis, hepatitis, allergic response (sulfa)
inhibits NaI symportperchlorate
s.e perchlorateaplastic anemia
inhibit NaI symport + organification (tx. before surgery -slows thyroid) (also prevents uptake of radioactive iodine)high dose iodide
tx thyroid carcinoma, hyperthyroidismI-131
inhibits deiodinase (acts like iodide)amiodarone
decreases TSHdopamine
gold standard for dx of hyperAldo (and other tests for dx)adrenal v. sampling(test blood of both vv. before and after ACTH stim→side with lower aldo = normal AG)
ARR>25→confirm with saline suppression test
PNMT enzymecreates Epi from dopamine
von hippel lindau syndromerenal cell ca, hemangioblastoma, pancreatic ca, pheo
neurofibromatosisskin/CNS neurofibromas, cafe au laid spots, CNS tumors
test for pheo24 hr metanephrines + catecholamines, plasma free metanephrines
tx pheoα-adrenergic blockade(phentolamine, phoxybenzamine, doxazosin, prazosin) → laparoscopic surgery
indications for incidentaloma surgeryca or hormonally active
don't surgically remove adrenal adenoma ifstrong suspicion of CA (most likely is a met)
tx adrenal tumor (unresectable)ketoconazole, mitotane (stops adrenal synth)
adrenal crisis sx.hypOtension, weakness, N/V, dehydration, hyperthermia, hypoglycemia
MEN1hyperPTH, pancreatic islet cell, pituitary tumors
Carney complexskin pigmentation, myxomas, endocrine tumors, schwannoma (tx with bilateral adrenalectomy)
McCune-Albright syndromecafe au lait spots, premature puberty
Li-Fraumenibreast and brain CA, sarcoma, ACC
Beckwith-Wiedemannwilms tumor, hemihypertrophy, ACC
APCcolon polyps, thyroid CA
tx osteoporosis bisphosphonates (alendronate / risendronate)- inhiib osteoclastic resorption of bone, Ca2+/Vit D, estrogen
vit D activation pathwayprovitamin D3→(UVB) vit D3→ (vitD-25-HOase (liver))→ (1αHOase (kidney)) 1,25(OH)2 Vit D
diffuse bone pain / prox. m. weakness, fragility fractureosteomalacia
local bone pain (at fracture), kyphosis, fragility fractureosteoporosis
lab sign of increased bone turnoverALKP
paget's dzaccelerated rate of bone turnover with disorganized "woven" pattern
sx of paget's dzpain, focal deformities(long bones/skull), fx, high output CHF
dx paget's dzbone scan, alkp, ca2+
tx paget's dzbisphosphonates (or calcitonin)
1 gm albumin binds _________ Ca2+.8 mg
PTH works on ___ in kidneyDCT (Ca2+ channels)
loop diuretics + calcium↓ ca. reabsorption (lumen less pos.)
sx. of hypocalcemia↑ neuromuscular excitability (paresthesia, cramps, seizure, mental changes)
tap facial n.→ contraction(chvostek sign), trousseau's sign (BP cuff→ carpal spasm)
sx. of hypercalcemia↓ concentration, ↑ fatigue, confusion, coma, polyuria, N/V, short QT, m. weakness, bone pain
sx. of hyperparathyroidismnephrolithiasis, fatigability, weakness, cog. decline
pseudohypoPTHresistance to PTH by target organ (↑ PTH, ↓ Ca, ↑ Phos) (could be defect in Gsα)→ mental retardation, short stature, obesity, short 4th metacarpal
dif. between PTH and PTH-rp(HHM)PTH-rp does not ↑ renal 1α- hyroxylase activity
Familial hypocalciuric hypercalcemia (FHH)LOF of Calcium sensing receptor (CaSR) on both parathyroid and renal tubule ( ↑ reabsorption of Ca2+ even when there is ↑ ca2+) (distinguish from PHPT by FECa <.01)
granulomatous dz problem(sarcoid)1α hydroxylase is over-expressed (↑ Ca, phos, UCa, 1,25 Vit. D)
tx graves dz / toxic noduleβ blockers, PTU/MMI, surgery, radioactive iodine
3 major sx of gravesexopthalmos, goiter, pretibial myxedema
labs indicating permanent hypothyroidismTSH >15, Ab titer >1:1500
sx subacute thyroiditisacute viral illness(fever, sore throat, myalgia), tender thyroid, pain in neck→ transient thryrotoxicosis(1-2 wks)→ transient hypothyroidism(2 months)
1st step after finding thyroid nodulemeasure TSH
nodules that need to be biopsied / FNAcold nodules (not hot nodules)
tx. suspicious FNAtotal thyroidectomy (60% chance of cancer)
papillary ca spread, etiologynodes, radiation exposure
follicular ca spread, etiologyhematogenous lungs / bones, iodine deficiency
MEN2A, MEN2B ca on RET genemedullary carcinoma (c-cells)
tx papillary/follicular catotal thyroidectomy + radioactive iodine therapy (if larger than 1 cm, multifocal, metastatic) thyroid hormone suppression of TSH
tx MTCprophylactic thyroidectomy
f/u for PTC txTg blood test, neck US, I-131 scan
f/u for FTC txTg blood test, I-131 scan
f/u for MTCcalcitonin, CEA, neck US
3 defects in TH actionligand binding domain mutation, carrier protein problem, failure to form t3 from t4 inside cell
effects of thyroid hormoneCNS development, Growth (promotes closure of growth plates, stimulates GH expression), ↑ BMR (↑ O2 consumption / ATP hydrolysis), ↓ cho(↑ liver uptake)l / trig,
pendrin↑ I uptake into colloid
converts T4-T35' deiodinase (D2) (selenocysteine enzyme)
carbohydrate _________ 5' deiodinase
epi + glucosestimulates glycogenolysis and FA release (during acute stress) provides early warning signs
cortisol + glucosestimulates AA + FA release + gluconeogenesis (maintains homeostasis over time and in periods of acute stress) - antagonizes insulin action at the receptor
meal composition + insulin/glucagon↑ carbs = ↑ insulin, ↑ AA = ↑ glucagon.
balanced meal= ↑ insulin, NL glucagon
insulin + glucose↑ uptake/storage by m. + fat cells
↑ glycogen storage in liver + fat
↑synth of VLDL→↑ storage of fats as triacylglycerols
↑uptake/synth of AA/proteins in liver + m.
glucagon + glucose↑ glycogenolysis + gluconeogenesis in liver
activates adipose hormone sensitive lipase→mobilization of FFA + glycerol
glycogenolysis pathwayglucagon stimulates adenylate cyclase→ ATP→cAMP→activates PKA→phosphorylates (inactivates) glycogen synthase + (activates) phosphorylase kinase→PPK activates phosphorylase b to phosphorylase a→ phosphorylase a degrades glycogen producing gluc-1-P→ converted to gluc-6-P→glucose
cause of diabetic ketoacidosisinsulin turns off hormone sensitive lipase (if ↓ insulin = ↑ breakdown of FA→ ↑ ketones)
difference between LPL and HSLLPL - activated during fed state- ↑ FA uptake by adipose
HSL- activated by glucagon (fasting) - release of FAs + glycerol from adipose
whipple's triadhypoglycemia= 1. signs and sx of hypoglycemia, 2. glucose <45, 3. reversibility of sx with glucose
NICTH (non-islet cell tumor hypoglycemia)tumors secrete IGF-II→acts on insulin receptors + tumor has ↑ uptake of glucose
insulinoma -1010- 10% malignant, 10% multiple, 10% MEN1
gastric surgery - hypoglycemiadumping syndrome, food not staying in stomach long enough causes an exaggerated release of insulin in the small intestine
auotimmune dz assoc. w/ DM1polyglandular syndrome, celiac sprue, pernicious anemia, thyroiditis/graves, adrenal insuff.
DKAdef. in insulin→↑hepatic gluc, ↑ lipolysis→↑ FFA to liver→ketone production / gluconeogenesis, ↑ proteolysis (↑ gluconeogenic precursors), ↓ gluc uptake
Na+ correction for hyperglycemia1 meq/L for ever 62 mg/dL rise in glucose
insulin + k+k+ drops rapidly with insulin due to intracellular k+ entry
tx DKAfluid, insulin drip, k+
amylinco-secreted with insulin- slows gastric emptying, regulation of glucagon, promotes satiety
incretinsGLP-1, GIP - released by entero-intestinal cells after nutrient loading
GLP-1augments insulin secretion (stimulates insulin release from β cells, suppresses glucagon secretion, slows gastric emptying)
prevent progression of diabetic nephropathytx HTN (ACEi / ARB) (A1C<7, protein restriction, sodium restriction)
tx symmetric polyneuropathyglucose control, pain control(TCA,duloxetine, topical creams), foot care
when do you do retinopathy screening for DM?DM1 5 years after diagnosis / DM2- @ diagnosis
when to start ASA therapyhigh risk pts.- macrovascular dz or >50(men) >60 (women) with one other risk factor
diazoxideKATP ch. agonist on β cells (↓ insulin secretion (hyper polarizes cell))
octreotidesomatostatin analog - inhib. insulin secretion (large doses)
lispro/aspart/glulisinebolus insulin
glargine / detemirbasal insulin
start meds if A1C =A1C >6, combo therapy if >7
glucose targetsbefore meals 80-120, before bed 100-140
MOA metformin(biguanide)↓ gluc prod.(hepatic gluconeogenesis) ↑ insulin sensitivity
SE metforminlactic acidosis, GI, avoid if high cr
Sulfonlureas (gl-) stimulate pancreas to secrete insulin
meglitinides (-glinides)stimulates pancreas to secrete insulin (w/ glucose)
SE sulfonylureahypoglycemia, weight gain, no response
SE meglitinidemultiple daily doses
thiazolidinediones(-tazone)insulin sensitizer(@ m. / fat>liver)
SE tazonesvolume expansion/edema, ↓ OCP, caridiac, bladder
α-glucosidease inhibitorsdelay absorption of complex carb
SE αGiGI, limited post-prandial lowering
DPP-4 Antagonists (-gliptin)prolongs action of GLP-1 and GIP(incretins)→ ↑ insulin levels and ↓ glucagon secretion
works on fasting gluc(3)metformin, sulfonylurea, thiazolidinediones
GLP-1 agonist↑ insulin ↓ glucagon secretion, ↓ gastric emptying
acarboseα-glucosidase inhibitor
miglitol α-glucosidase inhibitor
voglibose α-glucosidase inhibitor
-gliptinDPP-4 Antagonists
exenatidesynthetic GLP1
liraglutidesynthetic GLP1
pramlintidesynthetic amylin