endo Flashcards
islet of langerhans organization
alpha -> glucagon = peripheral. beta -> insulin = central (insulin inside). delta -> somatostatin = interspersed
zona glomerulosa
control: renin-angiotensin system. product: aldosterone
zona fasciculata
control: ACTH, CRH. products: cortisol, sex hormones
zona reticularis
control: ACTH, CRH. products: sex hormones
adrenal medulla
chromaffin cells. control: preganglionic sympathetic fivers. product: catecholamines (epi, NE). pheochromocytoma: most common adult tumor. neuroblastoma: most common in kids - rarely -> HTN.
CRH
fxn: inc. ACTH, MSH, beta-endorphin. dec. w/exogenous steroid use
DA
fxn: dec. prolactin. DA antagonists can -> galactorrhea due to hyperprolactinemia
GHRH
fxn: inc. GH. analog (tesamorelin) used to Tx HIV-associated lipodystrophy
GnRH
fxn: inc. FSH, LH. regulated by prolactin. tonic GnRH suppresses HPA axis. pulsatile GnRH -> puberty, fertility
somatostatin
fxn: dec. GH, TSH. analogs used to Tx acromegaly
TRH
fxn: inc. TSH, prolactin
17alpha-hydroxylase deficiency
inc. mineralocorticoids, dec. cortisol, sec. sex hormones, inc. BP, dec. K, dec. androstenedione. presentation: XY: pseudo-hermaphroditism. XX: lack secondary sex development
21-hydroxylase deficiency
dec. mineralocorticoids, dec. cortisol, inc. sex hormones, dec. BP, inc. K, inc. renin, inc. 17-hydroxy-progesterone. most common. presents in infancy w/salt wasting or childhood w/precocious puberty. females = virilized.
11beta-hydroxylase deficiency
dec. aldosterone, inc. 11-deoxycorticosterone (inc. BP), dec. cortisol, inc. sex hormones, inc. BP, dec. K, dec. renin. XX: virilization
effect of inc. pH on ionized Ca
inc. affinity for albumin -> inc. % bound -> hypocalcemia
effects of vit D
= cholecalciferol. -> inc. absorption of dietary Ca and PO4 + inc. bone resorption -> inc. available Ca and PO4.
effects of PTH
inc. bone resorption of Ca and PO4. inc. kidney reabsorption of Ca in distal convoluted tubule. dec. reabsorption of PO4 in proximal convoluted tubule. inc. 1,25-(OH)2D3 (calcitriol) production by stimulating kidney 1alpha-hydroxylase in proximal convoluted tubule. stimulates osteoblasts to produce RANK-L to stimulate osteoclasts. PTH: Phosphate Trashing Hormone.
PTH regulators
+: dec. serum Ca, inc. serum PO4, dec. serum Mg. -: very low serum Mg.
vit D regulators
+: PTH, low [Ca], dec. PO4. -: 1,25-(OH)2D3
cAMP hormones
FLAT ChAMP: FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2-receptor), MSH, PTH, calcitonin, GHRH, glucagon
cGMP hormones
vasodilators: ANP, BNP, NO (EDRF)
IP3 hormones
GOAT HAG: GnRH, Oxytocin, ADH (V1-receptor), TRH, Histamine (H1-receptor), Angiotensin II, Gastrin
intracellular receptor hormones
VETTT CAP: Vit D, Estrogen, Testosterone, T3/T4, Cortisol, Aldosterone, Progesterone
intrinsic tyrosine kinase hormones
MAP kinase pathway: think grown factors: insulin, IGF-1, FGF, PDGF, EGF
receptor-associated tyrosine kinase
JAK/STAT pathway: think acidophils and cytokines: PIGGlET: Prolactin, Immunomodulators (e.g. cytokines IL-2, IIL-6, IFN), GH, G-CSF, Erythropoietin, Thrombopoietin
sex hormone binding globulin
inc. solubility of lipophilic steroid hormones. in men, inc. SHBG -> dec. free testosterone -> gynecomastia. in women, dec. SHBG -> inc. free testosterone -> hirsuitism. OCPs, pregnancy -> inc. SHBG, free estrogen remains unchanged.
T3 fxns
4Bs: Brain maturation, Bone grown, Beta-adrenergic effects, Basal metabolism.
wolf-chaikoff effect
excess iodine temporarily inhibits thyroid peroxidase -> dec. iodine organification -> dec. T3/T4 production
peroxidase
enzyme responsible for oxidation and organification of iodide + coupling of monoiodotyrosine (MIT) and di-iodotyrosine (DIT). inhibited by PTU (also inhibits 5’-deiodinase) and methimazole (peroxidase only)
neuroblastoma
originates from neural crest cells. homer-wright rosettes. occurs anywhere along sympathetic chain. typical presentation: firm, irregular mass, can cross midline (unlike wilms). opsoclonus/myoclonus syndrome (dancing eyes, dancing feet). homovanillic acid and VMA are inc. in urine. bombesin and neuron-specific enolase +. HTN uncommon. overexpression of N-myc.
pheochromocytoma rule of 10s
10% malignant, 10% b/l, 10% extra-adrenal (bladder wall), 10% calcify, 10% kids
pheo Tx
irreversible alpha-antagonists (e.g. phenoxybenzamine, to avoid causing HTN crisis) followed by beta-clockers prior to tumor resection.
lipids, myxedema in hypo/hyperthyroid
hypo: myxedema = facial/periorbital -> deep voice. hypercholesterolemia 2/2 dec. LDL receptor expression. hyper: myxedema = pretibial, periorbital. hypocholesterolemia + hyperglycemia
hasimotos
HLA-DR5. inc. risk of NH lymphoma (presents w/enlarging thyroid). Abs = markers, not mediators. histo: hurthle cells (pink cytoplasm), lymphoid aggregate w/germinal centers.
cretinism
6Ps: Pot-bellied, Pale, Puffy-faces, Protruding umbilicus, Protuberant tongue, Poor brain development.
riedel thyroiditis
thyroid replaced by fibrous tissue -> hypothyroid. fibrosis may extend to local structures (e.g. airway), mimicking anaplastic CA (but in a younger person). manifestation of IgG4-related systemic dz (e.g. autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis). findings: fixed, rock-like, painless goiter
graves histo
hyperplasia, scalloping of the colloid
papillary CA
most common, excellent prognosis. “orphan annie eyes” cells (empty-appearing nuclei), psammoma bodies, nuclear grooves. lymphatic invasion = common. inc. risk w/RET and BRAF mutations + childhood irradiation
follicular CA
hematogenous spread. good prognosis. invades capsule (onlike follicular). uniform follicles. FNA isn’t helpful for Dx: need excision.
medullary CA
from parafollicular C cells. produces calcitonin, sheets of cells in amyloid stroma. hematogenous spread common. associated w/MEN 2a/b (RET mutuations), warranting prophylactic thyroidectomy
peudohypoparathyroidism
albright hereditary osteodystrophy: AD. unresponsiveness of kidney to PTH. hypocalcemia, shortened 4th/5th digits, short stature. defect in Gs protein
familial hypocalciuric hypercalcemia
defective Ca-sensing receptor on parathyroid cells. PTH cannot be suppressed by inc. Ca level -> mild hypercalcemia w/normal to inc. PTH levels
osteitis fibrosa cystica
cystic bone spaces filled w/brown fibrous tissue = “brown tumor” consisting of deposited hemosiderin from hemorrhages -> bone pain.
hyperparathyroid Sx
stones, bones, groans, psychiatric overtones: renal stones from hypercalcemia, hypercalciuria, weakness/constipation = groans. depression/seizures.
Tx for nephrogenic DI
HCTZ, indomethacin, amiloride, hydration
causes/Tx for SIADH
causes: ectopic ADH, CNS disorders/head trauma, pulm dz, drugs (cyclophosphamide). Tx: fluid restriction, IV hypertonic saline, conivaptan, tolvaptan, demeclocycline
histo of DM
T1: islet leukocytic infiltrate. T2: islet amyloid polypeptide (IAPP) deposits
glucagonoma
p/w dermatitis (necrolytic migratory erythema), DM, DVT, and depression
carcinoid syndrome
1/3 metastasize, 1/3 p/w 2ndary malignancy, 1/3 = multiple. neuroendocrine tumor = most common small intestine malignancy. no Sx if tumor is only in GI b/c of liver metabolism. Sx: recurrent diarrhea, cutaneous flushing, asthmatic wheezing, R-sided valve dz. inc. 5-HIAA in urine, niacin deficiency (pellagra). Tx: resection, somatostatin analog
somatostatinoma
-> achlorhydria (gastrin inhibition), cholelithiasis + steatorrhea (CCK inhibition)
VIPoma
excessive vasoactive intestinal peptide -> watery diarrhea, hypokalemia, achlorhydria
MEN1
AD. 3 Ps: parathyroid tumors, pituitary tumors (prolactin or GH), pancreatic endocrine tumors (SE syndrome, insulinomas, VIPomas, glucagonomas (rare)). associated w/MEN1 gene mutation (menin, = tumor suppressor)
MEN2A
AD. 2 Ps: parathyroid hyperplasia, pheochromocytoma. inc. risk of medullary thyroid CA. associated w/marfanoid habitus. RET gene mutation (receptor tyrosine kinase)
MEN2B
1P: pheochromocytoma. inc. risk of medullary thyroid CA. oral/intestinal ganglioneuromatosis (mucosal neuromas). associated w/marfanoid habitus. RET mutation.
sulfonylureas
1st gen: chlorpropamine, tolbutamide. 2nd gen: glimepiride, pglipizide, glyburide
sulfonylurea MoA
close K channel in beta-cell membrane -> cell depolarization -> insulin release via inc. Ca influx: stimulates insulin release.
glitazones/thiazolidinediones
inc. insulin sensitivity in peripheral tissue. binds to PPAR-gamma nuclear transcription regulator. side effects: wt. gain, edema, hepatotoxicity, HF, inc. risk of fractures
GLP-1 analogs
= exenatide, liraglutide. inc. insulin, dec. glucagon release. side effects: N/V/pancreatitis
DPP-4 inhibitors
= linagliptin, saxagliptin, sitagliptin. inc. insulin, dec. glucagon release. side effects: mild UTIs/URIs
amylin analogs
= pramlintide. dec. gastric emptying, dec. glucagon. can be used in T1. side effects: hypoglycemia, nausea, diarrhea.
SGLT-2 inhibitors
= canagliflozin. block reabsorption of glucose in PCT. side effects: glucosuria, UTIs, yeast infections
alpha-glucosidase inhibitors
= acarbose, miglitol. inhibit intestinal brush border alpha-glucosidases. delayed carb hydrolysis and glucose absorption -> dec. postprandial hyperglycemia. side effects: GI upset.
PTU/methimizole
block thyroid peroxidase, inhibiting oxidation of iodide and organification (coupling) of iodine -> inhibition of thyroid hormone synthesis. PTU also blocks 5’-deiodinase -> peripheral conversion of T4 -> T3. no methimizole in pregnancy. side effects: skin rash, agranulocytosis, aplastic anemia, hepatotoxicity (PTU). methimizole = possible teratogen
ADH-antagonists
conivaptan, tolvaptan. use: SIADH, block ADH at V2 receptor
octreotide
= somatostatin analog. Tx: acromegaly, carcinoid syndrome, gastrinoma, glucagonoma, esophageal varices.
demeclocycline
MoA: ADH antagonists (in tetracycline family). Tx: SIADH. toxicity: nephrogenic DI, photosensitivity, abnormalities of bone + teeth
glucocorticoids MoA
metabolic, catabolic, anti-inflammatory, immunosuppressive effects. inhibits phospholipase A2 and NF-kappaB.
cinacalcet
MoA: sensitizes Ca-sensing receptor (CaSR) in parathyroid gland to circulating Ca -> dec. PTH. Tx: hypercalcemia due to primary or secondary hyperPTH. toxicity: hypoCa
