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58 Cards in this Set
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where do parathyroid glands develop from? where are they located? size/weight? |
3rd and 4th pharyngeal pouches (migrate with the thymus) usually there are 2 superior and 2 infererior glands on the posterior surface of the thyroid gland
typically 4-6 mm, weight less than 50 mg |
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histologically, what the parathyroid glands composed of? |
75% are chief cells (secrete PTH) and oxyphil cells (distinctive eosinophilic cytoplasm) and the rest is fat |
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what are causes of hypoparathyroidism? (mechanism, plus 4 causes) |
dec secretion or sensistivity to PTH (pseudohypoparathyroidism)
caused by hypocalcemia, hyperphosphatemia most commonly iatrogenic resulting from surgical removal digeorge syndrome (22q11.2 deletion) |
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causes of primary hyperparathyroidism (3) |
parathyroid adenoma (80-90%) benign tumor, 1 gland-- mostly sporadic but also assoc with MEN1 and MEN2
parathyroid gland hyperplasia(10-15%)-- non clonal, benign proliferation of epithelium, usually involves ALL glands can be assoc with MEN1 and 2
parathryoid carcinoma (1%) |
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MEN 1 what are the classic tumors? what type of mutation? |
tumors of parathyroid glands (also hyperplasia), pituitary glands, and endocrine pancreas 100% will develop parathyroid tumors-- often presents with parathyroidism caused by MEN1 gene mutations-- loss of function of tumor suppressor gene |
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MEN2A what is associated? what type of mutation? |
medullary thryoid carcinoma, pheochromocytoma, parathyroid hyperplasia/adenoma caused by RET gene mutations (proto-oncogene)-- GAIN of function |
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MEN 2B/MEN3 |
medullary thryoid carcinoma, pheochromocytoma, marfanoid body type, mucosal neuromas (you would see it in oral) hyperparathyroidism not present caused by RET gene mutation |
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familial medullary thryoid carcinoma |
medullary thyroid carcinoma without other features of MEN2A or MEN2B caused by RET gene mutations |
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parathyroid carcinoma what is elevated? what is needed for dx |
rare PTH and Calcium levels are high large mass, infiltrative borders, adherence to surrounding structures
to dx: need capsular invasion, vascular invasion, or mets (cytologic atypia alone is not sufficient to dx)
morbidity/mortality due to hypercalcemia instead of tumor itself |
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osteitis fibrosa cystica what is it? features?
why is it important?
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brown tumor of hyperparathyroidism (not true neoplasm) complication seen in pt with hyperparathyroidism bone pain, bone swelling/cysts, pathologic fractures
PTH driven bone changes: increased osteoclast activity, fibrosis, hemorrhage, cyst formation
can mimic true bone neoplasms radiologically |
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pagets disease what is the path? |
not directly caused by parathyroid bonelesions caused by an initial episode of excessive bone resorption followed by disorganized and excessive bone formation - bone is thicker but brittle spine, skull, pelvis are common sites more common with age, etiology unknown |
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what contributes to calcium homeostasis? (3 other things besdies calcium) which hormones? |
calcium (total, ionized, urine) and albumin phosphorus and magnesium creatinine (renal function)
hormones: PTH, vitamin D and metabolites (25 OH vit D and 1, 25 OH2 vit D) PTH-rp and calcitonin |
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how much calcium is protein bound? ionized? what is special about ionized form? complexed? |
protein bound: 40-45%: albumin, globulins ionized: 45-50%, bioactive, (kept in narrow range) complexed: PO4, HCO3, lactate-- 5-10%
all are pH dependent! |
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what happens to ionized Ca in alkalemia? in acidemia?
how much does ionized Ca change with each 0.1 change in pH? what happens to total calcium? |
ionized Ca decreases in alkalemia (protein bound Ca increases with pH)
ionized Ca increases with acidemia (protein bound Ca decreases with pH)
for each 0.1 change in pH, ionized Ca changes by 5% total calcium does not change! |
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how does low albumin impact Ca? |
most common cause of apparent hypocalcemia 1 g of albumin binds 0.8 mg of Ca
albumin is decreased in poor nutrition, liver disease, renal disease, CHF
but ionized Ca is normal! |
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phosphate function? how is it regulated? when is it low? when is it high? |
function: bone structure, cellular ATP generation regulation: dec by PTH (renal excretion), inc by vitamin D (gut absorption) high: in renal failure, hypoparathyroidism, vitamin D toxicity low: hyperparathryoidism, vitamin D deficiency |
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what does PTH do? |
parathyroid gland makes pre-pro PTH, converts it into PTH, goes into blood, goes to: bone: increases bone resporption by activating osteoclasts to release Ca from bone kidney: inc tubular Ca resabsorption (and phosph secretion) indirect action on intestine: inc dietary Ca absorption by activating vitamin D activation
end effect: increase Ca, dec phosphorus (mainly through excretion at kidney) |
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what are the 2 forms of vitamin D? what are the equivalent pro-hormones? active hormones? |
vitamin D3 (cholecalciferol) in skin from sunlight ergocalciferol in yeast
both are converted to 25-OH-D3 in liver (vitamin D status) then are converted to 1,25-OH2-D3 in kidney (active hormone, calcium disorders) |
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compare 25-OH-D and 1, 25-OH2-D |
25-OH-D- storage form, indicator of vit D status dec with: dec exposure to skin, dec vitamin D intake, malabsorption, liver disease inc wtih: excess ingestion
long half live, present in higher concentration
1,25-OH2-D: biologically active form, indicator of 1alphahypdroxylase activity) dec with: dec kidney function inc with: granulomatous disease, type 1 rickets (vit D synthesis defect) and increased hyperparathyroidism
shorter half life, present in lower concentration |
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PTH-rp where does it act? what does it do? when is it increased? |
parathyroid hormone related protein, has smae effect as PTh at bone and kidney but less gut effect bc it doesnt stimulate 1,25-OH-D formation
teeth eruption, mammary gland development, lactation increased in humoral hypercalcemia of malignancy |
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calcitonin where is it secreted? what does it do? where is it used pharmacologically? |
secreted by C cells (parafollicular cells) of thyroid opposite effects as pTH at bone, kidney, gut (decreases calcium!) much less potent than PTH so doesnt play a role in Ca disorders
pharm: osteoporosis, hypercalcemia |
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what is the differential for hypercalcemia? drugs that cause it? |
primary hyperparathyroidism (adenoma, hyperplasia, carcinoma, MEN type 1 and 2) malignancy (3 mechanisms) familial hypocalciuric hypercalcemia mccune albright granulomatous disease
miscell: milk-alkali, hyperthryoid, pheochromocytoma, adrenal insufficiency, VIPoma, immobilization, volume contraction
pharm: chlorothiazide, lithium, vit A or D intox, milk-alkali syndrome |
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what labs do you run to verifty hypercalcemia? |
total calcium +albumin or ionized calcium urine calcium PTH PO4 vitamin D if PO4 elevated |
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how do labs look in primary hyperparathyroidism? |
inc PTH, inc Ca, normal Creatinine, inc urine Ca, low to normal PO4, normal to high 1,25-OH2-D high CL (met alc), inc bone alk phos
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what is tx of primary hyperparathyroidism? |
surgery PTH is monitored during operation (half life is 5 min)-- if 50% dec within 15 min after excision, surgery was success |
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what are three mechanisms of hypercalcemia due to malignancy? |
calcium rises rapidly >13 mg/dL
pTHrp-- humoral hypercalcemia of malignancy head and neck cancer, lung PTH like activity causes inc bone resportion and renal calcium reabsorption
osteolytic metastases-- local cytokine activity (breast cancer, multiple myloma) bone resorption
1,25-OH2-D prodcution or 1 alpha hydroxylase expression lymphomas, inc bone resorption and intestinal Ca absorption |
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how do labs look for primary hyperparathryoidism? malignancy? vit D tox? milk-alkali syndrome? |
primary: high cal, low pO4, high PTH, normal 25(OH)D, high 1,25(OH2)D
malig: high cal, N or low pO4, low PTH, normal 25(OH)D, variable 1,25(OH2)D
vit D tox: high cal, N or low pO4, low PTH, high25(OH)D, variable 1,25(OH2)D
milk-alkali: high cal, low pO4, low PTH, high 25(OH)D, variable 1,25(OH2)D |
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differential for hypocalcemia |
hypoalbuminemia chronic renal failure mg deficiency hypoparathyroidism pseudohypoparathyroidism vit D def or resistance more |
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what labs do you do to test for hypocalcemia? |
total Ca and albumin ionized Ca creatinine, BUN PO4 Mg PTH vitamin D
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what happens to calcium in chronic renal failure? |
hypoproteinemia, hyperphosphatemia, dec synth of 1,25(OH)2D you are unable to retain Ca
because Ca is low, you have secondary hyperparathyroidism, you get hypertrophy of parathyroids from chronic low Ca and high phos
you can get some reversibility with tx (ca supplements, Pa binders, synthetic 1,25-OH-D replacement) but if longstanding, can lead to "tertiary" hyperparathyroidism with autonomous hypertrophied parathyroids causing high Ca |
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how does Mg deficiency cause hypocalcemia? |
10% of admissions, 65% ICU patients GI or renal loss, drugs (diuretics, alcohol) impairs PTH secretion and causes resitance |
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what is the main cause of hypoparathyroidism? |
neck surgery (90%) or idiopathic pseudohypoparathyroidism looks like it but its caused by genetic resistance to PTH and PTH is high |
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lab results for hypocalcemia: hypoalbuminemia CRF hypoPTH vit D deficiency |
hypoalbunemia: low/normal Ca, normal PO4, normal PTH, normal 25(OH)d, normal 1,25(OH)2D
CRF: low Ca, high PO4, high PTH, normal 25(OH)d, low 1,25(OH)2D
hypoPTH: low Ca, high PO4, low PTH, normal 25(OH)d, low 1,25(OH)2D
vit D def: low Ca, low PO4, high PTH, low 25(OH)d, variable 1,25(OH)2D |
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where is 99% of calcium? |
in bones and teeth serum calcium is <0.2% of total calcium ions imortant for neuromuscular excitability, blood coagulation, hormonal secretion |
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what does hypercalcemia do to membrane excitability? hypocalcemia? |
hypercalcemia: inc depolarization threshold, results in hypoexcitability
hypocalcemia: dec depo threshold, results in inc excitability |
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what does the calcium sensing receptor do? |
in the parathyroid-- it senses calciu, inhibits PTH |
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what does calcitonin do? |
inhibits gut absorption of Ca, inhibits ca reabsorption at kidney, inhibits bone resorption |
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how does PTH work on phosphorus in the kidneys proximal tubular cell? |
PTH takes away cotransporter from membrane that is needed to reabsorb phosphorus so more is excreted |
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what are signs of hypercalcemia? |
serendipity: most pts are asymptomatic stones: nephrolithiasis, hypercalciuria bones : bone pain groans: abd pain, N/V, anorexia, constipation, pancreatitis psychiatric overtones: lethargy, depression, anxiety, psychosis, stupor/coma
nerumusclura: hypotonia, dec reflexes CV: hypertension, short QT |
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how does acute crisis of hypercalcemia look? |
hypercalcemia--> anorexia --> polyuria -> dehydration -> imparied mentation -> immboilization--> hypercalcemia |
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what is elevated in hypercalcemia of malignancy? |
PTHrp low PTH normal/lw 25-OH and 1,25OHD |
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what is elevated in granulomatous or lymphoproliferative disorders? |
1,25D low PTH tx with hydration, low Ca diet, steroids |
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what do labs look like in hyperthyroidism? |
low PTH, normal 25PH and 1,25D |
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familial hyperparathyroidism how do you distinguish this from primary hypperPTH? how do you test it? |
inactivating mutations of the CaSR hypocalcuria-- key difference from primary hyperparathyroidism! test Ca of first degree relatives |
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what is most common cause of secondary hyperparathyroidism> |
renal failure decreased excretion of phosphate, build up in blood, binds free calcium parathyroid sees less free calcium, stimulate PTH inc PTH leads to bone resorption
inc PTH, dec serum calcium, inc serum phosphate, inc alkaline phosphatase-- bc PTH is hitting the osteoblasts |
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HPTH-jaw tumor sydnrome? where are mutations? what will you see? |
mutations in HRPT2 tumor suppressor hyperparathyroidism (inc risk for parathyroid carcinoma) jaw fibroma |
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MN1 |
muutations in MEN1 tumor suppressor hyperparathyroidism, pituitary adenoma, pancreatic tumor |
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MEN2A |
mutation in REtr proto-oncogene-- a tyrosine kinase hyperparathyroidism (like MEN1) and medullary thyroid cancer, pheochromocytoma |
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mcune albright |
PTH "excess" due to constituively active G protein (GNAS)-- body sees excess of PTH bc the receptors are always activated-- so you see effects of excess PTH even though its normal
receptor defects extend to other hormones which means there is apparent excess of LH/FSH (precocious puberty) and TSH (hyperthyroidism) you get cafe au lait lesions- jagged-- border that respects midline
fibrous dysplasia, percocious puberty, hyperparathryoidism
inc Ca, inc 1,25D, inc alk phos, NORMAL PTH |
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what are endocrine causes of hypercalcemia? (4) |
hyperthyroidism- direct effect of T3 on bone adrenal insufficiency-- volume contraction, changes PTH set point pheochromocytoma-- volume contraction VIPoma, volume contraction |
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meds/supplements that cause hypercalcemia |
vit D overdose milk-alkali syndrome lithium (reduced renal Ca clearance) thiazide diuretics |
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ssigns and symptoms of hypocalcemia |
agitation, hyperreflexia, convlusions, hypotension, long QT
trosseu signs-- jerking of arm when pressure gets above systolic BP chvostek sign: tap on facial nerve and get muscle spasms |
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what does it mean if PTH is low and Mg is low? Mg is normal? |
Mg is low-- mg deficiciency mg is normal: hypoparathyroidism (post surgical or autoimmune |
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hypoarapthyroidism abs? what is it due to? |
dec Ca, low PTH, high Phos
can be due to thyroidectomy, idiopathic, antibodies activated against CaSR autoimmune |
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pesudohypoparathyroidism (albrights hereditary ostedystrophy |
labs: low Ca, high PTH, high Phos GNAS mutation that is unresponsive to PTH
maternal inheritance: skeletal phenotype: shortened 4th metacarpal hypocalcemia due to PTH resistance obesity, maternal allele only expressed in kidney
paternal inheritance: pseudopseudhypoparathyroidism-- skeletal phenotype without genetic features |
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what does vitamin D do? |
calcium translocation in gut-- enters enterocyte via TRPV6, binds to calbindin, moves through cytosol and calcium pumped into extracelllar space
increases calcium and phosphorus reabsorption in kidney
subtle effects on bone |
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what is vit d deficiency in kids? adults? signs? |
rickets in children osteomalacia in adults enlarged skull, kyphosis, pigeon chest, depressed ribs, protruding abdomen, curved arm bones, widened wrists and enlarged ankles, curved femur, tibia, fibular
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deficiency in 25-hydroxyvitamin D (calcidiol) calcitriol (1,25 dihydroxyvitamin D) |
calcidiol: dec synthesis in liver, drugs (anticonvulsants)
and calcitirol-- renal failure |
