Parathyroid Glands B&B Flashcards
What are the embryological origins of the parathyroid glands?
formed by the 3rd and 4th pharyngeal pouch
4 endocrine glands located behind the thyroid, secrete PTH
what are the 3 major triggers of PTH secretion from chief cells of the parathyroid glands?
- low calcium - major stimulates, generates fastest response
- high plasma phosphate
- low 1,25-(OH)2 vitamin D
how do magnesium levels affect PTH secretion from chief cells?
Mg2+ generally has same effect as Ca2+ on PTH secretion (recall they are next to each other on period table, therefore similar)
Mg2+ can activate CaSRs (calcium sensitive receptors) to decrease PTH secretion, while low Mg2+ can stimulate PTH release
HOWEVER, very low Mg2+ INHIBITS PTH release because some is needed for normal CaSR function (surprise!) - this is important because hypocalcemia is often seen in the context of severe hypomagnesium
PTH increases activation of 25-OH vitamin D to 1,25-OH2 vitamin D in the proximal tubule by activating which enzyme?
1-alpha-hydroxylase
if you forget what it’s called, just realize that 25-OH changes to 1,25-OH2…
what are the classical symptoms of primary hyperparathyroidism?
presents with symptoms of hypercalcemia: stones, bones, groans (GI discomfort, recurrent peptic ulcers), psychiatric overtones
now patients diagnosed much earlier, but recurrent kidney stones is a common presentation
other signs/symptoms more often see with malignancy
what is the classic bone disease which occurs with hyperparathyroidism?
osteitis fibrosa cystica: subperiosteal bone resorption causes irregular/indented edges to bones, “brown tumors” (osteoclastoma) made of giant osteoclasts
causes bone pain and fractures
what is osteitis fibrosa cystica and how does it present?
classic bone disease of hyperparathyroidism, subperiosteal (STEP buzz word!!) bone resorption causes irregular/indented edges to bones (commonly in fingers), “brown tumors” (osteoclastoma) made of giant osteoclasts
causes bone pain and fractures
what are the 2 major risks associated with parathyroidectomy to treat primary hyperparathyroidism?
- recurrent laryngeal nerve damage - may cause hoarseness
- post-op hypocalcemia - because remaining glands were suppressed by overactive adenoma, may cause numbness in fingertips/toes or twitching/cramping of muscles (if severe)
secondary hyperparathyroidism classically occurs in which patients? what does it typically cause?
occurs in renal failure patients - chronically low serum Ca2+ causes an increase in PTH (can become tertiary hyperparathyroidism if parathyroid begins to secrete PTH autonomously)
results in renal osteodystrophy - bone pain, fractures, can progress to osteitis fibrosa cystica
labs will show high PTH, low Ca2+
Familial Hypocalciuric Hypercalcemia (FHH)
rare AD mutation in CaSR (calcium sensing receptors, GPCR) in parathyroid and kidneys
—> higher than normal set point for calcium, so normal PTH despite high calcium
—> excess renal reabsorption of calcium, with low urinary calcium (hence the name)
must distinguish from primary hyperparathyroidism because it is usually mild and doesn’t require treatment
what do Trousseau’s sign and Chvostek’s sign indicate?
tetany (spasms) caused by hypocalcemia
Trousseau’s (more specific): hand spasm with BP cuff inflation
Chvostek’s: facial contractions with tapping on nerve
hypocalcemia can also cause neuromuscular irritability manifested as tingling
how can hemochromatosis and Wilson’s disease cause hypoparathyroidism?
hemochromatosis (iron deposition) and Wilson’s disease (copper deposition) can cause damage to the parathyroid glands —> decreased PTH secretion
Metastatic cancer can also do this
autoimmune polyendocrine syndrome, type 1 (APS-I)
rare autosomal recessive disorder, caused by mutations of autoimmune regulator (AIRE) gene (regulates protein antigen presentation in thymus)
Triad of:
1. Mucocutaneous candidiasis
2. Autoimmune hypoparathyroidism (—> low calcium)
3. Addison’s disease (autoimmune destruction of adrenal glands —> low cortisol)
Triad of:
1. Mucocutaneous candidiasis
2. Autoimmune hypoparathyroidism.
3. Addison’s disease (autoimmune destruction of adrenal glands)
= ?
autoimmune polyendocrine syndrome, type 1 (APS-I): rare autosomal recessive disorder, caused by mutations of autoimmune regulator (AIRE) gene
what is the cause of DiGeorge Syndrome, and what is the classic triad?
immunodeficiency, failure of 3rd/4th pharyngeal pouch to form, leading to:
- loss of thymus —> loss of T cells, recurrent infections
- loss of parathyroid gland —> hypocalcemia, tetany
- congenital heart defects
