Hyperparathyroidism and Hypocalcemia Flashcards
PTH secretion from
Chief cells
What percent of total body calcium is stored in the bone?
about 99%
Of the 1% of total body calcium that is not in the bone, what part of the serum calcium is protein bound?
40% (mainly to albumin)
10% complexed with anions
50% free ionized
Low calcium levels elicit the release of PTH from the parathyroid glands, what are the fast responses to this low calcium? Slow?
Fast: Increased bone resorption (calcium mobilization from bone), decreased phosphate reabsorption by inhibiting the Na/Pi cotransport in the PCT, Increased calcium rebsorption from the DCT.
Slow: Upregulates 1 alpha hydroxylase in the kidney which activates vitamin D to 1, 25 vit D3 which leads to increased calcium absorption in the gut.
85% of primary hyperparathyroidism is due to what?
Adenoma, the other 15% is due to hyperplasia
The three causes of PTH dependent hypercalcemia
Hyperparathyroidism
Familial Hypocaciuric Hypercalcemia
Li/HCTZ
WHat is the deal with PTH independent Hypercalcemia?
Bad news usually,
Generally due to metastatic cancer (osteolytic bone metastasis), Vitamin D toxicity, Immobilization, Drugs (thiazide diuretics),
Bones, stones, moans, groans
primary hyperparathyroidism
What is the mutation in familial hypocalciuria hypercalcemia
Autosomal dominant CaSR inactivating mutation.
FHH is generally benign…
truth.
Calcium may be mildly elevated and PTH may be mildly elevated.
Penetrance is 100%. Everybody in the family will have it!!
WHY LOW CALCIUM IN THE URINE? Because the mutated receptor is also present in the kidneys, therefore they think that there is not much calcium in the blood and don’t excrete calcium
Parathyroid adenomas are more common in
WOMEN
Secondary hyperparathyroidism is caused by?
Any condition that is associated with chronic depression in the serum calcium level thus leading to overactivity of the parathyroids.
The parathyroids are working fine.
Most common cause of secondary parathyroidism is
renal failure
Why does renal failure cause low calcium
renal failure means less phosphate excretion leading to high serum phosphate–> phosphate binds calcium with high affinity so you have a lower conc of free ionized calcium
ALSO …less vitamin D being activated since the kidney isn’t working so the gut isn’t absorbing the calcium as well.
Hypercalcemia of malignancy most commonly caused by
Breast or squamous cell lung cancer (can be any cancer)
Granulomatous disorders are also a cause of hypercalcemia with low PTH. Examples of such disorders are:
Sarcoidosis, lymphoma
Mech: the T-cells contain 1 alpha hydroxylase, this jacks up vit D3 which leads to high calcium absorption
What multiplie Endocrine neoplasm syndromes can hyperparathyroidism be associated with>
MEN 2A and MEN 1
What are the clinical symptoms of hyperrarathyroidism
Stones, Groans (abdominal), moans (psychic), bones
What kinds of work-up would you want to do on a pt with potential hyperparathyroidism?
- Look at calcium levels and Albumin levels
- PTH
- 25 OH Vitamin D
- 24 hour urine calcium to differentiate from familial hypocalciuric hypercacemia
How do you manage Primary HPT in a pt with osteoporosis
Bisphosphonates
What is the mechanism of granulomatous disease causing hypercalcemia
Activate alpha 1 hydroxylase in these tissues
Hypocalcemic pt. What do you replace first?
Magnesium actually *unless they just had a thyroidectomy,
Low magnesium is usually contributing to the low PTH
