Hyperparathyroidism and Hypocalcemia

Question 1

PTH secretion from

Answer 1

Chief cells

Question 2

What percent of total body calcium is stored in the bone?

Answer 2

about 99%

Question 3

Of the 1% of total body calcium that is not in the bone, what part of the serum calcium is protein bound?

Answer 3

40% (mainly to albumin)
10% complexed with anions
50% free ionized

Question 4

Low calcium levels elicit the release of PTH from the parathyroid glands, what are the fast responses to this low calcium? Slow?

Answer 4

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.

Question 5

85% of primary hyperparathyroidism is due to what?

Answer 5

Adenoma, the other 15% is due to hyperplasia

Question 6

The three causes of PTH dependent hypercalcemia

Answer 6

Hyperparathyroidism
Familial Hypocaciuric Hypercalcemia
Li/HCTZ

Question 7

WHat is the deal with PTH independent Hypercalcemia?

Answer 7

Bad news usually,
Generally due to metastatic cancer (osteolytic bone metastasis), Vitamin D toxicity, Immobilization, Drugs (thiazide diuretics),

Question 8

Bones, stones, moans, groans

Answer 8

primary hyperparathyroidism

Question 9

What is the mutation in familial hypocalciuria hypercalcemia

Answer 9

Autosomal dominant CaSR inactivating mutation.

Question 10

FHH is generally benign…

Answer 10

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

Question 11

Parathyroid adenomas are more common in

Answer 11

WOMEN

Question 12

Secondary hyperparathyroidism is caused by?

Answer 12

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.

Question 13

Most common cause of secondary parathyroidism is

Answer 13

renal failure

Question 14

Why does renal failure cause low calcium

Answer 14

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.

Question 15

Hypercalcemia of malignancy most commonly caused by

Answer 15

Breast or squamous cell lung cancer (can be any cancer)

Question 16

Granulomatous disorders are also a cause of hypercalcemia with low PTH. Examples of such disorders are:

Answer 16

Sarcoidosis, lymphoma

Mech: the T-cells contain 1 alpha hydroxylase, this jacks up vit D3 which leads to high calcium absorption

Question 17

What multiplie Endocrine neoplasm syndromes can hyperparathyroidism be associated with>

Answer 17

MEN 2A and MEN 1

Question 18

What are the clinical symptoms of hyperrarathyroidism

Answer 18

Stones, Groans (abdominal), moans (psychic), bones

Question 19

What kinds of work-up would you want to do on a pt with potential hyperparathyroidism?

Answer 19

• Look at calcium levels and Albumin levels
• PTH
• 25 OH Vitamin D
• 24 hour urine calcium to differentiate from familial hypocalciuric hypercacemia

Question 20

How do you manage Primary HPT in a pt with osteoporosis

Answer 20

Bisphosphonates

Question 21

What is the mechanism of granulomatous disease causing hypercalcemia

Answer 21

Activate alpha 1 hydroxylase in these tissues

Question 22

Hypocalcemic pt. What do you replace first?

Answer 22

Magnesium actually *unless they just had a thyroidectomy,

Low magnesium is usually contributing to the low PTH