What causes the inappropriate release of parathyroid hormone in familial hypocalciuric hypercalcemia?

Familial hypocalciuric hypercalcemia (FHH) is primarily caused by mutations in the calcium-sensing receptor (CASR) gene. The CASR is a G-protein coupled receptor that plays a key role in regulating calcium homeostasis. In normal physiology, this receptor senses the levels of circulating calcium and helps to maintain balance by regulating the release of parathyroid hormone (PTH) from the parathyroid glands.

When functioning properly, an increase in serum calcium levels activates the CASR, which in turn inhibits PTH secretion. However, in familial hypocalciuric hypercalcemia, mutations in the CASR gene lead to a reduced sensitivity of the receptor to extracellular calcium. As a result, even when calcium levels are elevated, the signaling is impaired, and the parathyroid glands inappropriately continue to release PTH. This causes elevated levels of calcium in the serum, alongside lower levels of calcium in the urine compared to what would be expected in primary hyperparathyroidism.

This mechanism clearly illustrates why mutations in the CASR gene are the underlying cause of the inappropriate release of parathyroid hormone in this condition, making this choice the correct answer. Other choices, such as excessive vitamin D intake