What is familial hypocalciuric hypercalcemia (FHH) and its key urinary finding?

• A. CaSR gain-of-function leading to hypercalcemia with hypercalciuria.
• B. Excess calcitriol production causing hypercalciuria.
• C. CaSR loss-of-function condition causing mild hypercalcemia with hypocalciuria.
• D. PTH-secreting tumor causing hypercalciuria.

Answer: (C)

FHH stems from inactivating mutations in the calcium-sensing receptor (CaSR) on parathyroid and kidney cells, which raises the set point for calcium regulation. Because the receptor is less responsive, the parathyroid glands don’t reduce PTH as much as they should at a given calcium level, and the kidneys reabsorb more calcium. The net effect is mild, often lifelong hypercalcemia with unusually low urinary calcium excretion. In practice, you’d see a low fractional excretion of calcium in the urine despite elevated serum calcium, a pattern that helps distinguish FHH from other causes of hypercalcemia that typically produce higher urinary calcium.