Hypercalcemia in granulomatous diseases can be mediated by extrarenal production of 1,25(OH)2D.

Hypercalcemia in granulomatous diseases can be mediated by extrarenal production of 1,25(OH)2D.

• A. True
• B. False
• C. Not sure
• D. Rarely

Answer: (A)

Extrarenal production of 1,25-dihydroxyvitamin D by activated macrophages within granulomas can drive hypercalcemia. In granulomatous diseases, macrophages express the enzyme 1α-hydroxylase outside the kidney, converting 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol) without normal kidney regulation by PTH. This leads to increased intestinal calcium absorption and can raise serum calcium, typically with suppressed PTH. This mechanism is well described in conditions like sarcoidosis and other granulomatous infections, and it’s often helped by steroids that reduce macrophage activity and calcitriol production.

Extrarenal production of 1,25-dihydroxyvitamin D by activated macrophages within granulomas can drive hypercalcemia. In granulomatous diseases, macrophages express the enzyme 1α-hydroxylase outside the kidney, converting 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol) without normal kidney regulation by PTH. This leads to increased intestinal calcium absorption and can raise serum calcium, typically with suppressed PTH. This mechanism is well described in conditions like sarcoidosis and other granulomatous infections, and it’s often helped by steroids that reduce macrophage activity and calcitriol production.