1,25(OH)2D, due to 1-hydroxylase activity in macrophages, may be produced to excess in granulomatous diseases and lymphoid disorders, leading to hypercalcemia.

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

Answer: (A)

Macrophages in granulomatous diseases can express 1-alpha-hydroxylase and convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (calcitriol) outside the kidney. This extrarenal production is not tightly regulated by parathyroid hormone, so calcitriol levels can rise during chronic inflammation. The elevated calcitriol increases intestinal calcium absorption (and can promote bone resorption), leading to hypercalcemia. Some lymphoid disorders can have similar ectopic 1-alpha-hydroxylase activity, producing calcitriol and causing hypercalcemia as well. So the statement is true because excess extrarenal production of calcitriol by macrophages in these diseases can drive hypercalcemia.