In sarcoidosis, what causes increased levels of calcium and phosphate?

In sarcoidosis, increased levels of calcium and phosphate are primarily due to increased activity of the enzyme 1-alpha-hydroxylase. This enzyme is responsible for the conversion of 25-hydroxyvitamin D to its active form, calcitriol (1,25-dihydroxyvitamin D), in the kidneys. In sarcoidosis, granulomas formed by activated macrophages can produce 1-alpha-hydroxylase independently of the normal regulatory mechanisms, leading to excess production of calcitriol. This results in increased intestinal absorption of calcium and phosphate, contributing to hypercalcemia and hyperphosphatemia.

The pathophysiology of sarcoidosis explains why patients can develop such mineral imbalances, as the granulomatous tissue actively participates in vitamin D metabolism, independent of parathyroid hormone (PTH) regulation. This mechanism distinguishes sarcoidosis from other conditions like primary hyperparathyroidism, which is a more direct hormone-driven process, and explains the specific elevations in these minerals without the need for alterations in renal function or excessive dietary intake of vitamin D.