Increased calcium intake does not suppress circulating 1,25-dihydroxyvitamin D in normocalcemic patients with sarcoidosis

Ca absorption is regulated by 1,25(OH)₂D, and serum values vary inversely with Ca intake. In sarcoidosis, 1,25(OH)₂D is produced by alveolar macrophages in response to γ-interferon, and patients may develop hypercalcemia after prolonged exposure to sunlight and increased dermal production of vitamin D₃. To determine if increased Ca intake suppresses serum 1,25(OH)₂D in normocalcemic patients and to identify those at risk, 17 normal subjects and 11 patients were studied on a metabolic ward for two and one-half days while receiving first 400 and then 1,000 mg/d of Ca. On the low Ca intake, serum angiotensin-converting enzyme (ACE), an index of disease activity, was higher in only three of the patients than in the controls, mean serum 1,25(OH)₂D was higher in the patients, and mean serum total Ca, serum Ca⁺⁺, and urinary Ca were not different in the two groups. On the higher Ca intake, mean urinary Ca increased in both groups, but mean serum 1,25(OH)₂D was suppressed only in the normal subjects. Thus, 1,25(OH)₂D production is abnormally regulated, indicating that (a) normocalcemic patients with sarcoidosis are at risk for developing abnormal Ca metabolism, and (b) a better index of disease activity is provided by the oral Ca suppression test than by serum ACE.