Biochemical indicators of disordered vitamin D and calcium homeostasis in sarcoidosis

Abstract

In an attempt to identify factors that may indicate which patients with sarcoidosis are likely to manifest a clinical abnormality in calcium homeostasis, we measured serum concentrations of calcium, angiotensin converting enzyme activity (ACE), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-(OH)2-D), and immunoreactive parathyroid hormone (iPTH) in 19 patients with biopsy proven sarcoidosis, seven of whom were either frankly hypercalcemic or hypercalciuric. These data were compared to the ability of cultured pulmonary alveolar macrophages (PAM) from the same patients to metabolize [3H]25-OH-D3 to [3H]1,25-(OH)2-D in vitro. All seven hypercalcemic/hypercalciuric patients with sarcoidosis had a serum ACE level greater than 40 IU/L (normal less than 35 IU/L). All five patients with hypercalcemia (Ca greater than or equal to 10.5 mg/dl) had a serum 1,25-(OH)2-D concentration above the normal range (greater than 60 pg/ml), and in all 19 patients the serum calcium was positively correlated to the serum 1,25-(OH)2-D concentration (r = 0.55, p less than 0.01). The capacity of PAM to synthesize [3H]1,25-(OH)2-D3 in vitro was. with one exception, greater in cells from patients with diffuse infiltrative pulmonary disease (roentgenographic stage II or III) and positively correlated to the serum calcium concentration (r = 0.72, p less than 0.001) and serum ACE (r = 0.43, p less than 0.05). Cultured PAM from the five hypercalcemic patients, all of whom demonstrated diffuse pulmonary disease on chest x-ray, showed a [3H]1,25-(OH)2-D3 synthetic capacity in vitro 2.5-fold greater than that for group as a whole and 6-fold greater than in cells from nonhypercalcemic patients with sarcoidosis.