Regulation of 1,25 (OH)2D synthesis in hypoparathyroidism and pseudohypoparathyroidism.

We examined the regulation of 1,25-dihydroxyvitamin D [1,25(OH)2D] synthesis in patients with hypoparathyroidism (n = 5) and pseudohypoparathyroidism (n = 5) by administration of parathyroid extract (PTE) and N6,O2-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) and by phosphorus deprivation with antacids. In response to PTE, patients with hypoparathyroidism increased serum 1,25(OH)2D from 17 +/- 5 to 30 +/- 5 (SD) pg/ml (P less than 0.01). An approximate doubling of the 1,25(OH)2D concentration also occurred following dbcAMP infusion or phosphorus deprivation (serum phosphorus 4.4 +/- 0.5 to 2.6 +/- 1.1, P less than 0.01). Serum phosphorus and 1,25(OH)2D concentrations were inversely correlated (r = -0.73, P less than 0.001). Patients with pseudohypoparathyroidism had negligible responses to PTE with respect to urinary adenosine 3', 5'-cyclic monophosphate excretion, serum phosphorus concentration, or 1,25(OH)2D synthesis. They did show a rise in serum 1,25(OH)2D from 17 +/- 4 to 44 +/- 5 pg/ml (P less than 0.001) in response to dbcAMP infusion. During phosphorus deprivation, serum phosphorus decreased from 4.1 +/- 0.8 to 3.2 +/- 1.2 mg/dl (P less than 0.05), but there was no change in serum 1,25(OH)2D concentration or any correlation between serum phosphorus and 1,25(OH)2D levels. Although reduction in mean serum phosphorus levels was generally not as great in patients with pseudohypoparathyroidism, one such patient attained serum phosphorus of 1.2 mg/dl and still did not increase serum 1,25(OH)2D concentration. In addition to an abnormal parathyroid hormone receptor-adenylate cyclase complex, patients with pseudohypoparathyroidism appear to have an abnormal renal 1 alpha-hydroxylase, which does not respond appropriately to phosphate deprivation.