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.