The administration of an active vitamin D3 analogue reduced the serum concentrations of 1-84 and truncated parathyroid hormone in pseudohypoparathyroidism type Ib patients

Abstract

Serum calcium is one of major regulators of PTH amino-terminal (N-terminal) truncation and secretion of full-length (1-84)PTH from parathyroid glands. However, the effect of active vitamin D(3) on PTH truncations remains controversial. To determine whether active vitamin D(3) accelerates the truncation of PTH, the vitamin D(3) analogue alfacalcidol was administered to patients with pseudohypoparathyroidism type Ib (PHP Ib). Both the (1-84)PTH molecule and N-terminally truncated fragments such as (7-84)PTH can be measured by commercially available two-site total PTH (T-PTH) assays. The development of whole PTH (W-PTH) assays specific for full-length (1-84)PTH has enabled us to distinguish between N-terminally truncated PTH and full-length (1-84)PTH. W-PTH/T-PTH ratios were calculated and used as an index of PTH N-terminal truncations. Both serum W-PTH and T-PTH levels were elevated in untreated PHP Ib patients. The administration of alfacalcidol reduced both the W-PTH and T-PTH levels; however, the W-PTH/T-PTH ratios were stable. Serum calcium levels were significantly and negatively correlated with both the W-PTH and T-PTH levels, but not with the W-PTH/T-PTH ratios. Thus, the administration of an active vitamin D(3) analogue did not seem to have a major effect on the rate of PTH N-terminal truncation, even though it did reduce the secretion of both full-length and truncated PTH. Possibly, active vitamin D(3) attenuates the effect of elevated calcium on PTH N-terminal truncation in PHP Ib patients.