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 fulllength (1-84)PTH from parathyroid glands. However, the effect of active vitamin D₃ on PTH truncations remains controversial. To determine whether active vitamin D₃ accelerates the truncation of PTH, the vitamin D₃ 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 D₃ 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 D₃ attenuates the effect of elevated calcium on PTH N-terminal truncation in PHP Ib patients.