Pseudohypoparathyroidism is a pleiotropic genetic disease of variable expression. Recent observations suggest that the hypocalcemia and bone refractoriness to parathyroid hormone, typical of this disorder, are secondary to impaired production of 1,25-dihydroxycholecalciferol. An incomplete variant of this disease entity, marked by normocalcemia, has been recognized. In this study we investigated whether variable expression of the apparent defect in vitamin D3 metabolism underlies the normocalcemic variant of this disease. An 18 year old woman with normocalcemic pseudohypoparathyroidism was studied. The diagnosis was confirmed by an absent phosphaturic and urinary cyclic adenosine monophosphate (AMP) response to parathyroid hormone (PTH). Despite this diagnosis the normal serum calcium concentration suggested the presence of normal bone responsiveness. Moreover, the presence of a calcemie response to PTH and a normal serum PTH concentration was consistent with normal PTH bone dynamics. Measurement of 1,25-dihydroxycholecalciferol yielded a normal value in contrast to the decreased concentration of this active vitamin D3 metabolite present in patients with "hypocalcemic" pseudohypoparathyroidism. The association of a normal serum calcium level, normal bone responsiveness to PTH and normal vitamin D3 metabolism, in our patient, is consistent with the hypothesis that a decreased serum concentration of 1,25-dihydroxycholecalciferol may be causal of the hypocalcemia in pseudohypoparathyroidism. In addition, these data suggest that variable expression of the apparent defect in vitamin D3 metabolism may underlie the normocalcemic variant of this disorder.
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