Parathyroid Hormone Effects on Serum 1,25-Dihydroxyvitamin D Levels in Patients with X-Linked Hypophosphatemic Rickets: Evidence for Abnormal 25-Hydroxyvitamin D-1-Hydroxylase Activity*

Patients with X-linked hypophosphatemic rickets (XLH) have normal or marginally low serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels despite manifesting hypophosphatemia and phosphate depletion, which increase 1,25-(OH)2D production in many animal species. These data are consistent with the possibility that regulation of vitamin D metabolism is abnormal in XLH. However, controversy concerning the role of phosphate in the regulation of 25-hydroxyvitamin D-1-hydroxylase activity in man has raised doubt about this proposed defect. The presence of a defect in vitamin D metabolism could be established if hormonal or metabolic factors, other than hypophosphatemia, were unable to stimulate 25-hydroxyvitamin D-1-hydroxylase activity normally in patients with XLH. Thus, we compared the effects of parathyroid hormone infusion on serum 1,25-(OH)2D levels in patients with XLH and normals. In response to iv infusion of parathyroid extract (200 U at 0915 and 1700 h), the serum 1,25-(OH)2D concentration increased 218% above base line (from 34.0 +/- 3.0 to 108.8 +/- 2.5 pg/ml) in normals and only 68% (from 30.6 +/- 3.0 to 48.8 +/- 5.5 pg/ml) in patients with XLH. The disparate response occurred in spite of an equivalent increase in urinary cAMP excretion in the normals (from 3.00 +/- 0.14 to 8.70 +/- 0.25 mumol/g creatinine . 24 h) and XLH patients (from 3.10 +/- 0.39 to 8.30 +/- 1.0 mumol/g creatinine . 24 h) as well as equivalent decreases in the renal tubular maximum for the reabsorption of phosphate per liter glomerular filtrate (1.2 +/- 0.1 and 0.9 +/- 0.2 mg/dl, respectively). These observations support the possibility that regulation of vitamin D metabolism is abnormal in XLH.