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

J Clin Endocrinol Metab. 1982 Mar;54(3):638-44. doi: 10.1210/jcem-54-3-638.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism*
  • Absorption
  • Adult
  • Calcitriol / blood*
  • Cyclic AMP / urine
  • Female
  • Humans
  • Hypophosphatemia, Familial / complications
  • Hypophosphatemia, Familial / enzymology*
  • Kidney Glomerulus / metabolism
  • Kinetics
  • Male
  • Middle Aged
  • Parathyroid Hormone*
  • Phosphates / metabolism
  • Rickets / etiology*
  • Steroid Hydroxylases / metabolism*
  • X Chromosome


  • Parathyroid Hormone
  • Phosphates
  • Cyclic AMP
  • Steroid Hydroxylases
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol