Parathyroid hormone sensitivity in familial X-linked hypophosphatemic rickets

X-Linked hypophosphatemic rickets is associated with low or normal serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations despite low circulating levels of inorganic phosphate. It is generally believed that the enzyme 25-hydroxyvitamin D 1 alpha-hydroxylase does not respond appropriately to either hypophosphatemia or PTH in this condition. We performed 6-h human PTH-(1-34) infusions in five patients with X-linked hypophosphatemic rickets who were receiving vitamin D and phosphate therapy. We measured changes in serum 1,25-(OH)2D, serum calcium, urinary nephrogenous cAMP, and phosphate clearance. Human PTH-(1-34) caused a rise in serum calcium, a rise in nephrogenous cAMP, a fall in renal phosphate reabsorption, and, in particular, a rise in serum 1,25-(OH)2D. All of these responses were indistinguishable from those in normal subjects or patients with surgical or idiopathic hypoparathyroidism. The population studied was not homogeneous, and in one elderly man with mild renal impairment serum 1,25-(OH)2D concentrations did not increase. Nevertheless, these results suggest that absolute PTH resistance is not a feature of X-linked hypophosphatemic ricket, although subtle forms of resistance at the level of the 25-hydroxyvitamin D 1 alpha-hydroxylase enzyme are not excluded by these data.