Synthetic human parathyroid hormone-(1-34) for the study of pseudohypoparathyroidism

Abstract

The synthetic amino-terminal fragment of PTH, PTH-(1-34), was recently released for clinical testing of PTH responsiveness. We measured the urinary cAMP and phosphaturic responses to infusion of PTH-(1-34) [3U/kg BW (200 U maximum), iv in 10 min] in patients with pseudohypoparathyroidism and idiopathic hypoparathyroidism, as well as normal subjects. The protocol used data from 5 30-min urine collections and 4 blood samples. Based on the results in 7 patients with pseudohypoparathyroidism (hypocalcemia with increased serum immunoreactive PTH concentrations), 2 patients with suspected pseudohypoparathyroidism, 9 patients with surgical hypoparathyroidism, and 10 normal subjects, this testing protocol differentiated well among these conditions. The patients with pseudohypoparathyroidism had blunted cAMP and phosphaturic responses to PTH-(1-34) administration compared to those of either normal or hypoparathyroid subjects. Induced hypercalcemia failed to restore a normal cAMP response to PTH-(1-34) infusion in 2 patients with pseudohypoparathyroidism. Calculation of the cAMP response to PTH-(1-34) as nanomoles per dL glomerular filtrate during the first 30 min after infusion provided better differentiation among groups than other parameters of cAMP metabolism. Calculating the phosphaturic response as the percent fall in tubular maximum for phosphate reabsorption during the first hour after infusion gave the best degree of statistical separation among groups. We conclude that this new diagnostic agent is effective for the study of renal responsiveness to PTH, and that the protocol described here reliably differentiates patients with pseudohypoparathyroidism from those with hypocalcemia due to other causes.