Pseudohypoparathyroidism Ia and hypercalcitoninemia

Pseudohypoparathyroidism Ia (PHP Ia) is characterized by resistance to PTH and many other stimuli because of deficiency of stimulatory G protein a-sub unit. To determine the incidence, natural history, and mechanism of C cell dysfunction in PHP, calcitonin assays were performed in six patients with P HP Ia and four with pseudopseudohypoparathyroidism from three unrelated fam ilies. Controls included healthy subjects and patients with PHP Ib or hypop arathyroidism. The mean basal level of calcitonin was higher in PHP Ia pati ents than in controls (95.3 +/- 112.7 vs. 3.7 +/- 2.4 pg/mL; P = 0.005; n < 10). In PHP Ia patients, calcitonin levels rose over the normal range (30 pg/mL) after pentagastrin infusion in five patients and remained normal in one. Familial medullary thyroid carcinoma was clinically, biologically, and ultrasonographically ruled out over a mean follow-up exceeding 3 yr. Genom ic screening for RET protooncogene mutations failed to reveal any anomaly. The calcitonin infusion test, which induced a significant increase in plasm a cAMP in controls 30 and 60 min after infusion, failed to produce this res ponse in PHP Ia patients, suggesting that the action of calcitonin was spec ifically impaired. PHP Ia may therefore be an independent etiology of hyper calcitoninemia and hyperresponsiveness to pentagastrin infusion.