PSEUDOHYPOPARATHYROIDISM AND RELATED DISORDERS

In 1942 Albright and his associates described the features of a new clinical syndrome "pseudohypoparathyroidism" (PHP). Patients with this disorder differ from those with idiopathic hypoparathyroidism: they show characteristic constitutional features (Albright's hereditary osteodystrophy - AHO) and do not respond to exogenous parathyroid hormone. Subsequent to the original report, patients lacking the typical somatic features of AHO but resistant to endogenous and administered PTH have been described. We found previously that in PHP, UcAMP (urinary cyclic AMP) does not increase normally in response to PTH administration. This indicated that there is a defective hormone receptor-adenylate cyclase complex in this disorder. We have now shown that many patients with PHP+AHO show an approximately 50% reduction in Gs (the stimulatory receptor adenylate cyclase coupling protein) in membranes from multiple tissues. Gs deficiency presumably accounts for resistance to multiple hormones in such patients. Most patients with PHP without AHO show normal Gs activity and preliminary studies suggest a PTH receptor defect in such patients.