Deficient Erythrocyte Membrane Gs Alpha Activity and Resistance to Trophic Hormones of Multiple Endocrine Organs in Two Cases of Pseudohypoparathyroidism

Patients with pseudohypoparathyroidism (PHPT) have been shown to have deficient cell membrane stimulatory GTP-binding regulatory protein activity (Gs activity) and other defects, which cause renal resistance to parathyroid hormone (PTH). Those patients also have a higher incidence of deficiency of other endocrine axes. To investigate the mechanisms of this syndrome on 2 patients, we measured erythrocytic ghost Gs activity by ADP-ribosylation method, which showed low and low normal levels for the 2 patients who were from the same family, suggesting type Ia of this syndrome. While basal T3, T4 and TSH were compatible with mild primary hypothyroidism in both patients, a TRH test showed exaggerated TSH responses. The estrogen, progesterone and testosterone levels were low and LH and FSH responses were marginally high, indicating gonadal resistance to gonadotropins. ACTH levels were also elevated and ACTH response to CRH was exaggerated in one patient, suggesting additional primary adrenal insufficiency. This finding indicates that systemic endocrine tests are essential for the management of PHPT patients who may have a deficiency of multiple endocrine axes subclinically.