Skeletal resistance to endogenous parathyroid hormone in pateints with early renal failure. A possible cause for secondary hyperparathyroidism.

Studies were carried out to evaluate whether skeletal resistance to acute increments in endogenous parathyroid hormone exists in patients with mild to moderate renal insufficiency. Hypocalcemia was induced with the infusion of ethyl-enediamine-tetra-acetate (EDTA) in 10 normal subjects and 13 patients with mild renal failure. After the induction of hypocalcemia, the concentration of serum calcium increased gradually and reached preinfusion levels by 22 h in the normal subjects; in contrast, the levels of serum calcium in patients with mild renal insufficiency were significantly lower than the preinfusion values even at the end of 26 h following the EDTA infusion. This delayed recovery occurred despite significantly higher levels of serum immunoreactive parathyroid hormone (IPTH) in the patients than in the normal subjects. The increase in the levels of IPTH reflect elevations in the concentrations of biologically active hormone since urinary cyclic AMP increased significantly. Urinary calcium excretion following the EDTA infusion was not different in both groups and, therefore, could not account for the delayed recovery of serum calcium values in the patients with renal insufficiency. These results indicate that secondary hyperparathyroidism exists early in patients with renal failure and such patients have exaggerated parathyroid hormone secretion in response to acute hypocalcemia. The data are consistent with the concept that skeletal resistance to increments in endogenous parathyroid hormone is present in such patients. This abnormality is, at least partly, responsible for the hypocalcemia and secondary hyperparathyroidism of renal insufficiency.