Renal adenylate cyclase assay for biologically active parathyroid hormone: clinical utility and physiological significance

Abstract

ABSTRACT The stimulation of cyclic AMP production by human renal cortical membranes in the presence of the GTP analogue 5′-guanylimidodiphosphate and a calcium chelator represents a homologous assay system for the evaluation of biologically active parathyroid hormone (bioPTH) in human serum. Bioactive PTH was raised above normal (normal range: undetectable to 4·6 pmol human PTH(1–34) per 1) in 13/17 (76%) patients with primary hyperparathyroidism, in 5/6 (83%) patients with surgically proven hyperparathyroidism secondary to chronic renal failure, in 4/5 (80%) patients with hyperparathyroidism secondary to hypocalcaemia, in all three patients with pseudohypoparathyroidism, in 5/17 (29%) patients with osteoporosis and in 1/9 (11%) patients with renal stones and/or hypercalciuria. Bioactive PTH correlated positively with immunoreactive PTH (iPTH) measured with a radioimmunoassay predominantly recognizing the middleand carboxyl-terminal region of the PTH molecule (r = 0·503, P<0·001). A positive correlation (r = 0·572, P<0·05) was found between values of serum calcium and bioPTH in the group with primary hyperparathyroidism. Immunoreactive PTH did not correlate significantly with calcium in this group. In the other patients except those who had chronic renal failure, a negative correlation between serum calcium and both bioPTH and iPTH was observed (P<0·01). When alkaline phosphatase was compared with bioPTH in all patients, the correlation was positive (r = 0·390, P<0·01); no significant correlation existed between iPTH and alkaline phosphatase in the patients studied. When comparing the metabolic status of the bones with bioPTH, there was a higher incidence of severe bone lesions in those patients with primary hyperparathyroidism who had extremely raised levels of bioPTH. In osteoporosis no simple relationship was apparent. J. Endocr. (1986) 108, 9–15