In 6 of 8 adults with severe
hypocalcemia and
osteomalacia due to
vitamin D depletion, basal excretion of nephrogenous cAMP (NcAMP) was increased, but the mean renal
phosphate threshold (
TmP/GFR) was normal, indicating that the steady state phosphaturic response to cAMP generated by endogenous PTH was impaired, as in
pseudohypoparathyroidism type II. In all 6 patients, correction of
hypocalcemia by administration of
vitamin D and
calcium restored the normal relationship between NcAMP and
TmP/GFR. By contrast, in 13 patients with normocalcemic
osteomalacia due to
vitamin D depletion,
TmP/GFR was reduced, with a significant negative regression on NcAMP, and rose to normal
after treatment. Bone histomorphometry after double
tetracycline labeling did not differ significantly between the 2 groups. In 72 patients with
primary hyperparathyroidism, the slope of the negative regression of
TmP/GFR on NcAMP was the same as in normocalcemic
secondary hyperparathyroidism, but the adjusted mean for
TmP/GFR was significantly lower. We conclude that the effect of endogenous PTH on
phosphate reabsorption varies with the level of plasma
calcium, and that dissociation between this effect and the generation of cAMP is nonspecific and can be a consequence of
hypocalcemia. Exclusion of
vitamin D depletion should be an additional diagnostic criterion for
pseudohypoparathyroidism type II.