Dissociation between the effects of endogenous parathyroid hormone on adenosine 3',5'-monophosphate generation and phosphate reabsorption in hypocalcemia due to vitamin D depletion: an acquired disorder resembling pseudohypoparathyroidism type II.
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.
Rao
D S
DS
Parfitt
A M
AM
Kleerekoper
M
M
Pumo
B S
BS
Frame
B
B
D000328:Adult; D000368:Aged; D001842:Bone and Bones / Q000473:pathology; D000242:Cyclic AMP / Q000096:biosynthesis*; D003937:Diagnosis, Differential; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006996:Hypocalcemia / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism*; D011547:Pseudohypoparathyroidism / Q000175:diagnosis; D014808:Vitamin D Deficiency / Q000150:complications* / Q000175:diagnosis / Q000378:metabolism
D010281:Parathyroid Hormone; D010710:Phosphates; D000242:Cyclic AMP