Effect of phosphate on parathyroid hormone secretion in vivo

Alterations in phosphate homeostasis play an important role in the developm ent of secondary hyperparathyroidism in renal failure. Until recently, it w as accepted that phosphate retention only increased parathyroid hormone (PT H) secretion through indirect mechanisms affecting calcium regulation and c alcitriol synthesis. However, recent in vitro studies have suggested that p hosphate may directly affect PTH secretion. Our goal was to determine wheth er in vivo an intravenous phosphate infusion stimulated PTH secretion in th e absence of changes in serum calcium. Three different doses of phosphate w ere infused intravenously during 120 minutes to increase the serum phosphat e concentration in dogs. Sulfate was also infused intravenously as a separa te experimental control. A simultaneous calcium clamp was performed to main tain a normal ionized calcium concentration throughout all studies. At the lowest dose of infused phosphate (1.2 mmol/kg), serum phosphate values incr eased to similar to 3 mM, but PTH values did not increase. At higher doses of infused phosphate (1.6 mmol/kg and 2.4 mmol/kg), the increase in serum p hosphate to values of similar to 4 mM and 5 mM, respectively, was associate d with increases in PTH, even though the ionized calcium concentration did not change. Increases in PTH were not observed until 30-60 minutes into the study. These increases were not sustained, since by 120 minutes PTH values were not different from baseline or controls despite the maintenance of ma rked hyperphosphatemia. During the sulfate infusion, serum sulfate values i ncreased by similar to 3-fold, but no change in PTH values were observed. I n conclusion, an acute elevation in serum phosphate stimulated PTH secretio n in the intact animal, but the magnitude of hyperphosphatemia exceeded the physiologic range. Future studies are needed to determine whether PTH stim ulation is more sensitive to phosphate loading in states of chronic phospha te retention, Moreover, the mechanisms responsible for the delay in PTH sti mulation and the failure to sustain the increased PTH secretion need furthe r evaluation.