Phosphaturic Effect of I. V. Administered Calcitonin in Man

Abstract

SynopsisPorcine calcitonin (CT) was administered intravenously to 4 patients whose kidney function and plasma Ca and P levels were normal. A significant increase in urinary P excretion with an increase in urinary cyclic AMP (cAMP) excretion was observed. Plasma P and cAMP levels which were determined simultaneously did not show any significant change. Furthermore, plasma PTH levels determined by the radioimmunoassay revealed that the increased PTH levels provoked by the CT infusion was not responsible for an increase in urinary P or cAMP excretion, since no increase in plasma PTH levels was found during the period when an increase in urinary P or cAMP excretion was observed. In addition, the CT infusion caused an increase in urinary excretion of Ca, Na and Mg as well as P.Based on these data, it can be concluded that CT administered intravenously acts directly on the kidney, resulting in an increase in urinary P excretion which could be mediated through cAMP in the kidney.It is well known that calcitonin (CT) administration causes phosphaturia, but there is a controversy about the mechanism. In the rat, CT has been shown to increase the renal excretion of P in both intact and thyroparathyroidectomized animals (Kenny et al., 1965;Milhaud et al., 1966;Robinson et al., 1966). However, in the dog this effect depended on the presence of the parathyroids (Pak et al., 1970). Ardaillou et al. reported that a patient with hypoparathyroidism responded to porcine CT with a significant phosphaturia (Ardaillou et al., 1968). Haas et al. infused porcine, human or salmon CT to 8 parients with untreated surgical hypoparathyroidism and documented that pharmacological doses of CT increased the renal clearance of P, Ca, Na and Mg independently of the parathyroids (Haas et al., 1972).In the present study, porcine CT was infused to 3 patients with advanced breast cancer and a patient with Turner's syndrome whose renal function or plasma Ca and P levels were normal. Plasma Levels of P, Ca, PTH and porcine CT as well as urinary excretion of P, Ca and creatinine were determined to clarify whether the phosphaturic effect of the intravenouly administered CT in man was due to a direct effect on the kidney or to the PTH secreted in response to the CT administration. In addition, urinary levels of Na, Mg and K were measured following the CT infusion to examine the CT effect on these electrolytes excretion from the kidney.Furthermore, urinary excretion of adenosine 3',5'-monophosphate (cAMP) as well as plasma levels of cAMP was determined following the CT administration in order to

Heterogeneity of plasma and urinary immunoreactive calcitonin in patients with medullary carcinoma of the thyroid.

“…The kidney is one of the most important target organs for calcitonin (Kenny and Heinkel, 1965;Ardaillow et al, 1967;Adachi et al, 1974;Heersche et al, 1974), and the biological activity of calcitonin is reportedly to be inactivated in the kidney probably by a specific endopeptidase in its microsome (Ito etal., 1976). Among other forms of hCT, hCT monomer, of the active form of hCT, decreased in concentration most rapidly in the circulation, but it was not recognized in the urine.…”