Induced hypocalcaemia controlled by a citrate clamp technique, and the intact parathyroid hormone response obtained

Abstract

In order to investigate (1) the possibility of controlled induction and maintenance of hypocalcaemia, and (2) the intact parathyroid hormone (PTH(1-84)) response obtained thereby, 14 healthy individuals were administered an i.v. infusion of trisodiumcitrate. The reproducibility of the method established was assessed in five of the 14 individuals. Aiming at a steady-state level of blood ionized calcium (B-Ca2+) = 1.00 mmol/l, obtained within 30 min and subsequently maintained for 90 min, the infusion was guided by frequent determinations B-Ca2+. The method established was as follows: infusion of 0.85 mmol citrate/kg body weight/h during the first 10 min, followed by 0.44 mmol citrate/kg body wt h 1.26 exp. ((actual B-Ca2(+)--target B-Ca2+)/0.02) mmol/l, until B-Ca2+ = 1.00 mmol/l. In the steady-state period the infusion rate was 0.29 mmol citrate/kg body wt. h 1.26 exp. ((actual B-Ca2(+)--target B-Ca2+)/0.02) mmol/l. The method showed reproducibility by an overall difference in B-Ca2+ measurements of -0.03 mmol/l, which did not statistically differ from zero (p less than 0.05). No severe side effects were observed during a total of 21 infusions. Intact serum parathyroid hormone concentrations (S-PTH(1-84)) obtained during induced hypocalcaemia rose to a peak within 5-10 min, and then declined to a steady-state level about three times the initial. The serum (S) PTH(1-84) response could be caused by a burst of S-PTH(1-84) from a depot source while the steady-state level may indicate a stimulated secretion from parathyroid glands. The S-PTH(1-84) response was shown to be reproducible by an overall difference in S-PTH(1-84) measurements of -0.52 pmol/l, which did not statistically differ from zero (p less than 0.10).