Cica‐clamp technique: a method for quantifying parathyroid hormone secretion: a sequential citrate and calcium clamp study

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Abstract
Objectives of the present study were to establish and investigate a standardized method for quantifying of intact parathyroid hormone secretion during sequential induction of hypo‐ and hypercalcaemia, and to explore the applicability to these data of a mathematical model derived from in vitro studies as presented in the literature.Twenty‐two healthy volunteers aged 20–80 years participated in one or more experiments. The experiments comprised three different protocols of sequential induction of a regular hypocalcaemic (citrate) clamp followed by increases in blood ionized calcium, ending in a regular hypercalcaemic (calcium) clamp.During protocol I, the induction of hypocalcaemia, blood ionized calcium 0.21 mmol 1‐‐1 (SD0.01, n= 76) below baseline, the release of serum parathyroid hormone rapidly increased to a concentration of four to seven times above baseline. The serum parathyroid hormone declined gradually to a steady state of about two to three times above baseline. During stepwise increases in blood ionized calcium, the serum para thyroid hormone rapidly declined to new steady state concentrations. When a hypercalcaemia of 0.20 mmol I‐1 (SD 0.02, n= 76) above baseline was reached, serum parathyroid hormone was suppressed to about one‐fourth of baseline concentration. Protocol II, the Cica‐clamp, and protocol III, are short versions of protocol I using a slow and gradual increase in blood ionized calcium from hypo‐ to hypercalcaemia. Proto col II reached a hypocalcaemia of blood ionized calcium 0.22 mmol l‐1 (SD 0.03, n= 57) below baseline and a hypercalcaemia of 0.19 mmol l‐1 (SD 0.04, n= 57) above baseline, whereas protocol III reached a hypocalcaemia of 0.38 mmol l‐1 (SD 0.06, n= 57) below baseline and a hypercalcaemia of 0.34 mmol l‐1 (SD 0.04, n= 57) above baseline blood ionized cal cium. During protocol II and III we obtained identical results of serum parathyroid hormone compared to protocol I (P>0.70), indicating that serum para thyroid hormone could neither be suppressed nor stimulated beyond what was observed applying the more tolerated protocol II (the standard procedure).Blood ionized calcium and serum parathyroid hormone demonstrate an inverse sigmoidal relationship with a blood ionized calcium concentration to the parathyroid hormone‐midpoint of 1.13 mmol l‐1 (SD 0.04, n=19), distinctly different from mean baseline blood ionized calcium, 1.25 mmol I ‐1 (SD 0.04, n = 38). Our data suggest an asymmetrical control of blood ionized calcium by serum Parathyroid hormone with a true calcium set‐point corresponding to about 85% inhibition of maximal parathyroid hormone secretion.In conclusion, the present data shows that it is possible to establish a standardized test for sequential induction of hypo‐ and hypercalcaemia suitably for quantifying of serum parathyroid hormone secretion in vivo. The Cica‐clamp test is short, easy to handle, reproducible and without discomfort to normocalcemic subjects. Its clinical usefulness remain to be determined.

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