Degradation of human calcitonin in human plasmas.

The degradation in vitro of human calcitonin (HCT) in plasma from normal subjects and patients with disorders of calcium metabolism was studied. As measured by radioimmunoassay, the hormone was stable at 37°C in phosphate buffer for 24 hr but progressively disappeared when incubated in normal human plasma. The loss was temperature and pH dependent, being maximal at 37°C between pH 6.0 and 7.0. Under these conditions ¹²⁵I-HCT appeared to be degraded to at least one labeled fragment that behaved on polyacrylamide gels as if it were smaller than 1000 daltons. The rate of formation of this fragment correlated well with the rate of loss of immunoreactive HCT. Compared to plasma from normal individuals, plasma from patients with hypercalcemia due to causes other than hyperparathyroidism degraded HCT significantly more rapidly. The mean loss of HCT in 5 hr in plasma from nine such patients was 54% ± 17% (± 2 SEM), compared to 22% ± 5% in plasma from 22 healthy volunteers (p < 0.001). Those patients whose plasma most rapidly degraded HCT had milkalkali syndrome, metastatic carcinoma of the colon, metastatic oat cell carcinoma of the lung, and metastatic breast carcinoma. Rates of HCT degradation in plasma from eight hypercalcemic patients with hyperparathyroidism and seventeen normocalcemic patients with malignancy were within the normal range. From these findings we conclude that human plasma contains one or more enzymes that degrade HCT and that the hormone is degraded more rapidly in plasma from some patients with hypercalcemia.