Differential calcium response of normal and adenomatous parathyroid glands

In vitro parathyroid hormone secretion of normal (n = 10) and adenomatous (n = 20) human parathyroid glands was compared in response to different calcium (Ca++) concentrations. The glands, prepared for tissue culture immediately after surgical removal, were incubated under identical conditions for 6 h. The medium was changed hourly and analyzed for PTH and cAMP using radioimmunoassay. During the first 2 h of the experiment, the Ca++ concentrations of all preparations was kept constant at 1.2 mM equivalent to the normal Ca++ level of the intercellular space. The PTH level of the 2nd h was defined as reference value corresponding to 100%. After the 2nd h of incubation the Ca++ concentration in the medium was shifted either to low (0.9 or 0.6 mM) or to high (1.9 or 2.6 mM) values. In low Ca++ concentrations (0.6 mM) the normal parathyroid glands responded by stimulation of the PTH release up to 310% in relation to the reference value, whereas the adenomas enhanced the PTH release to 160% only. The incubations in 0.9 mM Ca++ resulted in a slightly lower degree of stimulation. During the incubation in high Ca++ the PTH secretion was reduced to 28% by normal glands and to 52% by adenomatous parathyroid glands. Movements of cAMP measurements paralleled PTH values. The study provides evidence for an abnormally low responsiveness of parathyroid adenomas to Ca++ when compared with normal glands. The reduction in Ca++ responsiveness of adenomatous cells appears to have a fundamental role in primary hyperparathyroidism since the tumour cells may obviously recognize normal Ca++ levels as 'hypocalcaemic' and react by a stimulated PTH secretion.