Dissociation of secretory responses to low-calcium and β-adrenergic stimulation in primary hyperparathyroidism

Abstract

We have used a parathyroid cell perifusion system to evaluate the secretory responses to low-calcium and β-adrenergic stimuli in series of 13 adenomatous human parathyroid tissues. In cells from all chief cell adenomas PTH secretion could be influenced by changes in extracellular calcium concentrations (either an increase in response to lower calcium concentrations or a decrease following an increase in calcium levels). However, there was marked heterogeneity in the PTH secretory response to adrenergic stimulation. In most instances, adenomatous parathyroid tissue also responded quickly and vigorously to β-adrenergic agents (mean increase in secretion 322% ± 52 (SEM) over baseline), although five of the 13 tissues clearly showed no PTH secretory response. Furthermore, there was a dissociation between the responses to adrenergic and low-calcium stimulation in that the presence or magnitude of the response to one type of stimulus could not be used to predict the nature of the response to the other. Studies of cells from an oxyphil adenoma revealed a very vigorous response to adrenergic stimulation (1,400% over baseline), but no response to changes in extracellular calcium concentrations. These results indicate that human parathyroid tissue is capable of a marked secretory response to adrenergic stimulation. The dissociation between secretory responses to low-calcium conditions and adrenergic agents suggests that the mechanisms of secretion by low-calcium and adrenergic stimuli in adenomatous human parathyroid tissue are to some degree independent. Furthermore, aberrancies in the neoplastic parathyroid process apparently may affect either of these two secretory mechanisms. Finally, the lack of response to changes in calcium concentrations in the presence of a dramatic increase in secretion following adrenergic stimulation may be a reflection of a unique pathophysiology of PTH hypersecretion in oxyphil adenomas.