Calcium-regulated parathyroid hormone release in primary hyperparathyroidism: studies in vitro with dispersed parathyroid cells
Brown, E.M.; Gardner, D.G.; Brennan, M.F.; Marx, S.J.; Spiegel, A.M.; Attie, M.F.; Downs, R.W.; Doppman, J.L.; Aurbach, C.D.
American Journal of Medicine 66(6): 923-931
1979
ISSN/ISBN: 0002-9343 PMID: 453225 Document Number: 149544
Dispersed parathyroid cells were prepared from 3 normal human parathyroid glands as well as from pathologic parathyroid tissue of 30 patients with primary hyperparathyroidism (17 with adenoma, 12 with primary hyperplasia and 1 with carcinoma). Immunoreactive parathyroid hormone (PTH) release from cells of normal glands showed a set point (the Ca concentration half-maximally inhibiting PTH release) of 1.0 mM, similar to that of normal bovine and canine parathyroid cells. Cells from parathyroid tissue of 1 patient each with multiple endocrine neoplasia type I(MEN I) and unclassified familial hyperparathyroidism and from 8 of 12 glands from patients with sporadic hyperplasia had set-points of 1.0-1.1 mM. By contrast, only 2 of 17 cell preparations from adenomas had set-points of < 1.2 mM. Hormone secretion from cells of 8 of 17 adenomas, 4 of 12 sporadic hyperplastic glands and a gland from a single patient with multiple endocrine neoplasia type II (MEN II) had set-points of 1.2-1.5 mM. PTH release from dispersed cells from the remaining 7 adenomas, 1 sporadic hyperplastic gland and metastic parathyroid carcinoma in a single patient showed relatively poor suppressibility (12-43%) by 3.0 mM Ca. The present results and previous data from this laboratory in 20 additional patients with primary hyperparathyroidism suggest heterogeneous responsiveness to Ca in this disorder. In some cases (most primary hyperplasia and occasional adenomas), Ca-regulated PTH release is relatively normal. In others (most adenomas and some sporadic primary hyperplasia), maximal suppressibility of secretion is normal but with an elevated set-point. In the remaining adenomas, in rare primary hyperplasia and in the single carcinoma in this series, relative autonomy was observed. The relationship of these various secretory patterns to the pathophysiology of primary hyperparathyroidism is discussed.