Calcium-regulated parathyroid hormone release in primary hyperparathyroidism. Studies in vitro with dispersed parathyroid cells

Dispersed parathyroid cells were prepared from three 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 one with carcinoma). Immunoreactive parathyroid hormone (PTH) release from cells of normal glands showed a "set-point" (the calcium 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 one patient each with multiple endocrine neoplasia type I (MEN I) and unclassified familial hyperparathyroidism, and from eight of 12 glands from patients with sporadic hyperplasia had "setpoints" of 1.0 to 1.1 mM. By contrast, only two of 17 cell preparations from adenomas had "set-points" of < 1.2 mM. Hormone secretion from cells of eight of 17 adenomas, four 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 to 1.5 mM. PTH release from dispersed cells from the remaining seven adenomas, one sporadic hyperplastic gland and metastatic parathyroid carcinoma in a single patient showed relatively poor suppressibility (12 to 43 per cent) by 3.0 mM calcium. The present results and previous data from this laboratory in 20 additional patients with primary hyperparathyroidism suggest heterogeneous responsiveness to calcium in this disorder. In some cases (most primary hyperplasia and occasional adenomas), calcium-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.