Parathyroid Mitogenic Activity in Plasma from Patients with Familial Multiple Endocrine Neoplasia Type 1

Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [³H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P<0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P<0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause. (N Engl J Med 1986; 314:1287–93.), FAMILIAL multiple endocrine neoplasia type 1 is characterized by hyperfunction of parathyroid, pancreatic islet, and anterior pituitary cells.¹ The prevalence of this disorder is not known, but it accounts for a substantial proportion of cases of primary hyperparathyroidism,^{2 3 4} primary hypergastrinemia,⁵ and prolactinoma.⁶ Parathyroid hyperplasia involving all the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1⁷. Among the patients who express the gene for the disorder, 95 percent have primary hyperparathyroidism, whereas less than a third have either gastrinoma or prolactinoma.⁸ The findings that the primary hyperparathyroidism in the disorder rarely occurs before age 15…