Mitogenic activity on parathyroid cells in plasma from members of a large kindred with multiple endocrine neoplasia...

We tested plasma from 83 members of a large kindred with familial multiple endocrine neoplasia type 1 (FMEN1) for mitogenic activity on cultured bovine parathyroid cells. We evaluated the age dependency of parathyroid mitogenic activity (PMA) in plasma from affected and unaffected members of the kindred, and we analyzed the relation of plasma PMA to indices of activity of parathyroid, pancreatic islet, and anterior pituitary tissue. Plasma PMA was higher in members expressing the FMEN1 gene than in their unaffected first, second, third, or fourth degree relatives (P less than 0.05), and 10 of 20 members expressing the FMEN1 gene had plasma PMA above the 95% limit of the control range. Plasma PMA was not dependent on sex or age; the lack of age dependency and the high values in FMEN1 gene carriers suggested that plasma PMA is elevated in some FMEN1 gene carriers very early in life. Plasma PMA in known gene carriers varied significantly with one index of parathyroid function [plasma PMA was 2.5 times higher in the group with than in the group without prior parathyroidectomy (P less than 0.005), an indicator of more severe prior parathyroid disease] and correlated positively, although not significantly so, with indices of pancreatic islet function (serum gastrin by RIA) and anterior pituitary function (serum PRL by RIA). In summary, (1) plasma PMA levels are high in many known carriers of the FMEN1 gene, (2) the high plasma PMA levels in FMEN1 may precede overt endocrine hyperfunction; and (3) high plasma PMA levels vary with one index of parathyroid function, but do not correlate with indices of pancreatic islet or anterior pituitary function in members expressing the FMEN1 gene. The high plasma PMA levels in FMEN1 may be the direct cause of hyperfunction of the parathyroids, but the relation of high plasma PMA to hyperfunction of the pancreatic islets and anterior pituitary is uncertain.