Parathyroid hormone release in vitro in hyperparathyroidism associated with multiple endocrine neoplasia type 1

Abstract

Hyperparathyroidism (HPT) in the syndrome of multiple endocrine neoplasia type 1 (MEN-1) exhibits a different picture regarding itsp r o p e n s i t y for recurrence compared with sporadic primary HPT. In order to shed further light on the MEN-1 syndrome an investigation in vitro was made of parathyroid hormone (PTH) release of dispersed parathyroid cell from 11 patients with parathyroid hyperplasia associated with MEN-1, 10 patients with single parathyroid adenomas, and 10 preparations of normal bovine parathyroid glands. The two patient groups had the same average serum calcium value prior to surgery. Immunoreactive concentrations of PTH were measured after 2-h incubations at extracellular calcium concentrations of 0.5\p=n-\3.0 mmol/l. Compared with the normal bovine parathyroid cells, the cells of the MEN-1 patients had a reduced calcium sensitivity of the PTH release and secreted smaller amounts of hormone at both low and high extracellular calcium concentrations. A similar abnormality of the PTH release was found for the cells of the hyperplastic and adenomatous parathyroid glands. Although individual parathyroid glands were investigated in only three MEN-1 patients, the results suggested the secretory regulation to be less defective in the small glands of each patient. It is concluded that in patient groups matched for serum calcium, the parathyroid tissue of MEN-1 patients has an abnormality of the PTH release similar to that of parathyroid adenomas.

Findings and long‐term results of parathyroid surgery in multiple endocrine neoplasia type 1

“…Previous in vitro investigations have supported that a larger size of the parathyroid glands in MEN-1 patients with HPT maY be accompanied by greater derangements in the PTH release and that this also applies to parathyroid cells within the hyperplastic nodules of HPT in renal insufficiency [24,25]. Analysis of the present material, however, revealed no significant differences between the patients demonstrating normocalcemia or recurrent HPT at follow-up with respect to pre-operative serum calcium, glandular weight, or the proportional incidence of nodular parathyroid gland enlargement.…”

Cellular physiology and pathophysiology of the parathyroid glands

“…The regulation of PTH release by extracellular calcium is disturbed in all pathological parathyroid tissue whether associated with hypercalcemia of adenomatous or hyperplastic primary HPT of the sporadic type, familiar HPT due to multiple endocrine neoplasia (MEN) syndromes, Secondary HPT, or parathyroid carcinoma [27,32,64,73]. The derangement is characterized by a relative calcium insensitivity of PTH secretion with right shifts in the dependency on extracellular calcium (Fig.…”

“…There is evidence that the functional cellular abnormality may be more pronounced in larger as compared to smaller glands as well as in nodular compared to diffusely enlarged portions of hyperplastic parathyroid tissue [73,74]. Thus, when uremic patients with hypercalcemia have undergone parathyroid surgery, asymmetrical nodular hyperplasia has been a common finding with deranged hormone regulation in mainly one or a few dominating nodules [74].…”