Abnormal Regulation of Parathyroid Hormone Release by Calcium in Secondary Hyperparathyroidism due to Chronic Renal Failure*
EDWARD M. BROWN,
RICHARD E. WILSON,
RICHARD C. EASTMAN,
JOHANNA PALLOTTA and
SAMUEL P. MARYNICK
Departments of Medicine Boston, Massachusetts 02115
Surgery, Brigham and Women’s Hospital and Harvard Medical School Boston, Massachusetts 02115
Division of Endocrinology, Maine Medical Center Portland, Maine 75246
The Division of Endocrinology, Beth Israel’Hospital Boston,Massachusetts 02115
Division of Endocrinology, Baylor University Hospital Dallas,Texas 04102
Address requests for reprints to: Dr. Edward M. Brown, Endocrine-Hypertension Unit, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
Dispersed parathyroid cells were employed to study calcium-regulatedparathyroid hormone (PTH) release in severe secondary hyperparathyroidismdue to chronic renal insufficiency. Cell preparations were obtainedfrom 16 parathyroid glands of 6 patients undergoing subtotalparathyroidectomy for parathyroid bone disease and/or hypercalcemia.The effects of increasing ambient calcium concentration on immunoreactivePTH release in vitro were assessed and compared with resultsobserved in cells prepared from 7 adenomas and 6 normal parathyroidglands. There was no difference in maximal PTH release for the3 types of tissue (mean ± SEM, 8.48 ± 1.9, 8.1± 3, and 10.1 ± 0.78 ng/105 cells-h respectively).In 14 of 16 hyperplastic glands, 6 of 7 adenomas, and all ofthe normal glands, PTH release was inhibited more than 50% by2–3 mM calcium (suppressible glands). Of the normal glands,half of the maximal inhibition of PTH release (the set-point)occurred at less than 1.03 mM calcium in 5 of 6 cases. In 12of 14 suppressible hyperplastic glands and all of the 6 suppressibleadenomas, on the other hand, the set-point was 1.03 mM or higher(P < 0.01 and P< 0.002, respectively). Thus, in severesecondary parathyroid hyperplasia due to chronic renal insufficiency,there is frequently an increase in the set-point for calciumwithout a change in the maximal secretory rate per cell. Abnormalcalcium-regulated PTH release at the cellular level, therefore,is not limited to parathyroid neoplasia (i.e. adenoma or primaryhy-perplasia), but may occur in secondary hyperplasia as well.
* Presented in part at the meeting of the American Federationfor Clinical Research, Washington, D.C., May 10–12, 1980[Clin Res28: 388A, 1980 (Abstract)]. This work was supportedin part by USPHS Grant R01-AM-25910–02.
Recipient of Research Career Development Award 1K04-AM-00627-02.
Received June 15, 1981.
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RICHARD E. WILSON,
RICHARD C. EASTMAN,
JOHANNA PALLOTTA and
SAMUEL P. MARYNICK
Recipient of Research Career Development Award 1K04-AM-00627-02. 
