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Treatment of Hypercalcemia Secondary to Parathyroid Carcinoma with a Novel Calcimimetic Agent

Developmental Endocrinology Branch, National Institute of Child Health and Human Development (M.T.C.), Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (M.C.S., A.M.S., S.J.M.), National Institutes of Health, Bethesda, Maryland 20892; and the Department of Medicine (S.J.S. J.P.B.) and Pharmacology (J.P.B.), College of Physicians and Surgeons, Columbia University, New York, New York 10032

Address all correspondence and requests for reprints to: Dr. Michael T. Collins, Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive MSC1862, Building 10 Room 10N262, Bethesda, Maryland 20892; E-mail: collinsm{at}cc1.nichd.nih.gov

Abstract

Parathyroid carcinoma is one cause of primary hyperparathyroidism, a condition in which there is hypercalcemia and dysregulated hypersecretion of PTH. In normal, and in some neoplastic parathyroid cells, PTH secretion is mediated by the cell surface calcium-sensing receptor. We describe the first therapeutic use of a novel molecule, a calcimimetic, that has agonist action at the calcium-sensing receptor.

A 78-yr-old man with parathyroid carcinoma was admitted with hypercalcemia, markedly elevated PTH, and a change in mental status. He was treated for 17 days with conventional therapy, which included saline hydration, furosemide, pamidronate, and calcitonin. This was ineffective, and on hospital day 18, calcimimetic at a dose of 50 mg, orally, every 6 h was added. On hospital day 25, the dose was increased to 100 mg, orally, every 6 h, and on hospital day 30, saline and furosemide were discontinued. He was discharged on hospital day 40. With several dose adjustments, he has been treated with monotherapy calcimimetic for over 600 days and has not required any other interventions for his parathyroid carcinoma.

Mean daily precalcimimetic treatment values of serum ionized calcium and PTH were 1.83 mmol/L and 872 pg/mL, respectively. During hospitalization, at the lower dose of calcimimetic, calcium and PTH decreased to 1.67 mmol/L and 538 pg/mL; with the higher dose they further decreased to 1.51 mmol/L and 444 pg/mL. Since discharge, and despite increasing levels of PTH, serum calcium has remained high, but lower than the admission level and acutely responsive to changes in calcimimetic doses.

This compound, a calcimimetic, the first of a new class of compounds with activity at the calcium-sensing receptor, has been used to treat a patient with parathyroid carcinoma. During 2 yr of treatment, no adverse clinical effects have been observed, and it appears to have been effective at controlling hypercalcemia.

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