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Parathyroid Expression of Calcium-Sensing Receptor Protein and in Vivo Parathyroid Hormone-Ca²⁺ Set-Point in Patients with Primary Hyperparathyroidism¹

Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Medicina del Lavoro (F.C., A.P., P.C., E.V., S.B., A.P., C.M.), Dipartimento di Oncologia (P.V., A.G.N.) e Dipartimento Chirurgia (P.M.), Università di Pisa, 56125 Pisa, Italy; and Endocrine-Hypertension Division, Department of Medicine, Brigham and Women’s Hospital (O.K., E.M.B.), Boston, Massachusetts, 00000

Address all correspondence and requests for reprints to: Claudio Marcocci, M.D., Dipartimento di Endocrinologia e Metabolismo, Ortopedia e Medicina del Lavoro, Università di Pisa, Via Paradisa 2, 56125 Pisa, Italy. E-mail: c.marcocci{at}endoc.med.unipi.it

A reduced expression of calcium-sensing receptor (CaR) messenger ribonucleic acid and protein accompanied by abnormalities in parathyroid cell proliferation and PTH secretion are present in primary hyperparathyroidism. We studied the expression of CaR protein by immunohistochemistry in 36 sporadic parathyroid adenomas and investigated the relationship between CaR expression and several preoperative clinical parameters, including the set-point of Ca²⁺-regulated PTH secretion (measured in vivo). The adenomas were classified in 4 categories according to the intensity of immunohistochemical staining: 5 (14%) showed a CaR staining intensity similar to that of normal parathyroid (+++), 10 (27%) showed moderate staining (++), 16 (45%) showed weak staining (+), and 5 (14%) were negative (-). The intensity of CaR staining was not related to preoperative serum Ca²⁺, PTH levels or adenoma volume. Twenty-nine patients underwent preoperatively the calcium infusion test to evaluate the PTH-Ca²⁺ set-point. Individual values of PTH-Ca²⁺ set-point ranged from 1.38–1.93 mmol/L and were significantly correlated with basal Ca²⁺ levels (r = 0.96; P = 0.0001) and adenoma volume (r = 0.5; P = 0.01). The mean PTH-Ca²⁺ set-point values were significantly different in the 4 groups of patients classified according to immunohistochemical staining intensity of their adenoma (P = 0.025; F = 3.78); the mean PTH-Ca²⁺ set-point was significantly higher in the groups classified as negative than in those classified as weak or moderate. No correlation was observed between the PTH-Ca²⁺ set-point and basal PTH levels or between the percent maximal PTH inhibition and adenoma volume and basal PTH or Ca²⁺ levels. In summary, our data suggest that there is a relationship between apparent CaR protein expression and PTH-Ca²⁺ set-point abnormality, suggesting that a reduced receptor content might have an important role in the pathogenesis of primary hyperparathyroidism.

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