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Familial Hypocalciuric Hypercalcemia in a Woman with Metastatic Breast Cancer: A Case Report of Mistaken Identity

Dipartimento di Endocrinologia e Metabolismo, Università degli Studi di Pisa, 56124 Pisa, Italy

Address all correspondence and requests for reprints to: Claudio Marcocci, M.D., Dipartimento di Endocrinologia e Metabolismo, Università di Pisa, Via Paradisa 2, 56124 Pisa, Italy. E-mail: c.marcocci{at}endoc.med.unipi.it.

We describe a 45-yr-old woman with metastatic breast cancer and hypercalcemia previously diagnosed as hypercalcemia of malignancy and treated with bisphosphonates without changes of serum calcium (s-Ca). At the time of our evaluation, biochemical data [s-Ca, 10.8 mg/dl (2.70 mmol/liter); PTH, 24.4 pg/ml (2.6 pmol/liter); 24-h urinary calcium, 160 mg (4.0 mmol); calcium/creatinine clearance, 0.007] suggested the diagnosis of familial hypocalciuric hypercalcemia. Three of five relatives had mild hypercalcemia [s-Ca, 10.7–11.2 mg/dl (2.67–2.80 mmol/liter)] and detectable serum PTH [24.5–29.0 pg/ml (2.6–3.1 pmol/liter)]. A novel heterozygous I212T missense mutation in exon 4 of the calcium-sensing receptor (CaR) gene was found in the proband and affected relatives but not in unaffected relatives. Expression of the mutant I212T CaR in COS-7 cells resulted in no response of inositol phosphates to any calcium concentration. The calcium dose-response curve of the coexpressed receptors [wild-type/I212T] suggested that the mutant receptor interferes with the function of the wild-type receptor. In conclusion, we describe a case of familial hypocalciuric hypercalcemia due to a novel CaR mutation, in a woman with breast cancer in whom hypercalcemia was initially attributed to hypercalcemia of malignancy.

This work was supported in part by the University of Pisa, the Ministero dell’Università e della Ricerca Scientifica e Tecnologica, and the Ministero della Sanità.

Abbreviations: CaR, Calcium-sensing receptor gene; FHH, familial hypocalciuric hypercalcemia; HCM, hypercalcemia of malignancy; IP, inositol phosphate; s-Ca, serum calcium; WT, wild-type.