title: Familial hypocalciuric hypercalcemia in a woman with metastatic breast cancer: a case report of mistaken identity.
abstract: 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.
authors: Dipartimento di Endocrinologia e Metabolismo, Università degli Studi di Pisa, 56124 Pisa, Italy. c.marcocci@endoc.med.unipd.it
authors: Claudio
authors: C
authors: Marcocci
authors: Simona
authors: S
authors: Borsari
authors: Elena
authors: E
authors: Pardi
authors: Giada
authors: G
authors: Dipollina
authors: Tamara
authors: T
authors: Giacomelli
authors: Aldo
authors: A
authors: Pinchera
authors: Filomena
authors: F
authors: Cetani
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000150:complications* / Q000556:secondary*; D002118:Calcium / Q000097:blood; D003951:Diagnostic Errors; D004164:Diphosphonates / Q000627:therapeutic use; D005192:Family Health; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D044169:Receptors, Calcium-Sensing / Q000235:genetics*
chemical_list: D004164:Diphosphonates; D044169:Receptors, Calcium-Sensing; D002118:Calcium