Endocrine Abstracts (2016) 41 EP142 | DOI: 10.1530/endoabs.41.EP142

Atypical cases of familial hypocalciuric hypercalcemia: utility of genetic testing in the diagnosis

Fernando García1, Guillermo Martínez de Pinillos1, Mariana Tomé2, Ignacio Fernández1, Ignacio Fernández1, Eyvee Arturo Cuéllar1, José Álvaro Romero1, Juan Manuel García de Quirós1 & María Victoria Cózar1

1Hospital Universitario de Valme, Sevilla, Spain; 2Hospital Punta de Europa, Gibraltar, Spain.

Introduction: Familial hypocalciuric hypercalcemia (FHH) has been classically characterized as an asymptomatic disease with mild hypercalcemia, hypocalciuria and inappropriately normal or high serum PTH concentration. The aim of our study is to assess the utility of genetic testing in patients with suspected FHH with atypical clinical manifestations, and the validity of classical biochemical parameters for the diagnosis.

Description of methods: A retrospective study of seven patients with HHF confirmed by genetic testing was conducted. The following variables were measured: calcemia, phosphatemia, renal function, serum PTH, 25-hydroxyvitamin D, 24-h calciuria, urinary calcium/creatinine clearance ratio (UCCR) and type of mutation.

Results: Mean age 51.4±16.2 years. Average serum calcium 11.1 mg/dl ±0.4. Two patients had values above 11.5 mg/dl. Average PTH 51.8 pg/ml ±27.3. Mean urinary calcium was 166 mg 24 h±113.6. Five patients presented 24-hour calciuria >100 mg/24 h. The UCCR was <0.01 in five patients, between 0.01 and 0.02 in one patient and >0.02 in one patient although intermittently. In those patients with calciuria >100 mg/24 h, the UCCR was less than 0.01 in three cases, between 0.01 and 0.02 in one case and one patient alternated UCCR values between 0.01 and 0.02 and above 0.02. Previously to the diagnosis, two patients underwent not curative parathyroidectomy. Three different types of mutation of CaSR gene were observed in genetic testing, one of which has not been previously described in literature (C.2101 C>G).

Conclusion: The isolated use of classical clinical parameters for the diagnosis of HFF can determine errors in the diagnosis of those patients with atypical presentations. We believe that UCCR is preferable to the absolute value of 24-h calciuria, as some patients show no frank hypocalciuria. In these patients, genetic studies can help to avoid unnecessary surgical interventions as well as excessive costs.