Endocrine Abstracts

Introduction: Familial hypocalciuric hypercalcaemia (FHH) is a rare genetically heterogeneous disorder, with 3 variants described. An inactivating mutation in the calcium sensor receptor (CASR) gene causes the subtype 1, which represents 65% of the cases.

It is charaterised by hypercalcaemia and hypocalciuria with normal or elevated PTH. FHH is generally assymptomatic and treatment is not needed. Differential diagnosis with primary hyperparathyroidism (PHPT) is crucial and based on calcium-creatinine clearance ratio (CCCR), which, when under 0.02 points to the diagnosis of FHH. Genetic test is necessary for confirmation.

Case report: An assymptomatic 16-year-old girl was referred to Endocrinology Department due to hypercalcaemia. Family history of several malignancies was present. Her mother died at 39 years old from hepatocellular carcinoma, her maternal-aunt at 13 from sarcoma and her maternal cousin at 18 from ovarian carcinoma. Laboratory work-up: Ca 11.5 mg/dl (8.8–10.4); P 3.1 mg/dl (2.5–4.5); Ca(u) 92 μg/24 h (20–90); PTH 32 pg/ml (10–70); creatinine 0.7 mg/dl; and CCCR 0.007. DNA sequence analysis of CASR gene identified a frameshift mutation in exon 7, (c.1945delG), in heterozigoty, not previously described. Her father and half-brother had normal Ca and PTH levels. Some months later, patient maternal grandmother was observed for multinodular goitre and laboratory work-up revealed Ca 11.9 mg/dl, P 3.1 mg/dl, PTH 93 pg/ml, 25OHD3 21.8 ng/ml (30–100), and Ca(u) 86 mg/24 h. Genetic study confirmed the same mutation.

Conclusions: FHH is a benign condition that must be considered in the differential diagnosis of hypercalcaemia with normal or elevated PTH. CCCR is used to distinguish it from PHPT, however the definitive diagnosis demands genetic study, in order to avoid needless parathyroidectomy. In this family, a novel mutation in CASR gene was identified.