Familial hypocalciuric hypercalcemia: the challenge of diagnosis

Familial hypocalciuric hypercalcemia (FHH) is an autosomal dominant genetic disorder classically characterized by lifelong mild-to-moderate asymptomatic hypercalcemia with inappropriately normal to elevated serum parathyroid hormone (PTH) concentrations and hypocalciuria, best expressed by a urine calcium-to-creatinine clearance ratio (CCCR)CASR inactivating mutation[5]. More rarely FHH is due to AP2S1 or GNA11 inactivating mutation, both genes encoding for proteins involved downstream of CASR activation[6]. These molecular alterations are found in all parathyroid cells, explaining disease persistence following partial parathyroidectomy and the ineffective surgical management of these patients. FHH phenotypes could however overlap with primary hyperparathyroidism (PHPT). Indeed, even if patients with FHH are currently asymptomatic, some of them present chondrocalcinosis, kidney stones or bone fracture and very high level of PTH or calcemia[7]. Nonetheless, the distinction has to be adressed since the therapeutic approach significantly differs between these two conditions. Surgery is usually recommended for PHPT[8] while follow-up is preferred in the latter case[9,10]. We report and discuss 7 cases, 6 out 7 being operated for a presumed PHPT.