Differentiating familial hypocalciuric hypercalcemia from primary hyperparathyroidism.

OBJECTIVE: Because the clinical features of familial hypocalciuric hypercalcemia (FHH) overlap significantly with those of primary hyperparathyroidism (PHPT), various means of differentiating between the two diseases have been suggested. Here we present a review of the clinical delineation of these two diseases.
METHODS: Review of the English language literature on FHH and PHPT.
RESULTS: FHH is a rare genetic disorder generally resulting in asymptomatic hypercalcemia of minimal clinical consequence. It is easily misdiagnosed as PHPT because both entities can manifest as hypercalcemia with an inappropriately normal or elevated level of parathyroid hormone. The 2 disorders differ in renal processing of calcium, and a number of indices of renal calcium excretion have been proposed to differentiate the 2 entities. However, the two disorders have considerable overlaps in their ranges on these indices making differentiation a challenge. There are many mutations in the calcium-sensing receptor (CaSR) gene associated with FHH and it is becoming increasingly recognized that the CaSR has broad functional variability.
CONCLUSION: The calcium:creatinine clearance ratio (CCCR) is the consensus biochemical test to differentiate between PHPT and FHH. However, this test is still limited by a considerable indeterminate range, and definitive diagnosis of FHH requires genetic testing. A combination of clinical suspicion, biochemical testing, and genetic analysis is required to differentiate PHPT from FHH and thus spare patients with FHH from nontherapeutic operative treatment.