Primary hyperparathyroidism and familial hypocalciuric hypercalcemia: relationships and clinical implications.

Objective: To discuss the unusual occurrence of both familial hypocalciuric hypercalcemia (FHH) and primary hyperparathyroidism in the same patient and to explore potential mechanisms of association and issues related to clinical management.

Methods: We discuss the diagnosis, compare the clinical presentations of FHH and primary hyperparathyroidism, review the literature regarding patients who have presented with both disorders, and discuss management considerations. We also describe 2 patients who have both FHH (confirmed by genetic testing for a mutation in the gene encoding the calcium-sensing receptor [CASR]) and primary hyperparathyroidism.

Results: The occurrence of both FHH and primary hyperparathyroidism in the same patient has been reported in a few cases, including 2 patients described here, one of whom was documented to have a novel CASR mutation. In those with clinical sequelae of hyperparathyroidism, parathyroidectomy has led to reduction, but not normalization, of serum calcium levels.

Conclusions: The coexistence of FHH and primary hyperparathyroidism should be considered in patients with hypercalcemia, hypophosphatemia, frankly elevated parathyroid hormone levels, and low urinary calcium excretion. Genetic testing for inactivating CASR gene mutations can confirm the diagnosis of FHH. Although surgical intervention does not resolve hypercalcemia, it may be beneficial by reducing the degree of hypercalcemia, alleviating the symptoms, and preventing potential complications of hyperparathyroidism.