Background: Familial primary hyperparathyroidism is associated with tumor-susceptibility syndromes, which are unrelated to mutations in the calcium receptor gene. This study describes parathyroidectomy in a kindred with hypercalcemia due to a heterozygous point mutation in the calcium receptor gene.
Methods: Seventeen family members were studied, and postoperative follow-up averaged 5.1 years.
Results: Radical parathyroid resection with total parathyroid remnants of 10 to 20 mg or total parathyroidectomy with autotransplantation normalized the serum calcium and parathyroid hormone values in 12 family members. Persistent hypercalcemia was noted in 3 of 5 patients subjected to less radical procedures. Diffuse to nodular hyperplasia and microscopic findings, interpreted incorrectly as a single adenoma, were found. Weight of the parathyroid tissue increased with the age of the patients (P <.05), and almost one third of them (29%) had 1 to 3 atypically located glands. There were no patients with recurrent hypercalcemia during follow-up.
Conclusions: The heterozygous inactivating mutation of the calcium receptor gene of this family is accompanied by mild increases in parathyroid gland x weight and diffuse parathyroid hyperplasia with possibly secondary genetic events causing nodule formation. Radical parathyroid resection is advocated in this hypercalcemic disorder, which may represent an intermediary stage between primary hyperparathyroidism and familial hypocalciuric hypercalcemia.