Hyperparathyroidism in multiple endocrine neoplasia type II A

Primary hyperparathyroidism (PHPT) in multiple endocrine neoplasia (MEN) 2A occurs in only 15-30% of patients. It is rarely the first feature recognized in the syndrome, is generally mild and is sometimes expressed only as parathyroid tumors discovered during surgery for medullary thyroid carcinoma. A predisposition to MEN 2 is caused by germline mutations of the RET proto-oncogene on chromosome 10q11.2. Genetic studies have demonstrated the association of PHPT with a specific mutation at codon 634 (C634R). Therefore, all codon 634 mutation carriers are at some risk for hyperparathyroidism and should be submitted to an early screening of the disease. The rarity of MEN 2A-related PHPT has prevented the establishment of a well-defined therapeutic strategy for treating this condition, so that recommendations about the surgical approach have been controversial. Patients with MEN 2A should have annual screenings for hyperparathyroidism by serum calcium and intact parathyroid hormone level measurements. Parathyroidectomy should be considered in all patients who have some evidence of symptomatic disease. The objectives of parathyroid surgery are to a) obtain and maintain normocalcemia for the longest time possible, b) avoid iatrogenic hypoparathyroidism, and c) facilitate future surgery for recurrent disease. Finally, most of the patients with MEN 2A-related PHPT have mild disease and they could be classified as asymptomatic based on the NIH consensus conference regarding the diagnosis and management of asymptomatic PHPT. Therefore, these patients can be followed up safely without parathyroid surgery.