Hyperparathyroidism in MEN 2A syndrome

Multiple Endocrine Neoplasia Syndrome Type 2A

Multiple endocrine neoplasia syndrome type 2A (MEN 2A) is an autosomal dominant inherited disorder caused by mutations in the RET proto-oncogene on chromosome 10. 5–30% of gene carriers will develop primary hyperparathyroidism (PHPT). MEN 2A is defined as the presence of medullary thyroid carcinoma (MTC), pheochromocytoma, and PHPT associated with a germline RET mutation. In a patient with one or two of the clinical features of MEN 2A, the only way to be certain of a diagnosis of MEN 2A is to identify a RET mutation or identify the clinical features of MEN 2A in other first-degree relatives. In the absence of an autosomal dominant familial inheritance pattern or RET mutation, at least two of the classical clinical features of MEN 2A are required to make a clinical diagnosis of MEN 2A. In the presence of a germline RET mutation and in the absence of any clinical features, that individual is said to be at risk for the clinical features of MEN 2A, and appropriate medical management should ensue. MEN 2B is defined as the presence of MTC, marfanoid habitus, medullated corneal nerve fibers, ganglioneuromatosis of the gut and oral mucosa, pheochromocytoma and no primary hyperparathyroidism. This syndrome should also be associated with a germline RET mutation.

Primary Hyperparathyroidism in MEN 2A syndrome

Primary hyperparathyroidism in MEN 2A is generally not an aggressive disease. Hypercalcemia is commonly mild. Primary hyperparathyroidism is asymptomatic in 60% of patients. Primary hyperparathyroidism is rarely the first diagnosed endocrinopathy in MEN 2A (15). In most affected patients, MEN 2A-related primary hyperparathyroidism is present in the third and fourth decade of life. Patients with MEN 2A-related primary hyperparathyroidism often have one gland disease (adenoma), rather than multiglandular disease (hyperplasia).

Surgery for Primary Hyperparathyroidism in MEN 2A syndrome

A more conservative approach with selective resection of enlarged glands is justified rather than a subtotal or total parathyroidectomy. This is in line with most reports on primary hyperparathyroidism in MEN 2A. A minimally invasive parathyroidectomy (MIP) is considered the initial procedure of choice for patients with MEN 2A. MIP has low rates of persistent and recurrent primary hyperparathyroidism, and the complications are minimal, a minimal risk of damage to surrounding tissues, better cosmetic results, patient comfort, and a shorter hospital stay. MIP can be performed if preoperative imaging studies are concordant. In the current time of genetic screening and prophylactic total thyroidectomy at a young age, almost all patients with MEN 2A will undergo some form of neck surgery for MTC before the presentation of and surgery to treat primary hyperparathyroidism.

References

Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr. Medullary thyroid cancer: management guidelines of the American Thyroid Association. American Thyroid Association Guidelines Task Force. Thyroid. 2009 Jun;19(6):565-612.

Scholten A, Schreinemakers JM, Pieterman CR, Valk GD, Vriens MR, Borel Rinkes IH. Evolution of surgical treatment of primary hyperparathyroidism in patients with multiple endocrine neoplasia type 2A. Endocr Pract. 2011 Jan-Feb;17(1):7-15