Long-term follow-up of a large North American kindred with multiple endocrine neoplasia type 2A

Sixty-one patients with multiple endocrine neoplasia (MEN) type 2A (27 men; 34 women; mean age, 39 years) from a single kindred (76 affected, 49 at risk) were followed 1 month to 33 years (median, 14 years) after diagnosis for disease expression.

Peripheral basal and pentagastrin-stimulated calcitonin, parathyroid hormone, and calcium levels were measured in 60 patients, 58 of whom had undergone previous thyroidectomy; the calcitonin concentration in four patients was concomitantly determined in the hepatic and internal jugular veins. Biochemical or radiographic screening for pheochromocytoma was performed in 58 patients.

Recurrence of medullary thyroid carcinoma (MTC) developed in nineteen (33%) of 58 patients after they underwent thyroidectomies. In 14 of 19 patients regional metastases were inapparent at initial operation, and lymphadenectomy was not undertaken. Three patients underwent neck reexploration with removal of micrometastases after selective venous studies were performed. One patient, 33 years of age, died of MTC, and two patients who refused thyroidectomy are alive at 76 and 83 years of age. Fifteen patients are alive with disease 8 to 33 years after they underwent thyroidectomies. All patients identified by prospective screening remain pentagastrin negative. Pheochromocytoma developed in six patients (10%), and four patients have Hirschsprung's disease. Hyperparathyroidism was present in seven patients and did not occur in those with minimal MTC.

These observations suggest that (1) the course of MTC in MEN 2A is highly variable, (2) early treatment of C-cell disease can be curative, (3) routine lymphadenectomy for occult micrometastases may be necessary for cure of MTC, and (4) the hyperparathyroidism of MEN 2A may not be a primary genetic event.