Multiple endocrine neoplasia type iia: report of a family with a study of three generations in qatar.

OBJECTIVE

To study the pattern of multiple endocrine neoplasia type IIA (MEN IIA) and describe the clinical features and results of genetic testing and treatment in 21 members of the first reported family with MEN IIA in Qatar.

METHODS

After identification of the proband, we screened all her family members (21 members) with genetic testing for the RET proto-oncogene mutation. Those subjects with the mutation were further assessed for pheochromocytoma by measurement of the 24-hour urinary vanillylmandelic acid, metanephrines, and catecholamines, and those with high levels underwent a metaiodobenzylguanidine scan and adrenalectomy. The serum calcium was measured in a effort to detect hyperparathyroidism. Those family members who had the mutation and were eligible for surgical treatment underwent total thyroidectomy and central compartment dissection. In those patients with high postoperative calcitonin levels, residual disease was sought with radiologic imaging, and follow-up was done with pentagastrin stimulation tests.

RESULTS

Of the 21 family members screened, 10 had the RET proto-oncogene mutation (codon 634, TGC->GGC) (5 females and 5 males; 6 adults and 4 children). All the adults had bilateral medullary thyroid carcinoma (MTC); four of them had lymph node metastatic lesions, and one had metastatic involvement of the liver. Two adults had pheochromocytomas. Two family members were reported to have parathyroid hyperplasia, although both were normocalcemic.

CONCLUSION

This family with MEN IIA showed classic mendelian autosomal dominant inheritance. All adult patients had MTC, two had pheochromocytomas, and two had parathyroid hyperplasia. Although one child had a high stimulated calcitonin level, the histopathologic findings were normal; another child with high stimulated calcitonin levels showed C-cell hyperplasia on histopathologic examination.