Endocrine Abstracts

Proto-oncogene RET encodes a receptor tyrosine kinase. Germline point mutations of RET result in development of multiple endocrine neoplasia, type 2 (MEN 2). MEN 2 phenotype is correlated with intragene localization of germline mutation. The disease has three main subtypes, MEN 2A, MEN 2B and FMTC. Each of subtypes is associated with high risk of medullary thyroid cancer, MEN 2A and MEN 2B with 50% risk of pheochromocytoma, MEN 2A with 15–30% risk of primary hyperparathyroidism. Pheochromocytomas in MEN 2 patients are usually localized in adrenal glands, being benign, and often bilateral.

The aim of this study was to evaluate the development of pheochromocytomas in patients with germline proto-oncogene RET mutations. Among 228 gene carriers, most often MEN 2 was caused by mutation in codon 634 (36.85%). Pheochromocytoma was diagnosed in 36 patients, in 24 with mutation in codon 634, in six in codon 918 and in three in codon 620, in two in codon 618 and in one in codon 611. The youngest age at pheochromocytoma onset was 15 years, this was in patient with mutation in codon 918. In 6 (16.7%) gene carriers the pheochreomocytoma was the first manifestation of MEN 2. Most of patients in time of pheochromocytoma diagnosis didn’t present classical symptoms. Pheochromocytomas were detected with use of adrenal imaging (TK, MR, MIBG scintigraphy) and determination of urinary metoxycatecholamines. In 11 (30.5%) tumor was bilateral, initially with mean size of 3.6 cm.

This study demonstrates necessity of regular follow-up in germline proto-oncogene RET mutation carriers using additional exams, not only clinical evaluation. Taking in to account different interferences influencing biochemical assessment, we suggest that adrenal imaging (TK/MR) should be used as complementary follow-up method. The start of regular monitoring depends on the age of the known youngest patient with diagnosed pheochromocytoma.