Multiple endocrine neoplasia 2A (MEN 2A) is a hereditary disease comprising medullary thyroid carcinoma (MTC) (95%), pheochromocytoma (50%), parathyroid hyperplasia or adenoma (15-30%). RET mutations are seen generally in exon 10. Exon 11, 631 codon mutations are not common in MEN.
A 29-year-old male patient applied to our clinic. His mother was operated and diagnosed with MTC. Heterozygous D631Y RET mutation was detected in his mother. After this result, our patient was evaluated for RET mutation and MEN. Calcitonin value of the patient was normal and no nodule was detected on thyroid ultrasound. RET oncogene was positive for our patient as D631Y mutation. For the screening of MEN components, twenty-four hour urinary metanephrine and normetanephrine were high. Magnetic resonance imaging revealed adrenal adenoma 29x27x31 mm in diameter at the left adrenal. The patient underwent an operation in 2014 and pathology was consistent with pheochromocytoma. Prophylactic thyroidectomy was recommended, however, the patient did not accept this. He has been followed for development of thyroid nodule and evaluation of calcitonin level. At last visit, laboratory examination revealed PTH of 31.3 pg/mL (15-65), Ca 10.2 mg/dL (8.6-10.2), TSH 3.98 µIU/mL (0.35-5.50), fT4 1.47 ng/dL (0.89-1.76), calcitonin 5.77 pg/mL (0-10), and 24-hour urinary metanephrine and normetanephrine were normal.
RET 631 codon mutation is seen rarely in MEN patients. This genetic profile might be related to the less vigorous clinical disease behavior and the late onset of MTC.
Pheochromocytoma might be the first manifestation prior to the development of MTC.