Endocrine Abstracts

Background: Multiple endocrine neoplasia type 2A (MEN2A) is a rare genetic tumor syndrome due to germline mutations of the RET proto-oncogene, which is characterized by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). The age at onset, aggressiveness of MTC, and the penetrance of other components depend on the genotype. Early prophylactic thyroidectomy and life-long screening for PHEO from childhood are recommended in most cases.

Clinical case: A 73-year-old male was found to have progressively increasing PSA levels during routine check-ups. Prostate biopsy confirmed a prostatic adenocarcinoma (Gleason 3+4 and 4+4). 18F-Choline PET/CT was done next; however, this imaging did not only exclude metastatic disease, but also showed a highly metabolically active thyroid nodule. An ultrasound-guided fine needle biopsy of the nodule confirmed MTC (Bethesda 6). Calcitonin level was high at 1290 ng/l (ref. 8.3 – 14.3 ng/l). Catecholamines and nor/metanephrines were routinely measured in a 24h urine sample before thyroidectomy and were positive. Abdominal CT scan showed a 44 mm partially cystic formation of the left and an 11 mm nodule of the right adrenal gland, both with CT characteristics of PHEO. Laboratory testing for PHPT was negative. After a course of phenoxybenzamine, the patient was planned for laparoscopic total left and partial right adrenalectomy, however, bilateral total operation was finally done due to technical issues. Histopathological report confirmed bilateral PHEO with a PASS score of 8/20 on the left, and 3/20 on the right side. Total thyroidectomy and laparoscopic radical prostatectomy followed in the next weeks. Genetic testing was consistent with MEN 2A (NM_020975.6(RET):c.1900T>G (p.Cys634Gly)). Currently, the patient is doing well on hydrocortisone, fludrocortisone, and levothyroxine supplementation. The family history for MEN2A-related manifestations was negative. Genetic testing results of patient’s close relatives are pending.

Discussion: Genetic testing classified our patient as high risk MEN2A-MTC (Level C American Thyroid Association Risk Level) where prophylactic thyroidectomy should be performed before age of 5 and yearly screening for PHEO commenced at eight. The presented patient experienced an indolent, incidentally diagnosed disease, which might be in line with a recent finding that considered age at diagnosis as the most important marker of MTC outcome in MEN2A. Additional yet to be determined factors may enable better understanding of such phenotypic variability.