Endocrine Abstracts

Introduction: MEN 2A is a rare hereditary cancer syndrome, which is inherited, as variety of autosomal dominant germline variants in the RET proto-oncogene.

Case report: We report a 29-year-old female with a past medical history of aggressive medullary thyroid carcinoma, with a high level of calcitonin, which occurred in the 2nd decade of her life. Total thyroidectomy was conducted in 2016, followed by the surgical extraction of a retroperitoneal paraganglioma approximately one year later in 2017. These manifestations were suspicious in terms of MEN 2 syndrome. Genetic testing for the most common RET proto-oncogene mutation (exon 16, codon 956) was conducted to rule out hereditary origins of the symptoms, yielding a negative result. After surgical interventions and therapy, stability was achieved, with a relative remission maintained for about five years. In 2023, during the visit ultrasound was performed and bilateral adrenal gland formations were revealed. Daily urine analysis indicated very high level of metanephrines. Also, hypercalcemia and hyperparathyroidism were indicated. Additionally, cutaneous lichen amyloidosis was noted during the objective clinical examination. Considering the clinical signs, investigation results, and the patient’s history of aggressive MTC, paraganglioma, hyperparathyroidism, prematurely developed bilateral pheochromocytoma, and presence of cutaneous lichen amyloidosis, MEN2A appeared to be the most likely diagnosis. Importantly, there is no family history of MEN syndrome in the patient’s family. At this stage, genetic testing using Next-Generation Sequencing was performed to detect RET germline variants, revealing a Cys634Arg mutation.

Conclusion: Numerous studies have demonstrated a strong association between the presence of Cys634Arg and susceptibility to hyperparathyroidism and bilateral pheochromocytoma. The objective of this case report is to underscore and draw attention to the propensity of the Cys634Arg mutation to manifest not only aggressive MTC but also premature pheochromocytoma and appear as comprehensive syndrome in the early stages of life. We highlight the fact that the premature onset of a highly aggressive form of medullary thyroid carcinoma, distinguished by extremely elevated calcitonin levels, is linked to an increased probability of earlier manifestation of accompanying symptoms. This case report emphasizes that more accurate attention to the general appearance of the patients and a precise physical examination could reveal the settings in which chronic manifestations take place, and the clinician might be able to prevent the irreversible aftermaths of the disease and save the patient from disastrous complications.