# Metastatic Medullary Thyroid Carcinoma in Multiple Endocrine Neoplasia Type 2B (MEN 2B) With RET M918T Mutation: Challenges in Long-Term Management and Targeted Therapy

## TL;DR

This case study highlights the aggressive progression and treatment challenges of a rare genetic disorder causing thyroid cancer and other tumors.

## Contribution

The paper presents a real-world case emphasizing the need for continuous targeted therapy in RET M918T-mutated MEN2B.

## Key findings

- RET M918T mutation leads to early and aggressive medullary thyroid carcinoma in MEN2B.
- Treatment interruptions due to funding and follow-up challenges worsened disease control.
- Selpercatinib therapy at a reduced dose was tolerated and maintained disease stability.

## Abstract

Multiple endocrine neoplasia type IIB (MEN2B) is a rare hereditary cancer syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and distinctive mucosal neuromas. MEN2B-associated MTC is most often caused by RET M918T mutations and confers an earlier and more aggressive disease progression. The aggressive nature of RET M918T-mutated MEN2B emphasizes the necessity of vigilant lifelong surveillance. It also highlights the real-world challenges of maintaining continuity of targeted therapy, where treatment interruptions may compromise disease control. This reports the case of a 25-year-old woman diagnosed with MTC in the setting of MEN2B. Initial evaluation revealed extensive metastases involving the regional neck lymph nodes, lungs, and adrenal glands. She underwent total thyroidectomy with bilateral neck dissection. Genetic testing confirmed the pathogenic RET M918T mutation. Family screening was negative for RET mutations in her mother and brother; her father, who died at 37 from uncontrolled hypertension, may have had an undiagnosed pheochromocytoma. Two years postoperatively, biochemical surveillance detected elevated plasma metanephrines, and subsequent workup confirmed bilateral pheochromocytomas. She underwent staged adrenal-sparing surgeries. Given progressive metastatic disease, selpercatinib therapy was initiated but required dose adjustments due to gastrointestinal intolerance. Treatment interruptions occurred secondary to funding and follow-up challenges. Upon re-evaluation one year later, imaging revealed recurrent paratracheal, pulmonary, hepatic, and possible adrenal metastases, prompting re-initiation of selpercatinib at a reduced dose, which she tolerated and continues to this day with surveillance of symptoms, serial electrocardiograms, laboratory work, and imaging. This case illustrates the aggressive course of RET M918T-mutated MEN2B and underscores the importance of early genetic diagnosis, vigilant surveillance, and continuity of selective RET inhibitor therapy to optimize disease control.