A 2-month-old male infant is referred for genetic counseling after his father is diagnosed with medullary thyroid cancer and a pheochromocytoma. Genetic testing reveals an activating mutation in the structure marked **D** at codon 918. Which of the following management decisions is most appropriate for this infant?

Explanation

## Why option 1 is right The structure marked **D** is the RET proto-oncogene on chromosome 10. Activating mutations at codon 918 (M918T) define MEN 2B, which presents with the most aggressive form of medullary thyroid cancer (MTC) that can metastasize in infancy. According to Robbins and Harrison, prophylactic total thyroidectomy is the standard of care for ALL RET mutation carriers, with timing stratified by mutation type: MEN 2B mutations mandate thyroidectomy **before 1 year of age** because of the extremely high risk of early metastatic disease. Critically, plasma metanephrines must be screened preoperatively to exclude pheochromocytoma and prevent intraoperative hypertensive crisis. This infant's codon 918 mutation confirms MEN 2B phenotype, making early intervention life-saving. ## Why each distractor is wrong - **Option 2**: Watchful waiting with delayed surgery contradicts the evidence-based management of MEN 2B. Calcitonin and CEA are useful for postoperative surveillance, not for deferring prophylactic surgery in a codon 918 mutation carrier. Waiting until age 10 risks metastatic spread in a disease known to metastasize in infancy. - **Option 3**: Immediate thyroidectomy without preoperative pheochromocytoma screening is dangerous—induction of anesthesia in an undiagnosed pheochromocytoma patient can precipitate a hypertensive crisis and catecholamine storm. Screening for pheochromocytoma MUST precede thyroid surgery. - **Option 4**: Parathyroid and pancreatic involvement are hallmarks of MEN 1 (caused by inactivating MENIN mutations on chromosome 11), not MEN 2B. The RET proto-oncogene (chromosome 10) causes MEN 2A and 2B, which feature medullary thyroid cancer and pheochromocytoma, not parathyroid or pancreatic neuroendocrine tumors. This confuses the two syndromes. **High-Yield:** RET codon 918 (M918T) = MEN 2B = most aggressive MTC = thyroidectomy before age 1 + preoperative pheochromocytoma screening. MEN 1 (MENIN, chromosome 11) = different tumor spectrum (parathyroid, pancreas, pituitary). [cite: Robbins 10e Ch 24; Harrison 21e Ch 401]