**ALERT** Phaeochromocytoma MUST be excluded when surgery is being considered in all patients with MEN2, regardless of age, given the high risks of a life-threatening hypertensive crisis peri-/post-operatively with an undiagnosed phaeochromocytomar
Medullary thyroid cancer (MTC)
In MEN2, early intervention with risk-reducing thyroidectomy has been shown to significantly lower the mortality associated with MTC. The strongest predictor of survival from MTC is stage of disease at diagnosis. Individuals should be referred to endocrine surgeons and endocrinologists familiar with the revised American Thyroid Association (ATA) guidelinesr to discuss the timing and extent of risk-reducing thyroidectomy.
Thyroidectomy is recommended by 1 year of age for ATA highest risk (ATA-HST) and by 5 years of age for ATA high risk (ATA-H) variants. In these variants there is a narrow window of opportunity for curative thyroidectomy and early surgery is recommended.rr
For patients with ATA moderate risk (ATA-MOD) variants, thyroidectomy is generally performed by 5 to 10 years of age. Recent guidelines suggest that surgery could be delayed until 10 to 15 years of age in some patients, but even then only if strict criteria are met, including normal annual calcitonin/neck ultrasound; less aggressive family history of MTC; regular attendance for surveillance and parental consent including the risk of developing MTC not cured by thyroidectomy.r This decision should be individualised taking into account the family history of thyroid cancer, including age at diagnosis. The decision should also balance the risks of thyroidectomy at a younger age with the risks of delaying surgery, including loss to follow up and the risk of developing MTC that has extended beyond the thyroid at the time of diagnosis.r
Post-operatively, the most recently published expert consensus recommends surveillance with calcitonin/CEA at 3 months, 6 months and 12 months, then annually thereafter if undetectable.r
Patients with MEN2-associated RET variants should have surveillance for phaeochromocytoma with either plasma free metanephrines or fractionated urine metanephrines. Link to further information on measurement of biogenic amines. Imaging is only required if a phaeochromocytoma is suspected biochemically and is NOT recommended for surveillance.
Expert consensus is that annual surveillance should commence by age 11 years in patients with ATA-HST and ATA-H variants and by age 16 years in patients with ATA-MOD variants, earlier if hypertensive.r More frequent surveillance could be considered in early-mid adulthood (age 20 to 50 years) when the incidence is highest.r
Patients who have a unilateral phaeochromocytoma have a high risk of developing bilateral disease. When contralateral tumours do occur, most develop within 10 years of the first.r
Primary hyperparathyroidism is most strongly associated with codon 630 and 634 pathogenic variants and is less commonly seen with variants in other codons.r Clinically significant primary hyperparathyroidism is rare in childhood.
The age to commence surveillance for primary hyperparathyroidism and the optimal screening interval are both unclear. The most recently published expert consensus recommends screening for primary hyperparathyroidism occur annually and start by age 11 years in children with ATA-H variants, and by age 16 years for ATA-MOD variants.r Hypercalcaemia should also be excluded prior to thyroidectomy, for adequate surgical planning.
In patients with MEN2B the risk of primary hyperparathyroidism is no higher than that of the general population and surveillance is not required.