Medullary thyroid cancer
In MEN2, early intervention with prophylactic thyroidectomy has been shown to significantly alter the mortality associated with MTC. The most recent guidelines suggest a watchful waiting approach may be reasonable in some patients with an ATA moderate risk mutation where the risk of medullary thyroid cancer in childhood and adolescence is lower. However, regardless of mutation category most RET mutation carriers will eventually need thyroidectomy. There are risks in delaying surgery in family members who have inherited a mutated RET allele; regardless of the patient's age, the decision to delay risk reducing surgery must balance the risks of thyroidectomy against the possibility that MTC develops and it is not cured by therapeutic thyroidectomy.r
The most recently published expert consensusr recommends that after surgery consideration be given to screening with annual calcitonin, although this recommendation is made in the absence of high level evidence.
There is evidence to support the routine use of catecholamine screening in patients at high risk of phaeochromocytoma.rr
Urine and plasma free plasma metanephrines have diagnostic sensitivities greater than 97% with better specificity (85-100%) than total metanephrines or catecholamines.r Measurement of parent catecholamines (noradrenaline, adrenaline and dopamine) has low diagnostic sensitivity (<85%) and is not recommended.
The most recently published expert consensusr recommends biochemical screening only, with radiological imaging reserved for the workup of individuals with abnormal results. There is no consensus on the role of imaging to screen for adrenal phaeochromocytoma in individuals with no symptoms and normal biochemistry.
The age to commence screening for adrenal phaeochromocytoma and the optimal screening interval are both unclear. The most recently published expert consensusr recommends screening for adrenal phaeochromocytoma occur annually and start by age 11 years in children with the highest risk mutations (ATA high and highest risk), and by age 16 years for lower risk mutations (ATA moderate risk).
There is some evidence that screening should occur more frequently in early-mid adulthood (20-50 years; when the risk of tumours is highest) compared to childhood and later adulthood.r
Primary hyperparathyroidism is most strongly associated with codon 630 and 634 mutations and is less commonly described in other RET mutations (Waguespack et al 2011). Clinically significant primary hyperparathyroidism is rare in childhood.
The age to commence screening for primary hyperparathyroidism and the optimal screening interval are both unclear. The most recently published expert consensusr recommends screening for primary hyperparathyroidism occur annually and start by age 11 years in children with ATA high risk mutations, and by age 16 years for ATA moderate risk mutations.
Primary hyperparathyroidism is not associated with MEN2B and screening is not recommended in individuals with this phenotype.
PGD / prenatal diagnosis
With early recognition MEN2 is a treatable disorder. All RET mutation carriers of childbearing age, particularly those with MEN2B, should be made aware of the option of pre-implantation or prenatal diagnostic testing.