MEN 2A syndrome

• Autosomally dominantly inherited mutation in the RET proto-oncogene on chromosome 10

MEN 2A syndrome (2Ps 1M)

• Manifestations
  • Primary hyperparathyroidism
  • Phaeochromocytoma
  • Medullary thyroid cancer
• Specifics
  • Medullary thyroid cancer
    • The medullary thyroid cancer patient with 2a get tend to be less aggressive and multifocal.
    • Nearly 100% lifetime penetrance
  • Phaeochromocytoma
    • About 50% of patients with 2a will develop a phaeo.
    • In 60-80% of patients with 2a – the phaeo will be bilateral.
  • Primary hyperparathyroidism
    • Usually hyperplasia thus need to do a multi-gland exploration. Occurs in about 505% of patients.
  • Can be born with Hirschsprung’s disease.

MEN 2B syndrome (1P 2M’s)

• Manifestations
  • Phaeochromocytoma
  • Medullary thyroid cancer
  • Marfan’s habitus
• Specifics
  • Is more likely to result from a sporadic mutation
  • Medullary thyroid cancer
    • The medullary thyroid cancer is often much more aggressive and often happens earlier in life.
  • Marfan’s habitus
    • They also get a Marfanoid body habitus
  • Mucosal neuromas
    • Neuroma’s on the tongue and lips (has been a spot question
• Different mutations and different codons on the gene has been associated with different manifestations of the disease (and this can determine at what age they usually get their medullary thyroid cancer)
  • Thus if you diagnose MEN2 you should do this additional testing to determine when they should have thyroidectomy.
• Other MEN2a subtypes
  • MEN2a with cutaneous lichen amyloidosis.
  • MEN2a with Hirschsprung’s disease
  • Familial medullary thyroid cancer (FMTC) - is a form of MEN2 where the patient only gets medullary thyroid cancer.

Testing for MEN 2

• RET mutation analysis
• Indications
  • Anyone that presents with a medullary thyroid cancer
  • Patients with bilateral phaeochromocytoma, phaeochromocytoma in a young patient, or phaeochromocytoma in a patient with a FHx of phaeo.
    • Patients with bilateral phaeochromocytoma should also best tested for NFM1, Von-Hippel Lindau syndrome, SDH mutations
  • Four gland hyperplasia with a family history OR an associated MEN disease

Surveillance

• Medullary thyroid cancer
  • Need to determine the MEN subtype/codon mutation because if it’s a high risk mutation should have a total thyroidectomy early in life.
    • Both MEN2a and 2b have high risk subtypes.
  • Thyroidectomy for the highest risk groups is recommended in the first few months of life.
  • For the lowest risk groups – surveillance with a calcitonin followed by thyroidectomy in adulthood is reasonable
• Other surveillance
  • Yearly PTH and calcium levels.
  • Yearly plasma metanephrines and urinary catecholamines.
  • MRI or CT every 4-5 years for image the adrenals looking for phaeo.