MEN Syndromes

Last week at the VA, we discussed a case of MEN1 in morning report! Here are some pearls about MEN syndromes:

MEN1: The 3 Ps”

  • Primary hyperparathyroidism – 90%
  • (Anterior) Pituitary tumor – 40%
    • MC prolactinoma à GH + prolactin à GH  à non functioning
    • ACTH / TSH secreting tumors are rare
  • Pancreatic islet cell tumor
    • Gastrinoma (ZES) – 30-40%
    • Insulinoma – 10%
    • Non-functioning – 20-55%

Caused by autosomal dominant mutation in MEN1 tumor suppressor gene

Clinical dx: 2+ MEN1 tumor types OR occurrence of 1 MEN tumor in a family member of a patient with diagnosis of MEN1

Who gets genetic testing? Any index patient with clinical MEN1, 1st degree relative of known MEN1 carrier regardless of symptoms, individuals with “suspicious or atypical MEN1”; if asymptomatic, offer genetic testing first to avoid extensive imaging / lab work-up

Who to screen: index patients & 1st degree relatives.

How to screen: Follow clinically for amenorrhea, galactorrhea, ED, growth abnormalities, nephrolithiasis, cushingoid changes, PUD / diarrhea, hypoglycemia, HA, visual changes. Labwork:  annual Ca, PTH, gastrin (fasting), glucagon, VIP, pancreatic polypeptide, chromogranin A, insulin, fasting glucose, prolactin, IGF-1. Radiology: There is no consensus on radiologic screening guidelines – suggest annual pancreatic imaging with EUS/MRI/CT and MR pituitary q3-5 years

MEN2A & B:

  • caused by autosomal dominant mutation in RET proto-oncogene
  • MEN2A – has 4 variants, 60-90% of MEN2 syndromes
  • MEN2B –  5% of all MEN variants
  • Manifestations:
    • Medullary thyroid carcinoma – typically earliest manifestation & almost all patients with MEN2 have it
    • Pheochromocytoma – 50%
    • Primary hyperparathyroidism – 10-50% of only MEN2A patients
    • cutaneous lesions / mucosal neuromas, Hirschsprung’s disease
  • thyroid, parathyroid, adrenal glands are at risk of developing tumors that reduce life expectancy –> importance of early diagnosis because of the excellent prognosis of medullary thyroid cancer if diagnosed early
  • Who to screen: as a result, you screen first and second degree relatives of an index case.
  • How to screen: plasma metanephrines, calcium / PTH, calcitonin and thyroid / neck US