Describe the multiple endocrine neoplasia syndromes.

Definition and Classification

Clinical Presentation

• Men 1 most often presents with hypercalcaemia from parathyroid hyperplasia — often asymptomatic and found on biochemistry
• Gastrinoma in men 1 causes multiple, recurrent peptic ulcers in unusual sites with diarrhoea, resistant to standard treatment
• Men 2 presents with medullary thyroid carcinoma or with the catecholamine symptoms of phaeochromocytoma
• Men 2B has the worst prognosis, with medullary carcinoma appearing in infancy; the mucosal neuromas and marfanoid habitus may be recognised before any endocrine problem

Applied Aspects

• Always exclude phaeochromocytoma before any surgery in a patient with men 2 — operating on an undiagnosed phaeochromocytoma can precipitate a fatal hypertensive crisis
• Genetic testing of first-degree relatives is mandatory once a proband is identified; RET testing is straightforward and highly informative
• Prophylactic total thyroidectomy is offered to RET mutation carriers, with the timing determined by the specific codon — in infancy for men 2B
• Serum calcitonin is used for diagnosis and for surveillance of medullary carcinoma
• Consider men in anyone with two endocrine tumours, or with a single endocrine tumour at an unusually young age or with a family history — the diagnosis changes management for the whole family, not just the patient
• Parathyroid disease in men 1 is usually multigland hyperplasia, not a single adenoma, so subtotal or total parathyroidectomy with autotransplantation is required — removing one gland fails
• Lifelong surveillance is needed, since new tumours continue to arise; biochemical screening is repeated annually with periodic imaging
• Other familial endocrine syndromes — von Hippel–Lindau (phaeochromocytoma, renal cell carcinoma, haemangioblastoma), neurofibromatosis 1, and Carney complex; the presence of a phaeochromocytoma should always prompt genetic assessment
• Genetic counselling before testing is essential, since a positive result has implications for insurance, employment and family relationships as well as for health
• Management should be by a multidisciplinary team — endocrinologist, surgeon, geneticist and pathologist — because no single specialty sees the whole syndrome
• The pancreatic tumours of men 1 determine survival, since they are often multiple, malignant and difficult to localise — unlike the parathyroid disease, which is readily treated
• Recurrent peptic ulceration with hypercalcaemia is a classical clue to men 1, and should not be treated as two unrelated problems
• Men syndromes are rare, but recognising one transforms outcomes for relatives who can be screened and treated before disease develops