Hereditary tumour syndromes with distinct patterns of organ involvement.
Mutations in the MEN1 gene typically cause type 1 multiple endocrine neoplasia (MEN1), and mutations in the RET proto-oncogene typically cause type 2 multiple endocrine neoplasia (MEN2).
Prophylactic thyroidectomy in childhood is indicated in MEN2.
Medical management of hormonal hypersecretion is important for symptom control.
Most tumours require surgical evaluation, although surgical cure is not always possible.
Genetic carriers require lifelong monitoring, even after successful operations.
Morbidity and mortality result from both hormonal hypersecretion and metastases.
Multiple endocrine neoplasia (MEN) syndromes are hereditary tumour syndromes of variable neoplastic patterns and characterised by the development of multiple endocrine tumours. Tumours can include parathyroid adenomas, pituitary adenomas (which may be non-secretory or affect the profiles of adrenocorticotrophic hormone, growth hormone, TSH, and/or prolactin), enteropancreatic neuroendocrine tumours (which may affect the profiles of gastrin, insulin, glucagon, and/or vasoactive intestinal protein), facial lipomas, facial angiofibromas, medullary thyroid cancers, and phaeochromocytomas.
History and exam
- young age (MEN1/2)
- positive family history (MEN1/2)
- episodic triad of sweating, palpitations, and headache (MEN2)
- clinical features of kidney stones (MEN1/2)
- facial angiofibromas or collagenomas (MEN1)
- mucosal neuromas (MEN2B)
- arm span and upper-to-lower-body-segment ratio (MEN2B)
- palpable thyroid nodule (MEN2)
- irregular menses (MEN1)
- visual changes (MEN1)
- unexplained flushing (MEN2)
- infertility (MEN1)
- clinical features of acromegaly (MEN1)
- clinical features of thyrotoxicosis (MEN1)
- weight changes (MEN1/2)
- hypertension (MEN1/2)
- abdominal pain (MEN1/2)
- headache (MEN1/2)
- low-trauma fractures (MEN1)
- altered bowel habit (MEN1/2)
- palpitations (MEN1/2)
- easy bruising (MEN1/2)
- slow wound healing (MEN1/2)
- erectile dysfunction (MEN1)
- clinical features of hypercortisolism/Cushing's syndrome (MEN1/2)
- anxiety (MEN1/2)
- heat intolerance (MEN1)
- confusion (MEN1/2)
- dehydration (MEN1/2)
- gastrointestinal bleeding (MEN2)
- hepatomegaly (MEN2)
- serum calcitonin (MEN2)
- serum carcinoembryonic antigen (MEN2)
- plasma metanephrines (MEN2)
- serum parathyroid hormone and calcium (MEN1/2)
- fasting serum gastrin (MEN1)
- serum chromogranin A (MEN1)
- serum prolactin (MEN1)
- insulin-like growth factor-1 (MEN1)
- 24-hour urine metanephrines and catecholamines (MEN2)
- 24-hour urine calcium (MEN1/2)
- thyroid biopsy (MEN2)
- fasting serum glucose/insulin (MEN1)
- serum C peptide (MEN1)
- calcium-stimulated gastrin (MEN1)
- serum proinsulin (MEN1)
- serum pancreatic polypeptide (MEN1)
- serum glucagon (MEN1)
- T4 (free thyroxine) (MEN1)
- thyroid-stimulating hormone (TSH) (MEN1)
- dexamethasone suppression test (MEN1/2)
- urine sulphonylurea (MEN1/2)
- metaiodobenzylguanidine scintiscan (MIBG) (MEN2)
- 18F-fluorodihydroxyphenylalanine positron emission tomography (18F-DOPA PET)/CT abdomen and pelvis (MEN2)
- technetium 99 sestamibi scintiscan (MEN1/2)
- abdominal CT (MEN1/2)
- abdominal MRI (MEN1/2)
- chest CT or MRI (MEN1)
- pituitary MRI (MEN1)
- octreotide scan (MEN1)
- endoscopic ultrasonography (MEN1)
- upper GI endoscopy (MEN1)
- Helicobacter pylori breath test, biopsy, or stool antigen test (MEN1/2)
Rebecca Gorrigan, BSc, MBChB (hons), MRCP
Department of Endocrinology
Barts and the London NHS Trust and Queen Mary University of London
RG declares that she has no competing interests.
Maralyn Druce, MA, MRCP, PhD
Senior Lecturer & Honorary Consultant
Department of Endocrinology
Barts and the London Medical School
MD has been reimbursed for travel expenses and conference attendance for ENETS (European Neuroendocrine Tumour Society) by Novartis.
Dr Rebecca Gorrigan and Dr Maralyn Druce would like to gratefully acknowledge Dr Jennifer Mammen and Dr Roberto Salvatori, previous contributors to this monograph. JM and RS declare that they have no competing interests.
Michael Levine, MD, FAAP, FACP
Division of Endocrinology and Diabetes
The Children's Hospital of Philadelphia
ML declares that he has no competing interests.
Salvatore Corsello, MD
Associate Professor of Endocrinology
Catholic University School of Medicine
SC declares that he has no competing interests.
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