Disease Directory Multiple Endocrine Neoplasia Type 2
Endocrine

Multiple Endocrine Neoplasia Type 2

Also known as: MEN2, MEN2A, MEN2B, Sipple syndrome, RET proto-oncogene

Prevalence

1 per 35,000

Onset

Variable; medullary thyroid carcinoma can occur in infancy (MEN2B) to adulthood

Type

Autosomal dominant

Gene

RET

About Multiple Endocrine Neoplasia Type 2

Multiple Endocrine Neoplasia Type 2 is an autosomal dominant syndrome caused by activating mutations in the RET proto-oncogene, subdivided into MEN2A (medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism), MEN2B (medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, and marfanoid habitus without hyperparathyroidism), and familial medullary thyroid carcinoma. Medullary thyroid carcinoma, arising from calcitonin-secreting parafollicular C-cells, is the most penetrant and life-threatening component, with virtually 100% penetrance in RET mutation carriers, and prophylactic thyroidectomy is recommended at an age determined by the specific RET codon mutation. The genotype-phenotype correlation for RET mutations is among the best characterised in clinical genetics.

Common Clinical Features

Medullary thyroid carcinoma (elevated calcitonin and CEA) Neck mass or thyroid nodule on examination or ultrasound Pheochromocytoma causing hypertension and adrenergic symptoms Primary hyperparathyroidism with hypercalcaemia (MEN2A) Mucosal neuromas of the lips, tongue, and conjunctiva (MEN2B) Marfanoid body habitus (MEN2B) Intestinal ganglioneuromatosis causing constipation (MEN2B) Diarrhoea due to calcitonin or VIP secretion from MTC

Clinical Trial Eligibility Tips

What to know before applying to Multiple Endocrine Neoplasia Type 2 trials.

Identification of the specific RET codon mutation is essential; trials targeting RET kinase inhibitors require documented RET variant with known risk classification (moderate, high, or highest risk).

Exclude active phaeochromocytoma biochemically before enrolment in any surgical or systemic therapy trial, as unresected phaeochromocytoma is an absolute contraindication to many interventions.

Calcitonin and CEA doubling times are used as prognostic and eligibility criteria in MTC-focused trials; longitudinal serial measurements are more informative than single values.

Patient Resources

Patient Organization

Association for Multiple Endocrine Neoplasia Disorders

Visit website ↗

Natural History Registry

International MTC Registry

Join registry ↗

Orphanet

European reference resource for rare diseases (ORPHA:653)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

Search NORD ↗

Find recruiting Multiple Endocrine Neoplasia Type 2 trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for Multiple Endocrine Neoplasia Type 2. Updated daily.

Related Rare Diseases