Multiple endocrine neoplasia type 2B
Multiple endocrine neoplasia type 2B is an autosomal dominant RET proto-oncogene disorder producing early, aggressive medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, and a marfanoid habitus, without the parathyroid disease seen in MEN2A. First-line treatment is prophylactic total thyroidectomy at the earliest safe age, with pheochromocytoma resected first if both lesions are present, after alpha blockade.
- Topic reviewThe full article, organized the way the exam asks it.
- ABIM-format MCQsVignettes with an explanation for every wrong answer.
- Key factsThe numbers and thresholds worth memorizing, up front.
- AI tutorMedBrain answers the question you're stuck on.
What this article covers
- Overview
Definition: Multiple endocrine neoplasia type 2B (MEN2B) is an autosomal dominant tumor syndrome caused by germline mutation of the REarranged during Transfection (RET) proto-oncogene, producing…
- Epidemiology
Rarity: MEN2B is the least common subtype of MEN2, a family of autosomal dominant tumor syndromes.
- Risk factors
Germline RET mutation: The dominant risk factor is inheritance of (or de novo acquisition of) an activating RET proto-oncogene mutation.
- Pathophysiology
RET receptor tyrosine kinase: RET encodes a receptor tyrosine kinase expressed in neural crest-derived tissue, including thyroid C cells, adrenal medulla, and the enteric and mucosal neural plexus.
- Clinical features
Diagnostic triad: The defining clinical triad is medullary thyroid carcinoma, pheochromocytoma, and mucosal neuromas with intestinal ganglioneuromatosis; two or more of these findings in one person…
- Differential diagnosis
MEN2A: Shares medullary thyroid carcinoma and pheochromocytoma but includes primary hyperparathyroidism rather than mucosal neuromas, and lacks the marfanoid habitus.
- Diagnosis
Clinching basis: MEN2B is diagnosed clinically when two or more triad components (medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas/ganglioneuromatosis) occur in one individual, or when…
- Management
First, screen for and exclude pheochromocytoma before any thyroid surgery: Obtain plasma or urine metanephrines and, if positive, cross-sectional adrenal imaging in every patient before proceeding to…
- Complications
Metastatic medullary thyroid carcinoma: Because MTC in MEN2B is aggressive and often multicentric at diagnosis, delayed thyroidectomy allows nodal or distant metastasis, which is the leading cause of disease-specific mortality.
- Prognosis
Outcome depends on timing of thyroidectomy: Prognosis for MTC in MEN2B is strongly tied to how early total thyroidectomy is performed, since MTC in this syndrome progresses faster than in MEN2A or sporadic disease.
- Prevention
Prophylactic total thyroidectomy as early prevention: Because MTC risk in MEN2B approaches the rest of a carrier's lifetime, thyroidectomy performed as early as safely possible in a confirmed RET…
Read the whole article
Subscribing to Internal Medicine opens every article, the full question bank and MedBrain, on the web, iPhone and Android.
Related articles
- Multiple endocrine neoplasia type 2A
Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant RET-mutation syndrome causing medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism. First-line treatment is total thyroidectomy for medullary thyroid carcinoma and surgical resection of pheochromocytoma, always after preoperative alpha-then-beta adrenergic blockade if pheochromocytoma coexists.
- Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant tumor-suppressor syndrome causing parathyroid, pancreatic, and pituitary tumors, the '3 Ps.' First-line treatment is organ-specific: parathyroidectomy for hyperparathyroidism, dopamine agonists for prolactinoma, and surgical resection or acid suppression for pancreatic neuroendocrine tumors.
- Medullary thyroid carcinoma
Medullary thyroid carcinoma is a neuroendocrine tumor of the parafollicular C cells that secretes calcitonin and is familial (RET-mutant, part of MEN2A or MEN2B) in about 25% of cases. First-line treatment is total thyroidectomy with central neck lymph node dissection, with any coexisting pheochromocytoma resected first, followed by lifelong levothyroxine replacement and calcitonin/CEA surveillance; selpercatinib, a RET kinase inhibitor, is used for unresectable or metastatic RET-mutant disease.