Multiple Endocrine Neoplasia

MEN Overview - Syndrome Spotlight

⭐ Most MEN syndromes (MEN1, MEN2A, MEN2B) are inherited in an autosomal dominant pattern.

• Group of genetic disorders predisposing to tumors in ≥2 endocrine glands.
• Key syndromes: MEN1, MEN2A, MEN2B, and MEN4.
• Arise from specific germline mutations (e.g., MEN1, RET).
• Characterized by high penetrance but variable expressivity.
• Lifelong surveillance and early intervention are crucial.
• Genetic counseling and family screening are vital.

MEN 1 - Wermer's 3P Party

Autosomal dominant; MEN1 gene (menin) mutation. 📌 MEN1 = 3Ps.

• Parathyroid ( >90%): Hyperplasia/adenoma.
  • Leads to hypercalcemia, nephrolithiasis, bone issues.
• Pancreatic NETs (40-70%):
  • Gastrinoma (ZES), Insulinoma, VIPoma, Glucagonoma.
• Pituitary Adenoma (30-40%):
  • Prolactinoma (most common), GH-oma, ACTH-oma. Other tumors: Carcinoid (thymic, bronchial), adrenal cortical, lipomas, angiofibromas.

⭐ Primary hyperparathyroidism is the most common (>90%) and often the first clinical manifestation of MEN1.

MEN 2A - Sipple's MPT Trio

• Autosomal dominant; RET proto-oncogene mutation (codon 634 commonest).
• 📌 Mnemonic: MPH (Medullary thyroid ca, Pheochromocytoma, Hyperparathyroidism).
• Key Features:
  • Medullary Thyroid Carcinoma (MTC): ~100% penetrance.
  • Pheochromocytoma: Often bilateral; screen with plasma metanephrines.
  • Hyperparathyroidism: Parathyroid hyperplasia; ↑Ca, ↑PTH.
• Screening: Annual calcitonin, metanephrines, serum calcium.
• Management: Prophylactic thyroidectomy (by age 5-6 years).

⭐ Nearly 100% of untreated MEN2A individuals develop medullary thyroid carcinoma (MTC); prophylactic thyroidectomy is crucial.

MEN 2B - Gorlin's Neuroma Gang

• Autosomal dominant; RET proto-oncogene mutation (codon 918).
• 📌 MEN2B = Medullary thyroid ca, Marfanoid/ Mucosal neuromas, Pheochromocytoma.
• Features:
  • Medullary Thyroid Carcinoma (MTC): 100% penetrant, aggressive, early onset.
  • Pheochromocytoma: ~50%, often bilateral.
  • Mucosal Neuromas: Lips, tongue, eyelids.
  • Marfanoid Habitus: Tall, slim, high arched palate.
  • Intestinal ganglioneuromatosis.
• No hyperparathyroidism (unlike MEN 2A).

⭐ MEN2B is characterized by a very early onset and aggressive MTC; prophylactic thyroidectomy is often recommended within the first year of life.

MEN 4 & Genetics - Code & Counsel

• MEN 4:
  • Gene: CDKN1B (p27Kip1, cell cycle inhibitor).
  • Features: Pituitary adenomas, parathyroid tumors, NETs (pancreatic, GEP), adrenal, renal. Often MEN1-like.

⭐ MEN4 is a rare syndrome associated with mutations in the CDKN1B gene, and often involves pituitary and parathyroid tumors.

• Genetic Strategy (All MEN):
  • Testing: If clinical suspicion or +ve family history.
  • Counseling: Pre/post-test; discuss penetrance, surveillance, prophylactic options, family implications.

High‑Yield Points - ⚡ Biggest Takeaways

• MEN 1: Parathyroid, Pancreatic (e.g., gastrinoma), Pituitary tumors. MEN1 gene mutation.
• MEN 2A: Medullary Thyroid Cancer (MTC), Pheochromocytoma, Parathyroid hyperplasia. RET gene mutation.
• MEN 2B: MTC, Pheochromocytoma, Mucosal neuromas, Marfanoid habitus. RET gene mutation.
• MTC is common to MEN 2A/2B; screen for RET mutations.
• Always screen for Pheochromocytoma in MEN 2 before thyroid/parathyroid surgery.
• Calcitonin is the tumor marker for MTC.
• Primary hyperparathyroidism is most common in MEN 1.