MEN (복합내분비샘신생물증후군)

목차
Multiple endocrine neoplasia (MEN)(복합내분비샘신생물증후군)이란? 분류 진단

Multiple endocrine neoplasia (MEN)(복합내분비샘신생물증후군)이란?

  • 2개 이상의 다른 호르몬을 분비하는 장기에서 발생하는 신생물
  • 가족 구성원 중 다수에서 발견되는데, 여러 가지의 특정 유전적 장애가 내분비샘의 신생물이 발생하는 원인이 되어, 호르몬 과다증후군을 일으키게 된다.

 



분류

  • 4가지 major forms 존재: MEN types 1–4 (MEN 1–4)
  • MEN은 autosomal dominant하게 유전되거나 혹은 특별한 가족력 없이 sporadic하게 발생

 

Multiple Endocrine Neoplasia (MEN) Syndromes

Type (Chromosomal Location)

Tumors (Estimated Penetrance)

MEN 1 (11q13)

  • Parathyroid adenoma (90%)
  • Enteropancreatic tumor (30–70%) 
    • Gastrinoma (>50%)
    • Insulinoma (10–30%)
    • Nonfunctioning and PPoma (20–55%)
    • Glucagonoma (<3%)
    • VIPoma (<1%)
  • Pituitary adenoma (15–50%) 
    • Prolactinoma (60%)
    • Somatotrophinoma (25%)
    • Corticotropinoma (<5%)
    • Nonfunctioning (<5%)
  • Associated tumors
    • Adrenal cortical tumor (20–70%)
    • Pheochromocytoma (<1%)
    • Bronchopulmonary NET (2%)
    • Thymic NET (2%)
    • Gastric NET (10%)
    • Lipomas (>33%)
    • Angiofibromas (85%)
    • Collagenomas (70%)
    • Meningiomas (8%)

MEN 2 (10 cen-10q11.2)

MEN 2A

  • MTC (90%)
  • Pheochromocytoma (>50%)
  • Parathyroid adenoma (10–25%)

MTC only

  • MTC (100%)

MEN 2B (also known as MEN 3)

  • MTC (>90%)
  • Pheochromocytoma (>50%)
  • Associated abnormalities (40–50%)
    • Mucosal neuromas
    • Marfanoid habitus
    • Medullated corneal nerve fibers
    • Megacolon

MEN 4 (12p13)

  • Parathyroid adenoma①
  • Pituitary adenoma①
  • Reproductive organ tumors① (e.g., testicular cancer, neuroendocrine cervical carcinoma)
  • ?Adrenal + renal tumors①

①: Insufficient numbers reported to provide prevalence information.

 

Cf. Multiple Endocrine and Other Organ Neoplasia Syndromes (MEONs)

  • MEN 1–4 외에 multiple endocrine 과 연관된 적어도 6개 이상의 증후군이 존재한다. 
  • autosomal dominant disorders (예외: McCune-Albright syndrome - mosaic expression of a postzygotic somatic cell mutation)

 

Multiple Endocrine and Other Organ Neoplasia Syndromes (MEONs)
  • Hyperparathyroidism-jaw tumor (HPT-JT)
  • Carney complex: CNC1, CNC2
  • von Hippel-Lindau disease (VHL)
  • Neurofibromatosis type 1 (NF1)
  • Cowden’s syndrome (CWS): CWS1, CWS2, CWS3, CWS4, CWS5, CWS6, CWS7
  • McCune-Albright syndrome (MAS)

 


 

진단

  • MEN 혹은 MEON syndrome은 다음과 같은 3가지 기준 중 1개를 만족시킬 때 진단 가능
    1. clinical features (two or more of the associated tumors [or lesions] in an individual)
    2. familial pattern (one of the associated tumors [or lesions] in a first-degree relative of a patient with a clinical diagnosis of the syndrome)
    3. genetic analysis (a germline mutation in the associated gene in an individual, who may be clinically affected or asymptomatic)
  • 돌연변이 분석(Mutational analysis)은 MEN/MEON syndromes에서 다음과 같은 임상적 유용성을 가진다.
    1. confirm the clinical diagnosis 
    2. identify family members who harbor the mutation and require screening for relevant tumor detection and early/appropriate treatment
    3. identify the ~50% of family members who do not harbor the germline mutation and can, therefore, be alleviated of the anxiety of developing associated tumors

참고자료

  • 해리슨 20/e(2018). 381장
  • Thakker RV, Newey PJ, Walls GV, et al. Clinical Practice Guidelines for Multiple Endocrine Neoplasia Type 1 (MEN1). J Clin Endocrinol Metab 2012;97(9):2990–3011.
  • Newey PJ. Multiple endocrine neoplasia. Medicine 2017;45(9):538–42.
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