Multiple Endocrine Neoplasia

Multiple Endocrine Neoplasia

• MEN syndromes are a group of inherited diseases resulting in proliferative lesions of multiple endocrine organs

• Tumors arising in MEN differs from tumors occuring sporadiaclly by

  • occuring in younger age

  • arise in multiple endocrine organs synchronously or metachronously

  • In single organ, the tumors are multifocal

  • Tumors are preceeded by asymptomatic stage of hyperplasia of cell of origin

  • Tumors are more aggressive and recur

• There are 2 types of MEN syndrome

  • MEN 1

  • MEN 2

• MEN 1 (Wermer syndrome)

  • Occurs due to germ line mutations in MEN1 tumor suppressor gene, which encodes protein  called Menin.

  • Characteristic features of MEN1 syndrome are

    • Parathyroid hyperplasia/ adenoma

    • Endocrine tumors of Pancreas

    • Pituitory tumor – prolactinoma

    • Duodenum – Gastrinoma

    • other tumors which can develop are carcinoid tumors, thyroid and adrenal cortical adenomas and lipomas

• MEN 2  – It is further subclassified into 

  • MEN 2A

  • MEN 2B

  • Familial medullary thyroid cancer

• MEN 2A  (Sipple syndrome) 

  • Caused by germline gain of function mutation in the RET protooncogenes on chromosome 10Q11.2.

  • Characteristic features of this syndrome are 

    • Pheochromocytoma

    • Medullary carcinoma of thyroid

    • Parathyroid hyperplasia

• MEN 2B 

  • caused by germ line mutation that constitutively activate the RET receptor

  • It is characterized by 

    • medullary carcinoma of thyroid which is multifocal and aggressive

    • Pheochromocytoma

    • other features include 

      • Neuromas or ganglioneuromas of skin, mucosa, eyes, respiratory tract, Gastrointestinal tract

      • Marfanoid habitus

      • Long axial skeletal features

      • Hyperextensible joints

• Familial medullary thyroid carcinoma

  • This is a  variant of MEN-2A and patient has predisposition to develop medullary carcinoma

  • 20% cases are familial remaining are sporadic 

  • Familial cases occur at older age group and has more indolent course

Reference

• Anirban Maitra. The Endocrine system.In: Robbins and Cotran Pathologic basis of disease.9th edition.volume II.chapter 24. pp 1073-1141.