Multiple endocrine neoplasia type 1 pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2];Associate Editor(s)-in-Chief: , Ammu Susheela, M.D. [3], Aravind Reddy Kothagadi M.B.B.S[4]

Overview

Multiple endocrine neoplasia type 1 is an autosomal dominant syndrome that is usually caused by mutations of the MEN1 gene. The pathophysiology of multiple endocrine neoplasia type 1 depends on the histological subtype. Multiple endocrine neoplasia involves tumors in at least two endocrine glands, and tumors can also develop in other organs and tissues. These tumors may be either benign or malignant. A group of patients with MEN type 1 associated tumors may present with adrenal, gonadal, renal, or thyroid tumors.

Pathophysiology

Multiple endocrine neoplasia is part of a group of disorders that affect the the endocrine system. Multiple endocrine neoplasia involves tumors in at least two endocrine glands, and tumors can also develop in other organs and tissues. These tumors may be either benign or malignant. MEN type I is an autosomal dominant syndrome characterized by the development of the following tumors:[1]

Parathyroid Tumors

Pituitary Tumors

Duodenopancreatic Neuroendocrine Tumors

MEN type 4

  • A group of patients with MEN type 1 associated tumors may present with adrenal, gonadal, renal, or thyroid tumors. This rare group of patients carries a mutation in gene encoding a cyclin dependent kinase inhibitor belonging to KIP/CIP family that regulates cell cycle progression through its inhibitory effect on transition from G1 to S phase known as P27. P27 binds to cyclinE/CDK2 and cyclinA/CDK2 and inhibits them to arrest the cell cycle in G1. The mutant P27 thus cannot inhibit cyclin-CDK complexes which results in uninhibited cell growth in the affected tissues. The gene mainly responsible for this feature is CDKN1B. These group of patients with MEN type 1 associated tumors that carries this mutation are known as MEN type 4.[2][3]

Genetics

MEN1 Gene

MEN1 Protein (menin)

MEN Type 4

MEN 4 is caused by loss of function mutation in CDKN1B gene which is located on Chromosome 12 in humans.

Associated Conditions

Multiple endocrine neoplasia type 1 is associated with the following conditions:[29]

Gross Pathology

Microscopic Pathology

References

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  29. "Multiple endocrine neoplasia (MEN) type I [Dr Matt A. Morgan and Dr Frank Gaillard]".
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  32. [1] Pancreatic endocrine tumors

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