Multiple Endocrine Neoplasia Type 1 (MEN1): An Update and the Significance of Early Genetic and Clinical Diagnosis

Abstract

Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary tumor syndrome inherited in an autosomal dominant manner and characterized by a predisposition to a multitude of endocrine neoplasms primarily of parathyroid, enteropancreatic, and anterior pituitary origin, as well as nonendocrine neoplasms. Other endocrine tumors in MEN1 include foregut carcinoid tumors, adrenocortical tumors, and rarely pheochromocytoma. Nonendocrine manifestations include meningiomas and ependymomas, lipomas, angiofibromas, collagenomas, and leiomyomas. MEN1 is caused by inactivating mutations of the tumor suppressor gene MEN1 which encodes the protein menin. This syndrome can affect all age groups, with 17% of patients developing MEN1-associated tumors before 21 years of age. Despite advances in the diagnosis and treatment of MEN1-associated tumors, patients with MEN1 continue to have decreased life expectancy primarily due to malignant neuroendocrine tumors. The most recent clinical practice guidelines for MEN1, published in 2012, highlight the need for early genetic and clinical diagnosis of MEN1 and recommend an intensive surveillance approach for both patients with this syndrome and asymptomatic carriers starting at the age of 5 years with the goal of timely detection and management of MEN1-associated neoplasms and ultimately decreased disease-specific morbidity and mortality. Unfortunately, there is no clear genotype-phenotype correlation and individual mutation-dependent surveillance is not possible currently.

What is the appropriate management of nonfunctioning pancreatic neuroendocrine tumours disclosed on screening in adult patients with multiple endocrine neoplasia type 1?

“…4,5 In contrast, the age of onset of non-MEN1 (sporadic) pNETs usually ranges between 50 and 80 years. 6 Similar to sporadic pNETs, MEN-1 pNETs may be either nonfunctioning or secretory; however, MEN-1 pNETs are typically smaller, occur on a background of diffuse microadenomatosis with a complex multihormonal expression pattern, and exhibit a more indolent disease course when compared with their sporadic counterparts. [7][8][9] Multiple endocrine neoplasia type 1 patients often have contemporaneous (synchronous) occurrence of multiple tumours in the pancreas, and each one of these independent pancreatic tumours can proliferate and has malignant potential.…”

Justification of a combined study of the parathyroid and adrenal glands in patients with primary hyperparathyroidism

“…ПГПТ може бути спорадичним та в більшості (80-85 %) випадків виникати на тлі одиночної аденоми ПЩЗ. В 1-18 % випадків ПГПТ може бути пов'язаний із синдромом множинної ендокринної неоплазії 1-го типу (MEН1) та мати сімейний характер [3,4].…”

“…Класичний МЕН1 складається з гіперплазії або пухлини ПЩЗ, пухлини підшлункової залози та передньої частки гіпофіза, які розвиваються відповідно у 90, 30-70 та 30-40 % пацієнтів віком до 40 років [4,5].…”

“…На сьогодні добре відомо, що синдром МЕН1 може бути при різній комбінації більше 20 ендокринних (карциноїдні пухлини, ентерохромафіноподібні пухлини шлунка, пухлини надниркових залоз НЗ)) та неендокринних (ангіофіброми обличчя, колагеноми, ліпоми, менінгіоми, епендимоми тощо) пухлин [4,6].…”

“…Феохромоцитоми, більш характерні для синдрому множинної ендокринної неоплазії 2-го типу (МЕН2), зустрічаються у < 1 %. [4].…”