Multiple endocrine neoplasia

Published on 01/03/2015 by admin

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Last modified 01/03/2015

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Multiple endocrine neoplasia

Multiple endocrine neoplasias (MEN) are inherited tumour predisposition syndromes, characterized by tumours in two or more endocrine glands. Clinical manifestations of these syndromes result either from hormone overproduction by the tumours or from other adverse effects of tumour growth. Inheritance is autosomal dominant.

MEN 1

A clinical diagnosis of MEN 1 can be made if the patient has at least two of the following:

parathyroid adenoma

pancreatic endocrine tumour

pituitary adenoma

adrenal cortex adenoma

carcinoid tumour.

The approximate frequencies of these tumours in MEN 1 are shown in Figure 71.1.

Fig 71.1 Tumours associated with MEN syndromes. Percentages are approximate.

The inactivated gene in MEN 1 is a tumour suppressor gene, the protein product of which (menin) normally inhibits genes involved in cell proliferation. MEN 1 gene mutations invariably lead to endocrine tumours, but family members carrying the same MEN 1 gene mutation can have completely different clinical manifestations of the syndrome. Genetic testing for MEN 1 allows earlier recognition and surgical removal of tumours. In the past patients with MEN 1 died from, e.g. peptic ulceration due to gastrinoma, or nephrolithiasis resulting from hyperparathyroidism.

Pituitary tumours in MEN 1 most often overproduce prolactin, but sometimes produce ACTH or growth hormone, resulting in Cushing’s disease or acromegaly respectively. The pancreatic tumours can produce gastrin, insulin, vasoactive intestinal polypeptide (VIP), glucagon or somatostatin, resulting in characteristic clinical features. The adrenocortical tumours seen in MEN 1 are often non-functional.

MEN 2

In MEN 2 the RET (REarrranged during Transfection) gene encodes a tyrosine kinase receptor for a family of growth factors. Unlike MEN 1, different mutations of this gene are associated with specific tumours or tumour combinations. Clinically, MEN 2 presents as several distinct phenotypes.

MEN 2A

Medullary carcinoma of the thyroid (MCT) is present, often with phaeochromocytoma or hyperparathyroidism (Fig 71.1). Phaeochromocytoma is bilateral in about 50% of affected cases.

MEN 2B

MCT is again present, along with phaeochromocytomas, but parathyroid adenomas are rare. Additional features specific to MEN 2B include mucosal ganglioneuromas in the gastrointestinal tract and a Marfanoid habitus. MEN 2B presents at an earlier age than MEN 2A, and carries a worse prognosis.

Familial medullary carcinoma of the thyroid

This shares many of the genetic and clinical features of MEN 2, but phaeochromocytomas and parathyroid adenomas occur less frequently.

Screening and treatment

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