Multiple endocrine neoplasia

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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:



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



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.





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Jun 18, 2016 | Posted by in BIOCHEMISTRY | Comments Off on Multiple endocrine neoplasia

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