Multiple endocrine neoplasia

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    • The condition is inherited in an autosomal dominant manner
    • arise from the expression of recessive oncogenic mutations, most of which have been isolated.
    • Affected persons may pass on the mutation to their offspring in the germ cell, but for the disease to become evident a somatic mutation must also occur, such as deletion or loss of a normal homologous chromosome.
    • The defect in MEN 1 is in a novel gene (menin) on the long arm of chromo- some 11
      • Menin represses a transcription factor (JunD) and lack of JunD sup- pression leads to decreased apoptosis and oncogenesis.
    • What is the ‘two hit’ hypothesis in MEN Syndrome
      • Patients with the MEN1 gene carry one mutant gene and a wild type gene (i.e. are heterozygous).
      • When the wild type gene undergoes a random somatic mutation during life, this leads to loss of heterozygosity and explains the late onset of tumours at any stage (the ‘two hit’ hypothesis).
    • MEN 2a and 2b are caused by mutations of the RET proto-oncogene on chromosome 10
      • This gene encodes for a transmembrane glycoprotein receptor.
      • For MEN 2a the mutation is in the extracellular domain; for 2b it is in the intracellular domain.

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    Management

      • Treatment of established tumours in MEN is largely the same as treatment for similar tumours occurring sporadically.
      • In MEN 1 four-gland parathyroidectomy is usually recommended when surgery is needed since all glands are typically involved.
      • However, the essence of management in MEN is annual screening to detect tumours at an early, treatable stage.
      • Screening
        • Screening for type 1
          • Hyperparathyroidism is usually the first manifestation, and serum calcium is the simplest screening test in families with no identified mutation..
      • Screening for type 2
        • Serum calcium levels will easily detect hyperparathyroidism.
        • Medullary carcinoma of thyroid (MCT) with the known presence of the gene defect, total thyroidectomy is recommended in early childhood or as soon as the gene defect is identified.
        • Calcitonin is a useful tumour marker.
        • Phaeochromocytoma metanephrine or catecholamine estimations.

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