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Gene Mutations in Cushing's Syndrome.

BACKGROUND: Prolonged exposure to glucocorticoids can result in the development of Cushing's syndrome. Excess serum cortisol can occur due to several factors including exogenous steroids, pituitary and adrenal adenoma, and ectopic ACTH secretion.

SUMMARY: The last 2 decades have seen significant progress in identifying new genetic and molecular mechanisms underlying hypercortisolemia. This has implicated mutations seen in a multitude of aberrant pathways that underpin the pathophysiology of Cushing's syndrome.

KEY MESSAGES: There is much overlap between the different, with mutations affecting well-understood molecular pathways such as the cAMP/PKA/MAPK and Wnt signalling systems. Further work should delineate the exact involvement of specific mutations in Cushing's syndrome and the effect of epigenetic/microenvironmental interactions. This could have implications for screening, as the identification of specific mutations may lead to earlier identification and subsequently improved prognosis.

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