Cushing disease

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Cushing disease refers to ACTH-dependent hypercortisolism in the setting of a Pituitary adenomas.

Definition

Cushing syndrome is a serious disorder caused by chronically elevated cortisol levels. Cushing syndrome caused by an ACTH-secreting Pituitary adenoma is referred to as Cushing disease. Cushing syndrome can be caused by overproduction of cortisol by adrenal adenomas or carcinomas (ACTH-independent Cushing syndrome) or by ectopic ACTH secretion[^1].

Epidemiology

Cushing disease has an approximate prevalence of 40 cases per million people and an incidence of between 1 and 2.5 newly diagnosed cases per million people per year[^1]. The mean age at diagnosis is in the fourth decade of life in adults, and women are affected more often than men (4:1)[^1].

Diagnostic evaluation

Imaging

Most corticotroph pituitary adenomas (85 %-90 %) are microadenomas (<10 mm in diameter), with a mean diameter of 6 mm at the time of diagnosis. Only 10-15 % are macroadenomas (≥10 mm in diameter). Up to 40 % of microadenomas are not detectable on imaging, making tumor localization difficult and hindering tumor resection and biochemical remission[^3]. In particular, pituitary picoadenomas, adenomas measuring less than 3 mm, are less likely to be clearly identified on MRI. Tumor size does not necessarily correlate with hormonal activity, and patients with large macroadenomas may have mild hypercortisolism[^4].

Prognosis

Hypercorisolism is associated with high mortality and morbidity, as well as poor quality of life. Untreated Cushing disease has an estimated standardized mortality ratio (the ratio of observed Cushing disease–related deaths to the expected number of deaths in the general population) of up to 5.5. Successful complete resection of the ACTH-secreting pituitary adenoma results in immediate biochemical remission. Nevertheless, the physical symptoms and signs gradually resolve over a period of approximately 2 to 12 months, with a substantial long-term reduction in morbidity and potential mortality[^1] [^2].

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