Cushing disease refers to ACTH-dependent hypercortisolism in the setting of a Pituitary adenoma.
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 cortisol overproduction by adrenal adenomas or carcinomas (ACTH-independent Cushing syndrome) or by ectopic secretion of ACTH[^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 average age at diagnosis is in the forties among adults, and women are affected more often than men (4:1)[^1].
Diagnosis
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, which makes tumor localization more difficult and impedes tumor excision and biochemical remission[^3]. In particular, pituitary picoadenomas, adenomas measuring less than 3 mm, are less likely to be unequivocally identified by MRI. Tumor size does not necessarily correlate with hormonal activity, and patients with large macroadenomas may have mild hypercortisolism[^4].
Prognosis
Hypercortisolism 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 expected 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 the risk of death[^1] [^2].