**7. Cushing disease**

Cushing disease (CD) is a clinical syndrome caused by exposure to supraphysiological levels of cortisol due to adrenocorticotropic hormone (ACTH) hypersecretion from pituitary gland. Cushing disease has an annual incidence of about 2.4 cases/million and a prevalence of 39.1 cases/million [39, 40]. The cause of 70% of endogenous CD is by pituitary adenomas. 20–30% of endogenous CD are due to ectopic-ACTH secreting tumors, 50% of them are from lung cancer.

In normal physiological conditions, ACTH secretion from the anterior pituitary gland is under stimulatory effect by corticotropin-releasing hormone (CRH) released from the paraventricular hypothalamic nucleus. CRH is delivered to pituitary corticotroph cells through hypophyseal portal venous system. ACTH release will stimulate cortisol secretion from adrenal glands. Cortisol will exert an

#### *Pituitary Adenomas: Classification, Clinical Evaluation and Management DOI: http://dx.doi.org/10.5772/intechopen.103778*

inhibitory effect on ACTH and CRH release from pituitary gland and the hypothalamic nucleus, respectively, in a negative feedback-mechanism. Adenoma cells are not sensitive to high levels of cortisol, however, CRH levels will be suppressed.

ACTH-secreting adenomas are rare, they constitute around 6% of pituitary adenomas [41]. On diagnosis, the majority are microadenomas and only 4–10% are macroadenomas [40]. Unlike acromegaly, CD has female predominance (3:1). Unlike prolactinomas and GH-secreting adenomas, ACTH-secreting adenomas have no relationship between the size of the adenoma and the extent of hypersecretion. Mathioudakis et al. found that patients with microadenomas had more clinical signs and symptoms overall when compared to patients with macroadenomas [42].
