Ninety-five percent of all carcinoids are found in the appendix, rectum, or small intestine. 9 The remainder arise outside of the intestinal tract (., in the ovary or testis). In general, the larger the primary tumor, the greater the likelihood of metastasis, which provides prognostic implications. 9 Carcinoids of the appendix and rectum rarely manifest with the carcinoid syndrome. Forty percent to 50% of patients with carcinoids of the small intestine or proximal colon have manifestations of the carcinoid syndrome. 10 Tumors that secrete their hormonal product into the portal venous system do not cause flushing, because the released amines are inactivated by the liver. In contrast, liver metastases may escape hepatic inactivation and deliver their product directly into the systemic circulation, hence causing flushing. 9 Pulmonary or ovarian carcinoids release pharmacologic products directly into the venous circulation, bypassing the portal system, and can therefore cause symptoms without metastasizing to the liver. 1,10
The secretion of cortisol is mainly controlled by three inter-communicating regions of the body, the hypothalamus in the brain, the pituitary gland and the adrenal gland . This is called the hypothalamic–pituitary–adrenal axis. When cortisol levels in the blood are low, a group of cells in a region of the brain called the hypothalamus releases corticotrophin-releasing hormone , which causes the pituitary gland to secrete another hormone, adrenocorticotropic hormone , into the bloodstream. High levels of adrenocorticotropic hormone are detected in the adrenal glands and stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to block the release of corticotrophin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary. As a result the adrenocorticotropic hormone levels start to drop, which then leads to a drop in cortisol levels. This is called a negative feedback loop.