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Adrenal Disorders
(Addison’s Disease & Cushing’s Syndrome)

Causes and Risk Factors

Addison’s disease

Adrenal insufficiency, or decreased production of adrenal hormones, can occur for several reasons. Autoimmune Addison’s disease, in which the body’s own immune system attacks the adrenal glands, is the most common cause (Betterle 2002; Ten 2001). In other cases, diseases such as tuberculosis, cancer, or adrenal hemorrhage can damage the adrenal glands, leading to reduced function or complete loss of function (Ten 2001; Betterle 2002). Sometimes, mutations in certain genes at birth or an inherent inability of the adrenal glands to respond to adrenocorticotropic hormone (ACTH)* can lead to the stunted growth of the glands, thereby causing them to secrete abnormally low levels of adrenal hormones (Ten 2001). In some severe cases, people with gene mutations can be deficient in all 3 types of adrenal cortex hormones—glucocorticoids, mineralocorticoids, and androgens (Ten 2001). Drugs that inhibit the synthesis of steroids in the adrenal cortex (eg, the antifungal drug ketoconazole) can also impair adrenal hormone production (Tabarin 1991; Loose 1983; Sarver 1997; Hahner 2010). Finally, since adrenal gland function is controlled by the hypothalamus and pituitary gland, decreased adrenal function can arise from conditions or events that affect these brain regions, such as pituitary or hypothalamic tumors, pituitary surgery or radiation treatment, or head trauma (Betterle 2002).

*Adrenocorticotropic hormone (ACTH) is secreted from the pituitary gland and regulates the production and secretion of hormones from the adrenal cortex.

Cushing’s syndrome

ACTH* signals the adrenal glands to produce cortisol, thus excess secretion of ACTH results in excessive elevation of cortisol levels. A common cause of elevated cortisol is the presence of a pituitary gland tumor that continually secretes ACTH (Yaneva 2010; Bertagna 2009). This is referred to as Cushing’s disease and is considered distinct from Cushing’s syndrome. In Cushing’s syndrome, increased cortisol levels manifest after ACTH secretion from ectopic tumors (tumors in other organs, such as the lung) (Bertagna 2009). Since increased cortisol levels in these two conditions are a result of excess ACTH secretion, they are considered to be “ACTH-dependent.” Cushing’s syndrome can also occur due to the direct over-secretion of cortisol from adrenal gland tumors. This type of cortisol elevation is considered to be “ACTH-independent” (Stratakis 2008). Over-treatment with glucocorticoid medications is considered to be the most common cause of Cushing’s syndrome (Tritos 2012).

*Adrenocorticotropic hormone (ACTH) is secreted from the pituitary gland and regulates the production and secretion of hormones from the adrenal cortex.