John F. Kennedy's beautiful bronze complexion may have resulted not from sunbathing, but from a disorder of the adrenal glands. When he ran for the presidency in 1960, Kennedy knew he had Addison's disease, but his staff kept his secret, for fear it would affect his career. Kennedy had almost no adrenal tissue but was able to function by receiving mineralocorticoids and glucocorticoids, the standard treatment.

In Addison's disease, the adrenal cortex does not secrete hormones sufficiently, due to immune system attack (autoimmunity) or an infection such as tuberculosis. Signs and symptoms include decreased blood sodium, increased blood potassium, low blood glucose level (hypoglycemia), dehydration, low blood pressure, and increased skin pigmentation. Without treatment, death comes within days from severe disturbances in electrolyte balance.

An adrenal tumor or oversecretion of ACTH by the anterior pituitary causes hypersecretion of glucocorticoids (primarily cortisol), resulting in Cushing's syndrome. Tissue protein level plummets, accompanied by wasting of muscles and loss of bone tissue. Blood glucose level remains elevated, and excess sodium is retained. As a result, tissue fluid increases, and the skin appears puffy and thin, and may bruise easily. Adipose tissue deposited in the face and back produce a characteristic moon face and buffalo hump. At the same time, an increase in adrenal sex hormone secretion may masculinize a female, causing growth of facial hair and a deepening voice.

Treatment of Cushing's syndrome attempts to reduce ACTH secretion. This may entail removing a tumor in the pituitary gland or partially or completely removing the adrenal glands.