Several pathologies are associated with abnormal secretion of adrenal cortex hormones.

Addison's disease results from abnormally low levels of aldosterone and cortisol. The cause of many cases of Addison's disease is unknown, but it is a suspected autoimmune disease in which the body's defense mechanisms inappropriately destroy the adrenal cortex. Some cases of Addison's disease are caused by the destruction of the adrenal cortex by bacteria, such as tuberculosis bacteria, acquired immune deficiency syndrome (AIDS), fungal infections adrenal hemorrhage, or cancer. It can also be caused by suppression of pituitary gland function by prolonged treatment with glucocorticoids or results from neoplasms that damage the hypothalamus. Symptoms of Addison's disease include weakness, fatigue, weight loss, anorexia, and in many cases increased pigmentation of the skin. Reduced blood pressure results from the loss of sodium ions and water through the kidney. Reduced blood pressure is the most critical manifestation and requires immediate treatment. Low blood levels of sodium ions, high blood levels of potassium ions, and reduced blood pH are consistent with the conditions.

Aldosteronism is caused by excess production of aldosterone. Primary aldosteronism results from an adrenal cortex tumor, and secondary aldosteronism occurs when some extraneous factor such as overproduction of renin, a substance produced by the kidney, increases aldosterone secretion. Major symptoms of aldosteronism include reduced blood levels of potassium ions, increased blood pH and elevated blood pressure. Elevated blood pressure is a result of the retention of water and sodium ions, by the kidneys.

Cushing's syndrome is a disorder characterized by hypersecretion of cortisol and androgens and possible by excess aldosterone production. The majority of cases are caused by excess ACTH production by nonpituitary tumors, which usually result from a type of lung cancer, or by pituitary tumors. Sometimes adrenal tumors or unidentified causes can be responsible for hypersecretion of the adrenal cortex without increases in ACTH secretion. Elevated secretion of glucocorticoids results in muscle wasting, the accumulation of adipose tissue in the face and trunk of the body, and increased blood glucose levels.

Hypersecretion of androgens from the adrenal cortex cause a condition called adrenogenital syndrome, in which secondary sexual characteristics develop early in male children and female children are masculinized. If the condition develops before birth in females, the external genitalia can be masculinized to the extent that the infant's reproduction structures can be neither clearly female nor male. Hypersecretion of adrenal androgens in male children before puberty results in rapid and early development of the reproductive system. If not treated, early sexual development and a short stature result. The short stature results from the effect of androgens on skeletal growth. In adult females partial development of male secondary sexual characteristics such as facial hair and a masculine voice occurs.