Definition

Cushing’s syndrome results in diverse complex symptoms, signs, and biochemical abnormalities caused by excess glucocorticoid hormone.

Pathophysiology

The most common cause of Cushing’s syndrome today is the administration of supraphysiologic doses of glucocorticoids for conditions such as arthritis, asthma, various autoimmune disorders, allergies, and a myriad of other diseases.

Endogenous Cushing’s syndrome is most often the result of one of three distinct pathogenic disorders: pituitary tumor (Cushing’s disease), adrenal tumor, or ectopic hormone production.

Cushing’s disease specifically denotes an anterior pituitary tumor cause of the syndrome. The pituitary tumor produces excessive amounts of ACTH and is associated with bilateral adrenal hyperplasia. Patients often develop skin pigmentation as a result of excess ACTH. Cushing’s disease is the most common cause of endogenous Cushing’s syndrome.

Adrenal Cushing’s syndrome is caused by autonomous corticosteroid production (ACTH independent) by an adrenal tumor, usually unilateral. This form of hyperadrenalism accounts for 20% to 25% of patients with Cushing’s syndrome and is usually associated with suppressed plasma ACTH levels. Adrenal tumors that are malignant are usually large by the time Cushing’s syndrome becomes manifest.

Ectopic Cushing’s syndrome results from autonomous ACTH or corticotropin-releasing hormone (CRH) production by extrapituitary malignancies, producing markedly elevated plasma levels of ACTH. Bronchogenic carcinoma accounts for most of these cases. Carcinoid tumors and malignant tumors of the kidney, ovary, and pancreas also can cause ectopic production of ACTH.