Cushing’s Syndrome

– Hypersecretion of glucocorticoids by the adrenal gland, which produces a characteristic constellation of clinical abnormalities, including a moon face and truncal and neck fat pad deposits. It is classified into adrenocorticotropic hormone (ACTH)-dependent (75%) and ACTH-independent (25%) forms. ACTH-dependent forms are also referred to as Cushing’s disease.

Causes and Incidence

An ACTH-secreting tumor causes ACTH-dependent Cushing’s syndrome. The tumor may be a pituitary adenoma or an ectopic tumor. The causes of ACTH-independent Cushing’s syndrome include adrenal cancer, adrenal adenoma, micronodular adrenal disease, and factitious or iatrogenic factors. Cushing’s syndrome is most common in women of childbearing age. Iatrogenically induced cases are on the increase.

Disease Process

Increased glucocorticoid production is triggered by one of the causal agents. The increased glucocorticoids act as a sort of antianabolic, creating a mediated antagonism in insulin action that results in biochemical energy deprivation. This leads to protein wasting, glucose intolerance, fragility of the vascular system, and reduced effectiveness of the immune system.


Muscle weakness, muscle wasting; fragile, thinned skin, purple striae, easy bruising, poor wound healing; moon face, buffalo hump, heavy trunk, thin extremities; back pain, kyphosis; edema, hypertension; mood swings

Precocious puberty; cessation of linear growth

Masculinization: hirsutism, atrophy of breasts, clitoral enlargement, deepening voice, temporal baldness; menstrual irregularities

Feminization: breast enlargement, higher voice, lighter beard; impotence

Potential Complications Potential complications include osteoporosis, pathologic fracture, peptic ulcer, diabetes mellitus, congestive heart failure, and psychoses.

Diagnostic Tests

24-hour urine
Increased urinary free cortisol .250 {micro};g/day

Dexamethasone suppression
Dose of dexamethasone is given at night; positive test result shows reduced plasma cortisol levels next morning (,50% of baseline)

Metyrapone, ACTH stimulation, corticotropin-releasing hormone tests
To determine etiology

Computed tomography, magnetic resonance imaging
To detect adrenal tumors


Treatment is directed at the underlying cause.

Transsphenoidal pituitary resection of the tumor; resection of ectopic tumors, adrenal adenomas, adrenal carcinoma; bilateral adrenalectomy for treatment-resistant pituitary tumor and micronodular adrenal disease.

Glucocorticoid and mineralocorticoid lifelong replacement when bilateral adrenalectomy is performed; adrenal inhibitors or ketoconazole used when ectopic tumor cannot be removed; chemotherapy with mitotane for inoperable adrenal carcinomas.

Irradiation of the pituitary when surgery cannot be tolerated in treating a pituitary tumor; education that recovery can require a year or longer and that treatment initially makes the patient feel worse.