Cushing’s syndrome
A cluster of clinical abnormalities characterize Cushing’s syndrome. These abnormalities result from excessive levels of adrenocortical hormones (particularly cortisol) or related corticosteroids and, to a lesser extent, androgens and aldosterone. Its unmistakable signs include adiposity of the face (moon face), neck, and trunk and purple striae on the skin.
Cushing’s syndrome is most common in women. The prognosis depends on the underlying cause; it’s poor in untreated persons and in those with untreatable ectopic corticotropin-producing carcinoma.
Causes
In approximately 80% of patients, Cushing’s syndrome results from excess production of corticotropin and consequent hyperplasia of the adrenal cortex. Overproduction of corticotropin may stem from pituitary hypersecretion (Cushing’s disease) or corticotropin-producing tumor in another organ (particularly bronchogenic or pancreatic carcinoma). Excessive administration of exogenous glucocorticoids can also cause Cushing’s syndrome.
In the remaining 20% of patients, Cushing’s syndrome results from a cortisol-secreting adrenal tumor that’s usually benign. In infants, the usual cause of Cushing’s syndrome is adrenal adenoma or carcinoma.
Signs and symptoms
Like other endocrine disorders, Cushing’s syndrome induces changes in multiple body systems, depending on the adrenocortical hormone involved. Specific signs and symptoms vary with the system affected.
Endocrine and metabolic systems: diabetes mellitus, with decreased glucose tolerance, fasting hyperglycemia, and glycosuria
Musculoskeletal system: muscle weakness resulting from hypokalemia or loss of muscle mass from increased catabolism, pathologic fractures from decreased bone mineral, and skeletal growth retardation in children
Skin: purplish striae; fat pads above the clavicles, over the upper back (buffalo hump), on the face (moon face), and throughout the trunk, with slender arms and legs; little or no scar formation; poor wound healing; acne and hirsutism in women
GI system: peptic ulcer, resulting from increased gastric secretions and pepsin production, and decreased gastric mucus
Central nervous system (CNS): irritability and emotional lability, ranging from euphoric behavior to depression or psychosis; insomnia
Cardiovascular system: hypertension resulting from sodium and water retention; left ventricular hypertrophy; capillary weakness from protein loss, which leads to bleeding and ecchymosis
Immunologic system: increased susceptibility to infection because of decreased lymphocyte production and suppressed antibody formation; decreased resistance to stress; suppressed inflammatory response may mask even a severe infection or an acute abdominal disorder
Renal and urologic systems: sodium and secondary fluid retention; increased potassium excretion; inhibited secretion of antidiuretic hormone; ureteral calculi from increased bone demineralization with hypercalciuria
Reproductive system: increased androgen production, with clitoral hypertrophy, mild virilism, and amenorrhea or oligomenorrhea in women; sexual dysfunction also occurs.
Diagnosis
Initially, the diagnosis of Cushing’s syndrome requires determination of plasma steroid levels. In persons with normal hormone balance, plasma cortisol levels are higher in the morning and decrease gradually through the day (diurnal variation). In patients with Cushing’s syndrome, cortisol levels don’t fluctuate and typically remain consistently elevated; a 24-hour urine sample demonstrates elevated free cortisol levels.
