Cushing's syndrome is a cluster of clinical abnormalities caused by excessive adrenocortical hormones (particularly cortisol) or related corticosteroids and, to a lesser extent, androgens and aldosterone. Cushing's disease (adrenocorticotropin [ACTH] excess) accounts for about 70% of the cases of Cushing's syndrome.
Cushing's syndrome caused by ectopic corticotropin secretion is most common in adult men, with the peak incidence between ages 40 and 60. In 30% of patients, Cushing's syndrome results from a cortisol-secreting tumor. Adrenal tumors, rather than pituitary tumors, are more common in children, especially girls.
· Pituitary hypersecretion of ACTH
· Autonomous, ectopic ACTH secretion by a tumor outside the pituitary (usually malignant, frequently a pancreatic tumor or oat cell carcinoma of the lung)
· Administration of synthetic glucocorticoids or steroids
Cortisol excess results in anti-inflammatory effects and excessive catabolism of protein and peripheral fat to support hepatic glucose production. The mechanism may be ACTH-dependent, in which elevated plasma ACTH levels stimulate the adrenal cortex to produce excess cortisol, or ACTH-independent, in which excess cortisol is produced by the adrenal cortex or exogenously administered. This suppresses the hypothalamic-pituitary-adrenal axis, also present in ectopic ACTH-secreting tumors.
Signs and symptoms
· Fat pads above the clavicles, over the upper back (buffalo hump), on the face (moon face), and throughout the trunk (truncal obesity); slender arms and legs
· Increased susceptibility to infection; decreased resistance to stress
· Hypertension, left ventricular hypertrophy, bleeding and ecchymosis, dyslipidemia
· Increased androgen production—clitoral hypertrophy, mild virilism, hirsutism, and amenorrhea or oligomenorrhea in women; sexual dysfunction
· Sodium and secondary fluid retention, increased potassium excretion, ureteral calculi
· Irritability and emotional lability
· Little or no scar formation; poor wound healing
· Purple striae, facial plethora, acne
· Muscle weakness
· Pathologic fractures; skeletal growth retardation in children
Diagnostic test results
· Laboratory studies reveal hyperglycemia, hypernatremia, glucosuria, hypokalemia, and metabolic acidosis; elevated urinary free cortisol levels; elevated salivary free cortisol; and elevated serum cortisol.
· Dexamethasone suppression test confirms the diagnosis and determines the cause, possibly an adrenal tumor or a nonendocrine, corticotropin-releasing tumor.
· Ultrasound, computed tomography scan, and magnetic resonance imaging detect the presence of a pituitary or adrenal tumor.
· Specific for cause of hypercortisolism—pituitary, adrenal, ectopic
· Surgery for tumors of adrenal or pituitary glands or other tissue, such as lung
· Radiation therapy for tumor
· Cortisol replacement therapy after surgery
· Potassium supplements
· Antineoplastic, antihormone agents
· For inoperable tumor, drugs, such as mitotane or aminoglutethimide to block steroid synthesis
Most patients with Cushing's syndrome are treated with transphenoidal surgery, which has a high cure rate (80%). Pharmacotherapy is usually used as adjunctive rather than primary therapy.
MANIFESTATIONS OF CUSHING'S SYNDROME