Atlas of pathophysiology, 2 Edition

Part II - Disorders

Endocrine Disorders

Cushing's syndrome

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.

Age Alert

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.

Causes

·   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

Pathophysiology

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.

Treatment

·   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

·   Antihypertensives

·   Potassium supplements

·   Diuretics

·   Antineoplastic, antihormone agents

·   For inoperable tumor, drugs, such as mitotane or aminoglutethimide to block steroid synthesis

Clinical Tip

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.

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MANIFESTATIONS OF CUSHING'S SYNDROME

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