Cushing's syndrome
Cushing's syndrome: Excerpt from Professional Guide to Diseases (Eighth Edition)
Cushing’s syndrome is a cluster of clinical abnormalities caused by excessive levels of adrenocortical hormones (particularly cortisol) or related corticosteroids and, to a lesser extent, androgens and aldosterone. Its unmistakable signs include rapidly developing adiposity of the face (moon face), neck, and trunk and purple striae on the skin. (See Symptoms of cushingoid syndrome.) The prognosis depends on the underlying cause; it’s poor in untreated people and in those with untreatable ectopic corticotropin-producing carcinoma.
Causes and incidence
In approximately 70% of patients, Cushing’s syndrome results from excessive production of corticotropin and consequent hyperplasia of the adrenal cortex. Overproduction of corticotropin may stem from pituitary hypersecretion (Cushing’s disease), a corticotropin-producing tumor in another organ (particularly bronchogenic or pancreatic cancer), or excessive administration of exogenous glucocorticoids.
In the remaining 30% of patients, Cushing’s syndrome results from a cortisol-secreting adrenal tumor, which is usually benign. In infants, the usual cause of Cushing’s syndrome is adrenal carcinoma.
Cushing’s syndrome affects 13 of every 1 million people. It’s more common in females than in males and occurs primarily between ages between ages 25 and 40.
Signs and symptoms
Like other endocrine disorders, Cushing’s syndrome induces changes in multiple body systems, depending on the adrenocortical hormone involved. Clinical effects may include the following:
❑ Endocrine and metabolic systems: diabetes mellitus, with decreased glucose tolerance, fasting hyperglycemia, and glycosuria
❑ Musculoskeletal system: muscle weakness due to hypokalemia or to loss of muscle mass from increased catabolism, pathologic fractures due to 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 females
❑ 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 due to sodium and water retention; left ventricular hypertrophy; capillary weakness due to protein loss, which leads to bleeding, petechiae, and ecchymosis
❑ Immune system: increased susceptibility to infection due to decreased lymphocyte production and suppressed antibody formation; decreased resistance to stress (Suppressed inflammatory response may mask even a severe infection.)
❑ Renal and urologic systems: sodium and secondary fluid retention, increased potassium excretion, inhibited antidiuretic hormone secretion, ureteral calculi from increased bone demineralization with hypercalciuria
❑ Reproductive system: increased androgen production with clitoral hypertrophy, mild virilism, and amenorrhea or oligomenorrhea in females. Sexual dysfunction also occurs.
Diagnosis
Initially, diagnosis of Cushing’s syndrome requires determination of plasma steroid levels. In people with normal hormone balance, plasma cortisol levels are higher in the morning and decrease gradually throughout the day (diurnal variation). In patients with Cushing’s syndrome, cortisol levels don’t fluctuate and typically remain consistently elevated; 24-hour urine sample demonstrates elevated free cortisol levels.
Confirming diagnosis A low-dose dexamethasone suppression test confirms the diagnosis of Cushing’s syndrome. Salivary cortisol levels collected at midnight (usually performed on an outpatient basis) are elevated and are the most sensitive confirmatory test. (See Diagnosing Cushing’s syndrome.)
A high-dose dexamethasone suppression test can determine if Cushing’s syndrome results from pituitary dysfunction (Cushing’s disease). In this test, dexamethasone suppresses plasma cortisol levels, and urinary 17-hydroxycorticosteroid (17-OHCS) and 17-ketogenic steroid levels fall to 50% or less of basal levels. Failure to suppress these levels indicates that the syndrome results from an adrenal tumor or a nonendocrine, corticotropin-secreting tumor. This test can produce false-positive results.
In a stimulation test, administration of metyrapone, which blocks cortisol production by the adrenal glands, tests the ability of the pituitary gland and the hypothalamus to detect and correct low levels of plasma cortisol by increasing corticotropin production. The patient with Cushing’s disease reacts to this stimulus by secreting an excess of plasma corticotropin as measured by levels of urinary 17-OHCS. If the patient has an adrenal or a nonendocrine corticotropin-secreting tumor, the pituitary gland — which is suppressed by the high cortisol levels — can’t respond normally, so steroid levels remain stable or fall.
Ultrasound, computed tomography (CT) scan, or angiography localizes adrenal tumors; CT scan and magnetic resonance imaging of the head may identify pituitary tumors.
Treatment
Treatment to restore hormone balance and reverse Cushing’s syndrome may necessitate radiation, drug therapy, or surgery. For example, pituitary-dependent Cushing’s syndrome with adrenal hyperplasia and severe cushingoid symptoms (such as psychosis, poorly controlled diabetes mellitus, osteoporosis, and severe pathologic fractures) may require partial or complete hypophysectomy or pituitary irradiation. If the patient fails to respond, bilateral adrenalectomy may be performed. Nonendocrine corticotropin-producing tumors require excision of the tumor, followed by drug therapy (for example, with mitotane, metyrapone, or aminoglutethimide) to decrease cortisol levels if symptoms persist.
Aminoglutethimide and ketoconazole decrease cortisol levels and have been beneficial for many cushingoid patients. Aminoglutethimide alone, or in combination with metyrapone, may also be useful in metastatic adrenal carcinoma.
Before surgery, the patient with cushingoid symptoms should have special management to control hypertension, edema, diabetes, and cardiovascular manifestations and to prevent infection. Glucocorticoid administration on the morning of surgery can help prevent acute adrenal hypofunction during surgery.
Cortisol therapy is essential during and after surgery, to help the patient tolerate the physiologic stress imposed by removal of the pituitary or adrenals. If normal cortisol production resumes, steroid therapy may be gradually tapered and eventually discontinued. However, bilateral adrenalectomy or total hypophysectomy mandates lifelong steroid replacement therapy to correct hormonal deficiencies.
Special considerations
Patients with Cushing’s syndrome require painstaking assessment and vigorous supportive care:
❑ Frequently monitor vital signs, especially blood pressure. Carefully observe the hypertensive patient who also has cardiac disease.
❑ Check laboratory reports for hypernatremia, hypokalemia, hyperglycemia, and glycosuria.
❑ Because the cushingoid patient is likely to retain sodium and water, check for edema, and monitor daily weight and intake and output carefully. To minimize weight gain, edema, and hypertension, ask the dietary department to provide a diet that’s high in protein and potassium but low in calories, carbohydrates, and sodium.
❑ Watch for infection — a particular problem in Cushing’s syndrome.
❑ If the patient has osteoporosis and is bedridden, perform passive range-of- motion exercises carefully because of the severe risk for pathologic fractures.
❑ Remember, Cushing’s syndrome produces emotional lability. Record incidents that upset the patient, and try to prevent such situations from occurring if possible. Help him get the physical and mental rest he needs — by sedation if necessary. Offer support to the emotionally labile patient throughout the difficult testing period.
After bilateral adrenalectomy and pituitary surgery:
❑ Report wound drainage or temperature elevation to the patient’s physician immediately. Use strict sterile technique in changing the patient’s dressings.
❑ Administer analgesics and replacement steroids, as ordered.
❑ Monitor urine output, and check vital signs carefully, watching for signs of shock (decreased blood pressure, increased pulse rate, pallor, and cold, clammy skin). To counteract shock, give vasopressors and increase the rate of I.V. fluids, as ordered. Because mitotane, aminoglutethimide, and metyrapone decrease mental alertness and produce physical weakness, assess neurologic and behavioral status, and warn the patient of adverse CNS effects. Also watch for severe nausea, vomiting, and diarrhea.
❑ Check laboratory reports for hypoglycemia due to removal of the source of cortisol, a hormone that maintains blood glucose levels.
❑ Check for abdominal distention and return of bowel sounds after adrenalectomy.
❑ Check regularly for signs of adrenal hypofunction — orthostatic hypotension, apathy, weakness, fatigue — indicators that steroid replacement is inadequate.
❑ In the patient undergoing pituitary surgery, check for and immediately report signs of increased intracranial pressure (confusion, agitation, changes in level of consciousness, nausea, and vomiting). Watch for hypopituitarism.
Provide comprehensive teaching to help the patient cope with lifelong treatment:
❑ Advise the patient to take replacement steroids with antacids or meals, to minimize gastric irritation. (Usually it’s helpful to take two-thirds of the dosage in the morning and the remaining third in the early afternoon to mimic diurnal adrenal secretion.)
❑ Tell the patient to carry a medical identification card and to immediately report physiologically stressful situations such as infections, which necessitate increased dosage.
❑ Instruct the patient to watch closely for signs of inadequate steroid dosage (fatigue, weakness, dizziness) and of overdosage (severe edema, weight gain). Emphatically warn against abrupt discontinuation of steroid dosage because this may produce a fatal adrenal crisis.
Pictures
Book Source Details
- Book Title: Professional Guide to Diseases (Eighth Edition)
- Author(s): Springhouse
- Year of Publication: 2005
- Copyright Details: Professional Guide to Diseases (Eighth Edition), Copyright © 2005 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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