Cushing's syndrome
Cushing's syndrome: Excerpt from Handbook of Diseases
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.
Suppression test
A low-dose dexamethasone suppression test confirms the diagnosis of Cushing’s syndrome. A high-dose dexamethasone suppression test can determine whether Cushing’s syndrome results from pituitary dysfunction (Cushing’s disease) or from adenoma of the adrenal gland or ectopic corticotropin secretion.
In this test, dexamethasone suppresses plasma cortisol levels, and urinary 17-hydroxycorticosteroids (17-OHCS) and 17-ketogenic steroids 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.
Stimulation test
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 syndrome 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. The corticotropin-releasing hormone tests can also be used to help differentiate pituitary Cushing’s and ectopic corticotropin syndrome.
Other tests
Ultrasonography, a computed tomography (CT) scan, magnetic resonance imaging (MRI), or angiography localizes adrenal tumors; a CT scan and MRI of the head identify pituitary tumors.
Clinical tip Measuring resting cortisol at midnight is the most sensitive test. This can be done at home by collecting saliva at midnight. In the hospital, collecting serum from an indwelling catheter placed in the early evening may aid collection.
Treatment
Primary treatment is transphenoidal hypophysectomy radiation and drug therapy, are secondary treatments used to restore hormone balance and reverse Cushing’s syndrome. 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 adenectomy or pituitary irradiation. If the patient fails to respond, bilateral adrenalectomy may be performed.
Nonendocrine corticotropin-producing tumors require excision of the tumor. Drug therapy follows (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 insufficiency 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. (See Dealing with lifelong treatment.)
Special considerations
❑ 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.
Clinical tip 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 surgery:
❑ Watch carefully for wound drainage or temperature elevation. Use strict aseptic technique in changing the patient’s dressings.
❑ Administer analgesics and replacement steroids as necessary.
❑ Monitor urine output and check vital signs carefully, watching for signs of shock (decreased blood pressure, increased pulse rate, pallor, and cold, clammy skin).
❑ If shock develops, give vasopressors and increase the rate of I.V. fluids. 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.
❑ Watch for severe nausea, vomiting, and diarrhea.
❑ Check laboratory reports for hypoglycemia from removal of the source of cortisol, a hormone that maintains blood glucose levels.
❑ Check for abdominal distention and return of bowel sounds following 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, be alert for signs of increased intracranial pressure (confusion, agitation, changes in level of consciousness, nausea, and vomiting). Also, watch for hypopituitarism.
Pictures
Book Source Details
- Book Title: Handbook of Diseases
- Author(s): Springhouse
- Year of Publication: 2003
- Copyright Details: Handbook of Diseases, Copyright © 2003 Lippincott Williams & Wilkins.
More About Cushing's syndrome
More Medical Textbooks Online about Cushing's syndrome
Review other book chapters online related to Cushing's syndrome:
Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
|
|
More About This Book:
Title: Handbook of Diseases
Authors: Springhouse
Publisher: Lippincott Williams & Wilkins
Copyright: 2003
ISBN: 1-58255-266-5
|
|
» Next page: Surveys relating to Cushing's syndrome
Rate This Website
What do you think about the features of this website?
Take our user survey and have your say:
Website User Survey
Medical Tools & Articles:
Next articles:
Tools & Services:
Medical Articles:
Forums & Message Boards
- Ask or answer a question at the Boards:
