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Endocrine Disorders
Adrenal Hypofunction
Adrenogenital Syndrome
Cushing's Syndrome
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Cushing's Syndrome

What is Cushing's Syndrome?

Cushing's syndrome is the clinical manifestation of glucocorticoid (particularly cortisol) excess. Excess secretions of mineralocorticoids and androgens may also cause Cushing's syndrome. The disorder is classified as primary, secondary, or iatrogenic, depending on its etiology. It's most common in females.

The unmistakable Signs of Cushing's syndrome include adiposity of the face, neck, and trunk, and purple striae on the skin. The prognosis depends or early diagnosis, identification of the underlying cause, and effective treatment.

Causes of Cushing's Syndrome

In about 70% of patients, Cushing's syndrome results from excess production of corticotropin and consequent hyperplasia of the adrenal cortex. Corticotropin overproduction may stem from pituitary hypersecretion (Cushing's disease), a corticotropin-producing tumor in another organ (especially bronchogenic or pancreatic carcinoma), or administration of synthetic glucocorticoids or corticotropin. 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.

Signs & Symptoms of Cushing's Syndrome

Cortisol excess produces Significant and serious change in the appearance and health of affected individuals. Depending on the cause and duration of the Cushing's Syndrome, some people may have more dramatic changes, some might look more masculinized, some may have more blood pressure or weight changes.The following symptoms are listed common:

  • Children will show obesity and poor growth in height.
  • Irregular or stopped menstrual periods in females
  • Erectile dysfunction in males
  • High blood pressure
  • Body hair growth
  • Facial hair growth
  • Acne
  • Reddish-blue streaks on the skin
  • Adult Cushing's symptoms
  • Extreme weight gain
  • Upper body obesity
  • Rounded face
  • Increased neck fat
  • Diabetes mellitus
  • Sleep disturbances

Diagnostic tests

Diagnosis of Cushing's syndrome depends on a demonstrated increase in cortisol production and the failure to suppress endogenous cortisol secretion after administration of dexamethasone.

Initial screening may consist of a 24-hour urine test to determine free cortisol excretion rate and a low-dose dexamethasone test. Failure to suppress plasma and urine cortisol levels confirms the diagnosis of Cushing's syndrome.

A low-dose dexamethasone suppression test can be used to determine if Cushing's syndrome results from pituitary dysfunction (Cushing's disease). In this diagnostic test, dexamethasone suppresses plasma cortisol levels. Failure to suppress these levels indicates that the syndrome results from an adrenal tumor or a nonendocrine, corticotropin-secreting tumor. Urinary 17-hydroxycorticosteroids (17-0HCS) and 17ketogenic steroids decrease 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, metyrapone - which blocks cortisol production by the adrenal glands - is administered to test 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, measured by levels of urinary 17-0HCS. If the patient has an adrenal or a nonendocrine corticotropinsecreting tumor, the pituitary gland - which is suppressed by the high cortisol levels - can't respond normally, so steroid levels remain stable or decrease.

Radiologic evaluation for Cushing's syndrome is used to locate the causative tumor in the pituitary gland or the adrenals. Tests include ultrasonography, a computed tomography scan, magnetic resonance imaging, or angiography to locate tumors.

Blood chemistry may show hypernatremia, hypokalemia, hypocalcemia, and elevated blood glucose and lymphocyte counts.


Management to restore hormone balance and reverse Cushing's syndrome may require radiation, drug therapy, or surgery.

A patient with pituitary-dependent Cushing's syndrome with adrenal hyperplasia may need hypophysectomy or pituitary irradiation. If hypophysectomy and irradiation are unsuccessful or infeasible, bilateral adrenalectomy may be performed. A patient with a nonendocrine corticotropin-producing tumor requires excision of the tumor, followed by drug therapy with mitotane, metyrapone, or aminoglutethimide to decrease cortisol levels if there are symptoms. 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 requires management to control hypertensior, 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 adrenal glands. If normal cortisol production resumes, steroid therapy may gradually be tapered and eventually discontinued. However; bilateral adrenalectomy or total hypophysectomy mandates lifelong steroid replacement therapy to correct hormonal deficiencies.

Prevention Tips
  • Awareness of the Signs and symptoms of Cushing's syndrome may permit early intervention for patients prescribed corticosteroids.
  • Cushing's syndrome may be prevented by an awareness of the associated symptoms so that early detection can be made.
  • Use caution when taking corticosteroid medications.

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