Cushing's Syndrome /

Cushing's Syndrome / Hypercortisolism: Overview

Alternative names: Hypercortisolism, Adrenocortical Hyperfunction.

Cushing's syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol.

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Normally, the production of cortisol follows a precise chain of events.  First, the hypothalamus, a part of the brain which is about the size of a small sugar cube, sends corticotropin releasing hormone (CRH) to the pituitary gland.  CRH causes the pituitary to secrete ACTH (adrenocorticotropin), a hormone that stimulates the adrenal glands.  When the adrenals receive the ACTH, they respond by releasing cortisol into the bloodstream.

When the amount of cortisol in the blood is adequate, the hypothalamus and pituitary release less CRH and ACTH.  This ensures that the amount of cortisol released by the adrenal glands is precisely balanced to meet the body's daily needs.  However, if something goes wrong with the adrenals or their regulating mechanisms in the pituitary gland or the hypothalamus, cortisol production can become abnormal.

Some patients may have sustained high cortisol levels without the effects of Cushing's syndrome.  These high cortisol levels may be compensating for the body's resistance to cortisol's effects.  This rare syndrome of cortisol resistance is a genetic condition that causes hypertension and chronic androgen excess.

Incidence; Causes and Development

Cushing's syndrome is relatively rare and most commonly affects adults aged 20 to 50.

The most common cause of Cushing's is a tumor in the pituitary gland, and the least common is cancer of the adrenal gland.  Many people suffer the symptoms of Cushing's syndrome because they take glucocorticoid hormones – such as prednisone – as an antiinflammatory.  Some develop Cushing's syndrome because of overproduction of cortisol by the body.

Other causes include:

  • Ectopic ACTH Syndrome: Some benign or malignant tumors that arise outside the pituitary can produce ACTH.  This condition is known as ectopic ACTH syndrome.  Lung tumors cause over 50% of these cases and men are affected 3 times more frequently than women.  The most common forms of ACTH-producing tumors are oat cell, or small cell lung cancer, which accounts for about 25% of all lung cancer cases, and carcinoid tumors.  Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors, and medullary carcinomas of the thyroid.
  • Adrenal Tumors: Sometimes, an abnormality of the adrenal glands, most often an adrenal tumor, causes Cushing's syndrome.  The average age of onset is about 40 years.  Most of these cases involve non-cancerous tumors of adrenal tissue, called adrenal adenomas, which release excess cortisol into the blood.
  • Familial Cushing's Syndrome: Most cases of Cushing's syndrome are not inherited.  Rarely, however, some individuals have special causes of Cushing's syndrome due to an inherited tendency to develop tumors of one or more endocrine glands.  In Primary Pigmented Micronodular Adrenal Disease, children or young adults develop small cortisol-producing tumors of the adrenal glands.  In Multiple Endocrine Neoplasia Type I (MEN I), hormone secreting tumors of the parathyroid glands, pancreas and pituitary occur.  Cushing's syndrome in men may be due to pituitary, ectopic or adrenal tumors.

Diagnosis and Tests

Diagnosis is based on a review of the patient's medical history, physical examination and laboratory tests.  Often X-ray exams of the adrenal or pituitary glands are useful for locating tumors.  These tests help to determine if excess levels of cortisol are present and why.

Sometimes other conditions may be associated with many of the symptoms of Cushing's syndrome.  These include polycystic ovarian syndrome, which may cause menstrual disturbances, weight gain from adolescence, excess hair growth and sometimes impaired insulin action and diabetes.  Commonly, weight gain, high blood pressure and abnormal levels of cholesterol and triglycerides in the blood are associated with resistance to insulin action and diabetes; this has been described as the "Metabolic Syndrome-X."  Patients with these disorders do not have abnormally elevated cortisol levels.

Treatment and Prevention

Treatment depends on the specific reason for cortisol excess and may include surgery, radiation, chemotherapy or the use of cortisol-inhibiting drugs.  If the cause is long-term use of glucocorticoid hormones to treat another disorder, the doctor will gradually reduce the dosage to the lowest dose adequate for control of that disorder.  Once control is established, the daily dose of glucocorticoid hormones may be doubled and given on alternate days to lessen side-effects.

Signs, symptoms & indicators of Cushing's Syndrome / Hypercortisolism:

Lab Values - Cells

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Cushing's Syndrome / Hypercortisolism can lead to:

Lab Values

Recommendations for Cushing's Syndrome / Hypercortisolism:

Laboratory Testing

Test Adrenal Function

A 24-Hour urinary free cortisol level is the most specific diagnostic test.  Levels higher than 50 to 100mcg per day for an adult suggest Cushing's syndrome.  Once Cushing's syndrome has been diagnosed, other tests are used to find the exact location of the abnormality that leads to excess cortisol production.  These tests could include dexamethasone suppression test, CRH stimulation test, direct visualization of the endocrine glands (radiologic imaging), petrosal sinus sampling and the dexamethasone-CRH test.

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