Cushing's Syndrome

Signs and Symptoms

Cushing's syndrome is a rare hormonal disorder that occurs when the body's tissues are exposed to excessive levels of the hormone cortisol for a long period of time. Cortisol is produced by the adrenal glands and helps the body respond to stress, such as surgery and illness, and recover from infections. The hormone also helps maintain blood pressure and cardiovascular function and regulate the metabolism of proteins, carbohydrates and fats.

Benign, or non-cancerous, tumors of the pituitary gland called pituitary adenomas that secrete excessive amounts of adrenocorticotrophic hormone (ACTH) cause an estimated 70 percent of Cushing's syndrome cases in adults and is referred to as Cushing's disease. Other causes include tumors of the adrenal glands, which are located above the kidneys, as well as tumors occurring elsewhere in the body, such as the lungs, that secrete ACTH. This condition is known as ectopic ACTH syndrome. Rarely, some people may have an inherited tendency to develop tumors of one or more endocrine glands that can lead to Cushing's syndrome.

Cushing's syndrome is relatively rare, each year affecting only about 10 to 15 out of every million people. It most commonly occurs in adults between 20 and 50 years of age, with women accounting for over 70 percent of those diagnosed.

Symptoms of Cushing's syndrome may include:

• Change in body form, particularly weight gain in the face that is referred to as moon facies as well as fat deposition above the collar bone, called supraclavicular fat, and at the back of neck, called a buffalo hump.
• Skin changes with easy bruising, purplish stretch marks, called stria, and red cheeks
• Excess hair growth on face, neck, chest, abdomen and thighs
• Overall weakness and fatigue
• Loss of muscle bulk
• Menstrual disorders in women
• Decreased fertility and/or sex drive
• Hypertension
• Diabetes mellitus
• Depression with wide mood swings

Diagnosis

Diagnosis of Cushing's syndrome is based on a review of your medical history, physical examination and laboratory tests, which help to determine the presence of excess levels of cortisol. Often X-ray exams of the adrenal or pituitary glands are useful for locating tumors. In addition, comparison of old and recent photographs will often highlight the changes in facial and body appearance in patients who develop Cushing's syndrome.

The first step in diagnosing Cushing's disease is to confirm the presence of excessive cortisol secretion. This diagnosis is most easily made by the following tests:

• Low-dose dexamethasone suppression test that involves taking a small dose of a cortisol-like drug dexamethasone (1 mg) at 11 p.m. and having blood drawn for cortisol the following morning. Normal individuals typically have very low levels of cortisol in these samples, indicating that ACTH secretion is suppressed, while cortisol is readily detected and oftentimes is increased in patients with Cushing's disease.

• 24-hour urine collection to measure cortisol levels.

Once the diagnosis of Cushing's syndrome is established, the source of the excess cortisol needs to be determined. The source may be from an adrenal gland tumor, ACTH-producing tumor or a pituitary ACTH-producing adenoma. Petrosal sinus sampling is a test used to distinguish the source of the ACTH secretion and should never be performed before the diagnosis of Cushing's syndrome has been established.

If laboratory tests suggest a pituitary adenoma as the cause of Cushing's syndrome, a pituitary magnetic resonance imaging (MRI) is performed to confirm the diagnosis.

Treatment

Treatment for Cushing's syndrome depends on the specific reason for cortisol excess and may include surgery, radiation, chemotherapy or the use of cortisol-inhibiting drugs.

• Surgery -- Surgery typically involves transsphenoidal removal of the adenoma. It is one of the primary treatment method used to achieve a long-term cure of Cushing's syndrome.

• Medical Therapy -- In patients who fail to recover after surgery, there are several medications available to help control cortisol levels. These include adrenal-directed medications such as ketoconazole, aminoglutethemide and metyrapone, which all help to inhibit cortisol production in the adrenal glands. All are relatively effective but each has side effects and they only work to correct the hormonal problem, not the cause of Cushing's syndrome.

• Radiotherapy -- When Cushing's syndrome is not controlled with surgery, conventional external beam or stereotactic radiosurgery are effective in controlling cortisol levels and tumor growth in many patients. However, it generally takes significantly longer to lower cortisol levels with external beam radiotherapy as compared to stereotactic radiotherapy. Also, external beam radiation reliably causes loss of normal pituitary function five to 10 years after treatment. Neurologic complications such as vision loss, weakness and memory impairment rarely have been reported with both external beam and stereotactic radiotherapy.