Bad Moon Rising

By Peter Galvin, MD

Cushing syndrome is caused by persistently high levels of a hormone/steroid called cortisol. It can be due to the use of medications that raise cortisol levels, called exogenous Cushing syndrome, or excessive cortisol production within the body, called endogenous Cushing syndrome. The most common cause of exogenous Cushings is the use of steroids to treat diseases like asthma, lupus, and rheumatoid arthritis. About 60% to 70% of endogenous Cushings is caused by a benign tumor (adenoma) in a part of the brain called the pituitary gland. The adenoma pumps out high levels of adrenocorticotrophic hormone (ACTH) which stimulates the adrenal glands to produce excess cortisol. This form of the syndrome is known as Cushing disease, first described by American neurosurgeon Harvey Cushing in 1932. Incidentally, a pituitary adenoma may also cause acromegaly, or pituitary gigantism, a disease that the wrestler Andre the Giant had. Less commonly, the endogenous syndrome may be caused by tumors in the lungs, pancreas, or thyroid or adrenal glands. While the exact number of people with Cushing syndrome is unknown, it is diagnosed in about two to eight per million people each year, mostly in those aged 30 to 49 years, and women are diagnosed at about three times the rate that men are.

Whether endogenous or exogenous, the symptoms are usually the same, and can be striking and may include a round or “moon” face, muscle weakness, easy bruising, purple stretch marks, and a fat pad on the upper back (buffalo hump or lipodystrophy). Other symptoms may include rapid weight gain, menstrual irregularities, depression, high blood pressure, high blood sugar, excessive hair growth, acne, and sleep disorders. The attached photo is of a woman with the syndrome. Note the moon face, excessive hair growth, and acne. Untreated Cushing syndrome may lead to heart attacks, strokes, diabetes, blood clots, bone fractures, and premature death, so early and prompt diagnosis and treatment is essential.

If it is determined that the syndrome is caused by medications, the offending medication must be slowly withdrawn as the adrenal glands may have atrophied and sudden withdrawal may trigger adrenal insufficiency. If no causal medications are found, testing may include measuring cortisol levels in the urine or saliva plus a blood test for a fasting morning cortisol level. Brain MRI may be used to locate a pituitary adenoma, for which the first-line treatment is surgical removal. If surgery is not feasible or effective, either radiation therapy (which is 92% effective) and/or medications may be used. Medications include mifepristone (yes, that mifepristone, commonly used to induce abortion), ketoconazole, and a number of other drugs that are available and useful.

Following surgical removal of a pituitary adenoma, cortisol levels must be monitored as very often they will fall well below normal requiring hydrocortisone (i.e. prednisone) supplementation. Cortisol levels may take from seven months to 2.5 years to return to normal after surgery. Unfortunately, about one third of patients who undergo pituitary surgery for Cushing disease will develop a recurrence of the disease. For more information go to the website of the National Institute of Diabetes and Digestive and Kidney Diseases at www.niddk.nih.gov