Diabetes Drug May Treat Cushing's Syndrome

Researchers have found that pituitary tumors such as those in Cushing's syndrome express an abundance of a specific protein receptor that regulates sugar metabolism. They report that a common diabetes drug was effective in shrinking tumor size and reducing hormone production. The findings were reported in the November 2002 issue of Nature Medicine.

The protein receptor, called PPAR-gamma (peroxisome proliferator activating receptor), is a member of the steroid family and functions to regulate other genes involved in growth and metabolism. For example, the protein plays a role in the body's ability to respond to insulin, which lowers blood sugar. In fat cells, PPAR-gamma regulates sugar metabolism.

The most common type of Cushing's syndrome is caused by prolonged high-level exposure of a hormone called ACTH (adrenocorticotropin), secreted by tumors of the pituitary gland. The researchers found that PPAR-gamma was present selectively on normal ACTH-secreting pituitary cells, leading them to examine tumor specimens that secreted too much ACTH. In this analysis, they evaluated six ACTH-secreting pituitary tumors that had been surgically removed. They found that PPAR-gamma was abundantly expressed in all six tumors, as compared to modest expression in the normal pituitary tissue samples.

"Now that we know that this protein receptor plays a role in the pituitary tumors that cause Cushing's syndrome, we may have found a drug that can effectively treat this disease,” said Dr. Anthony Heaney, lead author of the study and assistant professor and medical director of the neuroendocrine tumor center at Cedars-Sinai Medical Center (Los Angles, CA, USA).

Following an investigation, the researchers found that rosiglitazone was effective in lowering ACTH and other steroid hormones and thus may help to slow tumor growth in humans. Clinical trials of the drug are planned.




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