It may soon be possible for doctors to better treat a condition called Cushing’s disease, in which the body has too much exposure to the hormone cortisol. Researchers have identified one of the proteins behind the development of pituitary tumors, a common effect of the disease. The protein is one of a type called nuclear receptors, which are responsible for identifying and responding to hormone activity.
The nuclear receptor involved, called TR4, activates the production of a chemical called adrenocorticotropic hormone. Overproduction of this chemical is a characteristic of the pituitary tumors that trigger Cushing’s disease, and produces the excess cortisol which leads to the condition. The discovery is the first indication of a link between TR4 and adrenocorticotropic hormone. This discovery could help give health care practitioners a new route by which to address the disorder.
Cushing’s disease is a specific type of the condition called Cushing’s syndrome. Also called endogenous Cushing’s syndrome, because the excess cortisol is produced in the body, it is one of the two main causes the syndrome, the other being the corticosteroids often prescribed for inflammatory disease. Whatever the cause, Cushing patients tend to gain weight and develop fat deposits in the face and shoulders. Other symptoms include bruising easily and cuts healing slowly, thin and fragile, skin, and acne. Women often develop more body hair and have irregular periods; men exhibit reduced libido and erectile dysfunction. Left untreated, the condition can lead to loss of bone and muscle mass, heightened vulnerability to infection, diabetes, and high blood pressure.
Patients with any form of Cushing’s syndrome who are taking corticosteroids need to be tapered off the drugs, since they can be dangerous if stopped abruptly. The possibility of treating Cushing’s disease by suppressing the activity of TR4 is being investigated. Current medications for the condition, such as mifepristone and ketoconazole, block the production or effects of cortisol. Often, however, the pituitary tumors in which the excess cortisol is produced are either treated with radiation or are removed surgically. Surgery is also a common option when the tumor is on the adrenal glands, lungs, or pancreas; in extreme cases, the adrenal glands themselves may be removed.