According to the National Institutes of Health (NIH), Cushing's disease is a syndrome in which the body is exposed to too much cortisol. People with this disorder tend to have an obese stomach and torso with a rounded face and excess fat at the back of the neck, but slender arms and legs. The skin becomes fragile and often develops stretch marks. Patients complain of fatigue, weakness and irritability and a doctor may note high blood pressure and blood glucose.
Effects of Cortisol
While there are many different causes for Cushing's disease, they are all related to the body's exposure to an excess of cortisol. Cortisol is a hormone produced by the adrenal glands that helps to maintain blood pressure, reduce the inflammatory response, maintain glucose balance, and regulate the metabolism of proteins, carbohydrates and fats. Even though cortisol is produced by the adrenal glands, the hypothalamus and the pituitary gland also play a role in cortisol release. The hypothalamus, which is located in the brain, releases a hormone called corticotropin-releasing hormone (CRH) to the pituitary gland. The pituitary gland, also located in the brain, sends adrenocorticotropin hormone (ACTH) to the adrenal glands in response. When the adrenal glands receive ACTH, they release cortisol.
Exogenous Medications
The use of medications that are similar in action and structure to cortisol is a frequent cause of Cushing's disease. Many patients with Cushing's disease take glucocorticoids, or steroid hormones. These medications are used for inflammatory diseases such as asthma and rheumatologic conditions. They are also used in patients who have received an organ transplant. Just as cortisol reduces the inflammatory response, glucocorticoids provide the same effect. When a patient is on high doses of glucocorticoids, however, he develops the symptoms of cortisol excess.
Pituitary Gland Tumor
According to the Mayo Clinic, certain types of pituitary gland tumors that are noncancerous secrete an excess amount of ACTH. The excess ACTH over-stimulates the adrenal gland and the adrenal gland thus releases too much cortisol. This happens more frequently in women than in men and is the most common cause of Cushing's disease that is not related to medication use.
ACTH-Secreting Tumor
In some cases, a tumor located in an organ that does not normally produce ACTH will secrete this hormone. As with a tumor located in the pituitary, the ACTH overstimulates the adrenal glands to produce cortisol and results in Cushing's disease. These tumors are most frequently located in the lungs, pancreas, thyroid or thymus and can either be cancerous or benign. A type of lung cancer called small cell lung cancer causes about half of these instances and is more common in men than in women.
Adrenal Tumors
An adrenal tumor or excess growth of the adrenal glands can also cause Cushing's disease. These tumors directly release excess cortisol into the bloodstream and can be either cancerous or benign, but are more frequently benign. Adrenal cancer, or adrenocortical carcinoma, does cause Cushing's disease, but tends to result in very high levels of cortisol and thus more aggressive symptoms.
Differentiating between Causes
A 24-hour urinary free cortisol test, which measures the amount of cortisol in the urine over a 24-hour period, can diagnose Cushing's disease. Differentiating between causes, however, can be more difficult. The CRH stimulation test is used to help differentiate between a patient with a pituitary tumor versus another cause. This test involves a blood draw and an injection of CRH. If this test is not conclusive, petrosal sinus sampling may be needed. This test is more complex as samples of blood are taken from the sinuses that run into the pituitary. Mild sedation is needed for this test. Diagnosing the cause of excess cortisol is important because both the pituitary gland and adrenal glands can have benign tumors that are not the cause of symptoms, and misdiagnosis could result in unnecessary surgery.
