In the early twentieth century, Harvey Cushing, (1869–1939), an American neurosurgeon, described a set of symptoms that he identified as a syndrome later called Cushing syndrome or disease. The cause of the syndrome at the time was unknown, but since then, a better understanding of the underlying causes of Cushing syndrome have been elucidated.
Cushing syndrome is a disorder that is caused by excessive exposure of the body's tissues to a hormone called cortisol for long periods of time. It is a rare disease that effects adults ages 20–50, with roughly 10–15 million people affected each year. People that take steroidal hormones such as prednisone for arthritis or asthma may develop symptoms similar to Cushing syndrome. Overproduction of cortisol also causes the disease. Cortisol is produced in the cortex of the adrenal gland. The adrenal cortex is the outer layer of the gland. The adrenal glands rest like limp, triangular caps atop each kidney. The adrenal glands release cortisol in response to stimulation by another hormone, adrenocorticotropin (ACTH), that is produced by the pituitary gland. The pituitary gland is located at the base of the brain and is the control center for the other glands. ACTH is only produced when there are inadequate levels of cortisol in the bloodstream. Dysregulated cortisol production can be due to abnormalities in the adrenal glands, the pituitary gland, or abnormal regulation of ACTH production.
Cortisol has a variety of functions throughout the body. It is important in the regulation of blood pressure and serves as an anti-inflammatory mediator. It also regulates insulin metabolism as well as plays a role in protein, carbohydrate, and lipid metabolism. High levels of cortisol can cause sodium and water retention. Excessive cortisol production also can affect heart functions, muscle movements, blood cell development as well as other necessary bodily functions. Perhaps one of the most important functions of cortisol is to help the body respond to stress.
Certain tumors and other conditions can upset the balance between the pituitary gland and the adrenal gland, resulting in excessive cortisol production. There are several types of tumors related to overproduction of cortisol. Pituitary adenomas are non-cancerous tumors that produce increased amounts of ACTH and cause the greatest number of cases of Cushing syndrome with a five-fold higher risk for women. Cancerous tumors that develop outside the pituitary can produce ACTH, a condition also known as ectopic ACTH syndrome. Other cases of Cushing syndrome come from adrenal tumors. A non-cancerous tumor in the adrenal tissue can result in excessive cortisol release. Symptoms rapidly develop in cancerous tumors of the adrenal glands due to high levels of hormone production. Familial Cushing syndrome is condition that involves an inherited susceptibility to developing endocrine gland tumors but only accounts for a small population of patients.
Cushing syndrome patients can develop a rounded, moon-shaped face, a large fat pad below the neck and on the back between the shoulders (called a buffalo hump), and an accumulation of fat on the abdomen. The volume of abdominal fat develops dramatically, often hanging over the beltline. Sometimes vertical purplish stripes or striations will appear on the abdomen. Weakness and wasting away of the muscles can occur. The skin bruises easily and wounds heal slowly. Women develop brittle bones, or osteoporosis, rendering them vulnerable to fractures, especially in the pelvis and spinal areas of the body. The beginning stages of diabetes can develop and include glucose intolerance. Psychiatric symptoms, excess hair growth in women, and high blood pressure can all be part of the symptomatology. Excessive cortisol production in children can result in growth retardation.
The first step in treating Cushing syndrome patients is to identify the cause of the excessive ACTH production. It may be the result of abnormalities in the function of the pituitary gland or the adrenal cortex, exposure to cortisone for unrelated medical treatment purposes, or a tumor that stimulates ACTH or cortisol production. Cushing syndrome symptoms in patients that are receiving treatment of cortisol can reverse the symptoms by refraining from taking these medications. A tumor of the pituitary gland may require surgical removal if other treatments such as chemotherapy, radiation, or cortisol inhibitors prove unsuccessful. Removal of the adrenal gland is necessary if the tumor lies within it. Removal of one adrenal gland will not affect the endocrine balance since the other gland will naturally compensate. If both glands are removed, however, the patient must be given cortisol and other hormones to compensate for the lack of adrenal gland function.
A better understanding of the contribution of cortisol or ACTH and the cause of altered hormonal regulation has lead to better diagnostic tests as well as improved therapies. Current research is underway to identify the specific genetic defects associated with developing the disease.
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