Cushing's syndrome

Cortical excess
Cushing's disease

Cushing's syndrome is a disease caused by an excess of cortisol production or by excessive use of cortisol or other similar steroid (glucocorticoid) hormones. Cortisol excess produces significant and serious change in the appearance and health of affected individuals. Some people may have more dramatic changes, some might look more masculinized, some may have more blood pressure or weight changes. Symptoms usually include fatigue, weakness, depression, mood swings, increased thirst and urination, and lack of menstrual periods in women. If untreated, Cushing's syndrome will cause continued weakness of the muscles, fatigue, poor skin healing, weakening of the bones of the spine (osteoporosis) and increased susceptibility to some infections including pneumonia and tuberculosis.


Dr. Harvey Cushing first described a woman with signs and symptoms of this disease in 1912, and in 1932 he was able to link the adrenal overproduction of cortisol to an abnormality in the pituitary.

Cortisol is a normal hormone produced in the outer portion, or cortex, of the adrenal glands, located above each kidney. The normal function of cortisol is to help the body respond to stress and change. It mobilizes nutrients, modifies the body's response to inflammation, stimulates the liver to raise the blood sugar, and it helps control the amount of water in the body. Cortisol production is regulated by adrenocorticotrophic hormone (ACTH), made in the pituitary gland, which is located just below the brain.

When too much cortisol is produced in the adrenal glands, or an excess is taken in treating other diseases, significant changes occur in all of the tissues and organs of the body. All of these effects together are called Cushing's Syndrome. Cushing's disease is the name given to a type of Cushing's Syndrome caused by too much ACTH production in the pituitary.

Spontaneous overproduction of cortisol in the adrenals is divided into two groups - those due to an excess of ACTH and those that are independent of ACTH. A pituitary tumour producing too much ACTH, stimulating the adrenals to grow (hyperplasia) and to produce to much cortisol, is the most common type, and this is called Cushing's disease. It is the cause of 70% of spontaneous Cushing's syndrome. ACTH can also be produced outside the pituitary in a benign or malignant tumour in the lung, thymus gland, pancreas, or other organ. This is called "ectopic" ACTH production.

When the source of excess cortisol production is a tumour of the adrenal gland itself, then it is not dependent on ACTH. The tumour makes cortisol on its own, and the other adrenal gland shrinks because ACTH production is suppressed. Adrenal cortex tumours can be benign (an adenoma), or malignant (a carcinoma) and are usually found on only one side. A very rare type is caused by multiple benign adenomas on both sides.

Although almost all types of spontaneous Cushing's Syndrome are ultimately caused by one type of tumour or another, little is known about what makes these tumours occur. There does not appear to be any specific genetic, immune, or environmental factor.

When cortisol or other glucocorticoid hormones (such as hydrocortisone, prednisone, methyl-prednisolone or dexamethasone) are taken in excess of the normal daily requirement for a prolonged period of time, it causes Cushing's syndrome. This "iatrogenic" (caused by the treatment) form is unfortunately a necessary side effect when high doses of these steroid hormones must be used to treat certain life-threatening illnesses.


Spontaneous Cushing's syndrome is relatively rare and most commonly affects adults aged 20 to 50. It has a greater frequency in women than men. An estimated 5 to 25 of every million people are affected each year. Ectopic ACTH as a cause of Cushing's Syndrome is more common because of the high rate of lung cancer (about 660 per million per year), but it often goes unrecognized. The incidence increases with age. Adrenal tumours are relatively rare, and cause Cushing's Syndrome in only 2 people per million per year for both adenomas and carcinomas. Both are also 4 to 5 times more common in women than men. Iatrogenic Cushing's Syndrome from taking steroid medication is extremely common because of the widespread use of glucocorticoid hormones for asthma, rheumatoid arthritis, systemic lupus inflammatory bowel disease, some allergies and other inflammatory diseases.

(G) Very specific problems