Hypercortisolism, Cushing's Disease, Ectopic ACTH Syndrome
What is Cushing's syndrome?
Cushing's syndrome comprises the signs and symptoms caused by excessive amounts of the hormone cortisol (hypercortisolism) or by an overdosage of drugs known as glucocorticoids. The term hypercortisolism and Cushing's syndrome may be used interchangeably.
The adrenal glands located on top of the kidneys produce cortisol. Under normal conditions, the release of cortisol is controlled by the pituitary gland in the brain. The pituitary gland produces a hormone called ACTH (adrenocorticotropic hormone). ACTH is the signal for the adrenal gland to produce cortisol. When a tumor (adenoma) of the pituitary gland produces excessive amounts of ACTH, there is a subsequent release of excess cortisol by the adrenal glands. This condition is called Cushing's disease, and it accounts for about 70% of the naturally occurring (endogenous) cases of Cushing's syndrome.
About 20% to 25% of the naturally occurring cases of Cushing's syndrome can also be caused by release of cortisol from benign and malignant tumors of the adrenal gland (adrenal adenoma and adrenal carcinoma), with the remaining five percent of cases caused by the production of ACTH by a tumor (malignancy) located elsewhere in the body (ectopic ACTH production).
The most common cause of Cushing's syndrome is due to the administration of glucocorticoid drugs (cortisone) or ACTH for various medical reasons (exogenous or iatrogenic Cushing's).
Cushing's disease affects women nine times more frequently than men and can occur at any age, but it is rare in childhood. Cushing's syndrome from ectopic ACTH production affects men ten times more frequently, and there is no difference between the sexes in the case of adrenal gland tumors.
How is it diagnosed?
History: Frequent complaints include weight gain, fatigue, muscle weakness (especially of the upper arms and thighs), easy bruising, poor wound healing, thinning scalp hair, abnormal growth of body hair, purple streaking (striae) of the breasts, flanks, lower abdomen and thighs.
Individuals may also complain of excessive thirst and frequent urination.
Psychiatric symptoms include mood swings, depression, and personality changes (steroid psychosis). Women may notice changes in the menstrual flow (oligomenorrhea or amenorrhea), and men may complain of decreased libido and impotence.
Physical exam: Hypertension is seen in over 80% of the cases. There are some striking physical changes in Cushing's syndrome. The face is round and florid. Acne may be present. Obesity is common, 50% of individuals will present with centripetal weight gain, (the arms and legs are normal and the weight gain is carried in the abdomen and buttocks). Fat pads appear over the collarbones and upper spine.
Tests: If it has been determined from the history and physical exam that the individual is not showing the signs of Cushing's syndrome from prescribed medications, further testing is carried out at two levels.
First, it must be determined whether the individual is showing the effects of elevated levels of cortisol. A 24-hour urine collection is taken and the amount of excreted cortisol is measured. The cortisol level will be elevated in individuals with Cushing's syndrome.
Another test is the overnight dexamethasone suppression test. Dexamethasone will suppress ACTH release in normal individuals and lower the early morning levels of blood cortisol, but have no effect in individuals with Cushing's syndrome.
The second level of testing is carried out once the diagnosis of Cushing's syndrome is established. The cause of the disease must be determined: is it a tumor of the pituitary gland, adrenal glands, or a malignancy that is stimulating the adrenal glands through ectopic ACTH secretion.
Routine chest x-rays are done in all cases and CT scan of the chest is done in all cases of suspected cases of ectopic ACTH production. A CT scan of the adrenal glands can show an adrenal tumor, or in the case of a pituitary tumor that stimulates both glands, enlarged adrenal glands.
MRI of the pituitary gland is done in all cases of suspected pituitary tumors.
How is Cushing's syndrome treated?
If the condition is caused by over medication, it is treated by reducing the dosage of glucocorticoids or changing the medication. When the underlying cause is a benign or malignant tumor of the adrenal gland, it must be surgically removed.
The treatment of choice for tumors of the pituitary gland is surgical removal. Irradiation of the pituitary gland has a lower success rate, has a higher rate of complications, and notable improvement may not be noted for a year or more.
Hormone replacement therapy usually follows surgery, and, in some cases, must be continued for life.
Medical treatment (chemotherapy) is usually not recommended as the primary treatment for Cushing's syndrome but is an alternative if surgery is not possible and may be used with radiation treatments to hasten better results. If the cause of Cushing's syndrome is from ectopic ACTH produced by another type of malignancy, the treatment is directed at that disease.
- Drugs to suppress adrenal-gland function.
- Cortisone drugs, if adrenal glands must be removed surgically.
- Drugs to replace pituitary hormones (sometimes).
- Antihypertensive drugs to lower blood pressure.
- Calcium supplements to treat osteoporosis.
- Sedatives may be recommended.
Nizoral (Ketoconazole), Periactin (Cyproheptadine), Decadron (Dexamethasone)
What might complicate it?
Cushing's syndrome is complicated by high blood pressure, diabetes, infections, and emotional disturbances. The bones become fragile (osteoporosis), and compression fractures of the spine are common. Untreated, Cushing's disease has a 50% death rate within five years if untreated. Pituitary adenomas are only seen on 50% of the MRI tests, hence it is important that the biochemical testing is thorough before surgery. On the other hand, the smaller the pituitary tumor, the better the chances for a cure through surgery.
The effects of hypercortisolism secondary to a malignancy of the adrenal glands are usually detected in later stages of the disease after the cancer has spread to other organs such as the liver and lungs and has a poor prognosis. Surgery to remove pituitary and adrenal adenomas is generally successful, but there is a recurrence rate of up to twenty percent over the next ten years, and the individual may require hydrocortisone therapy from six months to three years until the normal hormone balance by the body is fully restored. Individuals with pituitary tumors treated by irradiation rather than surgery have a recurrence in about 75% of cases. The greatest success rates are found in individuals whose condition has been caused by underlying adrenal tumors and who have had surgery without immediate complications.
Endocrinologist, surgeon, neurosurgeon, radiation oncologist, and urologist.
Notify your physician if
- You or a family member has symptoms of Cushing's syndrome.
- Signs of infection occur, such as fever, chills, muscle aches, headache and dizziness.
- There are signs of steroid underdosage (fatigue, weakness, dizziness) or overdosage (swelling in hands or feet, weight gain).
Last updated 8 August 2011