Cushing's disease is a serious condition of an excess of the steroid hormone cortisol in the blood level caused by a pituitary tumor secreting adrenocorticotropic hormone (ACTH). ACTH is a hormone produced by the normal pituitary gland. ACTH stimulates the adrenal glands (located on top of the kidneys) to produce cortisol, commonly referred to as the stress hormone.
Our comprehensive approach to diagnosis and treatment of Cushing's disease sets the UCLA Pituitary Tumor Program apart. Our physicians treat a high volume of patients every year and perform over 100 pituitary surgeries a year, making us one of the top programs in the United States
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Cushing's disease is rare, affecting 10 to 15 people per million each year, most commonly adults between 20 and 50 years of age. Women account for more than 70 percent of cases.
Most patients with Cushing's disease have small tumors (pituitary microadenomas). However, it can be difficult to diagnosis Cushing's disease, and the diagnosis is often delayed. An endocrinologist should always supervise the evaluation for Cushing's disease. At the UCLA Pituitary Tumor Program, our specialists have years of experience diagnosing and managing Cushing's disease.
Cortisol affects the body in many ways, including:
The adrenal glands produce cortisol in varying amounts throughout the day:
Cushing's disease is not the same as Cushing's syndrome. Cushing's syndrome refers to the general state characterized by excessive levels of cortisol in the blood. Elevated cortisol levels can occur for reasons other than a pituitary tumor, including:
Cushing's syndrome is much more common than Cushing's disease. The most common cause of elevated cortisol levels is taking medications that have cortisol, including: hydrocortisone, prednisone pills, skin ointments, asthma inhalers and joint steroid injections
Less common causes of elevated cortisol levels:
Patients with "pseudo-Cushing's" may be difficult to distinguish from those with true Cushing's. Your doctor may need to order specialized hormonal tests to clarify the diagnosis.
Cushing's disease is used exclusively to describe the condition of excessive cortisol arising from a pituitary tumor secreting the hormone ACTH.
The symptoms related to Cushing's disease and Cushing's syndrome are the same, since both are related to an excess of cortisol. The symptoms may include:
Although uncommon, some patients with Cushing's disease have large pituitary tumors (macroadenomas). In addition to the severe hormonal effects related to increase blood cortisol levels, the large tumor can compress adjacent structures leading to:
The early stages of Cushing's disease may be difficult to recognize, especially because the body changes develop slowly. Comparing old and recent photographs often shows the changes in facial appearance and physical characteristics of the body.
The diagnosis may be difficult to make because sometimes the hormone elevations come and go: so called "cyclic" or "periodic" Cushing's disease.
In pregnant women, the pregnancy may worsen symptoms of Cushing's disease.
Your doctor will conduct a thorough physical exam and ask you about your symptoms and medical history. In general, the first step in making the diagnosis is establishing a state of excessive blood cortisol (i.e. Cushing's syndrome). Assuming cortisol intake is excluded, this typically is done by hormone testing. After this diagnosis is established, an MRI is obtained to determine if a pituitary tumor is visible.
In Cushing's disease, typically very small (microadenoma) tumors are found. If no tumor is visible, then inferior petrosal sinus sampling is indicated (see below).
The testing for excessive cortisol levels can be complex and challenging. Blood tests may not detect the presence of excessive cortisol secretion because blood levels of cortisol naturally vary throughout the day. Therefore a simple measurement of the blood cortisol level is usually not definitive. Tests we will order include:
The amount of cortisol found in urine collected over a 24-hour period is an important measurement in diagnosing Cushing's syndrome. This test sums the total daily production of cortisol.
In some cases, an endocrinologist may request testing for the level of cortisol in the saliva. Similar to blood cortisol levels, the amount of cortisol in the saliva at or near midnight is expected normally to be very low. Multiple elevated midnight salivary cortisol levels may help confirm the diagnosis of Cushing's syndrome.
It is important not brush the teeth just prior to collecting the sample.
This test may not be valid in smokers.
Once your doctor suspects Cushing's disease based on clinical findings and hormonal testing, a magnetic resonance imaging (MRI) scan of the pituitary gland is the best way to detect the presence of an adenoma in Cushing's disease.
MRI detects a pituitary adenoma in about 70 percent of cases. It is important that you undergo these imaging tests at a Pituitary center with special expertise in imaging small tumors. At the UCLA Pituitary Tumor Program, we use powerful 3T (Tesla) MRI scanners that may offer improved chances of identifying very small tumors.
At UCLA, our neuroradiologist personally oversees the MRI scan as it is being acquired in order to perform the optimal scanning sequences to detect tiny pituitary tumors not seen elsewhere.
In some cases, MRI fails to identify an abnormality. If your doctor suspects Cushing's disease, he or she may order super-selective inferior petrosal sinus sampling (IPSS).
IPSS must be performed by an experienced interventional neuroradiologist because it carries risk, and if done inappropriately, can give misleading results.
The inferior petrosal sinuses are veins that occur on both sides of the pituitary gland.
If the ACTH level is the same in the inferior petrosal sinus compared to the vein below the heart, this suggests that a tumor somewhere else in the body (ectopic, not pituitary) is producing ACTH.
In Cushing's disease, the ACTH level in the inferior petrosal sinus is much higher compared to the vein below the heart
If IPSS testing is not available, other tests include a dexamethasone suppression test. Dexamethasone is a powerful drug that acts similar to, but is more potent than cortisol. This type of testing can suggest either a pituitary or ectopic tumor, but is not as conclusive as IPSS.
Learn more about hormone testing at the UCLA Pituitary Tumor Program.
Treating Cushing's disease requires an experienced team of experts. To achieve the best outcome, you should seek treatment at a hospital that has a dedicated pituitary tumor program.
Treatment options include:
Surgically removing the pituitary adenoma offers the only long-term cure of Cushing's disease.
There is no effective drug that lowers ACTH production and shrinks the pituitary tumor. There are medications that inhibit the adrenal gland's production of cortisol. In some patients, these medications can effectively reduce the symptoms related to excessive cortisol when:
In some cases, surgeons may not be able to remove the tumor surgically. Radiation therapy can be very effective in controlling the growth of these tumors.
Stereotactic radiosurgery is a technique in which a highly focused of radiation can be delivered to the tumor target. Because the radiation beam is carefully sculpted, the surrounding brain structures receive only a fraction of the radiation dose and are typically unharmed (with the exception of the normal pituitary gland).
A consequence of radiation treatment is that it can cause delayed pituitary failure. This typically occurs several years after treatment, and therefore continued long-term follow-up with an endocrinologist is important. Hormone replacement may be required.
If the tumor cannot be removed surgically and does not respond to medication or radiation, your doctor may recommend removing the adrenal glands (bilateral adrenalectomy), or BLA. If you undergo BLA:
The UCLA Pituitary Program offers clinical trials for the treatment of Cushing's disease.
To schedule an appointment with one of our physicians at the Pituitary Tumor Program, please call (310) 825 5111.
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