Could It Be Cushing's?
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Diagnostic Tests for Cushing's Disease​

Remember, this website is not meant to diagnose you - it is for informational use only.

The diagnostic process for Cushing's can be very lengthy and at times, frustrating. You may find that your treating doctor will ask you to repeat tests two, three, even four times. You may feel like the testing process is a waste of your time, or that your doctor is not finding anything within the test results. Rest assured, there is a method behind this "madness."

Because this disease is so complex and because there is more than one source of origin that can be causing the body to mass produce cortisol, the basic diagnostics (urine, blood, and salivary collections) being ordered are instrumental in revealing ​the culprit (tumor). As with the disease, our bodies are also complex. Throughout the diagnostic process, a patient may either consistently or inconsistently overproduce cortisol, and with repeated testing, this can be key to determining whether or not a patient does have Cushing's.

Once it has been established that hypercortisolism is present, the next step is to introduce synthetic drugs that are used to suppress certain hormones within the body. This type of testing can help determine what type of Cushing's a patient has: Cushing's Disease (pituitary tumor) or Cushing's Syndrome (adrenal or ectopic tumor).

The final step is to ​
get a confirmation (visual) of the tumor. This is done through radiologic imaging: MRI, CT, or IPSS, depending on where the tumor has been determined to be located.

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24-hour Urine Collection

One of the first things your treating doctor will require from you is urine collection to measure cortisol levels. You may have initially been asked to submit an 8a.m. urine sample to get a baseline level, but this only measures cortisol for that particular time. 8a.m. is typically when your body produces the highest amount of cortisol for the day.

Your doctor will give you a lab slip (kind of like a prescription), and you will bring it to your nearest hospital or medical laboratory. The facility will give you a measuring "hat" that you will place under the lid of your toilet and urinate into every time you use the bathroom over the next 24 hours. They will also give you a large collection jug. After each elimination, you will pour the urine from the hat into a collection jug, and store the jug in a refrigerator or cooler. After your last collection, you will return the jug to the hospital or laboratory. At this time, your treating doctor may have the participating lab draw blood to test serum cortisol and  ACTH levels. (Remember: ACTH is the hormone that stimulates the adrenal glands to produce cortisol. If ACTH levels come back high in addition to elevated cortisol, this will be a key element in your diagnosis.)

If you have Cushing's, cortisol is produced in mass quantities throughout the day, and a collection of your urine over a 24-hour period will yield the best measurement. However, one 24-hour urine collection will not be sufficient. You may be asked to repeat this process a few more times; or, your treating doctor may request that you submit a 48-hour urine collection. The reason for repeating this test is to be absolutely certain that your body is consistently producing high outputs of cortisol.
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​Late Night Salivary Collection​

As your body winds down for the day, cortisol is normally at it lowest output at night, contrary to the high output in the early morning. If Cushing's is present, cortisol will be elevated late at night (hence the insomnia that some Cushing's patients experience). Measuring saliva for cortisol levels between 11p.m. and midnight has proven to be effective in the diagnostic process for Cushing's. Studies show that saliva, when measured at night, is the most sensitive clinical observation compared to all other techniques.

Your doctor will give you a lab slip (kind of like a prescription), and you will bring it to your nearest hospital or medical laboratory. The facility will give you a plastic vial with what looks like a sponge-tip applicator or a cotton roll​ inside. You will also receive instructions on how to submit your saliva sample, which usually involves refraining from certain foods and beverages before sucking on the sponge or cotton for a number of minutes.

Once the sponge or cotton is completely saturated with your saliva, you will insert it back into the vial. You may be asked to mark the date and time on the vial. Depending on the medical facility's instructions, you may be asked to return the sample to them immediately or to simply refrigerate the sample until you can deliver it to the lab.​​

If you have Cushing's, elevated cortisol levels will ​be present in the sample you submit. To determine that your body is consistently overproducing the hormone,  you may be asked to submit more than one saliva sample over a given period of time.
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Dexamethasone Suppression

After submitting urine collections and saliva samples, your treating doctor has most likely determined whether or not you have hypercortisolism. If you are consistently overproducing cortisol, the next step introduces a medication called dexamethasone, which helps determine the source of Cushing's through various administrations.

Once the pituitary gland releases ACTH, this hormone stimulates the adrenal glands to secrete cortisol. Once cortisol enters the blood and circulates throughout the body, ACTH levels regulate appropriately. Should cortisol levels drop, ACTH kicks back in.​ Dexamethasone is a synthetic steroid that is similar to cortisol, and it is known for decreasing ACTH levels. Normally after taking dexamethasone, a person's ACTH and cortisol levels should
both decrease. 

There are two types of ​dexamethasone suppression tests, low dose & high dose, and either can be done overnight or over a course of 3 days. Your doctor will give you a prescription for the dexamethasone. For the overnight test, you will take the med at 11p.m. and arrive at your nearest hospital or medical laboratory the next morning for an 8a.m. blood draw to measure cortisol levels.

For the 3 day test, your doctor will give you a lab slip for a urine collection hat & jug, as well as a prescription for the dexamethasone. You will collect your urine over the course of 3 days. On the morning of day 2 (
after the first 24 hours)​, you will take the dexamethasone every 6 hours for the next 48 hours (days 2 & 3). You will return the collection jug to the lab and cortisol will be measured from your urine.

With the low dose test, abnormal responses are indicative of Cushing's Syndrome, which is typically the result of a cortisol-producing adrenal tumor or an ACTH-producing ectopic tumor. These types of tumors can be either benign or malignant.

Normal responses to the high dose test distinguish the cause as being pituitary-related, known as Cushing's Disease. In layman's terms: ACTH and cortisol levels decreased as they should have, but
not on their own. Levels decreased only because of the administration of a high dose of dexamethasone.​ Pituitary tumors are usually benign.

DEX-CRH Test

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The DEX-CRH is a combined stimulation test, using both dexamethasone (DEX) and a synthetic form of corticotropin-releasing hormone (CRH). Your treating doctor will order to this test after it has been established that you have a form of Cushing's. The DEX-CRH test determines the source of the tumor causing hypercortisolism.

CRH is a hormone released by the hypothalamus gland that stimulates the pituitary gland to secrete ACTH; which in turn stimulates the adrenal glands to produce cortisol. Administering synthetic CRH will stimulate the endocrine system to do what its supposed to do by "means of force." Any abnormality within the endocrine system will reveal itself by responding to the synthetic hormone.

In preparation for this test (which is typically performed in a hospital setting, doctor's office, or medical laboratory), your treating doctor will give you a prescription for 8 tablets of dexamethasone. Two days prior to your test, you will take a dexamethasone tablet at noon, and ​​continue taking one tablet every six hours over the next 48 hours. Your last dexamethasone tablet will be taken at 6a.m. on the day of the DEX-CRH test. Your doctor will most likely ask that you fast and refrain from taking certain medications from midnight (the day of the test) until after the test is completed.

When you arrive at the facility (which is shortly after your last dexamethasone dose was taken), you will be asked to lie down for the DEX-CRH test. A nurse will insert an IV into your arm - this is so that blood samples can be drawn throughout the test.​ After approximately 30 minutes, baseline samples of ACTH and cortisol will be taken, followed by another round of these samples 15 minutes later. Shortly after, you will be given a dose of synthetic CRH through the IV. (It is very normal to experience a warm or hot sensation - called flushing - in the face, neck and upper chest. You will also feel the urge to inhale deeply. You may feel slightly nauseated or notice a metallic taste. All side effects are mild and short-lived.)​ After the administration of CRH, blood samples will be drawn every 15 minutes for one more hour. After the test is over, the IV is removed and you may eat and resume regular activities. ​(Please note: after my DEX-CRH test, I was in a state of sheer exhaustion! Not everyone will feel this way, but I did. Either reaction is completely normal.)

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​As far as the results go, people with ACTH-dependent (pituitary) tumors will show a spike in their ACTH and cortisol levels, followed by a decrease in cortisol levels but a continued elevation in ACTH levels. People with cortisol-producing adrenal tumors or ACTH-independent (ectopic) tumors do not usually respond to CRH.

Once the source of your tumor has been established through the diagnostic
​tests listed above, the appropriate imaging test will be administered.

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Imaging Tests
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