Cushing’s syndrome means that you have signs and symptoms that are due to too much cortisol. Cortisol is a very toxic hormone in excess levels. Adrenal Cushing’s syndrome means that the disease originates from the adrenal glands. This is in contrast to Cushing’s disease, where patients have a pituitary tumor producing ACTH that stimulates the adrenal glands to produce too much cortisol.

Adrenal Cushing’s syndrome is due to either one single tumor on the adrenal gland over-producing cortisol or enlargement of both adrenal glands over-producing cortisol.

There are many myths when it comes to adrenal Cushing’s syndrome and many doctors, other medical professionals and patients often get confused when it comes to adrenal Cushing’s syndrome.

Do not be confused! Read this post and educate yourself and help educate those around you. If you follow a logical, systematic reasoning you will see that understanding adrenal Cushing’s syndrome is quite straightforward.

The Top 5 Myths about Adrenal Cushing’s Syndrome

1. Adrenal Cushing’s syndrome is a rare disease.

2. All patients with adrenal Cushing’s syndrome are overweight or obese.

3. It is very difficult to diagnose adrenal Cushing’s syndrome.

4. Surgery for adrenal Cushing’s syndrome is very complicated and takes hours.

5. Taking pills is a great treatment for adrenal Cushing’s syndrome.

1) Adrenal Cushing’s syndrome is a rare disease.

If you ask your regular doctor or even most medical endocrinologist: Is adrenal Cushing’s syndrome common? Many would answer “adrenal Cushing’s syndrome is a very rare disease.” However, that statement is incorrect. The problem that so many people think it is rare is because patients go undiagnosed and untreated for years and decades.

In America, 2 to 3% of patients have an adrenal mass. Conservatively, out of those, 5 to 10% over produce cortisol. The USA has a population of about 330 million people. Using very conservative numbers that means that 6.6 million people have an adrenal mass and 300,000 people have adrenal Cushing’s syndrome.

I take care of a large percentage of all patients with adrenal Cushing’s syndrome in America and I do a lot of adrenal surgery. However, I certainly don’t perform 100,000 adrenal operations per year. So, is my math wrong? No.

The problem is failure to diagnose and failure to treat the disease.

As an illustration, let me discuss another type of tumor that also produces a toxic hormone. I am talking about parathyroid tumors which produce parathyroid hormone (PTH). Parathyroid tumors can make you very sick from a disease called primary hyperparathyroidism. It was thought, not that long ago in the 1990s, that this disease was exceedingly rare and should only be diagnosed and treated with surgery once in a blue moon. However, with the ability to accurately and easily measure parathyroid hormone and calcium, it has now been proven that about 1 to 2% of men and women, respectively. have these tumors. An easy operation cures the disease and gets rid of the toxic effects of too much parathyroid hormone (PTH). Thousands of patients are cured by our team here in Tampa, Florida.

Learn more about parathyroid tumors and primary hyperparathyroidism.

Adrenal Cushing’s syndrome is where primary hyperparathyroidism was in the 1970s. We are only scratching the surface of identifying and treating these patients.

So, adrenal Cushing’s syndrome is quite common and should always be checked for if you have symptoms that are consistent with the disease or if you have had a CT scan that shows an adrenal nodule or mass.

2) All patients with adrenal Cushing’s syndrome are overweight or obese.

In medical school and residency, a lot of doctors learn about the symptoms of Cushing’s syndrome, and they often remember a picture of a patient that looks like this:

It is true that the high cortisol levels can cause a lot of symptoms including weight gain with central obesity (fat tummy). We have a whole blog post about weight gain and adrenal tumor that you can review here. 

The problem is that a lot of patients with adrenal Cushing’s syndrome do not fit the textbook. Many of our patients look nothing like the woman in this schematic picture. We have patients with Cushing syndrome with all sizes, shapes, and symptoms. There are plenty of skinny patients with adrenal Cushing’s syndrome!

Some patients with too much cortisol have no obvious symptoms at all, they are completely asymptomatic. Other patients have no physical symptoms, but rather have emotional or even psychiatric changes (depression, anxiety, etc).

This means that it can be difficult for doctors and practitioners to identify and think about Cushing’s syndrome as a reason for the patient’s symptoms. If you have any symptom that is consistent with too much cortisol, you need to have your cortisol levels checked.

If you ever had a CT scan or an MRI of your abdomen, you need to double check that you do not have an adrenal mass. Every single week, we have patients who had a scan showing an adrenal mass, but nobody told them about it. If you have an adrenal mass on a scan, you need to have adrenal Cushing’s syndrome ruled out by lab tests.

Learn about symptoms of Cushing’s syndrome.

3) It is very difficult to diagnose adrenal Cushing’s syndrome.

No. Diagnosing adrenal Cushing’s syndrome is straightforward. Do not be confused!

The diagnosis is done in two steps:

1. Prove that there is too much cortisol (also known as hypercortisolism).
   
   The best test is the low dose dexamethasone suppression test (LDDST). The patient simply takes a 1 mg dexamethasone pill at 11 PM and have the cortisol measured in the morning. If the cortisol is greater than 1.8 (not suppressed) this is consistent with too much cortisol.
   
   You can also measure the cortisol in the saliva as well as performing a 24-hour urine free cortisol (UFC) measurement. The latter is not very sensitive, so most people with subclinical Cushing’s syndrome will have a normal 24-hour urine free cortisol (UFC). However, if it is elevated it proves that indeed you have Cushing syndrome.
   
   
2. Prove that the cortisol excess is due to an adrenal problem (not a pituitary tumor).
   
   Measuring the ACTH (pituitary hormone) will clarify this.  Patients with adrenal Cushing’s syndrome have ACTH levels on the low side.
   
   You have adrenal Cushing’s syndrome (99%; nothing is 100% in medicine) if you have this constellation:
   
   ACTH = 10 or lower
   
   Cortisol after LDDST = 1.8 or higher.
   
   See, easy!  If your ACTH is on the low side and the cortisol is on the high side, you have too much cortisol.
   
   NOTE: if both your cortisol and your ACTH is high you probably have a pituitary problem.

Learn more about diagnosing Cushing’s syndrome.

4) Surgery for adrenal Cushing’s syndrome is very complicated, dangerous and takes hours.

No. Adrenal surgery can be done in minutes, safely and almost without pain.

The reason many patients and doctors, even medical endocrinologist, think that adrenal surgery is complicated, dangerous and takes a long time is because in the olden days it used to.

Many endocrinologists, even those who trained at the most prestigious institutions, were only exposed to surgeons doing adrenal surgery the old-fashioned way through the belly. If you review the website of the Johns Hopkins Hospital in Baltimore, you can learn that they perform laparoscopic adrenalectomy (through the belly), it takes half a day, and they have to give a blood transfusion in one out of every 20 patients. WOW! No wonder doctors and patients think adrenalectomy is very complicated, dangerous, and time-consuming. Throw a robot in to the mix, and it gets even worse…

Also, the average number of adrenal surgeries performed by American adrenal surgeons is one operation per year. If you do an operation only once a year, you can certainly make it complicated, dangerous and it will take hours. I do not fly airplanes, but if I did, I am sure it would be both complicated and dangerous. It probably would not take a long time, though, since I would crash!

The truth is that the mini back scope adrenal (MBSA) operation can be done in minutes, and it is very safe, and patients have almost no pain.

Read up on why the mini back scope adrenalectomy (MBSA) is the best operation.

While you're at it, learn why laparoscopic adrenal surgery is not recommended (do not have your surgeon go through the belly to get to your adrenal tumor).

5) Taking pills is a great treatment for adrenal Cushing’s syndrome.

As these authors from Germany correctly identifies “Medical therapy to control hypercortisolism in adrenal Cushing's syndrome is currently not the first-line therapy”, and I will make a prediction: Pills will never be better than surgery for adrenal Cushing’s syndrome.

The reasons are quite simple, since pills

• Do not fix the underlying problem. The underlying problem is a tumor. The tumor does not disappear because you take a pill. It is like putting a Band-Aid on a large, bleeding artery. It does not fix the problem.
• Are very toxic and have a lot of side effects.
• Are highly expensive compared to surgery.

It is true that adrenal steroidogenesis inhibitors and glucocorticoid receptor blockers such as metyrapone, ketoconazole and mifepristone (Korlym) can be used to lower the cortisol levels. Also, mitotane can be used, but is considered second-line therapy because of its high toxicity.

To be fair, there are occasional times where these medications are useful. For instance:

• The patient has very high cortisol levels and the doctor needs to control it (as a bridge) until surgery.
• Korlym has some promising signs of lowering cortisol and reducing weight in patients with adrenal Cushing’s syndrome making adrenal surgery more straightforward. Again, pills would be used as a bridge to adrenal surgery.
• In patients who have adrenal cancer that has spread, and surgery is no longer an option.

Additional Resources: 

Learn more about the Carling Adrenal Center

Learn more about Dr. Tobias Carling

Learn more about our sister surgeons at the Norman Parathyroid Center, Clayman Thyroid Center and Scarless Thyroid Surgery Center

References:

• Braun LT, Reincke M. What is the role of medical therapy in adrenal-dependent Cushing's syndrome? Best Pract Res Clin Endocrinol Metab. 2020