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. Today we call this adrenal hypercortisolism (AHC), formerly called MACS or subclinical Cushing syndrome when it is mild. 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, dangerous 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 endocrinologists: Is adrenal Cushing’s syndrome common? Many would answer “adrenal Cushing’s syndrome is a very rare disease.” However, that statement is incorrect. The reason so many people think it is rare is that patients go undiagnosed and untreated for years and decades.

In America, 2 to 3% of people 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 the most conservative numbers, that means that at least 6.6 million people have an adrenal mass and more than 300,000 people have adrenal Cushing’s syndrome.

I do a lot of adrenal surgery. However, I certainly don’t perform hundreds of thousands of adrenal operations, and neither does anyone else. 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, 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 these tumors are common. An operation cures the disease and gets rid of the toxic effects of too much parathyroid hormone (PTH). Our colleagues at the Norman Parathyroid Center here in Tampa, Florida specialize in exactly this.

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 of 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 has the cortisol measured in the morning. If the cortisol is greater than 1.8 µg/dL (not suppressed) this is consistent with too much cortisol. A result between 1.2 and 1.8 is “possible” hypercortisolism: it must be interpreted together with ACTH and DHEA-S and is worth repeating.
   
   You can also measure the cortisol in the saliva late at night as well as performing a 24-hour urine free cortisol (UFC) measurement. These tests are not very sensitive, so most people with mild or moderate disease (subclinical Cushing’s syndrome) will have normal results, and a normal result does not rule the disease out. However, if the 24-hour urine free cortisol is elevated it strongly supports that 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 almost certainly have adrenal Cushing’s syndrome (nothing is 100% in medicine) if you have this constellation:
   
   ACTH = low (below 20 pg/mL in mild disease, below 10 in moderate disease and below 5 in severe disease)
   
   Cortisol after LDDST = above 1.8 µg/dL.
   
   See, easy!  If your ACTH is on the low side and the cortisol is on the high side, you have too much cortisol coming from the adrenal glands.
   
   NOTE: if both your cortisol and your ACTH are 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. In expert hands, adrenal surgery typically takes 20 to 30 minutes, is safe and causes very little pain.

The reason many patients and doctors, even medical endocrinologists, 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, which is a longer operation with a longer recovery. No wonder doctors and patients think adrenalectomy is very complicated, dangerous, and time-consuming. In our view, adding a robot adds cost without adding benefit.

Also, the typical surgeon who performs adrenal surgery in the United States does about one adrenal 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 typically takes 20 to 30 minutes, it is very safe, and most patients have very little pain.

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

While you're at it, learn why we do not recommend laparoscopic adrenal surgery (for most patients, we advise against going through the belly to get to the adrenal tumor).

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

As these authors from Germany correctly identify, “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.
• Can be 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 can be used to lower the cortisol levels (steroidogenesis inhibitors) or to block the effects of cortisol (mifepristone, which does not lower the cortisol level itself). 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.
• Mifepristone has shown some promising signs of blocking the effects of cortisol and reducing weight in patients with adrenal Cushing’s syndrome, which can make 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