The Patient:
Frank is a 62-year-old male with a history of type 2 diabetes, diagnosed in 2004. He also has several other medical problems including hypertension, abnormal cholesterol levels, morbid obesity, obstructive sleep apnea, and coronary artery disease.
The Patient’s Regimen:
Frank’s current medications include Mounjaro (the maximum weekly dose), Jardiance (25mg once per day), metformin (1000mg twice a day), U-500 insulin (150 units twice a day of this concentrated insulin), and fast-acting insulin NovoLog (25-50 units with every meal, depending on his blood sugar).
Medications for his cholesterol include Lipitor, Zetia, and Praluent. Medications for his high blood pressure include Lisinopril, Metoprolol, and HCTZ. He also sleeps with a CPAP machine at night for his obstructive sleep apnea.
Recent Laboratory Data:
Here’s data from one of Frank’s recent FreeStyle Libre 3 CGM downloads:
- His time in range is only 17% (goal is 70% or higher)
- 57% of his numbers are in the high range
- 26% of his numbers are above 250 mg/dL
- No low blood sugars
- His average glucose is 228 mg/dL
- His GMI (estimated A1c) is 10.2%
- He is above 180mg/dL over 20 hours each day
Here are his recent cholesterol panel results:
- LDL level of 175 mg/dL (optimal is less than 55 mg/dL since he has CAD)
- HDL level of 36 mg/dL (optimal is over 50)
- Triglycerides over 400 (a healthy level is less than 150 mg/dL)
Yikes!
My Suspicions:
When I first met Frank, I thought he probably wasn’t taking all his medications, but I checked his refill data and he’s been ordering and picking up his meds as prescribed. He told me on several occasions that he takes all of his medications religiously. Despite this, his blood sugars, cholesterol levels, blood pressure, and weight continue to increase over time.
One thing that stood out to me is that I’ve never seen anyone on the maximum dose of Mounjaro (a powerful GLP-1/GIP medication from Lilly) who did NOT lose a significant amount of weight.
Other things that struck me were his degree of central obesity, his very full face (in medicine we might use the term “moon facies”) and other physical stigmata that reminded me of someone with early Cushing’s Disease. All of Frank’s problems related to something called metabolic syndrome (which is what most people with type 2 diabetes have), but he was still not at goal with his multiple medical conditions despite taking several medications to treat each one. When I see a patient with type 2 diabetes who’s had challenges with control for some time despite the traditionally successful therapeutic interventions, I suspect hypercortisolism could be at play.
The Relationship between Hypercortisolism and Cushing’s Syndrome:
Cushing’s Disease is a condition of long-term and untreated hypercortisolism, but it’s certainly not obvious to most physicians. While Cushing’s syndrome is a condition most commonly associated with hypercortisolism, it’s important to note that not everyone with high cortisol has Cushing’s. Cushing’s syndrome occurs when the body is exposed to excessive cortisol over a long period, often due to an adrenal or pituitary gland tumor. According to the Cushing’s Syndrome definition by MedlinePlus, it occurs when the body is exposed to excessive cortisol over a long period, often due to an adrenal or pituitary gland tumor. In some cases, hypercortisolism can exist without meeting the full criteria for Cushing’s.
Can You Have High Cortisol without Cushing’s?
Yes, it’s possible to have high cortisol without having Cushing’s syndrome. Stress, medication, or other health conditions can also lead to elevated cortisol levels without developing the full-blown syndrome. It’s crucial for doctors to identify the underlying cause of the high cortisol to determine the best course of treatment.
What Is Hypercortisolism?
Hypercortisolism is a condition where the body produces too much cortisol. Cortisol is a stress hormone that helps other organ systems function appropriately. In normal levels, cortisol plays a role in controlling blood sugar, immune response, fat stores, muscle quality, bone density, blood pressure, blood clotting, emotions, sleep, and weight.
When you have chronically elevated levels of cortisol, it causes resistant hyperglycemia (high blood sugars) that can overcome even the most powerful type 2 diabetes medications out there, including all the hot new GLP-1s. If you’re wondering why your blood sugar management is difficult despite medications, it could be excess cortisol.
Symptoms of Hypercortisolism:
Symptoms of hypercortisolism can include rapid weight gain (especially around the abdomen), elevated blood pressure, changes in mood, and difficulties in managing blood sugar levels. Some physical signs, like a “moon face” or purple stretch marks, can also point to excess cortisol. If you’re experiencing these symptoms alongside difficulties controlling type 2 diabetes, it may be worth discussing hypercortisolism with your doctor. Learn more about the symptoms of hypercortisolism and their effects on the body.
What Causes Hypercortisolism?
Hypercortisolism can be caused by an adrenal tumor that is not malignant (not cancerous) but produces excess cortisol. Sometimes excess cortisol is caused by hormones from the pituitary gland in the brain.
Testing and Hypercortisolism Treatment:
I ordered an overnight dexamethasone suppression test for Frank. The test is very simple and involves taking a steroid pill at night that is supposed to suppress the body’s production of cortisol. If the cortisol is not suppressed in the morning, then the patient has hypercortisolism and further tests are warranted to find out where the cortisol is coming from (typically the adrenal or the pituitary glands).
I am currently waiting for Frank to do the overnight dexamethasone suppression test, but I suspect it will come back positive.
How to Treat Hypercortisolism:
Once hypercortisolism is confirmed, treatment therapies are available that include surgery or medication, depending on the source of the excess cortisol. For example, if there is a tumor on the adrenal glands that’s secreting too much cortisol, it can typically be removed. If there is excess cortisol production elsewhere in the body, medication can potentially be used.
Managing Type 2 Diabetes and Hypercortisolism Together:
Hypercortisolism is frequently discovered in people with type 2 diabetes. However, anyone can get hypercortisolism, including people with type 1 diabetes.
If you have really challenging type 2 diabetes despite doing all the right things like taking all of your medications and following your doctor’s guidance, you may have hypercortisolism.
Talk to your doctor about getting screened. Hypercortisolism is a tough disease and a challenging situation for both patients and providers, but surgical and medical treatment options are available that can make a huge difference in quality of life and help people reach their therapy goals.
This content was supported through a sponsorship from Corcept Therapeutics.
Additional Resources:
Is Your Diabetes Out of Whack? It Could Be Hypercortisolism!
So usually we suspect hypercortisolism in cases with metabolic syndrome not improving on medications, maybe not usually with classical cushingoid features like those textbook purple stria, muscle pains, buffalo humps, easy bruising, etc.
Intriguingly, they have hypercortisolism-producing metabolic syndrome resistant to multiple medications while still not exhibiting classical cushingoid features!
Does it mean cortisol is working selectively on some pathways and not on others ?
So I was thinking should suspect hypercortisolism in the general population with newly diagnosed Type 2DM and screen them too for hypercortisolism?
Wow, you described the typical case of hypercortisolism exactly right, and that’s why it’s missed so often. You are the poster child of physician’s who recognize the importance of this condition! I feel that the absence of physical appearance of Cushing’s is because the cortisol levels have not been high enough or around long enough, however I will check with my experts in the area and get back to you.
Thank you so much Dr Edelman! Feel humbled by your kind words!
This was really an intriguing case! Really enjoyed reading the case and learning something new!
Here is a little more information regarding your questions. Thank you again for your interest in this topic!
You can have hypercortisolism without the clinical presentation of all the discriminate features of the disease, like purple stria and buffalo hump. Regarding the question, “Does it mean cortisol is working selectively on some pathways and not on others?” No clear evidence suggests that cortisol works selectively on some pathways and not others. We know that cortisol receptors (glucocorticoid receptors) are found in most tissues and organs in the body, and they are involved in many physiological processes, including metabolism, inflammation, immune regulation, and growth and development. The clinical presentations of someone with hypercortisolism can be variable, with some patients presenting with many of the classic signs and symptoms of the disease (moon facies, truncal obesity, thin skin, and easy bruising). In contrast, others may present with just a few of these signs and symptoms and display other signs and symptoms like metabolic syndrome, depression, and muscle weakness.
To address your other question – “should we suspect hypercortisolism in the general population with newly diagnosed Type 2DM and screen them too for hypercortisolism?”. Based on the various studies evaluating the prevalence of hypercortisolism in populations with T2D and varying degrees of other metabolic derangement, the prevalence within the newly diagnosed population was ~5%. At this stage, it is probably not effective to screen all newly diagnosed T2D patients for hypercortisolism.
Thank you so much Dr Edelman for the great information!
It is really helpful to know about hypercortisolism and this spectrum of clinical presentation. Yes, I feel the reason for this variability in the clinical spectrum is not due to the mechanism of action of cortisol on glucocorticoid receptors because the receptors are on most cells of our body so maybe the reason for this variability comes down to the duration of time cortisol remains in the body.
I feel this case was really interesting and intriguing because it was about those outliers(5% population)that do have hypercortisolism!
Yes, definitely an interesting case, and a condition that more patients and providers need to be aware of!
I was told about 10 years ago that my cortisol stayed high all day, never dropping to a normal level. This was by a chiropractor I never saw again, so never followed up. Last year I was diagnosed with type 2. Am at a place where I am between doctors also. Where do I go from here?
You should definitely see an endocrinologist and they should test you for hypercortisolism, with the dexamethasone suppression (DST) test. You really need to know if you have hypercortisolism.