With a better understanding of hypercortisolism, Diabetes Care and Education Specialists (DCESs) and primary care clinicians can gain new insights and new tools to help explain and address difficult-to-manage diabetes.

The following content is made possible due to educational grant support from Corcept Therapeutics. Content was developed independently by ADCES. 

Why Identifying Hypercortisolism Is Critical In Diabetes Care

Hypercortisolism is a serious disorder that often goes unrecognized in people with difficult-to-manage Type 2 diabetes (T2D). That is in part because signs and symptoms of hypercortisolism overlap with other conditions commonly seen in clinical practice. As a result, people may live for years with elevated glucose levels, hypertension, and other comorbidities despite appropriate treatment.

As a Diabetes Care and Education Specialist (DCES) or primary care clinician, you are well positioned to spot hypercortisolism early and initiate appropriate next steps, including referral to a specialist who can confirm the diagnosis and determine the next steps in care. Starting with this introductory module, we aim to increase awareness and understanding of hypercortisolism as a hidden driver of diabetes.

Hypercortisolism: A Serious Health Concern

Hypercortisolism is a serious condition characterized by persistently elevated levels of cortisol, the steroid hormone produced by the adrenal glands. As excess cortisol affects nearly every organ, people with hypercortisolism can have a wide variety of symptoms and comorbidities, including elevated glucose, hypertension, weight gain, bone fractures, and psychological impacts such as depression and anxiety. Ultimately, people with hypercortisolism are at a significantly increased risk of death, with mortality rates two to five times higher than in the general population.

Today, there is increasing recognition that hypercortisolism is closely associated with diabetes (particularly T2D) that is not reaching glycemic targets or is difficult-to-manage. Hypercortisolism is a serious concern for people with T2D, as it can make achieving glucose targets more difficult by contributing to insulin resistance and increasing output of hepatic glucose. It is also linked to increased risks of cardiovascular disease and death in people with T2D.

Clinically, hypercortisolism can be traced back to causes that are either exogenous or endogenous. In exogenous cases, cortisol levels are elevated most often due to the use of glucocorticoid medications, such as prednisone. In endogenous hypercortisolism, the cause is internal. Endogenous cases may be caused by an ACTH-secreting pituitary adenoma, an adrenal gland tumor, or a hormone-secreting tumor in organs such as the lungs, pancreas, thymus, or thyroid.

Together, the exogenous and endogenous forms of hypercortisolism are collectively referred to as Cushing syndrome, while Cushing disease specifically refers to endogenous hypercortisolism caused by a hormone-secreting pituitary tumor, as described above. However, the individual presentations of hypercortisolism in the clinic are diverse, as we will discuss in the next section.

Spotting Hypercortisolism Is Not As Simple As It Seems

In the past, clinicians only considered hypercortisolism in people with overt symptoms of Cushing syndrome:

• A fatty pad between the shoulders (buffalo hump)
  
• A swollen and rounded face (moon face)
  
• Abdominal weight gain
  
• Pink or purple stretch marks
  
• Skinny arms and legs due to muscle wasting
  
• Thin, easily bruised skin
  
• Slow-healing wounds
  
• Acne, primarily on the face
  

However, we now know that hypercortisolism occurs in a broad spectrum of individuals, including those who may not exhibit these classic physical features. People may present with features such as T2D and hypertension that can be driven by hypercortisolism, but are so commonly found in the general population that they fail to raise suspicion. In some cases, they will present with features that are unusual for their age, such as osteoporosis.

Collectively, these clinically less apparent presentations often go undetected in clinical practice because they lack the overt features associated with Cushing syndrome.

Comorbidities Of Excess Cortisol: Looking Beyond Classic Features

An increasing number of clinicians are starting to recognize that people with hypercortisolism can experience a wide range of metabolic, cardiovascular, and psychological comorbidities, including but not limited to:

• Type 2 diabetes or prediabetes
• Hypertension
• High cholesterol or triglycerides
• Weight gain
• Muscle loss
• Osteoporosis (especially when diagnosed at a younger-than expected age)
• Serious infections
• Depression
• Problems with memory or concentration

Among these comorbidities, diabetes is one of the most common yet underappreciated. Hypercortisolism promotes high glucose and, in some individuals, can contribute to difficulty meeting glucose targets. Excess cortisol can be a driver of diabetes, disrupting glucose metabolism through a combination of increased insulin resistance and impaired insulin secretion. As a result, a substantial proportion of people with hypercortisolism have diabetes. Altogether, cardiovascular and metabolic comorbidities are highly prevalent in people with this condition. 

Hypercortisolism: More Common Than Generally Appreciated

While the link between hypercortisolism and high glucose is clear, screening for hypercortisolism in people with difficult-to-manage T2D is not yet commonplace. Part of the issue is the persistent perception that hypercortisolism is rare. However, new research shows that hypercortisolism is surprisingly common in people with difficult-to-manage T2D. In the recent study, published in Diabetes Care, approximately 24% of people with difficult-to-manage T2D had hypercortisolism. The prevalence of hypercortisolism was even higher, at nearly 37%, in people taking three (3) or more medications for hypertension. Of note, cardiac events were significantly more common among participants with hypercortisolism, which was defined based on results of a dexamethasone suppression test (DST); i.e., a post-DST cortisol >1.8 μg/dL (50 nmol/L).

This study demonstrates that the prevalence of hypercortisolism in people with difficult-to-manage diabetes is much higher than previously recognized. 



This study is important because many people with T2D are not meeting glycemic targets, putting them at risk for complications related to diabetes. The new findings give us important insights, suggesting hypercortisolism may be an underlying contributor for some patients. As such, the findings suggest a potential opportunity for increased hypercortisolism screening in patients with difficult-to-manage T2D.

Identifying Hypercortisolism Is A Major Opportunity To Improve Diabetes Care

Endogenous hypercortisolism frequently goes undiagnosed in routine diabetes care. This is because the symptoms of hypercortisolism can evolve gradually over time, and can overlap with common conditions, which makes recognition challenging and contributes to delayed diagnosis. On average, the time from the onset of suspicious symptoms to a definitive diagnosis of endogenous hypercortisolism is about three years.

For a person with diabetes, the implications of a diagnostic delay can be devastating, resulting in ongoing frustration, unnecessary intensification of glucose-lowering medications, poorer clinical outcomes, and diminished quality of life.

Fortunately, it is possible to improve both clinical outcomes and quality of life simply by learning more about hypercortisolism and applying the lessons learned. There are clinical clues that should lead the clinician to suspect this condition in people with diabetes and specific profiles that are more commonly associated with hypercortisolism. There are tests that can be performed, communication techniques to apply in clinical encounters, and strategies to engage with other clinicians committed to providing the best care possible for people with diabetes.

Key Takeaways

• Hypercortisolism is a potentially serious hormonal disorder that is frequently underrecognized as a contributor to difficult-to-manage diabetes.
• The prevalence of hypercortisolism in people with difficult-to-manage T2D is approximately 24%, which is substantially higher than previously appreciated. The prevalence is even higher, at 37%, in patients with difficult-to-manage hypertension despite taking multiple medications.
• DCESs and other health care professionals can play a key role in early recognition of hypercortisolism.
• With earlier recognition and referral, hypercortisolism can be diagnosed and treated effectively, supporting improved clinical outcomes and enhanced quality of life.
  

^{Aresta C, Soranna D, Giovanelli L, et al. When to Suspect Hidden Hypercortisolism in Type 2 Diabetes: A Meta-Analysis. Endocr Pract. 2021;27(12):1216-1224. doi:10.1016/j.eprac.2021.07.014}

^{Barbot M, Ceccato F, Scaroni C. Diabetes Mellitus Secondary to Cushing's Disease. Front Endocrinol (Lausanne). 2018;9:284. Published 2018 Jun 5. doi:10.3389/fendo.2018.00284}

^{Braun LT, Vogel F, Zopp S, et al. Whom Should We Screen for Cushing Syndrome? The Endocrine Society Practice Guideline Recommendations 2008 Revisited. J Clin Endocrinol Metab. 2022;107(9):e3723-e3730. doi:10.1210/clinem/dgac379}

^{Buse JB, Kahn SE, Aroda VR, et al. Prevalence of Hypercortisolism in Difficult-to-Control Type 2 Diabetes. Diabetes Care. 2025;48(12):2012-2020. doi:10.2337/dc24-2841}

^{Cleveland Clinic Health Library. Cushing Syndrome. https://my.clevelandclinic.org/health/diseases/5497-cushing-syndrome. Accessed November 21, 2025.}

^{Cushing H. The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism). 1932. Obes Res. 1994;2(5):486-508. doi:10.1002/j.1550-8528.1994.tb00097.x}

^{Endocrine Society. Endocrine Library: Cushing’s Syndrome and Cushing Disease. https://www.endocrine.org/patient-engagement/endocrine-library/cushings-syndrome-and-cushing-disease. Accessed November 21, 2025.}

^{Fleseriu M, Biller BM, Findling JW, et al. Mifepristone, a glucocorticoid receptor antagonist, produces clinical and metabolic benefits in patients with Cushing's syndrome. J Clin Endocrinol Metab. 2012;97(6):2039-2049. doi:10.1210/jc.2011-3350}

^{Handelsman Y, Aroda VR, Bailey T, et al. Prevalence of Hypercortisolism in Patients with Difficult-to-Control Type 2 Diabetes and High Blood Pressure: Results from CATALYST. Metabolism - Clinical and Experimental. 2025;168.}

^{Kushner P, Brown DR, Busch RS. Hypercortisolism Is More Common Than You Think-Here's How to Find It. Fed Pract. 2024;41(Suppl 6):S23-S28. doi:10.12788/fp.0532}

^{Mayo Clinic. Diseases & Conditions: Cushing Syndrome. https://www.mayoclinic.org/diseases-conditions/cushing-syndrome/symptoms-causes/syc-20351310. Accessed November 21, 2025.}

^{Naik C, Basu S. Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome. World J Nucl Med. 2017;16(2):126-132. doi:10.4103/1450-1147.203068}

^{National Library of Medicine. MedLine Plus: Cushing Syndrome. https://medlineplus.gov/ency/article/000410.htm. Accessed November 21, 2025.}

^{Nieman LK, Biller BM, Findling JW, et al. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526-1540. doi:10.1210/jc.2008-0125}

^{Ray R, Cruse DR. Should Hypercortisolism Be Part of Your Differential Diagnosis? The Journal for Nurse Practitioners. 2026;22(1):105562.}

^{Rubinstein G, Osswald A, Hoster E, et al. Time to Diagnosis in Cushing's Syndrome: A Meta-Analysis Based on 5367 Patients. J Clin Endocrinol Metab. 2020;105(3):dgz136. doi:10.1210/clinem/dgz136}

^{Sharma ST, Nieman LK, Feelders RA. Comorbidities in Cushing's disease. Pituitary. 2015;18(2):188-194. doi:10.1007/s11102-015-0645-6}

^{Sharma A, Vella A. Glucose metabolism in Cushing's syndrome. Curr Opin Endocrinol Diabetes Obes. 2020;27(3):140-145. doi:10.1097/MED.0000000000000537}

^{Scoffings K, Morris D, Pullen A, Temple S, Trigell A, Gurnell M. Recognising and diagnosing Cushing's syndrome in primary care: challenging but not impossible. Br J Gen Pract. 2022;72(721):399-401. Published 2022 Jul 28. doi:10.3399/bjgp22X720449}

^{Steffensen C, Pereira AM, Dekkers OM, Jørgensen JO. DIAGNOSIS OF ENDOCRINE DISEASE: Prevalence of hypercortisolism in type 2 diabetes patients: a systematic review and meta-analysis. Eur J Endocrinol. 2016;175(6):R247-R253. doi:10.1530/EJE-16-0434}

^{Varlamov EV, Han AJ, Fleseriu M. Updates in adrenal steroidogenesis inhibitors for Cushing’s syndrome – A practical guide. Best Practice & Research Clinical Endocrinology & Metabolism. 2021;35(1):101490.}