Don’t overlook hypercortisolism when managing patients with difficult-to-control type 2 diabetes (T2D)
Hypercortisolism may be contributing to clinical symptoms
Hypercortisolism is the standard clinical term representing a state of excessive cortisol in the body. This can contribute to metabolic, cardiovascular, and systemic complications. While severe cases may present as Cushing syndrome, many patients lack classic features, leading to frequent under-recognition and delayed evaluation.2,3
Clinical features that may indicate hypercortisolism4
Understanding the risk and recommendations
Hypercortisolism is associated with significant morbidity and mortality risk.5 In fact, chronically elevated cortisol levels can impact nearly every organ system in the body.5 Hypercortisolism is independently associated with cardiovascular disease and the increased mortality seen in individuals with T2D.3 Learn more by reading our provider insights article and listening to the Healthier World with Quest Diagnostics Podcast.
Screening for chronically elevated cortisol levels is recommended particularly for patients with difficult-to-control T2D who are taking multiple medications to lower glucose but still have HbA1c greater than 7.5%.2,3
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In primary care, screening for hypercortisolism may be appropriate when patients present with the following clinical features6:
- Adrenal incidentalomas–Warrant screening when discovered on imaging, regardless of symptoms
- Age-disproportionate disease–Includes osteoporosis, hypertension, or diabetes in patients < 50 years old
- Multiple progressive features–Includes rising blood pressure, worsening diabetes, and new osteoporosis
- Unexplained weight gain–Progressive weight gain or central obesity
- Persistent hyperglycemia–Hyperglycemia that does not respond to intensified therapy
- Cardiometabolic progression–Worsening hypertension or metabolic syndrome
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References
- American Diabetes Association. One in four patients with difficult-to-control type 2 diabetes experience high levels of cortisol. June 24, 2024. Accessed February 23, 2026. https://diabetes.org/newsroom/press-releases/one-four-patients-difficult-control-type-2-diabetes-experience-high-levels
- 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
- Nieman LK, Muniyappa R. Unmasking hypercortisolism in difficult-to-control type 2 diabetes: a useful paradigm shift? Diabetes Care. 2025;48(12):1994-1996. doi:10.2337/dci25-0038
- Healthline. What are the symptoms and causes of high cortisol levels? Updated March 20, 2025. Accessed March 24, 2026. https://www.healthline.com/health/high-cortisol-symptoms
- John TA, Anastasopoulou C. Hypercortisolism (Cushing syndrome). StatPearls [Internet]. Updated November 28, 2025. Accessed March 24, 2026. https://www.ncbi.nlm.nih.gov/books/NBK551526/
- Nieman LK, Biller BMK, 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.
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Endocrine Disorders
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