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Cushing Syndrome and Cancer Risk: A Call for Awareness and Treatment

Cushing Syndrome and Cancer Risk: A Call for Awareness and Treatment

Imagine a condition that not only disrupts your body's hormonal balance but may also increase your risk of developing cancer. This appears to be the case for those diagnosed with Cushing syndrome (CS), a rare but serious disorder caused by prolonged exposure to high levels of cortisol, the body's stress hormone. A study published in The Journal of Clinical Endocrinology & Metabolism in 2025 has shed new light on the link between CS and cancer, revealing a significantly higher cancer incidence among affected individuals. This discovery underscores the urgent need for early diagnosis, effective treatment, and specialized care, such as the advanced adrenal surgery offered at the Carling Adrenal Center. In this blog post, we'll explore the study's findings, the implications for those with CS, and why timely intervention is critical.

Understanding Cushing Syndrome

Cushing syndrome occurs when the body is exposed to excessive cortisol, often due to a tumor in the adrenal glands (adrenal CS), pituitary gland (Cushing disease), or, less commonly, ectopic sources. Cortisol plays a vital role in regulating metabolism, immune response, and stress, but too much of it can wreak havoc. Symptoms include weight gain (especially around the abdomen), a round face, thinning skin, muscle weakness, and mood changes. Beyond these visible signs, CS is associated with serious complications like obesity, diabetes, hypertension, and cardiovascular disease, all of which can significantly reduce quality of life and life expectancy.

The 2025 study, conducted in Taiwan using data from the National Health Insurance program (2006–2017), provides the first comprehensive look at CS epidemiology in an Asian population. It identified 1,278 newly diagnosed CS cases, with an incidence rate of 4.04–5.02 per million person-years, higher than previous estimates from Western countries (1.8–3.2 per million). Notably, 80% of patients were female, and the mean age at diagnosis was 45.3 years. The study also found that adrenal CS (64.6%) was more common than Cushing disease (35.4%) in Taiwan, a contrast to Western data where pituitary causes predominate.

 

Figure 1: Cushing Syndrome causes many symptoms throughout the body, as shown above.

The Cancer Connection

The most striking finding of the study is the increased cancer risk among CS patients. Among 1,246 CS patients without prior cancer, 54 developed cancer during an average follow-up of 5.56 years, yielding an incidence rate of 7.77 per 1,000 person-years. The standardized incidence ratio (SIR) for cancer was 2.08 (95% CI 1.54–2.75), meaning CS patients had more than double the cancer risk of the general population. This risk was consistent across genders, with women (SIR 2.04) and men (SIR 2.22) both showing elevated rates.

The cancers most commonly observed were liver (27.7%), kidney (16.7%), and lung (13.0%), followed by breast, pancreas, and colon. Compared to Taiwan’s general population, where breast and colon cancers are more prevalent, CS patients showed a disproportionately high incidence of liver, kidney, and pancreatic cancers. The study suggests that prolonged hypercortisolism, which drives obesity and diabetes, may contribute to this increased risk. These conditions are known to promote cancer through mechanisms like hyperinsulinemia, systemic inflammation, and enhanced activity of insulin-like growth factor-1 (IGF-1), which can stimulate tumor growth.

Why This Matters

The link between CS and cancer is a wake-up call for patients, healthcare providers, and researchers. CS is already associated with a high mortality rate, primarily due to cardiovascular complications. The standardized mortality ratio (SMR) in the study was 1.56 (95% CI 0.94–2.43), suggesting a higher risk of death compared to the general population, although this difference was not statistically significant. The addition of cancer as a significant risk further amplifies the urgency of managing CS effectively.

Obesity and diabetes, common in CS, are well-established cancer risk factors. The study notes that hypercortisolism can exacerbate these conditions, creating a perfect storm for cancer development. For example, glucocorticoids (like cortisol) may directly promote liver and pancreatic cancer progression through pathways involving endoplasmic reticulum stress and autophagy. Even after treatment, some patients continue to struggle with obesity and glucose abnormalities, suggesting that the effects of long-term cortisol exposure may persist.

The Need for Timely Treatment

The study emphasizes that early diagnosis and treatment of CS are critical to mitigating its complications, including cancer risk. Untreated CS can lead to irreversible damage, and the longer hypercortisolism persists, the greater the risk of developing obesity, diabetes, and potentially cancer. Treatment typically involves surgery to remove the tumor causing excess cortisol production, followed by medical therapy or radiation in some cases.

For adrenal CS, which was more common in the study, surgical removal of the affected adrenal gland (adrenalectomy) is the first-line treatment and the only cure. Cure of the cortisol excess is expected in nearly all patients whose excess cortisol comes from one adrenal gland. However, the success of surgery depends on the expertise of the surgical team and the quality of post-operative care. This is where specialized centers like the Carling Adrenal Center stand out.

The Carling Adrenal Center: Specialized Adrenal Surgery

When it comes to adrenal surgery, the Carling Adrenal Center in Tampa, Florida, is one of the highest-volume adrenal surgery centers in the world. Founded by Dr. Tobias Carling, one of the world’s most experienced adrenal surgeons, the center specializes in minimally invasive adrenalectomy techniques for CS patients. The center’s approach, particularly the Mini Back Scope Adrenalectomy (MBSA), is in our view the best operation for most adrenal tumors.

The MBSA is a minimally invasive procedure performed through a small incision in the back, allowing for precise removal of the adrenal tumor with minimal disruption to surrounding tissues. Compared to traditional open surgery or even standard laparoscopic approaches, the MBSA offers several advantages in our experience:

  • Reduced Recovery Time: Patients typically return to normal activities within days, compared to weeks for open surgery.
  • Avoiding the Abdomen: The procedure does not go through the abdominal cavity, which means little blood loss and no risk of abdominal adhesions or hernias.
  • Improved Cosmetic Outcomes: The small incision results in minimal scarring, a significant consideration for many patients.
  • High Success Rates: Removing the tumor cures the cortisol excess in nearly all patients with a one-sided adrenal source.

Dr. Carling’s expertise, combined with the center’s state-of-the-art facilities, ensures that patients receive personalized care tailored to their specific condition. The center also emphasizes comprehensive follow-up to monitor for recurrence and manage any residual metabolic complications, such as obesity or diabetes, which could contribute to cancer risk.

What Can Patients Do?

For individuals diagnosed with CS, the study’s findings highlight the importance of proactive management. Here are some steps to consider:

  1. Seek Early Diagnosis: If you experience symptoms like unexplained weight gain, fatigue, or high blood pressure, consult an endocrinologist. Early detection can prevent long-term complications.
  2. Choose Specialized Care: For adrenal CS, seek out centers like the Carling Adrenal Center, where expertise in minimally invasive adrenalectomy can maximize treatment success.
  3. Monitor Cancer Risk: After treatment, keep up with the cancer screening recommended for your age and tell your healthcare team about any new symptoms. The study did not test whether extra screening helps, so discuss with your doctor what is right for you.
  4. Manage Metabolic Health: Address obesity and diabetes through lifestyle changes, medication, or weight loss programs to reduce cancer risk.
  5. Stay Informed: Understanding the risks associated with CS empowers patients to advocate for their health and seek timely interventions.

Looking Ahead

The Taiwan study is one of the first nationwide cohorts to show a significant cancer risk in this population. It also fills a critical gap in understanding CS epidemiology in Asia, where adrenal CS appears more prevalent than previously thought. However, the study has limitations, such as its focus on treated CS cases and potential misclassification of CS etiology. It also studied overt, diagnosed Cushing syndrome, so its figures should not be applied to milder adrenal hypercortisolism (AHC), formerly called MACS or subclinical Cushing syndrome. Future research should explore the mechanisms linking hypercortisolism to cancer and investigate whether remission fully mitigates this risk.

For now, the message is clear: Cushing syndrome is not just a hormonal disorder—it’s a condition with far-reaching consequences, including a heightened cancer risk. By prioritizing early diagnosis, effective treatment, and specialized surgical care at places like the Carling Adrenal Center, patients can take control of their health and reduce the long-term impact of this challenging condition.

If you or a loved one has been diagnosed with Cushing syndrome, don’t wait. Consult a specialist, explore your treatment options, and consider the expertise of the Carling Adrenal Center for adrenal surgery. Timely treatment matters for your long-term health.

Reference

  • Wu WC, Wu JL, Huang TS, Li CY, Li HY. Cushing Syndrome Is Associated With a Higher Risk of Cancer-A Nationwide Cohort Study. J Clin Endocrinol Metab. 2025 Apr 22;110(5):1419-1426. PMID: 38867482.

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Author

Dr. Tobias Carling MD, PhD, FACS

Dr. Tobias Carling is a world-recognized endocrine surgeon and adrenal surgery expert, widely regarded as one of the highest-volume adrenal surgeons in the United States and globally. He is the Founder and Surgeon-in-Chief of the Carling Adrenal Center in Tampa, Florida, an international referral center dedicated exclusively to adrenal tumors and adrenal hormone disorders. Prior to founding the Carling Adrenal Center, Dr. Carling spent 17.5 years at Yale University School of Medicine, where he served as Chief of Endocrine Surgery, Associate Professor of Surgery, Endocrine Surgery Fellowship Director, and Founder of the Yale Endocrine Neoplasia Laboratory. His work helped advance the understanding and treatment of adrenal, thyroid, and parathyroid tumors. Dr. Carling specializes in advanced minimally invasive adrenal surgery, including complex and function-preserving adrenalectomy techniques. He holds both an MD and PhD from Uppsala University in Sweden and has published extensively in leading scientific journals, including The New England Journal of Medicine, Nature, Science, and PNAS. He is a Fellow of the American College of Surgeons (FACS) and a member of the American Association of Endocrine Surgeons and the International Association of Endocrine Surgeons. Patients from across the U.S. and around the world seek his expertise for complex adrenal disease.