Cancer risk elevated for adults after Cushing’s syndrome diagnosis
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Key takeaways:
- Adults with Cushing’s syndrome have a 78% higher risk for any cancer compared with controls.
- Cushing’s syndrome is tied to a higher risk for genitourinary cancers, thyroid cancer and adrenocortical carcinoma.
Adults diagnosed with endogenous Cushing’s syndrome have a higher risk for developing cancer compared with controls without the condition, according to data published in the European Journal of Endocrinology.
In a retrospective analysis of data from the Clalit Health Services’ electronic health record database in Israel, 19% of adults with endogenous Cushing’s syndrome were diagnosed with cancer during a median follow-up of 14.7 years compared with 11.1% of adults without Cushing’s syndrome (HR = 1.78; 95% CI, 1.44-2.2).
Adults diagnosed with Cushing’s syndrome also had a greater risk for genitourinary cancers (HR = 1.63; 95% CI, 1.02-2.61), thyroid cancer (HR = 3.68; 95% CI, 1.68-8.01) and adrenocortical carcinoma (HR = 24.72; 95% CI, 2.89-211.56) than controls.
“Our study is the first to demonstrate an elevated cancer risk in patients with Cushing’s syndrome, highlighting the importance of raising awareness and the need to establish guideline recommendations for cancer screening in this population, especially for genitourinary, thyroid and gynecological cancers,” Amit Akirov, MD, associate professor in the faculty of medicine at Tel Aviv University and in the Endocrine Institute at Rabin Medical Center in Petach-Tikva, Israel, told Healio.
Akirov and colleagues obtained health record data for 609 adults diagnosed with Cushing’s syndrome from 2000 to June 2023 (mean age at diagnosis, 48.1 years; 65% women; 41.2% with Cushing’s disease, 32.8% with adrenal Cushing’s syndrome; 25.9% with undetermined etiology). Those with Cushing’s syndrome were matched, 1:5, by age, sex, socioeconomic status and BMI with a control group of 3,018 adults who were never tested for hypercortisolism. The outcome of interest was the first diagnosis of any malignant cancer after Cushing’s syndrome diagnosis with the except of nonmelanoma skin cancer.
The increased risk for cancer among those with Cushing’s syndrome was observed both among adults younger than 60 years (HR = 2.15; 95% CI, 1.63-2.84) and those aged 60 years and older (HR = 1.42; 95% CI, 1.02-1.98). Adults with obesity and Cushing’s syndrome had a higher risk for cancer than those with obesity and no hypercortisolism (HR = 2.21; 95% CI, 1.44-3.4). No difference in cancer risk was seen among adults without obesity.
Akirov told Healio that the researchers suspected the presence of Cushing’s syndrome could increase cancer risk prior to conducting the study.
“While some studies suggest that excess growth hormone or prolactin may be linked to an increased cancer risk, this association had not been previously examined in patients with Cushing’s syndrome,” Akirov said in an interview. “However, we hypothesized that elevated cortisol levels could provide a foundation for tumor development.”
Adults with Cushing’s disease had a higher risk for any cancer (HR = 1.65; 95% CI, 1.15-2.36) and gynecological cancers (HR = 3.65; 95% CI, 1.16-11.52) than matched controls. Those with adrenal Cushing’s syndrome had an increased risk for any malignancy (HR = 2.36; 95% CI, 1.7-3.29), lung cancer (HR = 3.06; 95% CI, 1.11-8.42), genitourinary cancers (HR = 2.42; 95% CI, 1.22-4.82), thyroid cancer (HR = 4.97; 95% CI, 1.24-19.87) and adrenocortical carcinoma diagnosed more than 5 years after Cushing’s syndrome diagnosis (HR = 19.73; 95% CI, 2.21-176.5) than controls.
More research is needed to confirm the findings, further assess which cancers adults with Cushing’s syndrome are at the greatest risk for being diagnosed with and whether there are any predictors for cancer in Cushing’s syndrome, according to Akirov.
For more information:
Amit Akirov, MD, can be reached at amit.akirov@gmail.com.
Perspective
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Ricardo Correa, MD, EsD, FACE, FACP, CMQ
Endogenous Cushing's syndrome or hypercortisolism is a rare disorder characterized by chronic overproduction of cortisol, usually due to an abnormality within the body such as a pituitary adenoma, adrenal adenoma/carcinoma or ectopic adrenocorticotropic hormone-producing tumors. Cortisol is the main glucocorticoid produce by the zone fasciculata of the adrenal gland. Chronic exposure to high cortisol levels leads to a variety of metabolic disturbances, and there is increasing evidence suggesting that it is associated with an increased risk of cancer.
Some of the mechanisms that have been proposed to be related high cortisol levels and cancer are that cortisol has immunosuppressive and pro-inflammatory effects. Chronic cortisol excess can impair the body's immune surveillance, which is crucial in detecting and eliminating early cancerous cells. Long-term cortisol excess leads to insulin resistance, obesity, hyperglycemia and dyslipidemia, all of which are recognized risk factors for the development of certain cancers. Elevated cortisol levels can increase oxidative stress in the body, which in turn can damage DNA and potentially lead to malignancies.
A recent study by Rudman and colleagues published in European Journal of Endocrinology aimed to assess the cancer risk in patients with Cushing’s syndrome as compared with individually matched controls.
The authors review the data from nationwide retrospective matched cohort study of patients with endogenous Cushing’s syndrome diagnosed between 2000 and 2023 using the database of Clalit Health Services in Israel. They obtained 609 adults diagnosed with Cushing’s syndrome and pair them, 1:5, with a control group of 3,018 adults who were never tested for hypercortisolism.
The study showed an increased risk in patients with Cushing in any cancer but more specific on genitourinary cancer, thyroid cancer and adrenocortical carcinoma. Prior studies have also shown an increased risk for basal cell carcinoma, squamous cell carcinoma and small cell lung carcinoma. Some case reports have shown a relationship between Cushing’s syndrome and increased risk for colorectal cancer.
One confounder factor was the age, but they stratified by age and found similar results (The increased risk for cancer among those with Cushing’s syndrome was observed both among adults younger than 60 years and those aged 60 years and older).
This is the first observational study that analyze a correlation between having endogenous hypercortisolism and cancer risk. Many of prior data comes from case reports or case series.
Even though there are multiple limitations to this study, including retrospective design and the specific population used in a single center that prevents generalizability, the findings open a new area of research.
The clinical implication of this study is important. There is no routine cancer screening for patients with Cushing’s syndrome. Patients with endogenous Cushing's syndrome should be carefully monitored for cancer, given the increased risks associated with hypercortisolism. Early detection and prevention are key.
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