Despite remission, Cushing’s patients face higher risk of heart problems
Study finds diabetes, excess fat remain issues 7 years later
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People with Cushing’s syndrome may continue to have excess abdominal fat and diabetes years after achieving disease remission, putting them at an increased risk of experiencing cardiovascular, or heart-related, problems, a new study from Europe found.
The data showed that, seven years after remission, individuals who’d had Cushing’s were more likely than those who hadn’t to “exhibit adverse metabolic outcomes,” or metabolism-related problems, such as living with diabetes. While many symptoms of the rare condition were eased, treatment had not fully reversed them all, the researchers noted.
According to the team, these individuals “remain burdened by adverse metabolic profiles that may contribute to their increased long-term cardiovascular risk.”
These findings highlight the importance of continued monitoring for people with Cushing’s syndrome even after remission, the researchers noted.
“Clinically, this underscores the need for long-term management focused on weight control and optimization of cardiovascular risk factors,” the team wrote.
The study, “Long-term metabolic consequences: persistence of visceral obesity and diabetes mellitus after remission from Cushing’s syndrome,” was published in the journal Diabetes Research and Clinical Practice.
Cushing’s syndrome refers to a group of conditions driven by excessive levels of cortisol, known as hypercortisolism. Cushing’s disease, one of its most common forms, is caused by tumors in the brain’s pituitary gland. Less frequently, the disease is caused by tumors outside the pituitary gland (ectopic Cushing’s) or in the adrenal glands (adrenal Cushing’s) — the glands that produce cortisol.
Excess cortisol can cause weight gain, particularly around the abdomen, as well as high blood pressure and problems regulating blood sugar levels, which can lead to diabetes. Although these metabolic complications may ease after treatment and disease remission, some can persist and continue to increase the risk of cardiovascular disease and other complications.
20% of patients still had diabetes post-remission
To better understand the long-term metabolic effects of Cushing’s syndrome, researchers in Germany and Switzerland analyzed data from 99 patients. Among them, 62 had Cushing’s disease, 28 had adrenal Cushing’s, and nine had ectopic Cushing’s.
Patients were assessed during a period of active disease and again about seven years after achieving remission. Those results were compared with those of 396 people without Cushing’s syndrome who were matched for age and sex.
During active disease, people with Cushing’s had significantly higher body weight and body mass index (BMI), a measure of body fat based on the ratio between weight and height, than controls, the data showed. Those with Cushing’s also had more abdominal fat, reflected by a higher waist-to-hip ratio, and a greater relative fat mass.
Metabolic complications were also much more common — including type 2 diabetes, which affected 35% of patients with active Cushing’s compared with 2% of controls. Patients also had higher HbA1c levels, a measure of average blood sugar levels, and were more likely to have high blood pressure and elevated cholesterol levels. Patients were also more likely to be taking medications to manage these conditions than were controls.
Most patients with Cushing’s disease underwent transsphenoidal surgery to remove their pituitary tumor, with 35 achieving remission after surgery; the others required additional treatments. Patients with adrenal or ectopic Cushing’s were also mainly treated surgically to remove the tumors or affected adrenal glands.
The median duration of uncontrolled hypercortisolism, from diagnosis until remission, was 10.3 weeks, or about 2.4 months. Patients were followed for a median of 97 months, or about eight years.
Seven years after remission, several metabolic measures had improved, the data showed. Individuals in remission had less body fat, lower HbA1c levels, and a lower prevalence of diabetes. Specifically, the prevalence of diabetes fell from 35% during the period of active disease to 20% after remission. The use of diabetes medications also decreased from 26% to 20%, the researchers noted.
Researchers call for long-term management of Cushing’s patients
Still, even seven years later, patients continued to have a higher relative fat mass, a higher waist-to-hip ratio, higher HbA1c levels, and a higher prevalence of diabetes than controls, the scientists found, noting in particular the “sustained diabetes risk.”
According to the researchers, this suggests that successfully treating excess cortisol may reduce some metabolic complications, but may not completely reverse the changes caused by prolonged exposure to high cortisol levels.
Our findings highlight that cardiometabolic risk persists long after … remission, exceeding that of both the general population and matched controls.
Among the Cushing’s patients, those who continued to have diabetes seven years after remission had higher body weight and BMI during both active disease and remission. These individuals also had higher relative fat mass after remission.
Further analyses showed that BMI and relative fat mass were strongly associated with HbA1c levels. The levels of C-reactive protein, a marker of inflammation, and insulin, a hormone involved in blood sugar regulation, were also tied to HbA1c levels and greater amounts of body fat.
Additionally, the prevalence of diabetes at seven years post-remission was likewise associated with measures of body fat, HbA1c, and insulin.
The researchers suggested that some of these changes may persist because excess cortisol can leave behind a “reservoir of metabolically active fat cells” that may continue to promote inflammation and interfere with blood sugar regulation.
“Taken together, our findings highlight that cardiometabolic risk persists long after biochemical remission, exceeding that of both the general population and matched controls,” the researchers wrote. The team added that these results support long-term management, despite remission, that focuses on weight control and reducing other cardiovascular risk factors.
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