Cushing's Disease Stresses Your Heart and Your Mental Health

With Oskar Ragnarsson, MD, PhD, and Tamara Wexler, MD, PhD

Adults with Cushing's disease, also called hypercortisolism, have a three-fold higher risk of dying from heart disease compared to the general population,says Oskar Ragnarsson, MD, PhD, associate professor in internal medicine and endocrinology at Sahlgrenska University Hospital in Gothenburg, Sweden, in summarizing study findings, which appear in the Journal of Clinical Endocrinology & Metabolism.

Although these researchers found that the risk drops when patients are under ongoing care and their Cushing's disease is in remission, concerns about heart disease don't disappear completely. To gain some perspective, heart disease is common in the United States, affecting, one in four adults, regardless of health status,and now it's evident that people the risks associated with heart disease are amplified in people with Cushing's disease. 

Yoga is one way to reduce disease risks associated with Cushing's disease.Doing yoga helps to reduce risks of heart disease and depression, which occur at a higher rate in people with Cushing's disease. Photo: 123rf

Having Cushing's Requires Vigilance with Treatment Plan

Still, the news is not all bleak, he says. Simple awareness of the increased risks can help individuals make the adjustments necessary to improve your outcomes—just following your doctor’s treatment plan to remain in remission is most important, Dr. Ragnarsson tells EndocrineWeb. In addition, patients who received growth hormone replacement appear to have better overall outcomes,1 so this is something to discuss with your doctor.

Cushing’s syndrome occurs when your body is exposed to high levels of the hormone cortisol over a long period of time. This can arise when you must take corticosteroid medicine orally, or if your body just makes too much cortisol. Common symptoms of this condition include: having a fatty hump between the shoulders, a rounded face, and stretch marks with pink or purple coloring on the skin. Complications, if Cushing’s disease goes untreated, include bone loss (leading to increased risk of fractures and osteoporosis), high blood pressure, type 2 diabetes, and other problems. Usual treatment includes medication and surgery that are aimed to normalize cortisol levels.3

The authors arrived at the conclusions by analyzing data from 502 men and women, all of whom were diagnosed with Cushing's disease between 1987 and 2013 as indicated in a Swedish health database.1 The average age of these patients at diagnosis was 43 years, and, 83% of these individuals were in remission. During a median follow up of 13 years—half followed for longer, half followed for less time—the researchers noted 133 deaths, more than the 54 that had been anticipated in this patient population.

Risk of Heart Disease Appears Elevated in the Cushing's Disease

From their findings,1 Dr. Ragnarsson and his team calculated that people with Cushing's disease were about 2.5 times more likely to die from cardiovascular-related events than the general population. The most common reason, with more than a 3-fold increased risk, was attributed to events associated with cardiovascular disease, encompassing both heart disease and stroke. This group also appeared to have a higher risk of death from infectious and respiratory diseases, and conditions related to gastrointestinal problems.

Fortunately, just being in disease remission helps to reduce the risk of all-cause mortality,1 the researchers' report, with both men and women whose Cushing’s disease is well-managed having a two-fold lower risk of death during the follow-up period.1 Those in remission who were receiving growth hormone had an even lower risk of death than those on other forms of treatment. 

In addition, the researchers looked at the 55 patients whose Cushing’s disease was in remission and who also had diabetes; their heart disease risks remained the same. In other words, despite a strong relationship between diabetes and increased heart disease, the risks of death were not increased beyond those related to having Cushing's disease.1

In considering the impact that treatments may have, the researchers found:

  • 3 in 4 of these patients (75%) had undergone pituitary surgery
  • 28% had undergone radiotherapy
  • 1 in 4 (24%) had had both adrenal glands removed

Those who had their adrenal glands removal experienced a 2.7-fold higher risk of death, while those who were treated with radiotherapy or had pituitary surgery did not have an increased risk associated with cardiovascular events. When glucocorticoid therapy was added, it did not affect results, according to Dr. Ragnarsson and his research team.

Bottom line? "Even though patients in remission have a better prognosis than patients not in remission, they still have a more than 2-fold increased risk of mortality," he says. The study, he says, is the first to uncover a high rate of death from suicide in Cushing's patients. It has been reported before, but the numbers found in this study were higher than in others.

The findings, he says, emphasize the importance of treating Cushing's with a goal of remission. Ongoing surveillance and management are crucial, he says. "Also, evaluation and active treatment of cardiovascular risk factors and mental health is of utmost importance," Dr. Ragnarsson tells EndocrineWeb.

Remission Reduces But May Not Eliminate Health Risks 

"The study findings highlight the potential long-lasting impact of excess cortisol production in Cushing's, and that the priority for patients is to achieve biochemical remission," says Tamara L. Wexler, MD, PhD, a neuroendocrinologist at the NYU Langone Medical Center in New York CIty.

"I question whether patients listed as being in remission were truly in consistent remission, which isn't known because one or more testing methods may have been used, and we are limited by the data that was taken from medical record reviews. In addition, it may be the overall amount of excess cortisol—both the amount and duration—is what dictates risk," says Dr. Wexler. "Therefore, the negative health effects of excess cortisol exposure may continue to recede over time with sustained remission in patients with Cushing's disease."

While the study findings suggest that the adverse health effects of excess cortisol may remain, the authors' comments that cardiovascular effects are irreversible seems overly strong since continued remission may reduce a patient's risk, she says. "It is the most likely both the total cortisol exposure and the duration of a patient's remission that most likely play important roles in their ongoing heart health."

That said, the authors’ recommendation to treat cardiovascular risk factors more aggressively in patients with a history of Cushing's disease seems reasonable, according to Dr. Wexler. “it is certainly beneficial that you remain vigilant for signs of heart disease or psychiatric problems if you have active Cushing’s disease, and these are good concerns to raise this concern with your doctor,” she says.

The best course of action is to work closely with your doctor to stick to your overall treatment plan. to achieve and remain in remission.

Steps to Take to Reduce Your Risks for Heart Disease and Depression

Dr. Ragnarsson adds that for those with Cushing's disease, the recommended course of action, if you haven't already, is to make adjustments as needed to implement the following heart disease risk-reducing strategies:

  • Be sure your food choices meet the parameters of a heart-healthy diet
  • You are getting some kind of physical activity most every day
  • You see your doctor at least once a year to have annual checks of your blood pressure, blood sugar, and other heart disease risk factors.

Another note of caution—for those of you receiving cortisone replacement therapy—you may benefit from a boost in your medication dose with your doctors' supervision when you're are sick or experiencing increased health stresses.

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