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  1. Written by Kathleen Doheny With Oskar Ragnarsson, MD, PHD, and Tamara Wexler, MD, PhD Adults with Cushing's syndrome, also called hypercortisolism, have a three-fold higher risk of dying from heart disease compared to the general population,1 according to findings reported by a Swiss research team. Although the researchers found that the risk drops when patients are under care, receiving treatment, and are in remission, the risks don't disappear completely. For some perspective, heart disease is common in the United States, affecting, one in four adults, regardless of health status.2 "Patients with Cushing's disease have excess mortality [risk]," says Oskar Ragnarsson, MD, PhD, associate professor and a senior consultant in internal medicine and endocrinology at Sahlgrenska University Hospital in Gothenburg, Sweden. He is the author of the study, which appears in the Journal of Clinical Endocrinology & Metabolism. Having Cushing's Requires Vigilance Beyond Disease Symptoms Still, the news is not all bleak, he says. Simple awareness of the increased risks can help individuals reduce their risk, just as following your doctor’s treatment plan so remain in remission, Dr. Ragnarsson tells EndocrineWeb. In addition, patients who received growth hormone replacement appear to have better overall outcomes.1 Cushing’s syndrome occurs when your body is exposed to high levels of the hormone cortisol over a long period of time. This can be caused either by taking 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, may 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 Increased Risks Are Cause for Concern in Cushing’s Disease The researchers analyzed 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. From this data,1 Dr. Ragnarsson and his team calculated that people with Cushing's disease were about 2.5 times more likely to die 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 with Cushing’s disease who were in remission and also had diabetes, finding that their risks remained the same. In other words, despite a strong relationship between diabetes and increased heart disease, the risks of death were not increased in this group of patients.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 more than a 2-fold increased mortality [risk]," 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 Doesn't Eliminate Serious Risks The study findings underscore the message that ''the priority for patients is to achieve biochemical remission," says Tamara L. Wexler, MD, PhD, director of the NYU Langone Medical Center Pituitary Center, in reviewing the findings for EndocrineWeb. "One question raised by the study findings is whether patients listed as being in remission were truly in (consistent) remission," Dr. Wexler says. "One or more of several testing methods may have been used, and the data were based on medical record reviews so we can’t be certain about the status of these patients’ remission. In addition, we don’t know how much excess cortisol patients were exposed over time, which may change their risks.'' I have another concern about the findings, she says. While the method of analysis used in the study suggests that the length of time from diagnosis to remission is not associated with increased death risk, ''it may be that the total exposure to excess cortisol—the amplitude as well as duration—is related to morbidity [illness] and mortality [death] risk.'' And, she adds, any negative effects experienced by patients with Cushing’s disease may be reduced further as remission status continues. In addition, Dr. Wexler considers the authors' comments that sustained high cortisol levels may impact the cardiovascular system in a way that is chronic and irreversible ''may be overly strong." She believes that the total cortisol exposure and the duration of remission may both play important roles in patients' ongoing health. She does agree, however, with the researchers' recommendation of the need to treat heart disease risk factors more aggressively in patients with a history of Cushing's disease. Equally important, is for patients to be warned that there is an increased concern about suicide, she says, urging anyone with Cushing’s disease to raise all of these concerns with your health practitioner. Overall, the study findings certainly suggest that it is important for you to know that if you have Cushing’s syndrome, you are at increased risk for not just heart disease but also mental health disorders and other ailments than the general population, she says, and that the best course of action is to work closely with your doctor to achieve remission and stick to your overall treatment plan. Steps to Take to Reduce Your Risks for Heart Disease and Depression Dr. Ragnarsson suggests those with Cushing's disease make adjustments as needed to achieve the following 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. For those of you receiving cortisone replacement therapy, you should be mindful of the need to have a boost in your medication dose with your doctors' supervision when you're are sick or experiencing increased health stresses. From https://www.endocrineweb.com/news/adrenal-disorders/61675-cushings-disease-stresses-your-heart-your-mental-health
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