Study of the Week: Cushing’s Disease Remission via Surgery May Boost Autoimmune Disease Risk

Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

 

This week’s study is…

Autoimmune disorders associated with surgical remission of Cushing’s disease: A cohort study

We previously published about this research in a story titled “Achieving Cushing’s Disease Remission After Surgery Could Increase Risk of New-Onset Autoimmune Disease” which can be found here. The study was originally published in the research journal Annals of Internal Medicine. You can read the full text of the study here

This research was affiliated with the Harvard Medical School.

What Happened?

Cushing’s disease is an illness caused by excess exposure to glucocorticoids, especially cortisol, the stress hormone. It’s typically the result of a tumor of the pituitary gland called a pituitary adenoma, resulting in overproduction of hormones. Therefore, a common treatment approach is removal of the tumor via transsphenoidal surgery. Glucocorticoids have the effect of suppressing inflammation. As a result, once remission is achieved and hormonal levels are normal, the risk of autoimmune disease may increase as inflammatory activity resumes.

The goal of this study was to investigate the incidence of autoimmune disorders in patients that had achieved surgical remission of their Cushing’s disease. The team sought to understand risk factors, disease presentations, and comparisons with individuals with nonfunctioning pituitary adenomas (which do not cause Cushing’s disease or affect hormones).

This was a retrospective study of patients aged 17.5 years or older who had achieved remission after receiving surgical treatment for Cushing’s while at the Massachusetts General Hospital from 2005 through 2019. This group included 194 patients, who were matched with a group of 92 adults with nonfunctional pituitary adenomas. In the three years following surgery, a total of 17 individuals developed an autoimmune disease for the first time.

Six had autoimmune thyroiditis, three had Sjögren’s syndrome, and two were diagnosed with autoimmune seronegative spondyloarthropathy. Meanwhile, only one person in the nonfunctional pituitary adenoma group developed an autoimmune disease. Overall, 10.4% of patients developed an autoimmune disorder after surgical remission, compared to just 1.6% in the nonfunctional adenoma group. 

Adults in the surgical remission group also had much higher prevalence of postoperative adrenal insufficiency (93.8% vs 16.5%). The researchers concluded that the findings indicated an association between adrenal insufficiency and the development of autoimmune disease, though the mechanism was unclear. The researchers suggested that low cortisol could have a triggering effect but stressed that further research was needed. The team also found that patients with a family history of autoimmune diseases were more likely to develop one following surgery. 

Overall, the team concluded that surgical remission of Cushing’s disease appeared to increase the risk of autoimmune disease.

Why Does it Matter?

The findings from this study indicate an additional risk from treating Cushing’s disease with surgery:

“Patients with remission following Cushing’s disease should be evaluated for autoimmune and inflammatory disorders, if they have suggestive symptoms or signs, in the years following surgical therapy.” – Lisa B. Nachtigall, MD, clinical director, Neuroendocrine and Pituitary Tumor Clinical Center, endocrine division, Massachusetts General Hospital, and associate professor, department of medicine, Harvard Medical School

These patients should also be questioned about their family history of autoimmune disease, which may be an additional risk factor:

“In patients who have symptoms of steroid withdrawal after being treated for Cushing’s disease, such as joint and muscle pain and weakness, a new inflammatory process or flare of a preexisting autoimmune disease should be suspected. The incidence of autoimmune disease in patients after remission of Cushing’s disease was more likely in patients who have a family history of autoimmune disease, and therefore such patients would deserve closer observation for the development of autoimmune disease in the setting.” – Dr. Nachtigall

Future research will investigate potential mechanisms behind the increased risk, and may also include research into the risk of autoimmune diseases in other diseases that cause major fluctuations of cortisol, such as severe acute injury or PTSD.

About Cushing’s Disease

Cushing’s disease is a disease that appears as the result of prolonged cortisol exposure. It is a frequent trigger of Cushing’s syndrome. Cushing’s disease is caused by abnormalities that cause the body to release more cortisol than usual, such as a tumor affecting the pituitary or adrenal glands. Cushing’s disease is also associated with diabetes, which is a common comorbidity. The illness can cause a variety of symptoms that appear with Cushing’s syndrome and can become more serious over time, including cerebral atrophy, hypercholesterolemia, rapid weight gain, baldness, mood instability, depression, hirsutism, sexual dysfunction, muscle and bone weakness, menstrual abnormalities, osteoporosis, diabetes, hypertension, sleep problems, immune system suppression, and memory problems. Treatment may include surgery to remove tumors, certain medications, and pituitary radiation therapy. To learn more about Cushing’s disease, click here.

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