Remission of Cushing's disease increases the risk of autoimmune disease

A cohort study of more than 250 patients undergoing surgical therapy for Cushing’s disease (CD) or nonfunctioning pituitary adenomas (NFPAs) revealed that patients who achieved remission of CD were more likely to develop new-onset autoimmune disease within 3 years after remission, than those with surgically treated NFPAs. The study is published in Annals of Internal Medicine.

Cushing's disease occurs when a tumor in the pituitary gland produces excess ACTH hormone, leading to high levels of cortisol in the body. Surgery to remove the tumor, called transsphenoidal surgery, is usually the first treatment. After surgery, when the tumor is gone, the body might not make enough cortisol, causing adrenal insufficiency. While the symptoms of excessive cortisol usually get better over time, some people may experience withdrawal symptoms when Cushing's disease goes into remission.

Researchers from Harvard Medical School identified 194 individuals with Cushing's disease (CD) and 92 individuals with non-functioning pituitary adenomas (NFPAs) who underwent pituitary surgery, matched for age and sex. They discovered that individuals CD who achieved remission were more likely than those with surgically treated NFPAs to develop new-onset autoimmune disease within 3 years after remission. The cumulative incidence stood at 10.4 percent.

The study's findings suggest that the higher prevalence of adrenal insufficiency and lower nadir serum cortisol levels in the CD group could have played a role in the development of autoimmune diseases post-surgery. The researchers emphasize the importance of closely monitoring patients with a family history of autoimmune disease after achieving remission from CD.

Additionally, the researchers suggest that administering higher doses of glucocorticoid replacement therapy in the early postoperative period might lower the risk of autoimmune disease development. These results shed light on the natural progression of autoimmune diseases and their connection to fluctuations in cortisol levels.

Reference: David A. Savitz, PhD; Lauren A. Wise, MSc, ScD; Julia C. Bond, MPH; Elizabeth E. Hatch, MS, PhD; Collette N. Ncube, DrPH, MPH, MS; Amelia K. Wesselink, PhD; Mary D. Willis, PhD, MPH; Jennifer J. Yland, PhD; Kenneth J. Rothman, DrPH DOI: 10.7326/M23-2024