Surgical remission of Cushing’s disease may increase odds for autoimmune disease
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Key takeaways:
- Of adults who achieved Cushing’s disease remission after surgery, 10.4% developed new-onset autoimmune disease.
- Autoimmune disease was more commonly seen among adults with a family history.
Adults who achieved remission after surgery for Cushing’s disease are more likely to develop autoimmune disease than those with nonfunctioning pituitary adenomas, according to data published in Annals of Internal Medicine.
“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 at the Neuroendocrine and Pituitary Tumor Clinical Center in the endocrine division at Massachusetts General Hospital, and associate professor in the department of medicine at Harvard Medical School, told Healio. “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.”
Nachtigall and colleagues conducted a retrospective study of data from adults aged 17.5 years and older who underwent transsphenoidal surgery for Cushing’s disease at Massachusetts General Hospital from 2005 to 2019, achieved remission after surgery and had at least one postsurgical follow-up with a pituitary expert. Adults with Cushing’s disease were matched by age and sex, 2:1, with a control group of adults with nonfunctioning pituitary adenomas. Participants were considered to have autoimmune or autoinflammatory disease based on clinical symptoms and diagnoses from providers. All data were collected from medical records.
There were 194 adults with Cushing’s disease who achieved remission after transsphenoidal surgery matched with 92 adults with nonfunctioning pituitary adenomas. Within 3 years of surgery, 17 participants in the Cushing’s disease group developed new-onset autoimmune disease. Of those who developed autoimmune disease, six had autoimmune thyroiditis, three developed Sjögren’s syndrome and two developed autoimmune seronegative spondyloarthropathy. Of those in the nonfunctioning pituitary adenoma group, one developed autoimmune disease.
Adults who achieved Cushing’s disease remission had a higher cumulative incidence of new-onset autoimmune disease than the nonfunctioning pituitary adenoma group (10.4% vs. 1.6%). There were six cases of flares, with four in the Cushing’s disease group and two among the nonfunctioning pituitary adenoma group. Adults in the Cushing’s disease group had a higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and a lower nadir serum cortisol level (63.8 nmol/L vs. 282.3 nmol/L) than adults with nonfunctioning pituitary adenomas.
“This paper shows an association between adrenal insufficiency after therapy for Cushing's disease and the development of autoimmune disease, but the exact mechanism is not known,” Nachtigall said. “It is possible that low cortisol stimulates an inflammatory process, but further investigation on the mechanism remains needed.”
Among the Cushing’s disease group, those who had new-onset autoimmune disease had a lower BMI (31.8 kg/m2 vs. 34.8 kg/m2), larger tumor size (7.2 mm vs. 5.6 mm) and a lower preoperative baseline urine free cortisol ratio (2.7 vs. 6.3) than adults who did not develop autoimmune disease. Adults who developed autoimmune disease were more likely to have a family history for autoimmune disease than those who did not have new-onset autoimmune disease (41.2% vs. 20.9%).
In addition to studies that will explore the mechanisms, Nachtigall said future research should explore whether the incidence of autoimmune disease increases after posttraumatic stress syndrome, severe acute injury or illness and other events when cortisol levels increase.
For more information:
Lisa B. Nachtigall, MD, can be reached at lnachtigall@mgh.harvard.edu.
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