medwireNews: The risk for autoimmune disorders is increased in patients with Cushing’s disease (CD) who achieve remission following surgery, suggests research.
Lisa Nachtigall (Massachusetts General Hospital, Boston, USA) and colleagues found that “the 3-year cumulative incidence of new-onset autoimmune disease in patients with CD remission was above 10%,” which they note “seems to be greater that what would be expected in the general population.”
Their results, published in the Annals of Internal Medicine, also showed that a family history of autoimmune disease may be a potential risk factor for the development of autoimmune disease among these patients, while adrenal insufficiency may be a trigger.
The researchers retrospectively assessed the 3-year incidence of new-onset autoimmune disease in 194 patients with CD who had undergone transsphenoidal surgery and achieved remission, defined as a 24-hour urine free cortisol (UFC) or serum morning cortisol level below the lower limit of normal or postoperative central adrenal insufficiency.
These patients were matched for age and sex with 92 individuals who had undergone surgery for nonfunctioning pituitary adenomas (NFPAs).
At 3 years, 10.4% of patients with CD had developed autoimmune diseases, such as Sjögren’s syndrome, subacute thyroiditis, and Graves thyroiditis. This was a significant 7.8 times higher than the 1.6% rate among those with NFPAs.
The investigators note that patients with CD who developed autoimmune diseases following surgery had a lower preoperative UFC ratio (UFC value divided by the upper limit of normal) than those who did not, at 2.7 versus 6.3. Moreover, after surgery, these patients had a mean nadir serum cortisol level that was higher than that of patients with CD who did not develop autoimmune disease, at 65.1 versus 63.6 nmol/L, and they were significantly more likely to have adrenal insufficiency, at a rate of 23.5% versus 20.5%.
This suggests that “postoperative adrenal insufficiency in the CD group might have contributed to autoimmune disease pathogenesis,” say Nachtigall and team. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”
The researchers also found that patients with CD who developed autoimmune disorders were significantly more likely than those who did not to have a family history of autoimmune disease, at 41.2% versus 20.9%, “indicating a possible genetic predisposition,” and therefore recommend such individuals should be “carefully monitored” for the presence of adrenal insufficiency.
While most of the patients with CD received physiologic hydrocortisone replacement therapy in the first week after surgery, patients who went on to develop autoimmune disorders were less likely to receive supraphysiologic doses of glucocorticoids above 25 mg hydrocortisone equivalent, at 17.6% versus 41.8%.
“The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” suggest the authors. “However, given the retrospective nature of this study, further research is needed to confirm these associations and to address causality.”
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