Immune cells may drive inflammation after Cushing’s remission: Study
Findings help explain why patients are at higher risk of certain disorders
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Even after people with Cushing’s syndrome achieve remission, the inflammatory activity of certain immune cells is increased, according to a new study.
The findings may help to explain data suggesting that Cushing’s patients in remission are at higher risk of certain autoimmune and inflammatory disorders, researchers said.
The study, “Increased cytokine production capacity and persistent inflammation after achieving remission of Cushing’s syndrome,” was published in the Journal of Clinical & Translational Endocrinology.
Cushing’s patients may have long-lasting health issues after remission
Cushing’s syndrome is marked by abnormally high levels of the stress hormone cortisol. Cushing’s disease, the most common form of the syndrome, is specifically driven by a tumor in the brain’s pituitary gland. The tumor secretes a signaling molecule that triggers the adrenal glands, located over the kidneys, to produce excess hormones. Tumors in the adrenal glands themselves can also cause excess cortisol production, leading to Cushing’s syndrome, known as adrenal Cushing’s.
In people with Cushing’s disease or adrenal Cushing’s, the initial line of treatment is usually surgery aimed at removing the disease-driving tumor. This is often successful at driving the disease into remission, where cortisol levels are no longer elevated.
But even after achieving remission, people with Cushing’s may still experience some long-lasting health issues. For example, some data suggest that people with Cushing’s are at increased risk of inflammatory disorders like rheumatoid arthritis after remission.
Inflammation broadly refers to the activation of the immune system and is a normal part of the body’s defenses against infectious invaders, but uncontrolled inflammation can also drive disease. If Cushing’s patients in remission are more likely to have inflammatory disorders, it implies that the immune system may be dysregulated after Cushing’s remission is achieved. The biological details remain unclear, however.
After achieving remission of [Cushing’s syndrome], the proinflammatory [signaling molecule] production capacity of monocytes increases and anti-inflammatory [signaling molecule] production capacity decreases, which could partially explain the higher prevalence of autoinflammatory diseases after remission of [Cushing’s syndrome.
In this study, a team led by scientists in the Netherlands set out to better characterize how remission affects immune activity in people with Cushing’s. To that end, they conducted a series of detailed analyses of blood samples collected from Cushing’s patients before and after achieving remission. The study included samples from three people with Cushing’s disease and six with adrenal Cushing’s.
Results showed that, following remission, levels of certain immune cells, called lymphocytes, tended to increase, while levels of other immune cells, called monocytes, tended to decrease. But even though monocyte levels were usually lower after remission, tests indicated that these immune cells were actually more active following remission. In response to simulated infectious threats, post-remission monocytes pumped out far more inflammatory signaling molecules than monocytes collected before remission. Consistently, post-remission monocytes also produced fewer anti-inflammatory molecules.
“After achieving remission of [Cushing’s syndrome], the proinflammatory [signaling molecule] production capacity of monocytes increases and anti-inflammatory [signaling molecule] production capacity decreases, which could partially explain the higher prevalence of autoinflammatory diseases after remission of [Cushing’s syndrome],” the researchers wrote.
The scientists emphasized that this analysis was limited to data from less than a dozen patients, underscoring a need for further work to validate and expand upon these findings. They said that “future, larger studies are needed to confirm these findings and … investigate whether the changes in [inflammatory signaling molecules] can be used as biomarkers for [co-occurring health problems in people with Cushing’s syndrome].”
