Cushing’s syndrome is a rare hormonal disorder that is caused by the overproduction of cortisol in the body. This excess cortisol production leads to a variety of symptoms, including weight gain, high blood pressure, and low-grade inflammation. While surgical removal of tumors that cause Cushing’s syndrome can effectively normalize cortisol levels, recent studies have shown that patients continue to experience low-grade inflammation even after the tumors are removed. In this article, we will delve deeper into the persistent inflammation seen in patients after Cushing’s tumors are removed and discuss its potential implications.
Cushing’s syndrome is a condition characterized by excessive production of cortisol, leading to hypercortisolism. The condition is usually caused by noncancerous tumors in the pituitary gland or adrenal glands. Surgical removal of these tumors is the first line of treatment to reduce cortisol to normal levels. However, recovery from hypercortisolism can be slow, with some symptoms persisting for a long time. The reasons for this are not clear, but a recent study suggests that low-grade inflammation after surgery may be the cause.
The study, published in the European Journal of Endocrinology, found that low-grade inflammation persisted in people with Cushing’s syndrome one year after surgery to remove the disease-causing tumors. High levels of inflammatory markers were associated with post-surgical obesity, high blood sugar levels, and worse long-term muscle function. The findings may explain some of the lingering symptoms that occur in patients after successful tumor removal surgery, possibly due to the reversal of immunosuppression brought on initially by excess cortisol.
Researchers also noted that their findings suggest that inflammatory markers can be used to monitor patients during the post-surgical cortisol withdrawal phase. Cortisol belongs to a class of hormones called glucocorticoids that play a major role in immune function. High cortisol levels induce immunosuppression, weakening immune responses and increasing the risk of infections, which are seen commonly in Cushing’s patients.
To find out the reasons for incomplete recovery after successful surgery, the team examined clinical and biochemical data from 80 Cushing’s patients who were studied before and after undergoing successful tumor removal surgery. Among them, 55 (69%) had pituitary tumors, 21 (26%) had adrenal involvement, and four (5%) had ectopic Cushing’s. Most patients (89%) received temporary glucocorticoid replacement therapy one month after surgery to treat adrenal insufficiency.
Analyses revealed that the median level of C-reactive protein (CRP), an inflammation marker, was 4.8-times higher in the early remission phase one month after surgery than it was before surgery. CRP levels remained significantly high over the course of one year of follow-up. After adjusting for age and severity of hypercortisolism, high levels of postoperative CRP correlated significantly with body composition features, such as a larger waist circumference, higher body fat percentage, and higher body mass index (BMI). High levels of markers of insulin resistance and glucose intolerance (high blood sugar) also correlated with high CRP after adjustments.
To support these findings, researchers conducted a subgroup analysis comparing data from 25 Cushing’s patients to 25 age-, gender-, and body composition-matched control patients who had been evaluated for Cushing’s, but not diagnosed with the condition. The median level of interleukin-6 (IL-6), an immune signaling protein, was 4.2-times higher one month after surgery — a sign of inflammatory activity — compared with the period before surgery. In Cushing’s patients, IL-6 levels were three times higher than in matched controls and remained significantly high after follow-up visits at three and six months.
Across all patients, high CRP and IL-6 levels during early remission were associated significantly with worse muscle function, as assessed by hand grip strength and standing-up tests. As evaluated with three questionnaires, lower quality of life (QoL) also correlated with high levels of these pro-inflammatory markers.
In conclusion, low-grade inflammation after surgery may be the cause of incomplete recovery in Cushing’s syndrome patients, with high levels of inflammatory markers being associated with post-surgical obesity, high blood sugar levels, and worse long-term muscle function. CRP and IL-6 could serve as biomarkers to monitor patients during the glucocorticoid withdrawal phase.
In conclusion, the journey of recovery after Cushing’s syndrome can be a long and challenging one. While surgery to remove the tumors responsible for excessive cortisol production is an important step towards healing, it is not the final destination. The persistence of low-grade inflammation post-operation can hinder recovery and lead to other health complications. That is why ongoing medical monitoring and treatment targeted at managing inflammation is crucial to reduce the risk of long-term health problems. The good news is that with proper care and management, the majority of individuals with Cushing’s syndrome can resume a healthy and fulfilling life.
