High Copeptin Levels After Surgery May Be Linked to Remission

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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High levels of the hormone precursor copeptin following surgery might be associated with remission in people with Cushing’s disease who do not later develop water balance disorders, new data indicate.

However, the scientists stressed the need for further research on this potential biomarker, noting that copeptin levels after surgery did not show a clear association with risk of remission.

Their study, “Copeptin Levels Before and After Transsphenoidal Surgery for Cushing Disease: A Potential Early Marker of Remission,” was published in the Journal of the Endocrine Society.

Cushing’s disease is caused by a tumor in the brain’s pituitary gland, which causes it to produce excessive amounts of a signaling molecule called ACTH. High ACTH levels lead to the overproduction of the stress hormone cortisol, which is mainly responsible for the disease’s symptoms.

The first-line treatment for Cushing’s disease is usually surgical removal of the disease-driving cancer.

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Copeptin is a precursor of a hormone called arginine vasopressin (AVP), which helps regulate the release of ACTH from the pituitary gland. Here, a team led by scientists at the National Institutes of Health tested the hypothesis of whether measuring copeptin levels in the blood might help predict the risk of remission after surgery in Cushing’s patients.

“We hypothesized that an increase in copeptin could be an early marker of remission of [Cushing’s disease] after TSS [transsphenoidal surgery],” the researchers wrote.

The study included 44 adult and pediatric patients with Cushing’s disease who underwent surgery between 2016 and 2019. Patients ranged in age from 7 to 55, and more than three-quarters (77.2%) were children under 18. About two-thirds (64%) of the patients were female.

After surgery, eight patients developed diabetes insipidus (DI), and 13 developed syndrome of inappropriate anti-diuresis (SIADH) — both of which are conditions that affect the body’s ability to regulate salt and water levels. Four patients had both conditions, while 19 (43%) had neither.

Follow-up data after surgery were available for 33 patients, with a median follow-up time of just over a year.

A total of 85% of these patients were deemed to be in remission from Cushing’s disease. This was defined by a decrease in cortisol levels and symptom resolution, among other criteria.

Analyses of those 33 individuals showed no significant differences in peak copeptin levels following surgery between those who were or were not in remission. Analyses of changes in copeptin levels before and after surgery also showed no difference based on remission status.

An additional analysis that excluded patients with DI or SIADH also did not show statistically significant differences in these measures. However, further parametric testing — a type of mathematical test that relies on making certain statistical assumptions about the data — indicated that peak copeptin levels after surgery were higher in those who were in remission.

“Although a clear difference in peak postoperative and [change in] copeptin was not observed in this study, a higher peak postoperative copeptin was found in those in remission after excluding those who developed DI/SIADH when analyzing this comparison with parametric testing,” the researchers wrote.

“Therefore, postoperative plasma copeptin may be a useful early marker to predict remission of [Cushing’s disease] after [surgery],” they wrote, adding, “The utility of this test may be limited to those who do not develop water balance disorders postoperatively.”

The team speculated that this study might have been too small to detect such a difference with non-parametric testing.

“Further studies with larger sample sizes are needed to further evaluate postoperative plasma copeptin as an early marker to predict remission of [Cushing’s disease],” the team wrote.