Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly

Abstract

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7–16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 μg/l) or a suppressed GH nadir (< 0.4/μg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity.