Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.
Department of Neurosurgery, Kantonsspital St.Gallen, Rohrschacher Strasse 95, 9007, St. Gallen, Switzerland.
Sci Rep. 2022 Aug 30;12(1):14765. doi: 10.1038/s41598-022-19078-8.
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.
可溶性 klotho(sKl)是一种疾病特异性生物标志物,在肢端肥大症患者中升高,并在垂体腺瘤手术后下降。大约 25%的患者手术后无法缓解,因此在疾病早期对患者进行风险分层可能有助于确定需要辅助治疗的患者。生长激素(GH)和胰岛素样生长因子-1(IGF-1)已被评估为疾病活动的生物标志物,但 sKl 作为手术成功的预测生物标志物的价值尚未得到评估。在这项研究中,我们在 55 例未经治疗的患者中测量了经蝶窦垂体手术后的血清生物标志物。根据随访时的生化发现(7-16 年),我们将患者分为三组:(A)长期缓解(定义为 IGF-1 正常且随机 GH 低(<1μg/l)或口服葡萄糖试验时 GH 谷值抑制(<0.4/μg/l);(B)初始缓解但随后疾病活动;(C)持续的临床和/或生化疾病活动。sKl 水平与 GH、IGF-1 水平和肿瘤体积呈正相关。有趣的是,长期缓解组和持续疾病活动组之间 sKl 的术前和术后水平存在统计学差异。这项研究首次提供了证据表明 sKl 可能作为手术成功的附加标志物,在所有初始临床缓解的患者中显著降低,而在持续疾病活动的患者中手术后仍保持高水平。