Soluble α-Klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas

Objective: Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble alpha-Klotho (alpha KL) is released into the circulation. In this study, we present baseline alpha KL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery. Design: Prospective controlled study. Methods: We measured soluble alpha KL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples. Results: Soluble alpha KL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812-6623 pg/ml) and declined after surgery during early follow-up (2-6 days; median 645 pg/ml, IQR 550-1303 pg/ml) (P < 0.001) and during late follow-up (2-3 months post-operatively; median 902 pg/ml, IQR 497-1340 pg/ml; P < 0.001). In controls, preoperative soluble alpha KL was significantly lower than in acromegalics, 532 pg/ml (400-677 pg/ml; P < 0.001). Following surgery, soluble alpha KL remained low during early and late follow-up - changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls. Conclusion: High soluble alpha KL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble alpha KL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum alpha KL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma). European Journal of Endocrinology 168 575-583