Soluble alpha-klotho as an adjunct biomarker of disease activity in acromegaly: Added value beyond GH and IGF-1.

PURPOSE: Assessment of disease activity in acromegaly is mainly based on growth hormone and insulin-like growth factor 1. However, discordance between these markers is common and may make follow-up difficult. This study evaluated soluble alpha-Klotho as an adjunct biomarker of biochemical disease activity in acromegaly. METHODS: This case-control study included 80 patients with acromegaly and 80 controls. Patients were categorized as controlled, discordant, uncontrolled, or active disease. Serum soluble alpha-Klotho was measured by sandwich enzyme-linked immunosorbent assay and analyzed across groups, disease-status categories, and clinical-biochemical variables. Receiver operating characteristic analysis and nested models assessed its diagnostic and incremental value. RESULTS: Alpha-Klotho concentrations were higher in acromegaly than controls [1551.9 (835.0-3158.3) vs. 759.7 (625.0-898.5) pg/mL; P < 0.001] and increased across disease-status categories: controlled treated acromegaly [722.0 (668.4-837.8)], discordant treated acromegaly [1426.9 (1119.0-1499.9)], uncontrolled treated acromegaly [2980.0 (2585.0-3650.0)], and newly diagnosed active acromegaly [3820.0 (2460.0-4620.0) pg/mL; overall P < 0.001]. Alpha-Klotho correlated with growth hormone and insulin-like growth factor 1 and identified active/uncontrolled disease with an area under the curve of 0.983. Its addition to growth hormone, insulin-like growth factor 1, age, sex, and body mass index improved discrimination from 0.947 to 0.986. Alpha-Klotho ≥ 1579.8 pg/mL was independently associated with active/uncontrolled disease. CONCLUSION: Soluble alpha-Klotho may serve as an adjunct marker of current biochemical activity in acromegaly, particularly for identifying uncontrolled treated or newly diagnosed active disease. It may aid selected cases with difficult biochemical interpretation, but should be used alongside GH, IGF-1, clinical assessment, and pituitary imaging, not as a replacement test.