Soluble Alpha Klotho in Acromegaly: Comparison With Traditional Markers of Disease Activity

Schweizer, Junia R. O. L.; Schilbach, Katharina; Haenelt, Michael; Giannetti, Alexandre; Bizzi, Mariana F.; Soares, Beatriz S.; Paulino, Eduardo; Schopohl, Jochen; Störmann, Sylvere; Ribeiro-Oliveira, Antonio und Bidlingmaier, Martin (2021): Soluble Alpha Klotho in Acromegaly: Comparison With Traditional Markers of Disease Activity. In: Journal of Clinical Endocrinology & Metabolism, Bd. 106, Nr. 8, E2887-E2899

Abstract

Context: Soluble alpha klotho (s alpha KL) has been linked to growth hormone (GH) action, but systematic evaluation and comparisons with traditional biomarkers in acromegaly are lacking. Objective: To evaluate the potential of s alpha KL to aid classification of disease activity. Methods: This retrospective study at 2 academic centers included acromegaly patients before surgery (A, n=29);after surgery (controlled, discordant, or uncontrolled) without (B1, B2, B3, n=28, 11, 8);or with somatostatin analogue treatment (C1, C2, C3, n=17, 11, 5);nonfunctioning pituitary adenomas (n=20);and healthy controls (n=31). s alpha KL was measured by immunoassay and compared with traditional biomarkers (random and nadir GH, insulin-like growth factor I [IGF-I], IGF binding protein 3). Associations with disease activity were assessed. Results: s alpha KL was correlated to traditional biomarkers, particularly IGF-I (r(s)=0.80, P <0.0001). High concentrations before treatment (A, median, interquartile range: 4.04 x upper limit of normal [2.26-8.08]) dropped to normal after treatment in controlled and in most discordant patients. A cutoff of 1548 pg/mL for s alpha KL discriminated controlled (B1, C1) and uncontrolled (B3, C3) patients with 97.8% (88.4%-99.9%) sensitivity and 100% (77.1%-100%) specificity. s alpha KL was below the cutoff in 84% of the discordant subjects. In the remaining 16%, elevated s alpha KL and IGF-I persisted, despite normal random GH. Sex, age, body mass index, and markers of bone and calcium metabolism did not significantly affect s alpha KL concentrations. Conclusion: Our data support s alpha KL as a biomarker to assess disease activity in acromegaly. s alpha KL exhibits close association with GH secretory status, large dynamic range, and robustness toward biological confounders. Its measurement could be helpful particularly when GH and IGF-I provide discrepant information.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0021-972X
• Sprache: Englisch