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 Jr, Eduardo; Schopohl, Jochen; Störmann, Sylvere; Ribeiro-Oliveira Jr, 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