Soluble Alpha Klotho in Acromegaly: comparison with traditional markers of disease activity

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dc.creatorJúnia r o Lschweizer
dc.creatorAntônio Ribeiro-oliveira
dc.creatorMartin Bidlingmaier
dc.creatorKatharina Schilbach
dc.creatorMichael Haenelt
dc.creatorAlexandre v Giannetti
dc.creatorMariana f Bizzi
dc.creatorBeatriz s Soares
dc.creatorEduardo Paulino Júnior
dc.creatorJochen Schopohl
dc.creatorSylvère Störmann
dc.date.accessioned2023-06-20T20:45:23Z
dc.date.accessioned2025-09-09T00:27:43Z
dc.date.available2023-06-20T20:45:23Z
dc.date.issued2021
dc.format.mimetypepdf
dc.identifier.doihttps://doi.org/10.1210/clinem/dgab257
dc.identifier.issn0021972X
dc.identifier.urihttps://hdl.handle.net/1843/55180
dc.languageeng
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofThe Journal of Clinical Endocrinology & Metabolism
dc.rightsAcesso Aberto
dc.subjectBiomarcadores Farmacológicos
dc.subjectProteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina
dc.subjectSomatomedinas
dc.subjectFator de Crescimento Insulin-Like I
dc.subject.otherBiomarkers
dc.subject.otherInsulin-like growth factor
dc.subject.otherGrowth factor-binding protein 3
dc.subject.otherInsulin-like growth factor-binding protein 3
dc.titleSoluble Alpha Klotho in Acromegaly: comparison with traditional markers of disease activity
dc.typeArtigo de periódico
local.citation.epagee2899
local.citation.issue8
local.citation.spagee2887
local.citation.volume106
local.description.resumoAbstract Context: Soluble alpha klotho (sαKL) 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 sαKL 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 most discordant patients. A cutoff of 1548 pg/mL for sαKL discriminated controlled (B1, C1) and uncontrolled (B3, C3) patients with 97.8% (88.4%-99.9%) sensitivity and 100% (77.1%-100%) specificity. sαKL was below the cutoff in 84% of the discordant subjects. In the remaining 16%, elevated sαKL and IGF-I persisted, despite normal random GH. Sex, age, body mass index, and markers of bone and calcium metabolism did not significantly affect sαKL concentrations. Conclusion: Our data support sαKL as a biomarker to assess disease activity in acromegaly. sαKL 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 (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). sαKL 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: sαKL was correlated to traditional biomarkers, particularly IGF-I (rs =0.80, P <0.0001). High concentrations before treatment (A, median, interquartile range: 4.04 × 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 sαKL discriminated controlled (B1, C1) and uncontrolled (B3, C3) patients with 97.8% (88.4%-99.9%) sensitivity and 100% (77.1%-100%) specificity. sαKL was below the cutoff in 84% of the discordant subjects. In the remaining 16%, elevated sαKL and IGF-I persisted, despite normal random GH. Sex, age, body mass index, and markers of bone and calcium metabolism did not significantly affect sαKL concentrations.Conclusion: Our data support sαKL as a biomarker to assess disease activity in acromegaly. sαKL 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.
local.identifier.orcidhttps://orcid.org/0000-0001-6157-6511
local.publisher.countryBrasil
local.publisher.departmentICB - DEPARTAMENTO DE MORFOLOGIA
local.publisher.departmentMED - DEPARTAMENTO DE ANATOMIA PATOLÓGICA E MEDICINA LEGAL
local.publisher.departmentMED - DEPARTAMENTO DE CIRURGIA
local.publisher.departmentMED - DEPARTAMENTO DE CLÍNICA MÉDICA
local.publisher.initialsUFMG
local.url.externahttps://academic.oup.com/jcem/article/106/8/e2887/6232405

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