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Type:	Artigo de Periódico
Title:	Soluble Alpha Klotho in Acromegaly: comparison with traditional markers of disease activity
Authors:	Júnia r o Lschweizer Antônio Ribeiro-oliveira Martin Bidlingmaier Katharina Schilbach Michael Haenelt Alexandre v Giannetti Mariana f Bizzi Beatriz s Soares Eduardo Paulino Júnior Jochen Schopohl Sylvère Störmann
Abstract:	Abstract 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.
Subject:	Biomarcadores Farmacológicos Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina Somatomedinas Fator de Crescimento Insulin-Like I
language:	eng
metadata.dc.publisher.country:	Brasil
Publisher:	Universidade Federal de Minas Gerais
Publisher Initials:	UFMG
metadata.dc.publisher.department:	ICB - DEPARTAMENTO DE MORFOLOGIA MED - DEPARTAMENTO DE ANATOMIA PATOLÓGICA E MEDICINA LEGAL MED - DEPARTAMENTO DE CIRURGIA MED - DEPARTAMENTO DE CLÍNICA MÉDICA
Rights:	Acesso Aberto
metadata.dc.identifier.doi:	https://doi.org/10.1210/clinem/dgab257
URI:	http://hdl.handle.net/1843/55180
Issue Date:	2021
metadata.dc.url.externa:	https://academic.oup.com/jcem/article/106/8/e2887/6232405
metadata.dc.relation.ispartof:	The Journal of Clinical Endocrinology & Metabolism
Appears in Collections:	Artigo de Periódico

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