PDF(Pubmed)
Abstract：
Soluble alpha klotho (sαKL) has been linked to growth hormone (GH) action, but systematic evaluation and comparisons with traditional biomarkers in acromegaly are lacking.
To evaluate the potential of sαKL to aid classification of disease activity.
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). 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.
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.
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.
To evaluate the potential of sαKL to aid classification of disease activity.
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). 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.
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.
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.
摘要：
可溶性αklotho（sαKL）与生长激素（GH）作用有关，但缺乏与肢端肥大症传统生物标志物的系统评价和比较。
评估sαKL辅助疾病活动分类的潜力。
这项在2个学术中心进行的回顾性研究包括手术前的肢端肥大症患者（A，n=29)；手术后(控制，不和谐，或不受控制）无（B1，B2，B3，n=28，11，8）；或使用生长抑素类似物治疗（C1，C2，C3，n=17，11，5）；无功能的垂体腺瘤（n=20）；和健康对照（n=31）。通过免疫测定法测定sαKL，并与传统生物标志物(随机和最低点GH，胰岛素样生长因子I[IGF-I]，IGF结合蛋白3)。评估了与疾病活动的关联。
sαKL与传统生物标志物相关，特别是IGF-I（rs=0.80，P<0.0001）。治疗前的高浓度（A，中位数，四分位数间距：4.04×正常上限[2.26-8.08]）在对照和大多数不一致患者中治疗后降至正常。sαKL的临界值为1548pg/mL，区分了受控（B1，C1）和不受控（B3，C3）患者，敏感性为97.8％（88.4％-99.9％），特异性为100％（77.1％-100％）。在84%的不一致受试者中，sαKL低于临界值。剩下的16%，升高的sαKL和IGF-I持续存在，尽管正常随机GH。性,年龄,身体质量指数,骨和钙代谢标志物对sαKL浓度没有显着影响。
我们的数据支持sαKL作为评估肢端肥大症疾病活动的生物标志物。sαKL与GH分泌状态密切相关，大动态范围,以及对生物混杂因素的稳健性。特别是当GH和IGF-I提供不同的信息时，其测量可能会有所帮助。
评估sαKL辅助疾病活动分类的潜力。
这项在2个学术中心进行的回顾性研究包括手术前的肢端肥大症患者（A，n=29)；手术后(控制，不和谐，或不受控制）无（B1，B2，B3，n=28，11，8）；或使用生长抑素类似物治疗（C1，C2，C3，n=17，11，5）；无功能的垂体腺瘤（n=20）；和健康对照（n=31）。通过免疫测定法测定sαKL，并与传统生物标志物(随机和最低点GH，胰岛素样生长因子I[IGF-I]，IGF结合蛋白3)。评估了与疾病活动的关联。
sαKL与传统生物标志物相关，特别是IGF-I（rs=0.80，P<0.0001）。治疗前的高浓度（A，中位数，四分位数间距：4.04×正常上限[2.26-8.08]）在对照和大多数不一致患者中治疗后降至正常。sαKL的临界值为1548pg/mL，区分了受控（B1，C1）和不受控（B3，C3）患者，敏感性为97.8％（88.4％-99.9％），特异性为100％（77.1％-100％）。在84%的不一致受试者中，sαKL低于临界值。剩下的16%，升高的sαKL和IGF-I持续存在，尽管正常随机GH。性,年龄,身体质量指数,骨和钙代谢标志物对sαKL浓度没有显着影响。
我们的数据支持sαKL作为评估肢端肥大症疾病活动的生物标志物。sαKL与GH分泌状态密切相关，大动态范围,以及对生物混杂因素的稳健性。特别是当GH和IGF-I提供不同的信息时，其测量可能会有所帮助。
