Rozpuszczalne białko α-Klotho — nowy marker aktywności akromegalii?

Abstract

Introduction: Klotho is a transmembrane protein that attenuates insulin/insulin-like growth factor-1 (IGF-1) signalling and appears to be involved in ageing. Recent data suggest that soluble a-Klotho (sKlotho) is also elevated in acromegaly. The aim of this study was to assess serum levels of sKlotho in patients in relation to the activity of the disease and to compare with the control group. Material and methods: We studied 55 patients with acromegaly and 29 healthy controls (CG). Patients were divided into three subgroups according to minimal GH (growth hormone) concentration during the oral glucose tolerance test (OGTT) and the IGF-1 concentration: a surgically cured acromegalic group (SCA), well-controlled acromegalic group (WCA), and active acromegaly group (AA). In all subjects, blood samples were taken to assess the concentration of sKlotho, GH, IGF-1, and biochemical markers. Results: Soluble a-Klotho was highest in the AA group and lowest in the SCA group. The differences in sKlotho levels were statistically significant when the AA group was compared to the SCA, WCA, and CG groups (p = 0.000, p = 0.002, p = 0.001, respectively). There were no significant differences in sKlotho levels among the SCA, WCA, and CG groups. sKlotho positively correlated with GH levels in the WCA and WCA + SCA groups (r = 0.666, p = 0.009; r = 0.366, p = 0.047, respectively) and with the IGF-1 level in the AA group (r = 0.589, p = 0.021). Conclusions: sKlotho is increased in active acromegaly and normalises after successful treatment. It could be a new biomarker of acromegaly activity. (Endokrynol Pol 2016; 67 (4): 390-396)

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

“…Normalization of sαKL was seen to the same extent in patients controlled by surgery alone or by surgery and SSA treatment. This is in line with preliminary data from a smaller study reporting a decrease in sαKL concentrations in patients who were biochemically controlled with octreotide after surgery ( 28 ). In contrast to normalization in controlled patients, sαKL remained elevated in all our patients who were defined as uncontrolled by GH random and IGF-I after surgery with or without SSA.…”

“…Since klotho was first described in the context of longevity ( 17 ), one might expect its concentrations would correlate with age ( 19 , 49 ). However, while a weak negative correlation has been reported by 1 study ( 34 ), many others could not confirm this ( 50 , 51 ) and reported similar sαKL concentrations throughout life ( 26 , 28 , 34 , 41 , 52-54 ). The few previous studies in patients with acromegaly also did not report a correlation between sαKL and age ( 28 , 55 ).…”

“…However, while a weak negative correlation has been reported by 1 study ( 34 ), many others could not confirm this ( 50 , 51 ) and reported similar sαKL concentrations throughout life ( 26 , 28 , 34 , 41 , 52-54 ). The few previous studies in patients with acromegaly also did not report a correlation between sαKL and age ( 28 , 55 ). Therefore, in contrast to traditional biomarkers of disease activity like IGF-I ( 37 ) or GH nadir ( 9 ), there might be no need to adjust reference intervals for sαKL to age, sex, or BMI, potentially facilitating its use in a clinical setting.…”

Acromegaly, inflammation and cardiovascular disease: a review

“…In active, but not in controlled acromegaly, high levels of sKlotho and FGF-23 have been reported compared to controls [173]. After remission, sKlotho levels rapidly normalized [173]. The potentially beneficial effects of the high sKlotho levels on endothelial function and inflammation seem to be outweighed by negative effects of hyperphosphataemia and other disturbances related to GH/ IGF-1 excess, and are insufficient to reverse the increased cardiovascular risk in acromegaly.…”

“…Also in humans, lower sKlotho levels are associated with atherosclerosis and inflammation [226,229]. In active, but not in controlled acromegaly, high levels of sKlotho and FGF-23 have been reported compared to controls [173]. After remission, sKlotho levels rapidly normalized [173].…”