Soluble α-Klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas

Abstract

Objective: Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble a-Klotho (aKL) is released into the circulation. In this study, we present baseline aKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery. Design: Prospective controlled study. Methods: We measured soluble aKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples. Results: Soluble aKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812-6623 pg/ml) and declined after surgery during early follow-up (2-6 days; median 645 pg/ml, IQR 550-1303 pg/ml) (P!0.001) and during late follow-up (2-3 months post-operatively; median 902 pg/ml, IQR 497-1340 pg/ml; P!0.001). In controls, preoperative soluble aKL was significantly lower than in acromegalics, 532 pg/ml (400-677 pg/ml; P!0.001). Following surgery, soluble aKL remained low during early and late follow-up -changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls. Conclusion: High soluble aKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble aKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum aKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).

Rozpuszczalne białko α-Klotho — nowy marker aktywności akromegalii?

“…Our present study confirms the earlier findings of highly significant difference in sKlotho levels in patients with active acromegaly to other groups [11][12][13]. The difference was statistically significant when we compared the AA group to the SCA and WCA groups as well as to the CG group, so it was independent of methods of therapy or health conditions.…”

“…We did not observe any negative correlation between sKlotho and age in our groups. These results are consistent with earlier ones and confirm an autonomous GH secretion of sKlotho [11].…”

“…In our study we did not observe any correlation between soluble a-Klotho and any of the anthropometric measurements. The previous study showed no influence of age, and this was explained by the autonomy of GH adenoma [11]. The impact of BMI is unclear.…”

“…cantly higher levels of sKlotho compared to the control group patients with other adenomas, and the level of sKlotho declined after surgery during early as well as late follow-up [11]. The mechanism by which sKlotho increased in active acromegaly is unclear.…”

“…Recently, decreased sKlotho levels have been observed in children with organic growth hormone deficiency (GHD) [9], and also a strong association between sKlotho and IGF-1 was revealed in a study comprising 159 healthy children [10]. On the other hand, it was also found that soluble a-Klotho is increased in patients with active acromegaly and normalised after successful removal of GH-producing pituitary adenoma, at least as quickly as IGF-1 [11,12]. What is more, the level of sKlotho depends on gender and it is higher in women with acromegaly [13].…”