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Soluble alpha-Klotho: A novel serum biomarker for the activity of growth hormone producing pituitary adenomas


Neidert, Marian Christoph; Sze, Lisa; Zwimpfer, Cornelia; Sarnthein, Johannes; Seifert, Burkhardt; Frei, Karl; Leske, Henning; Rushing, Elisabeth Jane; Schmid, Christoph; Bernays, Rene (2013). Soluble alpha-Klotho: A novel serum biomarker for the activity of growth hormone producing pituitary adenomas. European Journal of Endocrinology, 168(4):575-583.

Abstract

OBJECTIVE: Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study we present baseline αKL serum levels of patients with acromegaly compared to controls with other pituitary adenomas, and assess changes following transsphenoidal surgery. DESIGN: Prospective controlled study. METHODS: We measured soluble αKL (sandwich ELISA) and IGF-1 (RIA) in sera of 14 patients (8 females, 6 males) with active acromegaly and in 22 control patients (13 females, 9 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 α-KL was high in the acromegaly group preoperatively (median 4217 pg/ml, 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 postop) (median 902 pg/ml, IQR 497-1340 pg/ml) (p<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400-77 pg/ml) (p<0.001). Following surgery, soluble αKL 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 to controls. CONCLUSION: High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL 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 αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).

Abstract

OBJECTIVE: Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble α-Klotho (αKL) is released into the circulation. In this study we present baseline αKL serum levels of patients with acromegaly compared to controls with other pituitary adenomas, and assess changes following transsphenoidal surgery. DESIGN: Prospective controlled study. METHODS: We measured soluble αKL (sandwich ELISA) and IGF-1 (RIA) in sera of 14 patients (8 females, 6 males) with active acromegaly and in 22 control patients (13 females, 9 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 α-KL was high in the acromegaly group preoperatively (median 4217 pg/ml, 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 postop) (median 902 pg/ml, IQR 497-1340 pg/ml) (p<0.001). In controls, preoperative soluble αKL was significantly lower than in acromegalics, 532 pg/ml (400-77 pg/ml) (p<0.001). Following surgery, soluble αKL 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 to controls. CONCLUSION: High soluble αKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble αKL 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 αKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurosurgery
04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Endocrinology and Diabetology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:11 Feb 2013 14:16
Last Modified:05 Apr 2016 16:31
Publisher:BioScientifica Ltd.
ISSN:0804-4643
Publisher DOI:https://doi.org/10.1530/EJE-12-1045
PubMed ID:23360820

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