Artikel
Soluble alpha-Klotho: A novel serum biomarker for the activity of growth hormone producing pituitary adenomas
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Autoren
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Marian Christoph Neidert
- University Hospital Zurich, Department of Neurosurgery, University of Zurich, Zurich, Switzerland
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Lisa Sze
- University Hospital Zurich, Division of Endocrinology and Diabetes, University of Zurich, Zurich, Switzerland; Kantonsspital St. Gallen, Division of Endocrinology and Diabetes, St. Gallen, Switzerland
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Cornelia Zwimpfer
- University Hospital Zurich, Division of Endocrinology and Diabetes, University of Zurich, Zurich, Switzerland
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Johannes Sarnthein
- University Hospital Zurich, Department of Neurosurgery, University of Zurich, Zurich, Switzerland
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Burkhardt Seifert
- Institute for Social and Preventive Medicine, Division of Biostatistics, University of Zurich, Zurich, Switzerland
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Karl Frei
- University Hospital Zurich, Department of Neurosurgery, University of Zurich, Zurich, Switzerland
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Henning Leske
- University Hospital Zurich, Department of Neuropathology, University of Zurich, Zurich, Switzerland
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Elisabeth Jane Rushing
- University Hospital Zurich, Department of Neuropathology, University of Zurich, Zurich, Switzerland
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Christoph Schmid
- University Hospital Zurich, Division of Endocrinology and Diabetes, University of Zurich, Zurich, Switzerland
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René-Ludwig Bernays
- University Hospital Zurich, Department of Neurosurgery, University of Zurich, Zurich, Switzerland
| Veröffentlicht: | 21. Mai 2013 |
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Gliederung
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Objective: Klotho is a lifespan-influencing gene expressed in the kidneys and other tissues, including the pituitary gland. Soluble alpha-Klotho (alpha-KL) is released into the circulation. The aim of this prospective controlled study is to present baseline serum levels of alpha-KL in patients with acromegaly compared to controls of patients with other pituitary adenomas and to assess changes over time following transsphenoidal surgery.
Method: We measured soluble alpha-KL (by sandwich ELISA) and IGF-1 (by RIA) in the sera of 14 patients (8 females, 6 males) with active acromegaly and in a control group of 22 patients (13 females, 9 males) operated for pituitary adenomas not producing GH. Detailed immunohistochemical staining patterns of the adenomas removed and of normal pituitary tissue are presented.
Results: Soluble alpha-KL was high in the acromegaly group preoperatively with a median soluble alphaKL of 4217 pg/ml (IQR, 1812–6623 pg/ml) and declined after surgery to a median of 645 pg/ml (550–1303 pg/ml) (p<0.001) during early follow-up (2–6 days postop) and to a median of 902 pg/ml (497–1340 pg/ml) (p<0.001) during late follow-up (2–3 months postop). In controls, the preoperative soluble alpha-KL was significantly lower than in acromegalics, 532 pg/ml (400–677 pg/ml) (p<0.001). Following surgery, soluble alpha-KL 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. Immunohistochemistry revealed the presence of Klotho in the healthy pituitary as well as in adenomas; staining for Klotho was unrelated to staining for GH.
Conclusions: High serum levels of soluble alpha-KL were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble alpha-KL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly.
