Soluble α-klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas.
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 with controls with other pituitary adenomas and assess changes following transsphenoidal surgery.


METHODS
Prospective controlled study.


METHODS
We measured soluble αKL (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 αKL 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 αKL was significantly lower than in acromegalics, 532 pg/ml (400-677 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 with controls.


CONCLUSIONS
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).
Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland. marian.neidert@usz.ch
Marian Christoph
MC
Neidert
Lisa
L
Sze
Cornelia
C
Zwimpfer
Johannes
J
Sarnthein
Burkhardt
B
Seifert
Karl
K
Frei
Henning
H
Leske
Elisabeth Jane
EJ
Rushing
Christoph
C
Schmid
René-Ludwig
RL
Bernays
D000236:Adenoma / Q000097:blood / Q000175:diagnosis*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D005966:Glucuronidase / Q000097:blood*; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012995:Solubility; D055815:Young Adult
D015415:Biomarkers; D005966:Glucuronidase; D000090265:Klotho Proteins