Endocrine Abstracts

Background: Recent studies reported high soluble α-klotho concentrations (α-klotho) in active acromegaly, with normalization after successful therapy. We showed that α-klotho correlates to GH and even better to IGF-I. So far, most studies employed an immunoassay from Immuno-Biological Laboratories (IBL) for measurement of α-klotho, but other assays are available. Agreement between assays remains questionable since α-klotho exists in several isoforms: KL1-KL2 (shed by α-cut), KL1 (shed by β-cut) and truncated KL1 (synthesized by alternative splicing). In vitro studies suggest that IGF-I stimulatesα-klotho shedding.

Objective: Our aim was to compare measurements by assays that presumably differ in specificity for α-klotho isoforms in healthy controls and patients with acromegaly.

Methods: Circulating concentrations of solubleα-klotho were measured in 32 healthy controls and 22 patients with acromegaly by immunoassays from IBL and Immundiagnostik (IDK).

Results: α-klotho concentrations (pg/ml, median, interquartile) measured by IDK were ~8 times higher compared to IBL in healthy controls (6000 (4648–8681) vs 731 (558–899.7); P<0.0001), but only ~2 times higher in patients with acromegaly (11310 (6659–18172) vs 4809 (3048–10267); P = 0.0017). Both Passing-Bablok and Bland-Altman showed greater disagreement between assays in all samples (Kendall’s τ = 0.04 and 0.55, respectively). While the assays did not correlate in healthy controls (r Spearman = 0.04, P = 0.83), there was intermediate correlation in acromegaly (r Spearman = 0.7, P = 0.0003).

Conclusion: Results from both assays disagree dramatically. Lack of correlation suggests this is mainly caused by different recognition of isoforms rather than different standards. Since the KL1-KL2 isoform is equally detected by both assays, while the smaller shedding products are not, the better correlation in active acromegaly suggests that the proportion of the KL1-KL2 isoform increases in acromegaly. Furthermore, it is obvious that only results from studies using the same α-klotho assay can be compared.