Endocrine Abstracts

Background: Alpha klotho is a transmembrane protein that regulates calcium metabolism. Its soluble portion has been linked to endocrine functions. We have recently shown high concentrations of serum soluble alpha klotho (sαKL) in active acromegaly. There is limited information about regulation of sαKL secretion. We aimed to gain insight about sαKL as a potential biomarker for H-related diseases.

Methods: SαKL was measured by ELISA (IBL, Hamburg, Germany) in healthy adults (A, n=890, ~120 subjects/decade) to calculate a reference interval for sαKL. It was compared to concentrations of patients with non-functional pituitary adenomas (NFPA, B, n=18) or prolactinomas (C, n=66). Moreover, we evaluated the potential impact of biological variables on sαKL concentrations.

Results: The reference interval (2.5-97.5 centile) for sαKL in healthy adults was 152-1303 pg/ml (median: 673 [IQR: 543-846]). SαKL was not different in NFPA (A vs. B, p>0.05), but higher in prolactinoma (902 [754-1228]; A vs. C, P<0.0001). SαKL in males was slightly lower than in females (651 [537-815] vs. 687 [546-881], P=0.01). As expected, IGF-I and IGFBP 3 significantly differed between age decades, while sαKL mainly differed between individuals <40 as compared to □70 years (P<0.05 for all comparisons). SαKL exhibited a weak negative correlation with age, BMI, waist-hip-ratio, (r_s=-0.30, -0.13, -0.12, respectively, P<0.001 for all) and a positive correlation with estimated glomerular filtration rate and IGF-I (r_s=0.11, 0.31, respectively, P<0.001 for all). These correlations were remarkably weaker than those observed for IGF-I and IGFBP 3. There was no correlation between sαKL and IGFBP 3 or parameters of glucose, liver and calcium metabolism (P>0.05 for all), while IGF-I and IGFBP 3 correlated with glucose and calcium metabolism. SαKL was slightly lower in individuals after >12h of fasting and on use of isolated estrogen (P<0.05 for all).

Conclusions: We provide a reference interval for sαKL from a large cohort of healthy adults. Furthermore, we show that many biological variables correlate only weakly with sαKL. Fasting and oral estrogens are associated with slightly lower sαKL, perhaps through induction of hepatic GH-resistance which was already described for IGF-I. In prolactinoma patients, sαKL concentrations were slightly higher, but within the reference interval. This could be due to the somatotropic activity of prolactin. Overall, our findings support the concept that sαKL might be a specific, GH-sensitive biomarker, and less impacted by biological variables as compared IGF-I and IGFBP 3. Our data could facilitate the use of sαKL as a biomarker in GH-related diseases.