THU056 Reference Interval For Serum Soluble Alpha Klotho, A Sensitive Biomarker Of Growth Hormone (GH) Excess

Abstract

Abstract Disclosure: J.R. Schweizer: None. K. Schilbach: None. M. Haenelt: None. A.P. Gagliardo: None. A. Peters: None. B. Thorand: None. S. Störmann: None. J. Schopohl: None. M. Bidlingmaier: None. Background: We recently have shown that serum concentrations of soluble alpha klotho (sαKL) are high in active acromegaly and decrease with disease control. This indicates it could be an interesting biomarker for growth hormone (GH)-related diseases. However, robust data on the reference interval of sαKL in healthy subjects are lacking. Furthermore, limited information is available about the potential impact of biological variables on sαKL in healthy subjects. Methods: SαKL was measured by ELISA (IBL, Hamburg, Germany) in healthy subjects (A, n = 890, ∼120 subjects/decade, 51% females, 20-89 years). Reference intervals were calculated by median (interquartile (IQR)) for each decade and 2.5-97.5% percentile for all healthy subjects. We also investigated the impact of biological variables (age, BMI, sex and use of estrogens). In addition, we analyzed samples from patients with non-functioning pituitary adenoma (NFPA) (B, n = 18, 50% females, 24-87 years) or prolactinoma (C, n = 66, 60% females, age 17-82 years). Results: In healthy subjects the median (IQR)) for the total group of IGF-I (μg/L), IGFBP 3 (μg/L) and sαKL (pg/mL) were 114.6 (88.4-152.7), 3869 (3318-4390) and 672 (543-846), respectively. The 2.5-97.5% percentiles for sαKL measured in the healthy subjects are 152-1303 pg/mL. 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 correlated to IGF-I (rs = 0.31, p < 0.0001), but not to IGFBP 3 (p = 0.56). SαKL exhibited a weak negative correlation to creatinine (rs = -0.12, p = 0.002), age and BMI (rs = -0.30 and rs = -0.13, respectively, p <0.0001 for both). These correlations were remarkably weaker than those observed for IGF-I to age and BMI (rs = -0.59 and rs = -0.24, respectively, p <0.0001 for both). Use of estrogen slightly reduced sαKL. SαKL was higher in prolactinoma (902 (754-1228) as compared to healthy subjects (673 (543-846), A vs. C, p < 0.0001), but not different between healthy subjects and NFPA (p > 0.05). Conclusion: Our study provides robust reference intervals for sαKL from a large sample of Caucasian subjects. They are similar to those previously reported from a smaller pilot study in an Asian population, indicating that ethnicity might have a minor impact. Notably, biological variables such as age, sex and BMI have less impact on sαKL than on IGF-I and IGFBP 3. Oral estrogens seem to slightly reduce sαKL, perhaps through induction of hepatic GH-resistance as described for IGF-I. In contrast, prolactin seems to somewhat increase sαKL concentrations within the reference intervals. This could be due to the somatotropic activity of prolactin. The availability of reference intervals might facilitate the use of sαKL as a biomarker in GH-related diseases. Presentation: Thursday, June 15, 2023