Endocrine Abstracts

Background: Soluble alpha klotho (sαKL) is high in active acromegaly, normalizes after disease control, and therefore is suggested as a new biomarker for growth hormone (GH) excess. However, little is known about the impact of biological variables other than GH.

Methods: Serum sαKL (pg/ml) was measured by ELISA (IBL, Hamburg, Germany). We first evaluated pre-analytical stability, defined a reference interval for sαKL in healthy subjects (A: n=890), and compared the concentrations to those in patients with non-functional pituitary tumors (NFPA, B, n=18) or prolactinomas (C, n=66). Moreover, we evaluated the potential impact of various biological variables on sαKL.

Results: The assay for SαKL exhibits excellent intra/inter-assay CVs (<10%) and linearity (92–107%). Concentrations were not significantly affected by storage at room temperature for 72 hours, or by up to 4 freeze/thaw cycles (recovery>90%). The reference interval (2.5–97.5%) for sαKL is 152–1303 (A: median: 673(IQR: 543–846)). SαKL was not different in NFPA (P>0.05), but higher in prolactinoma (902(754–1228); A vs.C, P<0.0001). Compared to IGF-I and IGFBP 3, SαKL exhibited a weaker negative correlation with age, BMI, waist-hip-ratio and cholesterol (r_s=−0.30, −0.13, −0.12, −0,16, respectively, P<0.05 for all). In contrast, a positive correlation was seen with glomerular filtration rate and IGF-I (r_s=0.11, 0.31, respectively, P<0.001 for all). While IGF-I and IGFBP 3 correlated with fasting glucose, sαKL did not (P>0.05), and it did also not vary significantly during oGTT (P>0.05). Slight reductions in SαKL were observed after >12h of fasting, and in females on estrogen monotherapy (P<0.05).

Conclusion: We stablished a reference range for sαKL, a highly stable biomarker of GH action. It is less affected by many biological variables than IGF-I and IGFBP 3. However, our data suggest it decreases in conditions of hepatic GH-resistance (prolonged fasting, oral estrogen), and is slightly increased by prolactin, most likely due to its somatotropic activity.