J. R.O.L. Schweizer*a (Dr), K. Schilbacha (Prof), M. Haenelta (Mr), AP. Gagliardob (Ms), R. Schwaigera (Ms), S. Störmannc (Dr), J. Schopohlc (Prof), M. Bidlingmaierd (Dr)

a Ludwig Maximilians Universität (LMU), Medizinische Klinik und Poliklinik IV, Endokrinologisches Labor, Munich, GERMANY ; b Ludwig Maximilians Universität (LMU), Munich, GERMANY ; c Ludwig Maximilians Universität (LMU), Medizinische Klinik und Poliklinik IV, Munich, GERMANY ; d Ludwig Maximilians Universität (LMU), Medizinische Klinik und Poliklinik IV, Endokrinologisches Labor, Munich, GERMANY

* junia.schweizer@med.uni-muenchen.de

Background: We previously have shown elevated serum soluble alpha klotho (saKL) concentrations in acromegaly. Here, we report data on its changes in patients with GH deficiency. Methods: SaKL concentrations were measured by ELISA-IBL after careful evaluation of pre-analytical stability. We evaluated saKL in comparison to the classical biomarkers of GH action in cross-sectional cohorts of adult patients with growth hormone deficiency (AGHD): without (n=80; A) or with rhGH (n=57; B) treatment, patients with pituitary disorders but without GHD (NFPA (n=20; C) or prolactinoma (n=30; D)), and healthy subjects (n=199; E). Twenty-two GHD patients were also evaluated longitudinally before and during rhGH therapy. Results: SaKL concentrations were not affected by storage at room temperature for up to 120h in whole blood (CV: 2.9%) and in serum (after centrifugation, CV:8.9%). Concentrations remained also unchanged after 4 freeze/thaw cycles (CV: 4.9%, recovery ratio (RR): 99.1%), after long-term storage (>2 years at -20oC; CV: 8.6%, RR: 89.1%) and did not differ between serum or EDTA samples (p=0.27). As expected, IGF-I and IGFBP 3 were lower in AGHD without rhGH (A) compared to the non-AGHD groups (C, D, E), and increased with rhGH (B) (p<0.05). saKL was also lower in AGHD without rhGH (A: 612 (468-785)) compared to NFPAs (C: 853 (687-3-962)), prolactinomas (D: 1036 (827-1399)) and healthy subjects (E: 869 (720-1122), p<0.05). Surprisingly, in the cross-sectional cohort treated with rhGH, concentrations of saKL remained lower compared to patients in the non-AGHD groups (B vs. D, E, p<0.0001; vs. C, p=0.09). In the longitudinal cohort, saKL increased with rhGH in each individual patient (599 (469-762) vs. 728 (605-926)), as did IGF-I: 48.5 (38.7-62.2) vs. 142 (108-162), IGFBP 3: 2681 (1840-3524) vs. 3270 (2541-4257) and P-III-NP: 7.8 (5.3-8.2) vs. 11.0 (10.1-13.9), (p<0.01 for all). Conclusion: SaKL is a GH-sensitive biomarker that is reduced in AGHD compared to non AGHD patients. Within a patient followed longitudinally, a significant increase in saKL is seen with rhGH treatment. However, in contrast to situations of GH excess, where saKL is greatly elevated, the increase is moderate, and concentrations remain within the range also seen in healthy subjects and non-AGHD patients.

The author has declared no conflict of interest.