Background: We recently have shown a close association of high concentrations of soluble alpha klotho (sαKL) to disease activity in acromegaly. Small pilot studies suggested that sαKL concentrations might be reduced in GH deficiency (GHD) and increase after recombinant human GH (rhGH) therapy. Our aim was to evaluate the potential of sαKL as a biomarker in GHD.
Methods: We evaluated sαKL in comparison to the classical biomarkers GH, IGF-I and IGFBP 3 in different cross-sectional cohorts: adult patients with GHD (AGHD) without (n=80; A) or with rhGH (n=57; B), patients without GHD having either NFPA (n=20; C) or prolactinoma (n=30; D), and in healthy subjects (n=199; E). Furthermore, 22 patients were evaluated longitudinally, before and during rhGH therapy.
Results: As expected, GH, IGF-I and IGFBP 3 were lower in AGHD without rhGH (A) compared to the non-AGHD groups (C, D and E), and increased with rhGH therapy (B) (P<0.05 for all comparisons). SαKL concentrations in the cohorts were as follows (median (interquartile ranges); all pg/ml: A: 612 (468-785), B: 668 (468-801), C: 853 (687-3-962), D: 1036 (827-1399) and E: 869 (720-1122). sαKL was significantly lower in AGHD without rhGH (A) compared to NFPAs (C), prolactinomas (D) and healthy subjects (E) (P<0.05 for all comparisons) but was not higher in AGHD patients with rhGH therapy (A vs. B, P>0.99). Instead, sαKL concentrations in AGHD patients with rhGH remained lower compared to patients with prolactinoma and healthy controls (B vs. D and E, P<0.0001), and tended to remain lower compared to NFPAs (B vs. C, P=0.09). However, in the longitudinal cohort, sαKL increased with rhGH (599 (469-762) vs. 728 (605-926)) as did IGF-I (μg/l): 48.5 (38.7-62.2) vs. 142 (108-162), and IGFBP 3 (μg/l): 2681 (1840-3524) vs. 3270 (2541-4257), P< 0.001 for all).
Conclusion: Our study suggests that sαKL is lower in AGHD than in patients with prolactinoma, NFPA and healthy subjects. During longitudinal assessment in the same patients, a significant increase in sαKL is seen in GHD subjects treated with rhGH. However, in contrast to situations of GH excess, where sαKL is greatly elevated, in GHD before and after treatment with rhGH, it remains within the normal range also seen in normal subjects and patients with pituitary disorders without GHD.
21 May 2022 - 24 May 2022