Skip to main content
ENDO 2026 Main banner

Neuroendocrinology and Pituitary

MON-031 - Soluble Alpha Klotho in Acquired Adult-Onset, and Congenital Growth Hormone Deficiency

Monday, June 15, 2026
9:00 AM - 2:00 PM CT


Background: Soluble alpha Klotho (sαKL) is a circulating protein with endocrine functions, which is associated with longevity. We previously demonstrated markedly elevated sαKL concentrations in acromegaly, suggesting a role of GH/IGF-I excess in its regulation. However, pilot studies in adult patients with GH deficiency (GHD) found that sαKL concentrations were not profoundly low, remaining within the reference interval for most patients, indicating that factors other than GH/IGF-I signaling are involved in the regulation of sαKL. In vitro studies suggested that insulin might stimulate sαKL secretion. To better understand the role of glucose metabolism in regulation of sαKL, we therefore studied two cohorts with GHD: 1. AGHD (patients with acquired adult-onset GHD), known to present insulin resistance and 2. IGHD (subjects with isolated congenital GHD) from the Itabaianinha cohort. The latter cohort carries a homozygous GHRH-R mutation (c.57+1G→A) and is characterized by severe short stature, extremely low GH, IGF-I, and IGFBP-3 levels, absence of cancer, exceptional longevity and preserved insulin sensitivity.

Methods: We measured concentrations of sαKL, GH, IGF-I and IGFBP-3 in: (1) homozygous IGHD, n=23, (2) heterozygous IGHD (HTZ, n=9), (3) homozygous wild-type controls (HMZ, n=11) and (4) patients with AGHD (n=78). No individual received GH therapy.

Results: As expected, GH, IGF-I and IGFBP-3 were lower in AGHD and even lower in IGHD (p < 0.001 for all), while HTZ and HMZ had normal concentrations. Unexpected, despite markedly reduced GH/IGF-I in IGHD, sαKL concentrations (pg/mL, median, interquartile (IQR)) in IGHD (1052 (782.8-1349.0) were not different from HTZ (1050 (950.5-1241.0) and HMZ (993.2 (921.7-1301.0), p>0.05 for all). In contrast, sαKL was lower in AGHD (616.7 (468.5-793.4)) compared to IGHD, HTZ and HMZ (p < 0.001 for all).

Conclusion: Low sαKL concentrations in AGHD patients confirm the influence of the GH/IGF-I axis on its concentration. However, sαKL concentrations were normal in the IGHD cohort, a GHD cohort with even lower concentrations of GH, IGF-I and IGFBP-3. This suggests other factors contribute to maintenance of normal sαKL concentrations in this population. Because preserved insulin sensitivity is one of the metabolic findings seen in IGHD, but not in AGHD, we speculate it might be the mechanism to compensate the effect of severe GH/IGF-I deficiency on sαKL in this unique cohort.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*