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Open Access 08-04-2024 | Insulins | Original Paper

Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer

Authors: Ann-Kathrin Fröhlich, Jan Porthun, Khawaja M. Talha, Alessia Lena, Sara Hadzibegovic, Ursula Wilkenshoff, Frederike Sonntag, Anja Nikolski, Luisa Valentina Ramer, Tanja Zeller, Ulrich Keller, Lars Bullinger, Stefan D. Anker, Wilhelm Haverkamp, Stephan von Haehling, Wolfram Doehner, Ursula Rauch, Carsten Skurk, John G. F. Cleland, Javed Butler, Andrew J. S. Coats, Ulf Landmesser, Mahir Karakas, Markus S. Anker

Published in: Clinical Research in Cardiology

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Abstract

Background

Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia.

Objectives

We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer.

Methods

We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height2 (women, < 50, 50–61, > 61 g/m2; men, < 60, 60–74, > 74 g/m2) and by presence of wasting syndrome with unintentional weight loss (BMI < 24 kg/m2 and weight loss ≥ 5% in the prior 12 months). Repeat echocardiograms were obtained usually within 3–6 months for 85 patients.

Results

Patients in the lowest LVmass/height2 tertile had higher plasma GH (median (IQR) for 1st, 2nd, and 3rd tertile women, 1.8 (0.9–4.2), 0.8 (0.2–2.2), 0.5 (0.3–1.6) ng/mL, p = 0.029; men, 2.1 (0.8–3.2), 0.6 (0.1–1.7), 0.7 (0.2–1.9) ng/mL, p = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48–116), 72 (48–95), 49 (35–76) ng/mL, p = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 ± 0.09, 2.02 ± 0.09, 1.88 ± 0.09, p = 0.004; men, 1.64 ± 0.09, 2.14 ± 0.11, 2.04 ± 0.11, p = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r =  − 0.591, p < 0.001; men, r =  − 0.575, p < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up (r =  − 0.318, p = 0.003).

Conclusion

In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associated with a decrease in relative LVmass during follow-up.

Graphical abstract

Appendix
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Metadata
Title
Association of an impaired GH-IGF-I axis with cardiac wasting in patients with advanced cancer
Authors
Ann-Kathrin Fröhlich
Jan Porthun
Khawaja M. Talha
Alessia Lena
Sara Hadzibegovic
Ursula Wilkenshoff
Frederike Sonntag
Anja Nikolski
Luisa Valentina Ramer
Tanja Zeller
Ulrich Keller
Lars Bullinger
Stefan D. Anker
Wilhelm Haverkamp
Stephan von Haehling
Wolfram Doehner
Ursula Rauch
Carsten Skurk
John G. F. Cleland
Javed Butler
Andrew J. S. Coats
Ulf Landmesser
Mahir Karakas
Markus S. Anker
Publication date
08-04-2024
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-024-02400-x