Vol 75, No 3 (2024)
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Published online: 2024-06-26

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Changes in body composition, adipokines, ghrelin, and FGF23 in growth hormone-deficient children during rhGH therapy

Alina D. Belceanu1, Ştefana C. Bîlha1, Letiţia Leuştean1, Maria-Christina Ungureanu1, Cristina Preda1
Pubmed: 38923900
Endokrynol Pol 2024;75(3):291-299.


Introduction: Beyond growth acceleration, growth hormone (GH) therapy improves body composition of GH-deficient (GHD) children due to the interaction of GH with lipid and carbohydrate metabolism, possibly mediated by adipokines secreted by adipose tissue and ghrelin. To promote linear growth, it is essential to have normal phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is a known regulator of serum phosphorus and may be responsible for the increased renal phosphorus reabsorption observed during GH therapy. This study aimed to assess the impact of one-year GH therapy on body composition, adipokines, acylated/unacylated ghrelin (AG/UAG), and FGF23 in GHD children.

Material and methods: A prospective observational study of 42 prepubertal, non-obese GHD children followed up in the first year of GH replacement therapy, investigating changes in adipokine profiles, AG/UAG, FGF23, and body composition. Data before therapy onset were compared with measurements obtained after 6 and 12 months of GH therapy.

Results: All children with a mean age of 9.2 ± 2.6 years grew at an accelerated pace. Total body fat decreased significantly, while the lipid profile improved, and total bone mineral density (BMD) significantly increased over the 12 months of treatment. Leptin and UAG levels decreased significantly, whereas adiponectin and AG values increased. A significant increase in plasma FGF23 and insulin growth factor 1
(IGF1) was accompanied by increased serum phosphate. Changes in FGF23 concentration did not have an impact on BMD. The strong association of FGF23 with IGF1 and height standard deviation (SD) could reveal a role of FGF23 in linear growth. In regression analysis models, GH therapy influences the changes of leptin and adiponectin, but not ghrelin, independently of body composition — lean or fat mass.

Conclusions: GH replacement therapy improves body composition and adipokine profile in GHD children and directly impacts leptin and adiponectin concentrations independently of body composition. Also, GHD children have increased serum phosphate, correlated with upregulation rather than with suppression of FGF23, an unexpected observation given the phosphaturic role of FGF23. Further research is needed to identify the molecular mechanisms by which the GH/IGF1 axis influences adipokines secretion and plasma
changes of FGF23.

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  1. Gkentzi D, Efthymiadou A, Kritikou D, et al. Fibroblast growth factor 23 and Klotho serum levels in healthy children. Bone. 2014; 66: 8–14.
  2. Efthymiadou A, Kritikou D, Mantagos S, et al. The effect of GH treatment on serum FGF23 and Klotho in GH-deficient children. Eur J Endocrinol. 2016; 174(4): 473–479.
  3. Bex M, Bouillon R. Growth hormone and bone health. Horm Res. 2003; 60 Suppl 3: 80–86.
  4. Ohlsson C, Bengtsson BA, Isaksson OG, et al. Growth hormone and bone. Endocr Rev. 1998; 19(1): 55–79.
  5. Cañete MD, Valle-Martos R, Martos R, et al. Effects of growth hormone therapy on metabolic parameters, adipokine and endothelial dysfunction in prepuberal children. Acta Paediatr. 2019; 108(11): 2027–2033.
  6. Capalbo D, Barbieri F, Improda N, et al. Growth Hormone Improves Cardiopulmonary Capacity and Body Composition in Children With Growth Hormone Deficiency. J Clin Endocrinol Metab. 2017; 102(11): 4080–4088.
  7. Metwalley KA, Farghaly HS, Abd El-Hafeez HA. Evaluation of left ventricular mass and function, lipid profile, and insulin resistance in Egyptian children with growth hormone deficiency: A single-center prospective case-control study. Indian J Endocrinol Metab. 2013; 17(5): 876–882.
  8. Ciresi A, Amato MC, Criscimanna A, et al. Metabolic parameters and adipokine profile during GH replacement therapy in children with GH deficiency. Eur J Endocrinol. 2007; 156(3): 353–360.
  9. Cañete R, Valle M, Martos R, et al. Short-term effects of GH treatment on coagulation, fibrinolysis, inflammation biomarkers, and insulin resistance status in prepubertal children with GH deficiency. Eur J Endocrinol. 2012; 167(2): 255–260.
  10. Capalbo D, Mattace Raso G, Esposito A, et al. Cluster of cardiometabolic risk factors in children with GH deficiency: a prospective, case-control study. Clin Endocrinol (Oxf). 2014; 80(6): 856–862.
  11. Šimják P, Anderlová K, Cinkajzlová A, et al. The possible role of endocrine dysfunction of adipose tissue in gestational diabetes mellitus. Minerva Endocrinol. 2020; 45(3): 228–242.
  12. Dardzińska JA, Wernio E, Małgorzewicz S. Fasting and postprandial ghrelin changes in older and younger volunteers. Minerva Endocrinol (Torino). 2022; 47(4): 413–420.
  13. Meazza C, Elsedfy HH, Pagani S, et al. Metabolic parameters and adipokine profile in growth hormone deficient (GHD) children before and after 12-month GH treatment. Horm Metab Res. 2014; 46(3): 219–223.
  14. Kirchner H, Heppner KM, Tschöp MH. The role of ghrelin in the control of energy balance. Handb Exp Pharmacol. 2012(209): 161–184.
  15. López-Siguero JP, López-Canti LF, Espino R, et al. Effect of recombinant growth hormone on leptin, adiponectin, resistin, interleukin-6, tumor necrosis factor-α and ghrelin levels in growth hormone-deficient children. J Endocrinol Invest. 2011; 34(4): 300–306.
  16. Al-Samerria S, Radovick S. Exploring the Therapeutic Potential of Targeting GH and IGF-1 in the Management of Obesity: Insights from the Interplay between These Hormones and Metabolism. Int J Mol Sci. 2023; 24(11).
  17. Vázquez-Borrego MC, Del Rio-Moreno M, Kineman RD. Towards Understanding the Direct and Indirect Actions of Growth Hormone in Controlling Hepatocyte Carbohydrate and Lipid Metabolism. Cells. 2021; 10(10).
  18. Xu J, Casserly E, Yin Y, et al. A Systematic Review of Growth Hormone in Pain Medicine: From Rodents to Humans. Pain Med. 2020; 21(1): 21–31.
  19. Fors H, Matsuoka H, Bosaeus I, et al. Serum leptin levels correlate with growth hormone secretion and body fat in children. J Clin Endocrinol Metab. 1999; 84(10): 3586–3590.
  20. Rauch F, Westermann F, Englaro P, et al. Serum leptin is suppressed by growth hormone therapy in growth hormone-deficient children. Horm Res. 1998; 50(1): 18–21.
  21. Takaya K, Ariyasu H, Kanamoto N, et al. Ghrelin strongly stimulates growth hormone release in humans. J Clin Endocrinol Metab. 2000; 85(12): 4908–4911.
  22. Broglio F, Gottero C, Prodam F, et al. Non-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans. J Clin Endocrinol Metab. 2004; 89(6): 3062–3065.
  23. Janssen JA, van der Toorn FM, Hofland LJ, et al. Systemic ghrelin levels in subjects with growth hormone deficiency are not modified by one year of growth hormone replacement therapy. Eur J Endocrinol. 2001; 145(6): 711–716.
  24. Edén Engström B, Burman P, Holdstock C, et al. Effects of growth hormone (GH) on ghrelin, leptin, and adiponectin in GH-deficient patients. J Clin Endocrinol Metab. 2003; 88(11): 5193–5198.
  25. Stawerska R, Smyczyńska J, Czkwianianc E, et al. High concentration of ghrelin in children with growth hormone deficiency and neurosecretory dysfunction. Neuro Endocrinol Lett. 2012; 33(3): 331–339.
  26. Balercia G, Giovannini L, Paggi F, et al. Growth hormone deficiency in the transition period: body composition and gonad function. J Endocrinol Invest. 2011; 34(9): 709–715.
  27. Kužma M, Killinger Z, Jackuliak P, et al. Pathophysiology of growth hormone secretion disorders and their impact on bone microstructure as measured by trabecular bone score. Physiol Res. 2019; 68(Suppl 2): S121–S129.
  28. Gardner J, Ashraf A, You Z, et al. Changes in plasma FGF23 in growth hormone deficient children during rhGH therapy. J Pediatr Endocrinol Metab. 2011; 24(9-10): 645–650.
  29. Romanian National Therapeutic Protocol for the diagnosis and treatment of growth hormone deficiency children, 2018. https://cnas.ro/wp-content/uploads/2022/03/Binder1.pdf.
  30. CDC. Growth Chart training resources. Centers for Disease Control and Prevention. (2022). https://www.cdc.gov/nccdphp/dnpao/growthcharts/index.htm.
  31. Calculating BMI Using the English System. https://www.cdc.gov/nccdphp/dnpao/growthcharts/training/bmiage/page5_2.html.
  32. Kurosu H, Kuro-O M. The Klotho gene family as a regulator of endocrine fibroblast growth factors. Mol Cell Endocrinol. 2009; 299(1): 72–78.
  33. Rothermel J, Reinehr T. Metabolic alterations in paediatric GH deficiency. Best Pract Res Clin Endocrinol Metab. 2016; 30(6): 757–770.
  34. Kopchick JJ, Berryman DE, Puri V, et al. The effects of growth hormone on adipose tissue: old observations, new mechanisms. Nat Rev Endocrinol. 2020; 16(3): 135–146.
  35. Liu X, Li X, Li C, et al. Study on regulation of adipokines on body fat distribution and its correlation with metabolic syndrome in type 2 diabetes mellitus. Minerva Endocrinol. 2019; 44(3): 259–263.
  36. Jørgensen JO, Vahl N, Hansen TB, et al. Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition. Clin Endocrinol (Oxf). 1996; 45(6): 681–688.
  37. van der Sluis IM, Boot AM, Hop WC, et al. Long-term effects of growth hormone therapy on bone mineral density, body composition, and serum lipid levels in growth hormone deficient children: a 6-year follow-up study. Horm Res. 2002; 58(5): 207–214.
  38. Giavoli C, Profka E, Verrua E, et al. GH replacement improves quality of life and metabolic parameters in cured acromegalic patients with growth hormone deficiency. J Clin Endocrinol Metab. 2012; 97(11): 3983–3988.
  39. Marzullo P, Buckway C, Pratt KL, et al. Leptin concentrations in GH deficiency: the effect of GH insensitivity. J Clin Endocrinol Metab. 2002; 87(2): 540–545.
  40. Silha JV, Krsek M, Hana V, et al. Perturbations in adiponectin, leptin and resistin levels in acromegaly: lack of correlation with insulin resistance. Clin Endocrinol (Oxf). 2003; 58(6): 736–742.
  41. Iñiguez G, Salazar T, Roman R, et al. Effects of the IGF-I/IGFBP-3 complex on GH and ghrelin nocturnal concentrations in low birth weight children. Clin Endocrinol (Oxf). 2006; 65(5): 687–692.
  42. Ito N, Fukumoto S, Taguchi M, et al. Fibroblast growth factor (FGF)23 in patients with acromegaly. Endocr J. 2007; 54(3): 481–484.
  43. Saggese G, Baroncelli GI, Bertelloni S, et al. Effects of long-term treatment with growth hormone on bone and mineral metabolism in children with growth hormone deficiency. J Pediatr. 1993; 122(1): 37–45.