An evaluation of IGF-1 and IGFBP-3 levels in patients receiving growth hormone therapy and these parameters therapeutic efficacy
Year 2022,
Volume: 39 Issue: 4, 1230 - 1234, 29.10.2022
Abdulvahit Aşık
,
Semih Bolu
Abstract
Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels in healthy children reflect endogenous growth hormone (GH) levels, and their daily variations are very low. This study investigated the relationship between growth response and serum IGF-1 and IGFBP-3 levels before and on the first year of treatment in children with GH deficiency (GHD) started on GH therapy. The records of 44 patients diagnosed with GHD, under follow-up at the Adıyaman Education and Research Hospital Pediatric Endocrinology Clinic, and receiving GH therapy for at least one year were examined retrospectively. Patients’ ages, pubertal development stages, peak GH-responses to GH stimulation tests and height standard deviation scores (SDS) measured before and at the first year of treatment, and IGF-1 and IGFBP-3 levels were recorded. Girls represented 27 (61.4%) of the cases in the study and boys 17 (3.6%), with ages ranging between 0.5 and 16.6 years (mean=11.5±3.3). Partial GHD was present in 33 patients (75%) and complete GHD in 11 (25%). Basal height SDS, IGF-1 and IGFBP-3 values were compared with those after one year of treatment. Patients with basal IGF-1 levels < -2 SDS exhibited significantly higher growth responses (p < .05). All three parameters’ mean values were significantly higher after one year compared to baseline. Δ IGF-1 and Δ IGFBP-3 values investigated in the fırst year of treatment together with basal IGF-1 levels can be a useful diagnostic tool in showing growth response in children with GHD started on GH therapy.
Thanks
Dear Editor,
The manuscript entitled “An evaluation of IGF-1 and IGFBP-3 levels in patients receiving growth hormone therapy and these parameters therapeutic efficacy” is being submitted for your consideration to be published in the Journal of Experimental and Clinical Medicine.
We state there are no prior publications or submissions with any overlapping information, the work is not and will not be submitted to any other journal while under consideration by Journal of Experimental and Clinical Medicine.
We also state that each author listed on the manuscript has seen and approved the submission of this version of the manuscript and takes full responsibility for the manuscript. On behalf of all authors, the corresponding author states that there is no conflict of interest. The informed consent was obtained from all parents before study entry.
Sincerely
Corresponding author: Abdulvahit Aşık
Adıyaman University Education and Research Hospital, Department of Pediatrics,
Kahta Street, 02000 Adiyaman, Turkey
Tel: (+90) 536 338 1083, Fax: (+ 90) 416 2252660
Email: vahit_asik@hotmail.com
References
- 1. Murray PG, Dattani MT, Clayton PE. Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence. Arch Dis Child. 2016;101(1):96-100.
- 2. Ghigo E, Bellone J, Aimaretti G, Bellone S, Loche S, Cappa M, et al. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J Clin Endocrinol Metab. 1996;81:3323-3327
- 3. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Daughaday WH, Rotwein P. Endocr Rev. 1989;10:68–91
- 4. Juul A, Skakkebaek NE. Prediction of the outcome of growth hormone provocative testing in short children by measurement of serum levels of insulin-like growth factor I and insulin-like growth factor binding protein 3. J Pediatr. 1997 Feb;130(2):197-204.
- 5. Lifshitz F. Growth and Growth disorders. Edby Liftshitz F. Pediatric Endocrinology (5th ed) New York: İnforma Health Care Inc. 2007, pp 1-40, pp 65-90, pp 113-145
- 6. Reiter EO and Rosenfeld RG. Normal and aberrant growth In: Wilson JD, Foster DW, Kronenberg HM and Larsen PR (eds). Williams Textbook of Endocrinology (9th ed). Philadelphia: W.B. Saunders Co 1998, pp 1427-1505.
- 7. Günöz H. Büyüme bozuklukları, Pediatrik Endokrinoloji. Editörler Günöz H, Öçal G, Yordam N, Kutoğlu S: Pediatrik Endokrinoloji ve Oksoloji yayınları 1, Ankara: Kalkan Matbacılık, 2003, ss 43-62, ss 66-131.
- 8. Cinaz P, Güran T, Bereket A. Boy kısalığı olan çocuğa yaklaşım. Güncel Çocuk Sağlığı Pediatrik Endokrinoloji Dergisi, 2008, 3: 2-9.
- 9. Bang P, Ahmed SF, Argente J, Backeljauw P, Bettendorf M, Bona G, et al. Identification and management of poor response to growth-promoting therapy in children with short stature. Clin Endocrinol (Oxf) 2012;77:169-181
- 10. Kim JH, Kim SJ, Lee J, Shin CH, Seo JY. Factors affecting IGF-I level and correlation with growth response during growth hormone treatment in LG Growth Study. PLoS One. 2021 Jul 19;16(7):e0252283.
- 11. Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab. 2000;85(11):3990-93.
- 12. Wilson TA, Rose SR, Cohen P, Rogol DA, Backeljauw P, Brown R et al. Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr. 2003;143(4):415-21.
- 13. Guven B, Can M, Mungan G, Acіkgoz S. Reference values for serum levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) in the West Black Sea region of Turkey. Scand J Clin Lab Invest. 2013 Mar;73(2):135-40.
- 14. Neyzi O, Günöz H, Furman A, Bundak R, Gökçay G, Darendeliler F, ve ark. Türk çocuklarında vücut ağırlığı, boy uzunluğu, baş çevresi ve vücut kitle indeksi referans değerleri. Çocuk Sağlığı ve Hastalıkları Derğisi;2008, 51:1-14.
- 15. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich- Pyle hand standards. J Pediatr XL 1952; 432-441.
- 16. Greulich WW, Pyle SI. Radiographic atlas of skeleral development of the hand and wrist, second edition. Standford, CA: Standford University Pres, 1959.
- 17. Cattoni A, Molinari S, Medici F, De Lorenzo P, Valsecchi MG, Masera N, et al. Dexamethasone Stimulation Test in the DiagnosticWork-Up of Growth Hormone Deficiency in Childhood: Clinical Value and Comparison With Insulin-Induced Hypoglycemia. Front Endocrinol (Lausanne). 2020 Dec 9;11:599302. doi: 10.3389/fendo.2020.599302. PMID: 33362716; PMCID: PMC7757782
- 18. Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clinical Chemistry 2011 57 555–559. , Schilbach K & Bidlingmaier M. Laboratory investigations in the diagnosis and follow-up of GH-related disorders. Archives of Endocrinology and Metabolism 2019 63 618–629.
- 19. Ibba A, Corrias F, Guzzetti C, Casula L, Salerno M, di Iorgi N, et al. IGF1 for the diagnosis of growth hormone deficiency in children and adolescents: a reappraisal. Endocr Connect. 2020 Nov;9(11):1095-1102.
- 20. Shen Y, Zhang J, Zhao Y, Yan Y, Liu Y, Cai J. Diagnostic value of serum IGF-1 and IGFBP-3 in growth hormone deficiency: a systematic review with meta-analysis. Eur J Pediatr. 2015 Apr;174(4):419-27.
- 21. Berberoğlu M, Sıklar Z, Darendeliler F, Poyrazoğlu S, Darcan S, Işgüven P, ve ark. Evaluation of permanent growth hormone deficiency (GHD) in young adults with childhood onset GHD: a multicenter study. J Clin Res Pediatr Endocrinol. 2008;1(1):30-7.
- 22. Federico G, Cianfarani S. Usefulness of serum insulin-like growth factor I assessment in the diagnosis of childhood-onset growth hormone deficiency. Horm Res Paediatr. 2010;74(2):145-8.
- 23. Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, et al. Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society: Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016; 86:361–397.
- 24. Ranke MB, Schweizer R, Elmlinger MW, Weber K, Binder G, Schwarze CP, et al. Relevance of IGF-I, IGFBP-3, and IGFBP-2 measurements during GH treatment of GH-deficient and non-GH-deficient children and adolescents. Horm Res. 2001;55(3):115-24.
- 25. Choi YJ, Lee YJ, Lee NY, Lee SH, Kim SK, Ahn MB, et al. Discriminatory performance of insulin-like growth factor 1 and insulin-like growth factor binding protein-3 by correlating values to chronological age, bone age, and pubertal status for diagnosis of isolated growth hormone deficiency. Ann Pediatr Endocrinol Metab. 2020 Dec;25(4):240-247.
- 26. Cutfield WS, Lundgren F. Insulin-like growth factor I and growth responses during the first year of growth hormone treatment in KIGS patients with idiopathic growth hormone deficiency, acquired growth hormone deficiency, turner syndrome and born small for gestational age. Horm Res. 2009 Jan;71 Suppl 1:39-45.
- 27. Kim M, Kim EY, Kim EY, So CH, Kim CJ. Investigating whether serum IGF-1 and IGFBP-3 levels reflect the height outcome in prepubertal children upon rhGH therapy: LG growth study database. PLoS One. 2021 Nov 1;16(11):e0259287.
- 28. Lanes R, Jakubowicz S. Is insulin-like growth factor-1 monitoring useful in assessing the response to growth hormone of growth hormone-deficient children? J Pediatr. 2002 Nov;141(5):606-10.
- 29. David A, Hwa V, Metherell LA, Netchine I, Camacho-Hübner C, Clark AJ, et al. Evidence for a continuum of genetic, phenotypic, and biochemical abnormalities in children with growth hormone insensitivity. Endocr Rev. 2011 Aug;32(4):472-97.
- 30. Frystyk J. Utility of free IGF-I measurements. Pituitary. 2007;10(2):181-7.
- 31. Polidori N, Castorani V, Mohn A, Chiarelli F. Deciphering short stature in children. Ann Pediatr Endocrinol Metab. 2020 Jun;25(2):69-79.
- 32. Johannsson G, Bidlingmaier M, Biller BMK, Boguszewski M, Casanueva FF, Chanson P, et al. Growth Hormone Research Society perspective on biomarkers of GH action in children and adults. Endocr Connect. 2018; 7:R126–R134.
- 33. Mohanraj L, Kim HS, Li W, Cai Q, Kim KE, Shin HJ, et al. IGFBP-3 inhibits cytokine-induced insulin resistance and early manifestations of athelosclerosis. Plos One. 2013; 8:e55084.
- 34. Costalonga EF, Antonini SR, Guerra-Junior G, Mendonca BB, Arnhold IJ, Jorge AA. The -202 A allele of insulin-like growth factor binding protein-3 (IGFBP3) promoter polymorphism is associated with higher IGFBP-3 serum levels and better growth response to growth hormone treatment in patients with severe growth hormone deficiency. J Clin Endocrinol Metab. 2009 Feb;94(2):588-95.
Year 2022,
Volume: 39 Issue: 4, 1230 - 1234, 29.10.2022
Abdulvahit Aşık
,
Semih Bolu
References
- 1. Murray PG, Dattani MT, Clayton PE. Controversies in the diagnosis and management of growth hormone deficiency in childhood and adolescence. Arch Dis Child. 2016;101(1):96-100.
- 2. Ghigo E, Bellone J, Aimaretti G, Bellone S, Loche S, Cappa M, et al. Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children. J Clin Endocrinol Metab. 1996;81:3323-3327
- 3. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Daughaday WH, Rotwein P. Endocr Rev. 1989;10:68–91
- 4. Juul A, Skakkebaek NE. Prediction of the outcome of growth hormone provocative testing in short children by measurement of serum levels of insulin-like growth factor I and insulin-like growth factor binding protein 3. J Pediatr. 1997 Feb;130(2):197-204.
- 5. Lifshitz F. Growth and Growth disorders. Edby Liftshitz F. Pediatric Endocrinology (5th ed) New York: İnforma Health Care Inc. 2007, pp 1-40, pp 65-90, pp 113-145
- 6. Reiter EO and Rosenfeld RG. Normal and aberrant growth In: Wilson JD, Foster DW, Kronenberg HM and Larsen PR (eds). Williams Textbook of Endocrinology (9th ed). Philadelphia: W.B. Saunders Co 1998, pp 1427-1505.
- 7. Günöz H. Büyüme bozuklukları, Pediatrik Endokrinoloji. Editörler Günöz H, Öçal G, Yordam N, Kutoğlu S: Pediatrik Endokrinoloji ve Oksoloji yayınları 1, Ankara: Kalkan Matbacılık, 2003, ss 43-62, ss 66-131.
- 8. Cinaz P, Güran T, Bereket A. Boy kısalığı olan çocuğa yaklaşım. Güncel Çocuk Sağlığı Pediatrik Endokrinoloji Dergisi, 2008, 3: 2-9.
- 9. Bang P, Ahmed SF, Argente J, Backeljauw P, Bettendorf M, Bona G, et al. Identification and management of poor response to growth-promoting therapy in children with short stature. Clin Endocrinol (Oxf) 2012;77:169-181
- 10. Kim JH, Kim SJ, Lee J, Shin CH, Seo JY. Factors affecting IGF-I level and correlation with growth response during growth hormone treatment in LG Growth Study. PLoS One. 2021 Jul 19;16(7):e0252283.
- 11. Growth Hormone Research Society. Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: summary statement of the GH Research Society. GH Research Society. J Clin Endocrinol Metab. 2000;85(11):3990-93.
- 12. Wilson TA, Rose SR, Cohen P, Rogol DA, Backeljauw P, Brown R et al. Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr. 2003;143(4):415-21.
- 13. Guven B, Can M, Mungan G, Acіkgoz S. Reference values for serum levels of insulin-like growth factor 1 (IGF-1) and IGF-binding protein 3 (IGFBP-3) in the West Black Sea region of Turkey. Scand J Clin Lab Invest. 2013 Mar;73(2):135-40.
- 14. Neyzi O, Günöz H, Furman A, Bundak R, Gökçay G, Darendeliler F, ve ark. Türk çocuklarında vücut ağırlığı, boy uzunluğu, baş çevresi ve vücut kitle indeksi referans değerleri. Çocuk Sağlığı ve Hastalıkları Derğisi;2008, 51:1-14.
- 15. Bayley N, Pinneau SR. Tables for predicting adult height from skeletal age: revised for use with the Greulich- Pyle hand standards. J Pediatr XL 1952; 432-441.
- 16. Greulich WW, Pyle SI. Radiographic atlas of skeleral development of the hand and wrist, second edition. Standford, CA: Standford University Pres, 1959.
- 17. Cattoni A, Molinari S, Medici F, De Lorenzo P, Valsecchi MG, Masera N, et al. Dexamethasone Stimulation Test in the DiagnosticWork-Up of Growth Hormone Deficiency in Childhood: Clinical Value and Comparison With Insulin-Induced Hypoglycemia. Front Endocrinol (Lausanne). 2020 Dec 9;11:599302. doi: 10.3389/fendo.2020.599302. PMID: 33362716; PMCID: PMC7757782
- 18. Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clinical Chemistry 2011 57 555–559. , Schilbach K & Bidlingmaier M. Laboratory investigations in the diagnosis and follow-up of GH-related disorders. Archives of Endocrinology and Metabolism 2019 63 618–629.
- 19. Ibba A, Corrias F, Guzzetti C, Casula L, Salerno M, di Iorgi N, et al. IGF1 for the diagnosis of growth hormone deficiency in children and adolescents: a reappraisal. Endocr Connect. 2020 Nov;9(11):1095-1102.
- 20. Shen Y, Zhang J, Zhao Y, Yan Y, Liu Y, Cai J. Diagnostic value of serum IGF-1 and IGFBP-3 in growth hormone deficiency: a systematic review with meta-analysis. Eur J Pediatr. 2015 Apr;174(4):419-27.
- 21. Berberoğlu M, Sıklar Z, Darendeliler F, Poyrazoğlu S, Darcan S, Işgüven P, ve ark. Evaluation of permanent growth hormone deficiency (GHD) in young adults with childhood onset GHD: a multicenter study. J Clin Res Pediatr Endocrinol. 2008;1(1):30-7.
- 22. Federico G, Cianfarani S. Usefulness of serum insulin-like growth factor I assessment in the diagnosis of childhood-onset growth hormone deficiency. Horm Res Paediatr. 2010;74(2):145-8.
- 23. Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, et al. Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society: Guidelines for growth hormone and insulin-like growth factor-I treatment in children and adolescents: growth hormone deficiency, idiopathic short stature, and primary insulin-like growth factor-I deficiency. Horm Res Paediatr. 2016; 86:361–397.
- 24. Ranke MB, Schweizer R, Elmlinger MW, Weber K, Binder G, Schwarze CP, et al. Relevance of IGF-I, IGFBP-3, and IGFBP-2 measurements during GH treatment of GH-deficient and non-GH-deficient children and adolescents. Horm Res. 2001;55(3):115-24.
- 25. Choi YJ, Lee YJ, Lee NY, Lee SH, Kim SK, Ahn MB, et al. Discriminatory performance of insulin-like growth factor 1 and insulin-like growth factor binding protein-3 by correlating values to chronological age, bone age, and pubertal status for diagnosis of isolated growth hormone deficiency. Ann Pediatr Endocrinol Metab. 2020 Dec;25(4):240-247.
- 26. Cutfield WS, Lundgren F. Insulin-like growth factor I and growth responses during the first year of growth hormone treatment in KIGS patients with idiopathic growth hormone deficiency, acquired growth hormone deficiency, turner syndrome and born small for gestational age. Horm Res. 2009 Jan;71 Suppl 1:39-45.
- 27. Kim M, Kim EY, Kim EY, So CH, Kim CJ. Investigating whether serum IGF-1 and IGFBP-3 levels reflect the height outcome in prepubertal children upon rhGH therapy: LG growth study database. PLoS One. 2021 Nov 1;16(11):e0259287.
- 28. Lanes R, Jakubowicz S. Is insulin-like growth factor-1 monitoring useful in assessing the response to growth hormone of growth hormone-deficient children? J Pediatr. 2002 Nov;141(5):606-10.
- 29. David A, Hwa V, Metherell LA, Netchine I, Camacho-Hübner C, Clark AJ, et al. Evidence for a continuum of genetic, phenotypic, and biochemical abnormalities in children with growth hormone insensitivity. Endocr Rev. 2011 Aug;32(4):472-97.
- 30. Frystyk J. Utility of free IGF-I measurements. Pituitary. 2007;10(2):181-7.
- 31. Polidori N, Castorani V, Mohn A, Chiarelli F. Deciphering short stature in children. Ann Pediatr Endocrinol Metab. 2020 Jun;25(2):69-79.
- 32. Johannsson G, Bidlingmaier M, Biller BMK, Boguszewski M, Casanueva FF, Chanson P, et al. Growth Hormone Research Society perspective on biomarkers of GH action in children and adults. Endocr Connect. 2018; 7:R126–R134.
- 33. Mohanraj L, Kim HS, Li W, Cai Q, Kim KE, Shin HJ, et al. IGFBP-3 inhibits cytokine-induced insulin resistance and early manifestations of athelosclerosis. Plos One. 2013; 8:e55084.
- 34. Costalonga EF, Antonini SR, Guerra-Junior G, Mendonca BB, Arnhold IJ, Jorge AA. The -202 A allele of insulin-like growth factor binding protein-3 (IGFBP3) promoter polymorphism is associated with higher IGFBP-3 serum levels and better growth response to growth hormone treatment in patients with severe growth hormone deficiency. J Clin Endocrinol Metab. 2009 Feb;94(2):588-95.