EC Paediatrics

Research Article Volume 14 Issue 3 - 2025

The Role of Insulin-Like Growth Factor-1 (IGF-1) in Diagnosis of Growth Hormone Deficiency from Childhood to Young Adulthood

Najya Attia1,2*

1Pediatric Department, Endocrine Unit, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia
2King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Jeddah, Saudi Arabia

*Corresponding Author: Najya Attia, Pediatric Department, Endocrine Unit, King Abdullah International Medical Research Center and King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Jeddah, Saudi Arabia.
Received: February 13, 2025; Published: February 25, 2025




Objective: To evaluate the accuracy of IGF-1 in diagnosing children with abnormal (low) growth hormone.

Design: A national multicenter cross-sectional study.

Method: Two hundred and seventeen patients with short stature (140 boys and 77 girls), age (5 - 18 years) were evaluated. Anthropometric measurements and pubertal stage evaluations were performed for all children. All patients underwent laboratory tests (CBC, thyroid function, serum IGF-1) and wrist X-rays to determine bone age by using the method of Greulich and Pyle. A provocative GH test was performed with clonidine and glucagon or insulin. Abnormal (low) GH is defined as peak level of GH < 10 μg/T. The patients ts distributed into two groups based on the level of GH. Normal group has normal GH and the abnormal group has low GH response to provocation tests.

Results: A significant difference in BMI (P < 0.05), between GHD and ISS groups, BMI was higher in abnormal GH group than normal GH group; however, age (p = 0.821) and BA (p = 0.479) did not. A significant difference in age means (P = 0.001) was found between abnormal and normal IGF-1g groups Sensitivity and specificity of IGF-I were 79% and 38.6%, respectively, using -2SD as cutoff value for IGF-1. The distribution of IGF-1 z scores looks similar for both groups in the range of ± 1SD.

Conclusion: Our study suggests that IGF-1 levels had a poor predicting value for abnormal GH. The presence of abnormal IGF-I levels in a short child with normal GH response to provocative tests and presence of normal IGF-1 in children with abnormal GH response to provocative tests indicate the presence of other strong factors that influence the IG1 levels rather than GH. Increasing cut-off value of IGF = 1 to -1SD as a pilot study did not increase the prediction of children and adolescents with abnormal GH. Our recommendation is that measuring IFG-1 as screening or diagnostic for children with short stature may be of no value, as it is not changing in evaluating or managing children with short stature.

 Keywords: Food and Drug Administration (FDA); Growth Hormone (GH); Growth Hormone Deficiency (GHD); Idiopathic Short Stature (ISS); Insulin-Like Growth Factor-1 (IGF-1)

  1. Ranke MB. “Towards a consensus on the definition of idiopathic short stature”. Hormone Research2 (1996): 64-66.
  2. GH 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”. Journal of Clinical Endocrinology and Metabolism11 (2000): 3990-3993.
  3. Lee HS and Hwang JS. “Influence of body mass index on growth hormone responses to classic provocative tests in children with short stature”. Neuroendocrinology4 (2011): 259-264.
  4. Loche S., et al. “Results of early reevaluation of growth hormone secretion in short children with apparent growth hormone deficiency”. Journal of Pediatrics4 (2002): 445-449.
  5. Juul A., et al. “Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3”. Journal of Clinical Endocrinology and Metabolism 4 (1997): 1195-1201.
  6. de Boer H., et al. “Clinical aspects of growth hormone deficiency in adults”. Endocrine Reviews1 (1995): 63-86.
  7. Clayton PE., et al. “Growth hormone state after completion of treatment with growth hormone”. Archives of Disease in Childhood3 (1987): 222-226.
  8. Cacciari E., et al. “Pitfalls in diagnosing impaired growth hormone (GH) secretion: retesting after replacement therapy of 63 patients defined as GH deficient”. Journal of Clinical Endocrinology and Metabolism6 (1992): 1284-1289.
  9. Wacharasindhu S., et al. “Normal growth hormone secretion in growth hormone insufficient children re-tested after completion of linear growth”. Clinical Endocrinology (Oxford)5 (1996): 553-556.
  10. Longobardi S., et al. “Re-evaluation of growth hormone (GH) secretion in 69 adults diagnosed as GH-deficient patients during childhood”. Journal of Clinical Endocrinology and Metabolism3 (1996): 1244-1247.
  11. Nicolson A., et al. “The prevalence of severe growth hormone deficiency in adults who received growth hormone replacement in childhood”. Clinical Endocrinology (Oxford) 3 (1996): 311-316.
  12. Tauber M., et al. “Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment”. Journal of Clinical Endocrinology and Metabolism2 (1997): 352-356.
  13. Ghigo E., et al. “Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children”. Journal of Clinical Endocrinology and Metabolism9 (1996): 3323-3327.
  14. Muller A., et al. “Harmonization of growth hormone measurements with different immunoassays by data adjustment”. Clinical Chemistry and Laboratory Medicine7 (2011): 1135-1142.
  15. Maghnie M., et al. “Diagnosing growth hormone deficiency: the value of short-term hypocaloric diet”. Journal of Clinical Endocrinology and Metabolism 5 (1993): 1372-1378.
  16. Stanley TL., et al. “Effect of body mass index on peak growth hormone response to provocative testing in children with short stature”. Journal of Clinical Endocrinology and Metabolism12 (2009): 4875-4881.
  17. Laron Z. “Insulin-like growth factor 1 (IGF-1): a growth hormone”. Molecular Pathology 5 (2001): 311-316.
  18. Laron Z. “Laron syndrome (Primary growth hormone resistance or insensitivity): The personal experience 1958-2003”. Journal of Clinical Endocrinology and Metabolism3 (2004): 1031-1044.
  19. Clemmons DR and Van Wyk JJ. “Factors controlling blood concentrations of somatomedin-C”. Clinics in Endocrinology and Metabolism1 (1984): 113-143.
  20. Rosenfeld RG., et al. “Insulin-like growth factors I and II in evaluation of growth retardation”. Journal of Pediatrics3 (1986): 428-433.
  21. Lee PDK., et al. “Efficacy of insulin like growth factor I levels in predicting the response to provocative growth hormone testing”. Pediatric Research 1 (1990): 45-51.
  22. Hasegawa Y., et al. “Clinical utility of insulin-like growth factor-I (IGF-I) and IGF binding protein- 3 levels in the diagnosis of GH deficiency (GHD) during childhood”. Endocrine Journal 43 (1996): S1-S4.
  23. Smith WJ., et al. “Use of insulin-like growth factor-binding protein-2 (IGFBP-2), IGFBP-3, and IGF-I for assessing growth hormone status in short children”. Journal of Clinical Endocrinology and Metabolism5 (1993): 1294-1299.
  24. Cameron N. “The measurements of human growth”. Sydney: Croom-Helm (1984).
  25. Tanner JM and Whitehouse RH. “Clinical longitudinal standards for height, weight, height velocity, weight velocity and stages of puberty”. Archives of Disease in Childhood3 (1976): 170-179.
  26. Greulich WW and Pyle SI. “Radiographic atlas of skeletal development of hand and wrist”. Stanford, CA: Stanford University Press (1959).
  27. Rosenfeld RG., et al. “The diagnosis of childhood growth hormone deficiency revisited”. Journal of Clinical Endocrinology and Metabolism5 (1995): 1532-1540.
  28. Cacciari EC., et al. “Value and limits of pharmacological and physiological tests to diagnose growth hormone (GH) deficiency and predict therapy response: first and second retesting during replacement therapy of patients defined as GH deficient”. Journal of Clinical Endocrinology and Metabolism6 (1994): 1663-1669.
  29. Rocchiccioli P., et al. “Association of pharmacological test and study of 24-hour growth hormone secretion in the investigation of growth retardation in children: analysis of 257 cases”. Hormone Research2 (1991): 70-75.
  30. Donaldson DL., et al. “Growth hormone secretory profiles: variation on consecutive nights”. Journal of Pediatrics1 (1989): 51-56.
  31. Donaldson DL., et al. “Reliability of stimulated and spontaneous growth hormone (GH) levels for identifying the child with low GH secretion”. Journal of Clinical Endocrinology and Metabolism3 (1991): 647-652.
  32. Blum WF. “Die Bedeutung von IGF-I, IGF-II und IGFBP-3 für die Diagnostik des Wachstumshormonmangels”. In: Ranke MB, Stolecke H, editors. Diagnostik des Wachstumshormonmangels. Ankum: Verlag Dokument und Bild (1994): 197-233.
  33. Blum WF. “Insulin-like growth factors and their binding proteins”. In: Ranke MB, editor. Functional endocrinologic diagnostics in children and adolescents. Mannheim: J&J Verlag (1993): 102-117.
  34. Tassoni P., et al. “Variability of growth hormone response to pharmacological and sleep tests performed twice in short children”. Journal of Clinical Endocrinology and Metabolism1 (1990): 230-234.
  35. Hasegawa Y., et al. “Clinical utility of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 levels in the diagnosis of GH deficiency (GHD) during childhood”. Endocrine Journal 43 (1996): S1-S4.
  36. Rosenfeld RG., et al. “Insulin-like growth factors I and II in evaluation of growth retardation”. Journal of Pediatrics3 (1986): 428-433.
  37. Adan L., et al. “Diagnostic markers of permanent idiopathic growth hormone deficiency”. Journal of Clinical Endocrinology and Metabolism2 (1994): 353-358.
  38. Smith WJ., et al. “Use of insulin-like growth factor binding protein 2 (IGFBP-2), IGFBP-3, and IGF-I for assessing growth hormone status in short children”. Journal of Clinical Endocrinology and Metabolism5 (1993): 1264-1299.
  39. Binoux M., et al. “Serum levels of insulin like growth factor (IGF) and IGF-binding protein in constitutionally short children and adolescents”. Acta Endocrinologica, Copenhagen 1 (1986): 145-152.
  40. Cacciari E., et al. “Differences in somatomedin-C between short normal subjects and those of normal height”. Journal of Pediatrics 6 (1985): 891-894.
  41. Rudman D., et al. “The short child with subnormal plasma somatomedin C”. Pediatric Research 10 (1985): 975-980.
  42. Thissen JP., et al. “Nutritional regulation of the insulin-like growth factors”. Endocrine Reviews1 (1994): 80-101.
  43. Miell JP., et al. “Effects of hypothyroidism and hyperthyroidism on insulin-like growth factors and growth hormone and IGF binding protein”. Journal of Clinical Endocrinology and Metabolism4 (1993): 950-955.
  44. Tonshoff B., et al. “Serum insulin-like growth factors and IGF binding protein 1, 2 and 3 in children with chronic renal failure: relationship to height and glomerular filtration rate”. Journal of Clinical Endocrinology and Metabolism9 (1995): 2684-2691.
  45. Zhu H., et al. “Reference ranges for serum insulin-like growth factor I (IGF-I) in healthy Chinese adults”. PloS one10 (2017): e0185561.
  46. Milani D., et al. “Variability and reliability of single serum IGF-I measurements: impact on determining predictability of risk ratios in disease development”. Journal of Clinical Endocrinology and Metabolism5 (2004): 2271-2274.
  47. Harrela M., et al. “Genetic and environmental components of interindividual variation in circulating levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-3”. Journal of Clinical Investigation11 (1996): 2612-2615.

Najya Attia. "The Role of Insulin-Like Growth Factor-1 (IGF-1) in Diagnosis of Growth Hormone Deficiency from Childhood to Young Adulthood". EC Paediatrics 14.3 (2025): 01-09.

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