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Exp Clin Endocrinol Diabetes 2015; 123(04): 209-214
DOI: 10.1055/s-0034-1395665
Article
© Georg Thieme Verlag KG Stuttgart · New York

Secondary IGF-I Deficiency as a Prognostic Factor of Growth Hormone (GH) Therapy Effectiveness in Children with Isolated, Non-acquired GH Deficiency

J. Smyczyńska
1   Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
,
R. Stawerska
1   Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
,
M. Hilczer
1   Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
2   Department of Pediatric Endocrinology, Medical University of Lodz, Poland
,
A. Lewiński
1   Department of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital – Research Institute, Lodz, Poland
3   Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, Poland
› Author Affiliations
Further Information

Publication History

received 24 June 2014
first decision 16 October 2014

accepted 19 November 2014

Publication Date:
21 January 2015 (online)

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Abstract

Objective: Growth hormone (GH) deficiency (GHD) has recently been classified as secondary IGF-I deficiency but the significance of IGF-I measurement in diagnosing GHD is still discussed. The aim of the study was to assess the relationships between IGF-I secretion and GH therapy effectiveness in children with GHD.

Patients and methods: The analysis comprised 300 children with isolated, non-acquired GHD (GH peak below 10 μg/l) who completed GH therapy and attained final height (FH). In all patients IGF-I concentration was measured before the treatment and IGF-I deficiency was diagnosed if IGF-I SDS for age and sex was below −1.0. The following auxological indices were assessed: patients’ height SDS before treatment (H0SDS), FH SDS and improvement of FHSDS vs. H0SDS (ΔHSDS).

Results: In the patients with IGF-I deficiency when compared with those with normal IGF-I secretion before treatment, significantly better FH SDS (−1.42±0.90 vs. −1.74±0.86, p=0.004) and ΔHSDS (1.64±1.01 vs. 1.32±1.05, p=0.010) were observed, despite similar H0SDS (− 3.07±0.78 vs. − 3.11±0.77, p=0.63) and GH peak (7.0±3.1 μg/l vs. 6.8±2.1 μg/l, p=0.55). The patients who achieved FH over 10th centile had significantly lower IGF-I SDS before treatment than those with FH below 10th centile (− 1.59±1.54 vs. − 1.20±1.64, p=0.04), despite similar GH peak (7.0±2.3 μg/l vs. 6.7±3.1 μg/l, p=0.45). The patients with ΔHSDS over the median value had significantly lower IGF-I SDS than those with ΔHSDS below the median value (− 1.59±1.71 vs. − 1.09±1.47, p<0.0001), despite similar GH peak (6.8±2.5 μg/l vs. 7.0±2.7 μg/l, p=0.86).

Conclusion: In children with isolated, non-acquired GHD, secondary IGF-I deficiency is an important predictor of better GH therapy effectiveness.

Key words

short stature - growth hormone stimulation tests - insulin-like growth factor-I - recombinant human growth hormone - final height
 

  • References

  • 1 Saggese G, Ranke MB, Saenger P et al. Diagnosis and treatment of growth hormone deficiency in children and adolescents: towards a consensus. Ten years after the Availability of Recombinant Human Growth Hormone Workshop held in Pisa, Italy, 27–28 March 1998. Horm Res 1998; 50: 320-340
    CrossrefPubMedSearch in Google Scholar
  • 2 GH Research Society . Consensus guidelines for the diagnosis and treatment of growth hormone deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab 2000; 85: 3990-3993
    PubMedSearch in Google Scholar
  • 3 Rosenfeld RG, Albertsson-Wikland K, Cassorla F et al. Diagnostic controversy: the diagnosis of childhood growth hormone deficiency revisited. J Clin Endocrinol Metab 1995; 80: 1532-1540
    PubMedSearch in Google Scholar
  • 4 Tillmann V, Buckler JM, Kibirige MS et al. Biochemical tests in the diagnosis of childhood growth hormone deficiency. J Clin Endocrinol Metab 1997; 82: 531-535
    PubMedSearch in Google Scholar
  • 5 Cappa M, Loche S. Evaluation of growth disorders in the paediatric clinic. J Endocrinol Invest 2003; 26 (Suppl. 07) 54-63
    PubMedSearch in Google Scholar
  • 6 Chaler EA, Rivarola MA, Guerci B et al. Differences in serum GH cut-off values for pharmacological tests of GH secretion depend on the serum GH method. Clinical validation from the growth velocity score during the first year of treatment. Horm Res 2006; 66: 231-235
    CrossrefPubMedSearch in Google Scholar
  • 7 Tenenbaum-Rakover Y. The need to revise the cut-off level for the diagnosis of GH deficiency in children. Pediatr Endocrinol Rev 2008; 5: 880-888
    PubMedSearch in Google Scholar
  • 8 Binder G, Huller E, Blumenstock G et al. Auxology-based cut-off values for biochemical testing of GH secretion in childhood. Growth Horm IGF Res 2011; 21: 212-218
    CrossrefPubMedSearch in Google Scholar
  • 9 Hilczer M, Smyczyńska J, Stawerska R et al. Stability of IGF-I concentration despite divergent results of repeated GH stimulating tests indicates poor reproducibility of test results. Endocr Regul 2006; 40: 37-45
    PubMedSearch in Google Scholar
  • 10 Hilczer M, Smyczyńska J, Lewiński A. Limitations of clinical utility of growth hormone stimulating tests in diagnosing children with short stature. Endocr Regul 2006; 40: 69-75
    PubMedSearch in Google Scholar
  • 11 Cianfarani S, Tondinelli T, Spadoni GL et al. Height velocity and IGF-I assessment in the diagnosis of childhood onset GH insufficiency: do we still need a second GH stimulation test?. Clin Endocrinol (Oxf) 2002; 57: 161-167
    CrossrefPubMedSearch in Google Scholar
  • 12 Badaru A, Wilson DM. Alternatives to growth hormone stimulation testing in children. Trends Endocrinol Metab 2004; 15: 252-258
    CrossrefPubMedSearch in Google Scholar
  • 13 Wilson DM, Frane J. A brief review of the use and utility of growth hormone stimulation testing in the NCGS: do we need to do provocative GH testing?. Growth Horm IGF Res 2005; 15: S21-S25
    CrossrefPubMedSearch in Google Scholar
  • 14 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: 145-148
    CrossrefPubMedSearch in Google Scholar
  • 15 Cianfarani S, Liguori A, Germani D. IGF-I and IGFBP-3 assessment in the management of childhood onset growth hormone deficiency. Endocr Dev 2005; 9: 66-75
    PubMedSearch in Google Scholar
  • 16 Wit J, Ranke MB, Kelnar CJH. ESPE classification of pediatric endocrine diagnoses. Short stature. Horm Res 2007; 68: 1-9
    PubMedSearch in Google Scholar
  • 17 Savage MO, Burren CP, Rosenfeld RG. The continuum of growth hormone-IGF-I axis defects causing short stature: diagnostical and therapeutical challenges. Clin. Endocrinol 2010; 72: 721-728
    PubMedSearch in Google Scholar
  • 18 Smyczyńska J, Lewiński A, Stawerska R et al. Assessment of insulin-like growth factor-I serum concentration as a screening procedure in diagnosing children with short stature. Neuro Endocrinol Lett 2007; 28: 274-278
    PubMedSearch in Google Scholar
  • 19 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; 130: 197-204
    CrossrefPubMedSearch in Google Scholar
  • 20 Palczewska I, Niedźwiecka Z. Indices of somatic development of children and adolescents in Warsaw. Medycyna Wieku Rozwojowego 2001; 5 1 to N°2 17-118 [in Polish]
    PubMedSearch in Google Scholar
  • 21 Romer TE, Walczak M, Wiśniewski A et al. Children with growth disorders qualified in Poland for growth hormone therapy. Pediatr Prakt 2001; 9: 41-54 [in Polish]
    PubMedSearch in Google Scholar
  • 22 Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford University Press; Stanford, California: 1993
    Search in Google Scholar
  • 23 Moore DC, Ruvalcaba RH, Smith EK et al. Plasma somatomedin-C as a screening test for growth hormone deficiency in children and adolescents. Horm Res 1982; 16: 49-55
    CrossrefPubMedSearch in Google Scholar
  • 24 Savage MO, Bang P. The variability of responses to growth hormone therapy in children with short stature. Indian J Endocrinol Metab 2012; 16 (Suppl. 06) S178-S184
    CrossrefPubMedSearch in Google Scholar
  • 25 Boquete HR, Sobrado PG, Fideleff HL et al. Evaluation of diagnostic accuracy of insulin-like growth factor (IGF)-I and IGF-binding protein-3 in growth hormone-deficient children and adults using ROC plot analysis. J Clin Endocrinol Metab 2003; 88: 4702-4708
    CrossrefPubMedSearch in Google Scholar
  • 26 Galluzzi F, Quaranta MR, Salti R et al. Are IGF-I and IGF-BP3 useful for diagnosing growth hormone deficiency in children of short stature?. J Pediatr Endocrinol Metab 2010; 23: 1273-1279
    CrossrefPubMedSearch in Google Scholar
  • 27 Smyczyńska J, Lewiński A, Hilczer M et al. Partial growth hormone deficiency (GHD) in children has more similarities to idiopathic short stature than to severe GHD. Endokrynol Pol 2007; 58: 182-187
    PubMedSearch in Google Scholar
  • 28 Federico G, Street ME, Maghnie M et al. Assessment of serum IGF-I concentrations in the diagnosis of isolated childhood-onset GH deficiency: a proposal of the Italian Society for Pediatric Endocrinology and Diabetes (SIEDP/ISPED). J Endocrinol Invest 2006; 29: 732-737
    CrossrefPubMedSearch in Google Scholar
  • 29 Lemaire P, Brauner N, Hammer P et al. Improved screening for growth hormone deficiency using logical analysis data. Med Sci Monit 2009; 15: MT5-MT10
    PubMedSearch in Google Scholar
  • 30 Smyczyńska J, Stawerska R, Lewiński A et al. Auxological and hormonal prognostic factors of growth hormone (GH) therapy effectiveness in children with GH deficiency, available before treatment. Pediatr Endocrinol 2013; 12: 9-20
    PubMedSearch in Google Scholar
  • 31 Reiter EO, Price DA, Wilton P et al. Effect of growth hormone (GH) treatment on the near-final height of 1258 patients with idiopathic GH deficiency: analysis of a large international database. J Clin Endocrinol Metab 2006; 91: 2047-2054
    CrossrefPubMedSearch in Google Scholar
  • 32 Lee PA, Germak J, Gut R et al. Identification of factors associated with good response to growth hormone therapy in children with short stature: results from the ANSWER Program®. Int J Pediatr Endocrinol 2011; 2011: 6
    CrossrefPubMedSearch in Google Scholar
  • 33 Darendeliler F, Lindberg A, Wilton P. Response to growth hormone treatment in isolated growth hormone deficiency versus multiple pituitary hormone deficiency. Horm Res Paediatr 2011; 76: 42-46
    PubMedSearch in Google Scholar
  • 34 Webb EA, Dattani MT. Diagnosis of growth hormone deficiency. Endocr Dev 2010; 18: 55-66
    PubMedSearch in Google Scholar