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Licensed Unlicensed Requires Authentication Published by De Gruyter January 24, 2019

IGF-1 assessed by pubertal status has the best positive predictive power for GH deficiency diagnosis in peripubertal children

  • Thais H. Inoue-Lima , Gabriela A. Vasques , Renata C. Scalco , Marilena Nakaguma , Berenice B. Mendonca , Ivo J.P. Arnhold and Alexander A.L. Jorge EMAIL logo

Abstract

Background

When evaluating peripubertal short stature patients, the interpretation of insulin-like growth factor 1 (IGF-1) levels based on chronological age (CA) can be inaccurate due to the influence of sex steroids and, presently, there is no evidence to support the assessment of IGF-1 values according to bone age (BA) and pubertal status (PS). Our objective was to assess the discriminatory performance of IGF-1 levels based on CA, BA and PS in the diagnosis of growth hormone (GH) deficiency.

Methods

We evaluated IGF-1 levels from 154 peripubertal short stature patients classified as GH deficient (GHD, n=23) or non-GHD (n=131). IGF-1 was assayed by a chemiluminescent immunometric assay and transformed into standard deviation scores (SDS) according to CA (IGF-1-SDS-CA), BA (IGF-1-SDS-BA) and PS (IGF-1-SDS-PS).

Results

The performances of IGF-1-SDS-CA, IGF-1-SDS-BA and IGF-1-SDS-PS in the receiver operator characteristics (ROC) curves were similar. There were greater accuracy and specificity of IGF-1-SDS-PS (98.4% and 93.3%, respectively) and IGF-1-SDS-BA (92.7% and 90.1%, respectively) when compared to IGF-1-SDS-CA (65.6% and 69.5%, respectively). The post-test probability of the IGF-1-SDS was also improved when compared to PS and BA – 44.8% (IGF-1-SDS-PS), 16.8% (IGF-1-SDS-BA) and 5.1% (IGF-1-SDS-CA), with similar negative predictive values.

Conclusions

The evaluation of IGF-1 levels based on CA has a higher sensitivity than those based on BA or PS, which justify its use as a screening tool. Additionally, IGF-1 assessed by PS has the best positive predictive power for GHD diagnosis in peripubertal age and could reduce the necessity of a second GH stimulation test.

Award Identifier / Grant number: 2013/03236–5

Funding statement: This work was supported by the São Paulo Research Foundation (FAPESP) Funder id: 10.13039/501100001807, Grant number 2013/03236–5 (to A.A.L.J.) and the National Council of Technological and Scientific Development – Brazil: Funder id: 10.13039/501100003593, Grant number CNPq-PQ 301871/2016-7 (to A.A.L.J.), Grant number CNPq-PQ 305743/2011-2 (to B.B.M.) and Grant number CNPq-PQ 307922/2013-8 (to I.J.P.A.).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Employment or leadership: None declared.

  3. Honorarium: None declared.

  4. Disclosure summary: The authors declare there is no conflict of interest that could be perceived as influencing the impartiality of the research reported.

References

1. Fayter D, Nixon J, Hartley S, Rithalia A, Butler G, et al. Effectiveness and cost-effectiveness of height-screening programmes during the primary school years: A systematic review. Arch Dis Child 2008;93:278–84.10.1136/adc.2006.109843Search in Google Scholar

2. Richmond E, Rogol AD. Treatment of growth hormone deficiency in children, adolescents and at the transitional age. Best Pract Res Clin Endocrinol Metab 2016;30:749–55.10.1016/j.beem.2016.11.005Search in Google Scholar

3. Ranke MB, Lindberg A, Tanaka T, Camacho-Hübner C, Dunger DB, et al. Baseline characteristics and gender differences in prepubertal children treated with growth hormone in Europe, USA, and Japan: 25 years’ KIGS® experience (1987–2012) and review. Horm Res Paediatr 2017;87:30–41.10.1159/000452887Search in Google Scholar

4. 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;85:3990–3. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11095419.10.1210/jc.85.11.3990Search in Google Scholar

5. Oostdijk W, Grote FK, De Muinck Keizer-Schrama SM, Wit JM. Diagnostic approach in children with short stature. Horm Res 2009;72:206–17.10.1159/000236082Search in Google Scholar

6. Guzzetti C, Ibba A, Pilia S, Beltrami N, Di Iorgi N, et al. Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: Study in patients with organic GHD. Eur J Endocrinol 2016;175:41–7.10.1530/EJE-16-0105Search in Google Scholar

7. Maxim LD, Niebo R, Utell MJ. Screening tests: a review with examples. Inhal Toxicol 2014;26:811–28.10.3109/08958378.2014.955932Search in Google Scholar

8. Cianfarani S, Tondinelli T, Spadoni GL, Scirè G, Boemi S, 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;57:161–7.10.1046/j.1365-2265.2002.01591.xSearch in Google Scholar

9. 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;130:197–204.10.1016/S0022-3476(97)70343-3Search in Google Scholar

10. Federico G, Street M, Maghnie M, Caruso-Nicoletti M, Loche S, 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 Investig 2006;29:732–7.10.1007/BF03344184Search in Google Scholar PubMed

11. Clemmons DR. Consensus statement on the standardization and evaluation of growth hormone and insulin-like growth factor assays. Clin Chem 2011;57:555–9.10.1373/clinchem.2010.150631Search in Google Scholar

12. Marwaha RK, Garg MK, Gupta S, Khurana AK, Narang A, et al. Assessment of insulin like growth factor-1 and IGF binding protein-3 in healthy Indian girls from Delhi and their correlation with age, pubertal status, obesity and thyroid hormonal status. J Pediatr Endocrinol Metab 2017;30:739–47.10.1515/jpem-2016-0359Search in Google Scholar

13. Elmlinger MW, Kühnel W, Weber MM, Ranke MB. Reference ranges for two automated chemiluminescent assays for serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3). Clin Chem Lab Med 2004;42:654–64.10.1515/CCLM.2004.112Search in Google Scholar

14. Stalman SE, Hellinga I, Van Dommelen P, Hennekam RC, Saari A, et al. Application of the Dutch, Finnish and British screening guidelines in a cohort of children with growth failure. Horm Res Paediatr 2015;84:376–82.10.1159/000440652Search in Google Scholar

15. Silva EG, Slhessarenko N, Arnhold IJ, Batista MC, Estefan V, et al. GH values after clonidine stimulation measured by immunofluorometric assay in normal prepubertal children and GH-deficient patients. Horm Res 2003;59:229–33.10.1159/000070222Search in Google Scholar

16. Wetterau LA. The pros and cons of sex steroid priming in growth hormone stimulation testing. J Pediatr Endocrinol Metab 2012;25:1049–55.10.1515/jpem.2011.327Search in Google Scholar

17. Šimundić A-M. Measures of diagnostic accuracy: basic definitions. Med Biol Sci 2008;19:1–9.Search in Google Scholar

18. Sizonenko PC, Clayton PE, Cohen P, Hintz RL, Tanaka T, et al. Diagnosis and management of growth hormone deficiency in childhood and adolescence. Part 1: diagnosis of growth hormone deficiency. Growth Horm IGF Res 2001;11:137–65.10.1054/ghir.2001.0203Search in Google Scholar

19. Lange M, Svenden OL, Skakkebæk NE, Müller J, Juul A, et al. An audit of the insulin-tolerance test in 255 patients with pituitary disease. Eur J Endocrinol 2002;147:41–7.10.1530/eje.0.1470041Search in Google Scholar

20. Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M. Utah growth study: growth standards and the prevalence of growth hormone deficiency. J Pediatr 1994;125:29–35.10.1016/S0022-3476(94)70117-2Search in Google Scholar

21. Vimpani GV, Vimpani AF, Lidgard GP, Cameron EH, Farquhar JW. Prevalence of severe growth hormone deficiency. Br Med J 1977;2:427–30.10.1136/bmj.2.6084.427Search in Google Scholar PubMed PubMed Central

22. Thomas M, Massa G, Craen M, de Zegher F, Bourguignon JP, et al. Prevalence and demographic features of childhood growth hormone deficiency in Belgium during the period 1986–2001. Eur J Endocrinol 2004;151:67–72.10.1530/eje.0.1510067Search in Google Scholar PubMed

23. Ahmed ML, Allen AD, Sharma A, MacFarlane JA, Dunger DB. Evaluation of a district growth screening programme: the Oxford growth study. Arch Dis Child 1993;69:361–5.10.1136/adc.69.3.361Search in Google Scholar PubMed PubMed Central

24. Clayton P, Bonnemaire M, Dutailly P, Maisonobe P, Naudin L, et al. Characterizing short stature by insulin-like growth factor axis status and genetic associations: results from the prospective, cross-sectional, epidemiogenetic EPIGROW study. J Clin Endocrinol Metab 2013;98:1122–30.10.1210/jc.2012-4283Search in Google Scholar PubMed

25. Velayutham K, Sivan Arul Selvan S, Jeyabalaji RV, Balaji S. Prevalence and etiological profile of short stature among school children in a South Indian population. Indian J Endocr Metab 2017;21:820–2.10.4103/ijem.IJEM_149_17Search in Google Scholar PubMed PubMed Central

26. Peters CJ, Dattani MT. How to use insulin-like growth factor 1 (IGF1). Arch Dis Child Educ Pract Ed 2012;97:114–8.10.1136/archdischild-2011-300265Search in Google Scholar PubMed

27. Badaru A, Wilson DM. Alternatives to growth hormone stimulation testing in children. Trends Endocrinol Metab 2004;15:252–8.10.1016/j.tem.2004.06.004Search in Google Scholar PubMed

28. Shen Y, Zhang J, Zhao Y, Yan Y, Liu Y, et al. Diagnostic value of serum IGF-1 and IGFBP-3 in growth hormone deficiency: a systematic review with meta-analysis. Eur J Pediatr 2015;174:419–27.10.1007/s00431-014-2406-3Search in Google Scholar PubMed


Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2018-0435).


Received: 2018-10-08
Accepted: 2018-11-20
Published Online: 2019-01-24
Published in Print: 2019-02-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

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