» Articles » PMID: 31616374

Diagnosis of Idiopathic GHD in Children Based on Response to RhGH Treatment: The Importance of GH Provocative Tests and IGF-1

Abstract

Serum IGF-1 (Insulin like growth factor 1) and Growth Hormone (GH) provocative tests are reasonable tools for screening and diagnosis of idiopathic GH Deficiency (IGHD). However, the average cut-off points applied on these tests have a lower level of evidence and produce large amounts of false results. The aim of this study is to evaluate the sensitivity, specificity, and accuracy of IGF-1 and GH stimulation tests as diagnostic tools for IGHD, using clinical response to recombinant human GH (rhGH) treatment as diagnostic standard [increase of at least 0.3 in height standard deviation (H-SD) in 1 year]. We performed a prospective study with 115 children and adolescents presenting short stature (SS), without secondary SS etiologies such as organic lesions, genetic syndromes, thyroid disorders. They were separated into Group 1 [patients with familial SS or constitutional delay of growth and puberty (CDGP), not treated with rhGH], Group 2 (patients with suspicion of IGHD with clinical response to rhGH treatment), and Group 3 (patients with suspicion of IGHD without growth response to rhGH treatment). Then, they were assessed for diagnostic performance of IGF-1, Insulin Tolerance Test (ITT) and clonidine test (CT) alone and combined at different cut-off points. Based on the ROC curve, the best cut-off points found for IGF-1, ITT, and CT when they were used isolated were -0.492 SDS (sensitivity: 50%; specificity: 53.8%; accuracy: 46.5%), 4.515 μg/L (sensitivity: 75.5%; specificity: 45.5%; accuracy: 52.7%), and 4.095 μg/L (sensitivity: 54.5%; specificity: 52.6%; accuracy: 56.9%), respectively. When we had combined IGF-1 with-2SD as cut-off alongside ITT or CT, we found 7 μg/L as the best cut-off point. In this situation, ITT had sensitivity, specificity and accuracy of 93.9, 81.8, and 90.1%, while CT had 93.2, 68.4, and 85.7%, respectively. Our data suggest that diagnosis of IGHD should be established based on a combination of clinical expertise, auxologic, radiologic, and laboratorial data, using IGF-1 at the -2SD threshold combined, with ITT or CT at the cut-off point of 7 μg/L. Additional studies, similar to ours, are imperative to establish cut-off points based on therapeutic response to rhGH in IGHD, which would be directly related to a better treatment outcome.

Citing Articles

Comparison of growth hormone stimulation tests in prepubertal children with short stature according to response to growth hormone replacement.

Chang S, Kim C Ann Pediatr Endocrinol Metab. 2024; 29(5):316-324.

PMID: 39506345 PMC: 11541089. DOI: 10.6065/apem.2346234.117.


Transient Isolated, Idiopathic Growth Hormone Deficiency-A Self-Limiting Pediatric Disease with Male Predominance or a Diagnosis Based on Uncertain Criteria? Lesson from 20 Years' Real-World Experience with Retesting at One Center.

Smyczynska J, Hilczer M, Smyczynska U, Lewinski A, Stawerska R Int J Mol Sci. 2024; 25(11).

PMID: 38891927 PMC: 11171613. DOI: 10.3390/ijms25115739.


Evolving growth hormone deficiency: proof of concept.

Chimatapu S, Sethuram S, Samuels J, Klomhaus A, Mintz C, Savage M Front Endocrinol (Lausanne). 2024; 15:1398171.

PMID: 38752175 PMC: 11095394. DOI: 10.3389/fendo.2024.1398171.


Insulin-like growth factor 1 and sex hormones for assessment of anthropometric and pubertal growth of Egyptian children and adolescents with type 1 diabetes mellitus (single center study).

Thabet R, Sherif E, ElAal A, Mahmoud R BMC Endocr Disord. 2024; 24(1):62.

PMID: 38724932 PMC: 11080226. DOI: 10.1186/s12902-024-01596-3.


Effects of different doses of long-acting growth hormone in treating children with growth hormone deficiency.

Xia W, Wang T, Pan J World J Clin Cases. 2023; 11(28):6715-6724.

PMID: 37901029 PMC: 10600835. DOI: 10.12998/wjcc.v11.i28.6715.


References
1.
Guzzetti C, Ibba A, Pilia S, Beltrami N, Di Iorgi N, Rollo A . 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(1):41-7. DOI: 10.1530/EJE-16-0105. View

2.
Cohen P, Rogol A, Deal C, Saenger P, Reiter E, Ross J . Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology.... J Clin Endocrinol Metab. 2008; 93(11):4210-7. DOI: 10.1210/jc.2008-0509. View

3.
Chung W, Yoo H, Hwang J, Ko C, Kim H, Jin D . Effect of Growth Hormone Therapy on Height Velocity in Korean Children with Idiopathic Short Stature: A Phase III Randomised Controlled Trial. Horm Res Paediatr. 2018; 90(1):44-53. PMC: 6214610. DOI: 10.1159/000491016. View

4.
Lemaire P, Brauner N, Hammer P, Trivin C, Souberbielle J, Brauner R . Improved screening for growth hormone deficiency using logical analysis data. Med Sci Monit. 2008; 15(1):MT5-10. View

5.
Grimberg A, Allen D . Growth hormone treatment for growth hormone deficiency and idiopathic short stature: new guidelines shaped by the presence and absence of evidence. Curr Opin Pediatr. 2017; 29(4):466-471. PMC: 5565215. DOI: 10.1097/MOP.0000000000000505. View