Ahmed AEA, Hassan MH, Hamdan RS, Sakhr HM. Evaluation of growth hormone provocative tests in Egyptian children with growth hormone-related short stature. World J Exp Med 2026; 16(2): 117853 [DOI: 10.5493/wjem.v16.i2.117853]
Corresponding Author of This Article
Mohammed H Hassan, MD, Professor, Department of Medical Biochemistry and Molecular Biology, Qena University, Qena 83523, Egypt. mohammedhosnyhassaan@yahoo.com
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Medicine, General & Internal
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Ahmed AEA, Hassan MH, Hamdan RS, Sakhr HM. Evaluation of growth hormone provocative tests in Egyptian children with growth hormone-related short stature. World J Exp Med 2026; 16(2): 117853 [DOI: 10.5493/wjem.v16.i2.117853]
World J Exp Med. Jun 20, 2026; 16(2): 117853 Published online Jun 20, 2026. doi: 10.5493/wjem.v16.i2.117853
Evaluation of growth hormone provocative tests in Egyptian children with growth hormone-related short stature
Ahmed El-Abd Ahmed, Mohammed H Hassan, Renada Saad Hamdan, Hala M Sakhr
Ahmed El-Abd Ahmed, Renada Saad Hamdan, Hala M Sakhr, Department of Pediatrics, Qena University, Qena 83523, Egypt
Mohammed H Hassan, Department of Medical Biochemistry and Molecular Biology, Qena University, Qena 83523, Egypt
Mohammed H Hassan, Department of Pathology, College of Medicine, Qassim University, Buraydah 51452, Kingdom of Saudi Arabia
Author contributions: Ahmed AEA, Sakhr HM, and Hassan MH contributed to study concept and design; Hassan MH, Sakhr HM, Hamdan RS, and Ahmed AEA contributed to literature research, statistical analysis, and data interpretation; Sakhr HM, Ahmed AEA, and Hamdan RS contributed to selection of the participants and their clinical evaluation; Hassan MH contributed to biochemical assays; Hassan MH and Sakhr HM contributed to first draft of the manuscript. All authors approved the final version of the manuscript.
Institutional review board statement: The study was performed according to the instructions presented in the Declaration of Helsinki, during the study period from February 2021 to December 2022. This study was approved by the local Ethics Committee of the Faculty of Medicine, Qena University, Qena, Egypt (Ethical approval code: No. SVU-MED-PED025-1-20-12-109).
Informed consent statement: Informed written consent was taken from parents or caregivers of the included participants for participation in the study and publication.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request, after obtaining the permission of our institute.
Corresponding author: Mohammed H Hassan, MD, Professor, Department of Medical Biochemistry and Molecular Biology, Qena University, Qena 83523, Egypt. mohammedhosnyhassaan@yahoo.com
Received: December 18, 2025 Revised: March 13, 2026 Accepted: April 13, 2026 Published online: June 20, 2026 Processing time: 177 Days and 22.8 Hours
Abstract
BACKGROUND
Diagnosing growth hormone deficiency (GHD) in children remains challenging because of the considerable variability in the results of growth hormone (GH) provocative tests.
AIM
To evaluate the validity of different GH provocative tests, determine the sampling time associated with the peak GH response, and identify optimal GH cut-off values for excluding GHD.
METHODS
This cohort study included 50 children aged 5-16 years presenting with proportionate short stature. GH secretion was stimulated using the insulin tolerance test, clonidine test, and levodopa (L-DOPA) test. Serum GH and insulin-like growth factor-1 levels were measured using commercially available enzyme-linked immunosorbent assay kits.
RESULTS
Among the studied participants, 48% were diagnosed with GHD, while 52% were classified as having idiopathic short stature. The clonidine stimulation test showed the highest median GH level at 90 minutes, followed by the insulin-induced peak at 45 minutes and the L-DOPA peak at 60 minutes. A statistically significant positive correlation was observed between the insulin-like growth factor-1 Z-score and the GH level measured at 90 minutes during the clonidine test. Receiver operating characteristic curve analysis demonstrated optimal GH cut-off values of 7.54 ng/mL for the insulin test, 8.48 ng/mL for the clonidine test, and 4.63 ng/mL for the L-DOPA test. These cut-offs showed sensitivities of 59.3%, 77.8%, and 80%, and specificities of 91.3%, 82.6%, and 70%, respectively.
CONCLUSION
Oral clonidine and L-DOPA stimulation tests appear to be useful and safe alternatives for diagnosing GHD, avoiding the risk of hypoglycemia associated with the insulin tolerance test. Lower GH peak cut-off values may improve the diagnostic performance of these provocative tests.
Core Tip: Growth hormone (GH) provocative testing in children demonstrates considerable variability, which can complicate the accurate diagnosis of GH deficiency. This study emphasizes that oral clonidine and levodopa stimulation tests represent safer, more practical, and reliable alternatives to the insulin tolerance test. Additionally, adopting lower, optimized cut-off values for GH levels enhances diagnostic precision and reduces the risk of misclassification in pediatric patients undergoing evaluation.
