Is L-dopa test effective in detecting adrenal insufficiency with preliminary diagnosis of growth hormone deficiency in children with short stature?

Gülümay Vural Topaktaş; Eren Er; Sevim Onguner; Benay Turan; Bumin Nuri Dündar

doi:10.1515/jpem-2025-0143

Article

Is L-dopa test effective in detecting adrenal insufficiency with preliminary diagnosis of growth hormone deficiency in children with short stature?

Gülümay Vural Topaktaş , Eren Er , Sevim Onguner , Benay Turan and Bumin Nuri Dündar

Published/Copyright: May 29, 2025

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From the journal Journal of Pediatric Endocrinology and Metabolism Volume 38 Issue 8

Abstract

Objectives

Growth hormone (GH) deficiency in children is characterized by impaired linear growth and reduced growth velocity, necessitating confirmation through two GH stimulation tests. At the time of diagnosis, approximately 4 % of children with GH deficiency exhibit concomitant adrenocorticotropic hormone (ACTH) deficiency, a prevalence that increases to 12 % over the course of follow-up. The insulin tolerance test is regarded as the gold standard for assessing both cortisol and GH secretion; however, its clinical application is constrained by potential risks and the requirement for close medical supervision. This study aims to evaluate the effect of the L-dopa stimulation test on cortisol secretion in pediatric patients with short stature.

Methods

This retrospective study included 138 children (65 females, 73 males) who underwent the L-dopa stimulation test for the assessment of GH deficiency at the Pediatric Endocrinology Clinic between January 2010 and December 2023. Serum cortisol concentrations were measured at the 90th and 120th min of the test. Patients with a peak cortisol response <18 μg/dL subsequently underwent a low-dose (1 μg) ACTH stimulation test to further evaluate adrenal function. Clinical, anthropometric, and biochemical data were extracted from medical records and subjected to statistical analysis.

Results

The mean age of the study cohort was 9.34 ± 3.79 years, with 65 (47.1 %) female and 73 (52.9 %) male patients. The mean height standard deviation score (SDS) was −2.62 ± 0.83, while the mean weight SDS was −1.81 ± 1.09. The mean peak GH response was 5.64 ± 4.0 ng/mL following the clonidine stimulation test and 7.29 ± 5.23 ng/mL following the L-dopa test. A total of 35 children exhibited a peak cortisol response <18 μg/dL during the L-dopa test. Among these, 35 underwent a low-dose (1 μg) ACTH stimulation test, and 7 patients (20 % of those tested; 5.1 % of the total cohort) were diagnosed with adrenal insufficiency, defined as a peak cortisol response <18 μg/dL. These patients were initiated on oral hydrocortisone therapy. Comparative analyses between patients with normal vs. impaired ACTH test responses (<18 μg/dL vs. ≥18 μg/dL) revealed no statistically significant differences in peak cortisol response to the L-dopa test, peak GH response to clonidine or L-dopa, age at presentation, gender, weight SDS, or height SDS.

Conclusions

The L-dopa stimulation test may represent a valuable adjunctive tool for the evaluation of cortisol sufficiency in children undergoing assessment for suspected GH deficiency. However, further prospective studies with larger sample sizes and standardized protocols are warranted to validate its diagnostic accuracy and clinical utility in detecting adrenal insufficiency.

Keywords: adrenal function; adrenal insufficiency; cortisol; cortisol deficiency; dopamine agonist; L-dopa

Corresponding author: Gülümay Vural Topaktaş, Pediatric Endocrinology Clinic, Izmir City Hospital, Izmir, Türkiye, E-mail: gulumayvural@hotmail.com

Research ethics: This study was approved by the İzmir City Hospital Ethics Committee on May 15, 2024, with the document ID Decision No: 2024/40. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).
Informed consent: Not applicable.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Use of Large Language Models, AI and Machine Learning Tools: None declared.
Conflict of interest: The authors state no conflict of interest.
Research funding: None declared.
Data availability: Not applicable.

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Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/jpem-2025-0143).

Received: 2025-03-15

Accepted: 2025-05-18

Published Online: 2025-05-29

Published in Print: 2025-08-26

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Keywords for this article

adrenal function; adrenal insufficiency; cortisol; cortisol deficiency; dopamine agonist; L-dopa