Testicular adrenal rest tumors in Indonesian boys with congenital adrenal hyperplasia

Epifani A. Chandra; Agustini Utari; Bas P.H. Adriaansen; Dineke Westra; Farah H. Ningrum; Antonius G. Santoso; Antonius E. van Herwaarden; Hedi L. Claahsen-van der Grinten

doi:10.1515/jpem-2025-0026

Artikel

Testicular adrenal rest tumors in Indonesian boys with congenital adrenal hyperplasia

Epifani A. Chandra , Agustini Utari , Bas P.H. Adriaansen , Dineke Westra , Farah H. Ningrum , Antonius G. Santoso , Antonius E. van Herwaarden und Hedi L. Claahsen-van der Grinten

Veröffentlicht/Copyright: 20. Juni 2025

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Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 38 Heft 8

Abstract

Objectives

Male patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) are at risk of developing testicular adrenal rest tumors (TART), which are benign but an important cause of infertility. The limited medical infrastructure and lack of knowledge and awareness of 21OHD in Indonesia has contributed to missed or delayed diagnoses, leading to a reportedly low prevalence of 21OHD and an expected high rate of undiagnosed patients. In Indonesia, TART has not been widely reported, with only a single patient documented in a recent paper. This study aim was to define the potential risk factors for developing TART in Indonesian pediatric patients with 21OHD.

Methods

This cross-sectional study was conducted in 20 boys with genetically proven 21OHD (0–18 years old). All had pathogenic variants associated with 0 % or 0–1% residual enzymatic activity. Medical history, clinical characteristics, genetic analysis results, biochemical measurements, bone age, and scrotal ultrasonography (US) data were evaluated.

Results

In 5 of 20 patients (25 %), TART was detected by US. The patients with TART were mainly in puberty (p=0.014). Higher androstenedione levels and advanced bone age were associated with TART.

Conclusions

TART is an important complication in Indonesian patients with 21OHD presenting before or during puberty. Factors associated with TART are pubertal age and longstanding poor hormonal control. Early diagnosis and optimization of treatment may help to prevent TART development and consequently improve fertility in these patients.

Keywords: testicular adrenal rest tumors; congenital adrenal hyperplasia; 21-hydroxylase deficiency; ultrasonography; screening

Corresponding author: Agustini Utari, MD, PhD, Division of Pediatric Endocrinology, Department of Pediatrics, Faculty of Medicine, Diponegoro University, Prof. Mr. Sunario Street, Semarang, 50275, Indonesia; and Center for Biomedical Research (CEBIOR), Faculty of Medicine, Diponegoro University, Prof. Mr. Sunario Street, Semarang, 50275, Indonesia, E-mail: agustiniutari@lecturer.undip.ac.id

Funding source: Faculty of Medicine Grant, Diponegoro University

Award Identifier / Grant number: 751/UN7.F4/PP/IV/2023

Funding source: European Society for Paediatric Endocrinology (ESPE) sponsored program “ESPE Visiting Professorship” supported by Pfizer

Acknowledgments

The authors appreciate the study participants, CEBIOR technicians for helping in collecting the samples, and Radboud university medical center clinical chemists and genome diagnosticians for their technical support in biochemical measurement and genetic analysis.

Research ethics: Ethical approval was obtained from the Medical Research Ethical Committee of Dr. Kariadi Central General Hospital (No. 1486/EC/KEPK-RSDK/2023) granted on 7 July 2023. This study was conducted according to the Declaration of Helsinki (as revised in 2013).
Informed consent: Written consent was acquired from the parents after a full explanation of the purpose and nature of all procedures in the study.
Author contributions: EA, AU, HC, and AG were involved in conceptualizing the study. EA and AU collected the data, FH analyzed the radiological examination, BA and AH measured and analyzed the hormonal examination, and DW supervised genetic analyses and reported the results. All authors critically reviewed and revised the manuscript. 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: This work was supported by the Faculty of Medicine Grant, Diponegoro University (Number 751/UN7.F4/PP/IV/2023) and collaboration through the European Society for Paediatric Endocrinology (ESPE) sponsored program “ESPE Visiting Professorship” supported by Pfizer.
Data availability: Not applicable.

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Received: 2025-01-12

Accepted: 2025-05-06

Published Online: 2025-06-20

Published in Print: 2025-08-26

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https://doi.org/10.1515/jpem-2025-0026

Schlagwörter für diesen Artikel

testicular adrenal rest tumors; congenital adrenal hyperplasia; 21-hydroxylase deficiency; ultrasonography; screening