Abstract
Objectives
To assess the incidence of testicular adrenal rest tumors (TARTs) among male children with congenital adrenal hyperplasia (CAH) in tertiary care centers.
Methods
All male children aged 1–14 years diagnosed with CAH due to 21-hydroxylase deficiency (21 HOD), 11β-hydroxylase deficiency, and 3β-hydroxysteroid dehydrogenase deficiency, confirmed by biochemical and/or genetic testing, underwent scrotal ultrasound examination to identify TARTs. After receiving the diagnosed patients’ data, patients’ electronic medical records were accessed to collect demographic data and scrotal ultrasound results, along with growth parameters and specific biochemical test results within 2 months of the ultrasound.
Results
TARTs were observed in 5 (10.9%) of 46 male children with CAH. Four patients with positive findings had 21 HOD classical CAH with salt loss and one had 21 HOD simple virilizing classical CAH. All patients had poor compliance and stage 2 bilateral TARTs. Three TART-positive patients (60.0%) had high ACTH levels, 5 patients (100%) had elevated 17-OHP levels, and 5 patients (100%) had advanced bone age. The youngest patient with positive findings was 4 years old.
Conclusions
The prevalence of TARTs increases with age and can be present in young males with classical CAH with 21 HOD. It is associated with elevated 17-hydroxyprogesterone (17-OHP) and advanced bone age SDS. TARTs are less likely to be associated with nonclassical CAH with 21 HOD or other less common CAHs due to 11β-hydroxylase deficiencies and 3β-hydroxysteroid dehydrogenase deficiencies in children. Our study recommends early and routine screening of TARTs in children with CAH.
Funding source: King Fahad Medical City
Award Identifier / Grant number: IRF 019-024
Acknowledgments
The researchers would like to thank Mrs. Nawal Almutairi, Mr. John Paul A. Serrano, and Mr. Abid for their efforts in assisting with this research.
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Research funding: This work was supported by the Grant Management Department, Research Center at King Fahad Medical City (grant number IRF 019-024).
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: The authors declare that there are no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The local Institutional Review Board deemed the study exempt from review.
References
1. Ozisik, H, Yurekli, BS, Simsir, IY, Altun, I, Soyaltin, U, Guler, E, et al.. Testicular adrenal rest tumor (TART) in congenital adrenal hyperplasia. Eur J Med Genet 2017;60:489–93. https://doi.org/10.1016/j.ejmg.2017.06.009.Search in Google Scholar PubMed
2. Al-Jurayyan, NA, Al-Herbish, AS, Abo, AB, Al-Rabeeah, AA, Al-Samarrai, AI, Abdullah, MA, et al.. Congenital adrenal hyperplasia in a referral hospital in Saudi Arabia: epidemiology, pattern and clinical presentation. Ann Saudi Med 1995;15:447–50. https://doi.org/10.5144/0256-4947.1995.447.Search in Google Scholar PubMed
3. Van Der Kamp, HJ, Wit, JM. Neonatal screening for congenital adrenal hyperplasia. Eur J Endocrinol 2004;151(3 Suppl):U71–5. https://doi.org/10.1530/eje.0.151u071.Search in Google Scholar PubMed
4. Manon, E, Paul, NS, Antonius E, van H, Fred, CGJS, Nike, MMLS, Hedi, LCG. Testicular adrenal rest tumors: current insights on prevalence, characteristics, origin, and treatment. Endocr Rev 2019;40:973–87.10.1210/er.2018-00258Search in Google Scholar PubMed
5. Al Jurayyan, NA. Congenital adrenal hyperplasia in Saudi Arabia. IJHSR 2016;6:302–10.Search in Google Scholar
6. New, MI, Lekarev, O, Mancenido, D, Parsa, A, Yuen, T. Congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. In: New, MI, Lekarev, O, Parsa, A, Yuen, TT, O'Malley, BW, Hammer, GD editors. Genetic steroid disorders. San Diego: Academic press; 2014:29–51 pp.10.1016/B978-0-12-416006-4.00003-XSearch in Google Scholar
7. Miller, W. Mechanisms in endocrinology: rare defects in adrenal steroidogenesis. Eur J Endocrinol 2018;7:EJE-18. https://doi.org/10.1530/EJE-18-0279.Search in Google Scholar PubMed
8. Claahsen-Van der Grinten, HL, Hermus, AR, Otten, BJ. Testicular adrenal rest tumours in congenital adrenal hyperplasia. Int J Pediatr Endocrinol 2009;2009:624823. https://doi.org/10.1186/1687-9856-2009-624823.Search in Google Scholar
9. White, PC, Bachega, TA. Congenital adrenal hyperplasia due to 21 hydroxylase deficiency: from birth to adulthood. Semin Reprod Med 2012;30:400–9. https://doi.org/10.1055/s-0032-1324724.Search in Google Scholar PubMed
10. Reisch, N, Rottenkolber, M, Greifenstein, A, Krone, N, Schmidt, H, Reincke, M, et al.. Testicular adrenal rest tumors develop independently of long-term disease control: a longitudinal analysis of 50 adult men with congenital adrenal hyperplasia due to classic 21-hydroxylase deficiency. J Clin Endocrinol Metab 2013;98:E1820–6. https://doi.org/10.1210/jc.2012-3181.Search in Google Scholar PubMed
11. Yu, MK, Jung, MK, Kim, KE, Kwon, AR, Chae, HW, Kim, DH, et al.. Clinical manifestations of testicular adrenal rest tumor in males with congenital adrenal hyperplasia. Ann Pediatr Endocrinol Metab 2015;20:155. https://doi.org/10.6065/apem.2015.20.3.155.Search in Google Scholar PubMed PubMed Central
12. Deshpande, SS, Shetty, D, Saifi, S. Sonographic appearance of testicular adrenal rest tumour in a patient with congenital adrenal hyperplasia. Pol J Radiol 2017;82:526–9. https://doi.org/10.12659/pjr.902013.Search in Google Scholar
13. Claahsen-van der Grinten, HL, Hermus, ARMM, Otten, BJ, Stikkelbroeck, MM, Sweep, FC. Testicular adrenal rest tumours in congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab 2009;23:209–20. https://doi.org/10.1155/2009/624823.Search in Google Scholar PubMed PubMed Central
14. Kim, MS, Koppin, CM, Mohan, P, Goodarzian, F, Ross, HM, Geffner, ME, et al.. Absence of testicular adrenal rest tumors in newborns, infants, and toddlers with classical congenital adrenal hyperplasia. Horm Res Paediatr 2019;92:157–61. https://doi.org/10.1159/000504135.Search in Google Scholar PubMed PubMed Central
15. Witchel, SF. Nonclassic congenital adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes 2012;19:151–8. https://doi.org/10.1097/med.0b013e3283534db2.Search in Google Scholar PubMed
16. Claahsen-van der Grinten, HL, Sweep, FC, Blickman, JG, Hermus, AR, Otten, BJ. Prevalence of testicular adrenal rest tumors in male children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur J Endocrinol 2007;157:339–44. https://doi.org/10.1530/eje-07-0201.Search in Google Scholar PubMed
17. Kim, MS, Goodarzian, F, Keenan, MF, Geffner, ME, Koppin, CM, De Filippo, RE, et al.. Testicular adrenal rest tumors in boys and young adults with congenital adrenal hyperplasia. J Urol 2017;197:931–6. https://doi.org/10.1016/j.juro.2016.09.072.Search in Google Scholar PubMed PubMed Central
18. Claahsen-van der Grinten, HL, Dehzad, F, Kamphuis-van Ulzen, K, de Korte, CL. Increased prevalence of testicular adrenal rest tumours during adolescence in congenital adrenal hyperplasia. Horm Res Paediatr 2014;82:238–44. https://doi.org/10.1159/000365570.Search in Google Scholar PubMed
19. Claahsen-van der Grinten, HL, Otten, BJ, Sweep, FC, Hermus, AR. Repeated successful induction of fertility after replacing hydrocortisone with dexamethasone in a patient with congenital adrenal hyperplasia and testicular adrenal rest tumors. Fertil Steril 2007;88:705.e5–8. https://doi.org/10.1016/j.fertnstert.2006.11.148.Search in Google Scholar PubMed
20. Speiser, PW, Arlt, W, Auchus, RJ, Baskin, LS, Conway, GS, Merke, DP, et al.. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice Guideline. J Clin Endocrinol Metab 2018;103:4043–88. https://doi.org/10.1210/jc.2018-01865.Search in Google Scholar PubMed PubMed Central
21. Mendes-dos-Santos, CT, Martins, DL, Guerra-Júnior, G, Baptista, MTM, de-Mello, MP, de Oliveira, LC, et al.. Prevalence of testicular adrenal rest tumor and factors associated with its development in congenital adrenal hyperplasia. Horm Res Paediatr 2018;90:161–8. https://doi.org/10.1159/000492082.Search in Google Scholar PubMed
22. Wang, Z, Yang, Z, Wang, W, Chen, L, Huang, Y, Li, W, et al.. Diagnosis of testicular adrenal rest tumors on ultrasound A retrospective study of 15 cases report. Medicine 2015;94:e1471. https://doi.org/10.1097/md.0000000000001471.Search in Google Scholar
23. Martinez-Aguayo, A, Rocha, A, Rojas, N, García, C, Parra, R, Lagos, M, et al.. Testicular adrenal rest tumors and Leydig and Sertoli cell function in boys with classical congenital adrenal hyperplasia. J Clin Endocrinol Metab 2007;92:4583–9. https://doi.org/10.1210/jc.2007-0383.Search in Google Scholar PubMed
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