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Cited by 51Sexual Differentiation and DisordersAdrenal Hormones and DisordersOvarian function and disorders

Testicular adrenal rest tumors in boys with 21-hydroxylase deficiency, timely diagnosis and follow-up

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Kocova, Mirjana, Janevska, Vesna, Anastasovska, Violeta·2018·Endocrine Connections
DOI 10.1530/ec-18-0097PMC PMC5887129
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Abstract

Background: Testicular adrenal rest tumors (TARTs) are found in 30–94% of adult males with congenital adrenal hyperplasia (CAH). We sought to explore TART appearance through yearly ultrasound examination of testes in young boys with CAH, and its association with metabolic control and genetic mutations. Methods: Twenty-five boys with 21-hydroxylase deficiency in the age group 4–18 years diagnosed during the period 2001–2016 were included in the study. ACTH, 17-hydroxyprogesterone, androstenedione and testosterone were measured at 4-month intervals. Growth and BMI were assessed at the time of evaluation. PCR/ACRS method was used for CYP21A2 gene analysis. Testicular ultrasound examination was performed yearly. Results: TARTs were detected by ultrasound in 8 children at the age of 6–16 years (13.2 years average). Five had salt-wasting form, two had simple virilizing form and one had non-classic form of CAH. Significant differences in the17OHP and androstenedione levels were detected between the boys, adherent and non-adherent to therapy. Inadequate metabolic control was not different in boys with and without TART (11/17 and 5/8 respectively). No significant difference was detected in the distribution of genetic mutations or adherence to therapy between patients with and without TARTs. One patient had a mutation not reported thus far in TART and another developed leukemia. Conclusion: TART is not rare in young boys with CAH, irrespective of the specific mutation or metabolic control. Ultrasound screening helps timely diagnosis and adjustment of therapy.

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  • In men with CAH, gonadal and reproductive function are often impaired due to primary gonadal failure from TARTs and/or secondary gonadal failure due to suppressed hypothalamic-pituitary-gonadal axis as a consequence of high adrenal androgen concentrations.

    “In men with CAH, gonadal and reproductive function are often impaired due to primary gonadal failure from TARTs and/or secondary gonadal failure due to suppressed hypothalamicpituitary-gonadal axis as a consequence of high adrenal androgen concentrations (378,437,438,625).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [437]

    The Introduction and Discussion (page numbers unavailable) link TARTs to testicular damage and impaired fertility in males with CAH. The paper does not attribute secondary gonadal failure to suppression of the hypothalamic-pituitary-gonadal axis by high adrenal androgen concentrations. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The reported prevalence of TARTs in CAH ranges from 14% to 86%, with an average of 25% in adolescents, and 46% in men.

    “The reported prevalence of TARTs in CAH ranges from 14% to 86% (437,634), with an average of 25% in adolescents, and 46% in men (378).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [437]

    The Discussion reports that TART prevalence varies in CAH, but gives ranges of 30–94% in adults and 18.3–48% in children, not the cited 14–86%. The adolescent and men averages are attached to a different citation in the citing sentence and are not assessed here. Page numbers were not available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • TARTs are rare in men with NC CAH.

    “TARTs are rare in men with NC CAH (437-439).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [437]

  • TARTs are benign testicular tumors typically found in males with classic CAH.

    “TARTs are benign testicular tumors typically found in males with classic CAH (378,437).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [437]

  • Poor hormonal control in CAH results in increased risk of hypogonadotropic hypogonadism, because high levels of adrenal androgen precursors will be aromatized to estrogens and suppress the hypothalamic-pituitary-gonadal axis.

    “Poor hormonal control in CAH results in increased risk of hypogonadotropic hypogonadism (437,626), because high levels of adrenal androgen precursors will be aromatized to estrogens and suppress the hypothalamic-pituitary-gonadal axis.”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [437]

    The Introduction links CAH-related infertility to testicular adrenal rest tumors, and the Discussion addresses hormonal control and tumor development. Searches for hypogonadotropic hypogonadism and suppression of the hypothalamic-pituitary-gonadal axis found no passage in our copy establishing the claimed risk or estrogen-mediated mechanism. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 30

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Cited by

Sorted by citations

Authors
Kocova, M., Janevska, V., & Anastasovska, V.
Affiliations
  • 1Department of Endocrinology and Genetics, Medical Faculty, University Pediatric Clinic, Ss. Cyril and Methodius University, Skopje, Republic of Macedonia
  • Ss. Cyril and Methodius University in Skopje (MK)
ORCID
Anastasovska, Violeta
Venue
Endocrine Connections
Publisher
Bioscientifica
Published
2018-04
Volume
7
Issue
4
Pages
544-552
ISSN
2049-3614 (ISSN-L)
DOI
10.1530/ec-18-0097
PMC
PMC5887129
OpenAlex
W2794212049
Cited by
51
References
8
Citations by year
2026: 4 · 2025: 1 · 2024: 3 · 2023: 5 · 2022: 22 · 2021: 6 · 2020: 6 · 2019: 4
FWCI
1.42
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine Connections (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
Keywords
testicular adrenal rest tumor, 21-hydroxylase deficiency, congenital adrenal hyperplasia, pediatric boys, metabolic control, CYP21A2 mutations, ACTH, 17-hydroxyprogesterone, androstenedione, salt-wasting CAH, medication adherence, leukemia

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