Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor

Aycan, Zehra; Keskin, Melikşah; Lafcı, Naz Güleray; Savaş‐Erdeve, Şenay; Baş, Firdevs; Poyrazoğlu, Şükran; Öztürk, Pınar; Öztürk, Ayşe Pınar; Ercan, Oya; Güran, Tülay; HATİPOĞLU>, Nihal; Uçaktürk, Seyit Ahmet; Çatlı, Gönül; Akyürek, Nesibe; Önder, Aşan; Kılınç, Suna; Çeti̇nkaya, Semra

doi:10.1016/j.ejmg.2022.104654

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…The relationship between the CAH genotype and the development of TART is unknown (38) (38) Given that genotypephenotype correlation in CAH is not found in all patients (1), genetic analysis of larger TART patient cohorts may reveal additional genotypes associated with TART (35,38). One of the limitations of our study is, despite clear diagnostic criteria and careful data editing, we cannot exclude arbitrary overestimation of the severity of clinical phenotypes.…”

Section: Discussionmentioning

confidence: 94%

Genetic and clinical characteristics including occurrence of testicular adrenal rest tumors in Slovak and Slovenian patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

et al. 2023

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ObjectiveTo analyze the mutational spectrum, clinical characteristics, genotype–phenotype correlations, testicular adrenal rests tumor prevalence, and role of neonatal screening in congenital adrenal hyperplasia (CAH) patients from Slovakia and Slovenia.Design and methodsData were obtained from 104 patients with CAH registered in Slovak and Slovenian databases. Low-resolution genotyping was performed to detect the most common point mutations. To detect deletions, conversions, point mutations, or other sequence changes in the CYP21A2 gene, high-resolution genotyping was performed. Genotypes were classified according to residual 21-hydroxylase activity (null, A, B, C).Results64% of the individuals had the salt-wasting form (SW-CAH), 15% the simple virilizing form (SV-CAH), and 21% the non-classic (NC-CAH). CYP21A2 gene deletion/conversion and c.293-13A/C>G pathogenic variant accounted together for 55.5% of the affected alleles. In SV-CAH p.Ile172Asn was the most common pathogenic variant (28.13%), while in NC-CAH p.Val282Leu (33.33%), CYP21A2 gene deletion/conversion (21.43%), c.293-13A/C>G (14.29%), Pro30Leu (11.90%). The frequency of alleles with multiple pathogenic variants was higher in Slovenian patients (15.83% of all alleles). Severe genotypes (0 and A) correlated well with the expected phenotype (SW in 94.74% and 97.3%), while less severe genotypes (B and C) correlated weaklier (SV in 50% and NC in 70.8%). The median age of SW-CAH patients at the time of diagnosis was 6 days in Slovakia vs. 28.5 days in Slovenia (p=0.01). Most of the Slovak patients in the cohort were detected by NBS. (24 out of 29). TARTs were identified in 7 out of 24 male patients, of whom all (100%) had SW-CAH and all had poor hormonal control. The median age at the diagnosis of TARTs was 13 years.ConclusionThe study confirmed the importance of neonatal screening, especially in the speed of diagnosis of severe forms of CAH. The prediction of the 21-OH deficiency phenotype was reasonably good in the case of severe pathogenic variants, but less reliable in the case of milder pathogenic variants, which is consistent compared to data from other populations. Screening for TARTs should be realized in all male patients with CAH, since there is possible remission when identified early.

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Section: Discussionmentioning

confidence: 94%

Genetic and clinical characteristics including occurrence of testicular adrenal rest tumors in Slovak and Slovenian patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

et al. 2023

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“…In a recent Turkish study, TARTs were detected only in 17.4% of the cohort of males with CAH and the youngest patient with a TART was 2 years old [ 14 ]. Based on what has been reported in numerous studies, it is known that the prevalence of TARTs is variable and higher among adolescents and young adults than among children.…”

Section: Discussionmentioning

confidence: 99%

Testicular Adrenal Rest Tumors in Congenital Adrenal Hyperplasia: Study of a Cohort of Patients from a Single Italian Center

Ortolano,

Cassio,

Alqaisi

et al. 2023

Children

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Testicular adrenal rest tumors (TARTs) are a common complication in male patients with congenital adrenal hyperplasia (CAH). The aim of our cross-sectional cohort study is to estimate the frequency of TARTs with the correlation of genotype and disease control on tumor development. Thirty-five male patients, aged 14–26 years, were included in the study, all followed by the same center of pediatric endocrinology in Bologna. We studied genotypes, hormonal profiles at different time intervals and testicular ultrasound. A logistic regression model with multivariant analysis was developed for the statistical analysis. TARTs were detected in 31.4% of the cases, 90.9% of them had a classic form with salt wasting, while 9.1% had a non-classic form. Additionally, a significant correlation between the incidence of TARTs and severity of genotype was detected. Patients with TARTs had markedly worse metabolic control on average (p = 0.027), reflected by high ACTH, 17OH progesterone, and overall delta4-androstenedione. In conclusion, a screening tool is mandatory, especially (but not exclusively) in patients with the most severe forms of CAH and poor endocrine control of the disease.

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“…Ectopic adrenal rests located in the testes (testicular adrenal rests tumor or TARTS) may be involved, albeit TARTS are usually associated with C-CAH instead of NC-CAH [1,6]. Recently, TARTS has been documented in 17-30% of male patients with CYP21A2 gene variants, of whom the majority (80-95%) displayed the SV form, but also two males with the NC-CAH showed TARTS [29,30]. TARTS likely originate from residual adrenal cells; then, the increased ACTH levels stimulate these cells to proliferate and form masses.…”

Section: Clinical Findingsmentioning

confidence: 99%

“…TARTS likely originate from residual adrenal cells; then, the increased ACTH levels stimulate these cells to proliferate and form masses. An increasing prevalence has been observed from pubertal onset onward and their frequency in prepubertal years remains largely unknown [1,29,30]. Although they are benign, the growing masses would compress the spermatogonium and ductulus efferens, which may lead to irreversible damage.…”

Section: Clinical Findingsmentioning

confidence: 99%

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Non-Classic Congenital Adrenal Hyperplasia in Childhood: A Review

Bertolucci,

Tyutyusheva,

Sepich

et al. 2023

Sexes

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Congenital adrenal hyperplasia (CAH) is a heterogeneous group of autosomal recessive disorders due to defects in adrenal steroid biosynthesis. In about 90% of patients, CAH is caused by pathogenetic variants in CYP21A2 gene, impairing the function of 21-hydroxylase (21-OH) enzyme. CAH can present as classical form (simple virilizing or salt wasting) or as non-classical form (NC-CAH). NC-CAH is due to pathogenetic variants in the CYP21A2 gene that result in 20–70% residual activity of 21-hydroxylase. Early diagnosis may be missed, mainly in childhood, jeopardizing long-term outcome. This paper will review some information on clinical findings, symptoms, diagnostic approaches, and treatments of NC-CAH in childhood, allowing better management and long-term outcome.

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Genotype of congenital adrenal hyperplasia patients with testicular adrenal rest tumor

Cited by 6 publications

References 33 publications

Genetic and clinical characteristics including occurrence of testicular adrenal rest tumors in Slovak and Slovenian patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Genetic and clinical characteristics including occurrence of testicular adrenal rest tumors in Slovak and Slovenian patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Testicular Adrenal Rest Tumors in Congenital Adrenal Hyperplasia: Study of a Cohort of Patients from a Single Italian Center

Non-Classic Congenital Adrenal Hyperplasia in Childhood: A Review

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