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Testicular adrenal rest tumors in congenital adrenal hyperplasia—cross-sectional study of 51 Croatian male patients

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Abstract

Testicular adrenal rest tumors (TARTs) are common cause of infertility in males with congenital adrenal hyperplasia (CAH). We studied the role of genotype and disease regulation on TART development, their impact on gonadal function, and frequency in 47 21-hydroxylase deficiency (21-OHD) and four 11-hydroxylase deficiency (11-OHD) male patients. Testicular ultrasound (TU), genotype, hormonal measurement in 51, and spermiogram in five patients were performed. TARTs were detected in 14 SW21-OHD and one 11-OHD patient: 1/8 patients aged <7 years (1.8 years old is the youngest), 1/8 patients aged <12 years, 5/17 patients aged <18 years, and in 8/18 adults. All 21-OHD TART patients had exclusively severe mutations of CYP21A2 gene. Poor hormonal control in 8/15 patients with and 12/36 patients without TART indicates correlation of tumor development with poor disease control. None of the TART patients fathered a child. Low inhibin-B was found in 7/15 TART patients. Azoospermia was found in four and oligoasthenozoospermia in one patient.

Conclusion: TART was detected exclusively in patients with severe CYP21A2 mutations. Disease regulation plays a role in development of TART that impairs testicular function and increases the risk of infertility. Screening for TART by TU is indicated from early childhood.

What is Known:

• Due to improved diagnostic and therapeutic possibilities, majority of the male patients with congenital adrenal hyperplasia nowadays reach adulthood and screening for long-term complications is becoming more important.

• Testicular adrenal rest tumors (TARTs) are common cause of infertility and impaired gonadal function in males with CAH.

What is New:

• A 1.8-year-old boy described in this paper is the youngest reported patient with TART.

• Screening for TART by testicular ultrasound from early childhood, especially in patients with severe CYP21A mutations, is recommended.

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Abbreviations

11-OHD:

11-h ydroxylase deficiency

17-OHP:

17-h ydroxyprogesterone

21-OHD:

21-h ydroxylase deficiency

A:

Androstenedione

ACTH:

Adrenocorticotropic hormone

BA:

Bone age

BMI:

Body mass index

CA:

Chronological age

CAH:

Congenital adrenal hyperplasia

FH:

Final height

FHSDS:

Final height standard deviation score

FLC:

Fetal Leydig cells

FSH:

Follicle-stimulating hormone

GnRHa:

Gonadotropin-releasing hormone analog

L:

Left

LH:

Luteinizing hormone

MLPA:

Multiplex ligation-dependent probe amplification

NC:

Nonclassical

PRA:

Plasma renin activity

R:

Right

RFLP:

Restriction fragment length polymorphism

SV:

Simple virilizing

SW:

Salt wasting

T:

Testosterone

TART:

Testicular adrenal rest tumor

TH:

Target height

THSDS:

Target height standard deviation score

TU:

Testicular ultrasound

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Funding

This research did not receive any specific grant from any funding agency in the public, commercial, or not-for-profit sector.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Clinical Hospital Centre Zagreb, University of Zagreb Medical School, Kispaticeva 12, 10000, Zagreb, Croatia

    Miroslav Dumic

  2. Clinical Department of Diagnostic and Interventional Radiology, Clinical Hospital Centre Zagreb, University of Zagreb Medical School, Zagreb, Croatia

    Vlatko Duspara

  3. Tissue Typing Centre, Department of Transfusion Medicine and Transplantation Biology, Department of Laboratory Medicine, Clinical Hospital Centre Zagreb, University of Zagreb Medical School, Zagreb, Croatia

    Zorana Grubic

  4. Endocrinological Laboratory, Department of Laboratory Medicine, Clinical Hospital Centre Zagreb, University of Zagreb Medical School, Zagreb, Croatia

    Sasa Kralik Oguic & Vesna Kusec

  5. Department of Pediatrics, Clinical Hospital Centre Split, University of Split Medical School, Split, Croatia

    Veselin Skrabic

Authors
  1. Miroslav Dumic
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  2. Vlatko Duspara
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  3. Zorana Grubic
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  4. Sasa Kralik Oguic
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  5. Veselin Skrabic
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  6. Vesna Kusec
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Contributions

MD designed the study, collected and analyzed the data, and wrote the manuscript; VD performed the ultrasounds and helped with writing the manuscript; ZG performed the DNA analysis, reviewed the study findings, and wrote the manuscript; SKO performed the hormonal analysis and reviewed the manuscript; VS contributed to the clinical aspect of the trial and reviewed the manuscript; and VK performed the hormonal analysis and wrote and reviewed the manuscript.

Corresponding author

Correspondence to Miroslav Dumic.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Communicated by Peter de Winter

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Dumic, M., Duspara, V., Grubic, Z. et al. Testicular adrenal rest tumors in congenital adrenal hyperplasia—cross-sectional study of 51 Croatian male patients. Eur J Pediatr 176, 1393–1404 (2017). https://doi.org/10.1007/s00431-017-3008-7

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  • DOI: https://doi.org/10.1007/s00431-017-3008-7

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