Reduced serum concentrations of biomarkers reflecting Leydig and Sertoli cell function in male patients with congenital adrenal hyperplasia

Trine Holm Johannsen; Jakob Albrethsen; Vassos Neocleous; Federico Baronio; Martine Cools; Lise Aksglaede; Niels Jørgensen; Peter Christiansen; Meropi Toumba; Pavlos Fanis; Marie Lindhardt Ljubicic; Anders Juul

doi:10.1530/EC-23-0073

Reduced serum concentrations of biomarkers reflecting Leydig and Sertoli cell function in male patients with congenital adrenal hyperplasia

Endocr Connect. 2023 Jul 14;12(8):e230073. doi: 10.1530/EC-23-0073.

Authors

Trine Holm Johannsen^{1

2}, Jakob Albrethsen^{1

2}, Vassos Neocleous³, Federico Baronio⁴, Martine Cools⁵, Lise Aksglaede^{1

2}, Niels Jørgensen^{1

2}, Peter Christiansen^{1

2}, Meropi Toumba^{3

6}, Pavlos Fanis³, Marie Lindhardt Ljubicic^{1

2}, Anders Juul^{1

2

7}

Affiliations

¹ Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.
² International Centre for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³ The Cyprus Institute of Neurology and Genetics, Department of Molecular Genetics, Function and Therapy, Nicosia, Cyprus.
⁴ S. Orsola-Malpighi University Hospital, Department of Medical and Surgical Sciences, Bologna, Italy.
⁵ Department of Pediatrics, Division of Pediatric Endocrinology, Ghent University Hospital and Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium.
⁶ Pediatric Endocrinology Clinic, Department of Pediatrics, Aretaeio Hospital, Nicosia, Cyprus.
⁷ Department of Clinical Medicine, University of Copenhagen, Denmark.

Abstract

Congenital adrenal hyperplasia (CAH) is a recessive condition that affects the adrenal glands. Despite life-long replacement therapy with glucocorticoids and mineralocorticoids, adult patients with CAH often experience impaired gonadal function. In pubertal boys and in men with CAH, circulating testosterone is produced by the adrenal glands as well as the testicular, steroidogenic cells. In this European two-center study, we evaluated the function of Leydig and Sertoli cells in 61 boys and men with CAH, primarily due to 21-hydroxylase deficiency. Despite conventional hormone replacement therapy, our results indicated a significant reduction in serum concentrations of both Leydig cell-derived hormones (i.e. insulin-like factor 3 (INSL3) and testosterone) and Sertoli cell-derived hormones (i.e. inhibin B and anti-Müllerian hormone) in adult males with CAH. Serum concentrations of INSL3 were particularly reduced in those with testicular adrenal rest tumors. To our knowledge, this is the first study to evaluate circulating INSL3 as a candidate biomarker to monitor Leydig cell function in patients with CAH.

Keywords: AMH; FSH; INSL3; LH; Testosterone; inhibin B.