Friedreich ataxia and impaired steroidogenesis

Ozge Bayrak Demirel; Ceyda Oney Yilmaz; Sinan Akbas; Tugce Kandemir; Ayca Dilruba Aslanger; Asli Derya Kardelen Al; Hulya Maras Genc; Melek Yildiz; Edibe Pembegul Yildiz; Sukran Poyrazoglu; Feyza Darendeliler; Firdevs Bas

doi:10.1530/endoabs.110.P184

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Endocrine Abstracts (2025) 110 P184 | DOI: 10.1530/endoabs.110.P184

ECEESPE2025 Poster Presentations Adrenal and Cardiovascular Endocrinology (169 abstracts)

Friedreich ataxia and impaired steroidogenesis

Ozge Bayrak Demirel ¹ , Ceyda Oney Yilmaz ² , Sinan Akbas ³ , Tugce Kandemir ¹ , Ayca Dilruba Aslanger ³ , Asli Derya Kardelen Al ¹ , Hulya Maras Genc ² , Melek Yildiz ¹ , Edibe Pembegul Yildiz ² , Sukran Poyrazoglu ¹ , Feyza Darendeliler ¹ & Firdevs Bas ¹

Author affiliations

¹Istanbul University, Istanbul Faculty of Medicine, Department of Pediatric Endocrinology, Istanbul, Türkiye, ²Istanbul University, Istanbul Faculty of Medicine, Department of Pediatric Neurology, Istanbul, Türkiye, ³Istanbul University, Istanbul Faculty of Medicine, Department of Medical Genetics, Istanbul, Türkiye

JOINT765

Introduction: Friedreich ataxia (FA) is an autosomal recessive disorder caused by an expansion of GAA repeats in the FXN gene, leading to impaired iron-sulfur (Fe-S) cluster biosynthesis and mitochondrial dysfunction. Fe-S clusters are essential for the activity of type 1 enzymes (CYP11A1, CYP11B1, CYP11B2) involved in steroidogenesis. Animal models and human cell culture studies have demonstrated reduced testosterone and progesterone levels in FA, particularly in males, which has been associated with a more severe disease course. However, no clinical studies in humans have been reported to date. This study aims to investigate potential steroidogenesis abnormalities in patients with FA.

Methods: This retrospective study analyzed data from four FA patients aged 13–17 years (3 males, 1 female). Data were obtained from patient records, including pubertal stages, basal steroid hormone levels, and standard-dose ACTH stimulation test results.

Results: At Tanner stage 5, basal cortisol levels were near the lower limit in three patients (2 males, 1 female). Progesterone levels were below the detection limit (<0.2 ng/ml) in the same patients. Androstenedione and DHEA-S levels were within normal ranges for all patients. Standard-dose ACTH stimulation tests showed adequate cortisol responses in all cases. Total testosterone levels were low in two male patients (2.06 and 2.88 ng/ml; Tanner stage 5 lower limit: 3.5 ng/ml) and near the lower limit in the third (3.65 ng/ml). The female patient had a normal estradiol level (54 pg/ml) in the follicular phase.

Conclusions: Potential steroidogenesis abnormalities in FA are characterized by reduced progesterone levels and testosterone deficiencies, particularly in males. These findings align with experimental data suggesting that impaired Fe-S cluster biosynthesis affects the activity of type 1 steroidogenic enzymes. Despite low basal cortisol levels, adequate responses to ACTH stimulation suggest preserved adrenal reserve. The normal estradiol level in the female patient supports the hypothesis that these abnormalities may be sex-specific. Further studies with larger cohorts and advanced techniques such as LC–MS to analyze steroidogenesis intermediates are needed to better understand the impact of FA on steroidogenesis and gonadal function. Investigating the effects of testosterone therapy on disease severity in males with FA through clinical trials could provide valuable insights.