ESPE Abstracts

Introduction and Purpose: Congenital Adrenal Hyperplasia (CAH) encompasses a group of genetic disorders arising from enzyme deficiencies crucial for the biosynthesis of cortisol and mineralocorticoids, resulting in decreased cortisol and increased androgen production. Standard treatment involves oral hydrocortisone administration 2-3 times daily. However, this treatment often fails to mimic the circadian rhythm and effectively suppress androgen production, especially during puberty. Preventing disease complications while minimizing treatment side effects remains a challenge. The advent of modified-release hydrocortisone, a new biotechnological product designed to mimic circadian rhythm through specific encapsulation and pharmacokinetic properties, offers promise. It is administered orally twice daily and indicated for patients over 12 years old. This study aims to compare the efficacy of conventional versus modified-release hydrocortisone in treating adolescents and young adults with CAH.

Patients and Methods: This retrospective observational study involved 9 patients (4 girls, 5 boys) aged 13.5 to 18.5 years, treated at two pediatric endocrinology clinics. 8 patients are diagnosed with 21-hydroxylase deficiency (5 nonclassical form, 3 simple-virilizing form), 1 with 11β-hydroxylase deficiency. All patients are currently being treated with modified-release hydrocortisone (duration of new treatment 2 to 17 months). 5 patients had reached final height before treatment switch. Comparative analysis was conducted on Δ4-androstenedione, 17-hydroxyprogesterone, cortisol, ACTH and fasting glucose conentration, clinical features, treatment compliance, and dosage adjustment, before and after the new treatment.

Results: Following the initiation of modified-release hydrocortisone, a decrease in 17-hydroxyprogesterone levels was observed in all patients, with Δ4-androstenedione levels decreasing in 6/7 patients. Morning cortisol levels increased in 6/9 patients, ACTH levels decreased in 8/9 patients. Hypertrichosis (4/4 patients), acne (3/3 patients), menstrual irregularities (1/1 patient), and clitoromegaly (1/ 1 patient) improved. No significant changes were noted in fasting glucose levels and BMI. 8/9 patients exhibited compliance, with 5 patients showing enhanced compliance compared to previous treatment. Dose reduction while maintaining effective disease control was achieved in 8/ 9 patients.

Conclusion: Modified-release hydrocortisone offers advantages in CAH treatment, including mimicry of the circadian rhythm of cortisol secretion, reduced androgen levels, remission of clinical manifestations, improved compliance and dose reduction compared to standard treatment. These findings are aligned with published research data, yet long-term efficacy studies are warranted to elucidate the drug's full therapeutic potential.