Prednisolone Therapy in Adolescents with Congenital Adrenal Hyperplasia: Effects on Hormonal Suppression, Puberty, and Gonadal Outcomes

Öz

Objective: Puberty complicates managing congenital adrenal hyperplasia due to hormonal and psychosocial changes. As patients approach their final adult height, a therapeutic window emerges for the use of more potent glucocorticoids, such as prednisolone, which may offer a practical and clinically effective treatment. This study evaluated the effectiveness of prednisolone on biochemical and clinical hyperandrogenemia in patients with congenital adrenal hyperplasia. Material and Methods: Patients who exhibited persistent biochemical/clinical hyperandrogenemia despite optimal hydrocortisone dosing, or who requested an increase in dosing intervals, were included in the study conducted at a single institution over the past 24 years (2000-2024). Participants were switched to prednisolone therapy at or near final height. Clinical and laboratory data, treatment outcomes for all participants, were retrospectively evaluated. Results: Twenty-one patients (karyotype 46,XX in 14/21, 46,XY in 7/21) with a mean age of 16.4±1.5 years were included in the study. 4 of 46,XX cases were male-reared, and so a total of 11/21 (52%) of the patients were male-reared, and 10/21 (48%) were female-reared. Following the transition to prednisolone therapy, 71% of the patients (15/21) had normal androgen levels. In female-reared patients, menstrual regularity improved in 1/7. Among the two male-raised patients who had not yet completed pubertal development, one (1/2, 50%) demonstrated pubertal progression; all three patients with an elevated androstenedione/testosterone ratio (3/3, 100%) showed a decrease in this ratio; and tumor size decreased in the one patient with an adrenal rest tumor. There was no change in the frequency of patients with obesity/overweight (p>0.05). Conclusion: Prednisolone treatment facilitated the normalization of adrenal androgens in a considerable number of patients, without inducing Cushingoid symptoms. However, attainment of normal gonadal function was observed only in a limited subset of patients. In instances where patients with congenital adrenal hyperplasia exhibit poor adherence to therapy, persistent hyperandrogenemia, and an inability to restore gonadal function, it may be appropriate to consider the use of more potent glucocorticoids administered once daily.

Anahtar Kelimeler

• Adolescents
• congenital adrenal hyperplasia
• prednisolone
• gonadal functions

KONJENİTAL ADRENAL HİPERPLAZİ TANILI ADÖLESANLARDA PREDNİZOLON TEDAVİSİNİN HORMONAL BASKILAMA, ERGENLIK VE GONAD İŞLEVLERI ÜZERİNDEKİ ETKİSİ

Öz

Amaç: Puberte dönemi, hem endokrin hem de psikososyal değişiklikler nedeni ile konjenital adrenal hiperplazi tedavisinde güçlüklere neden olabilir. Final boya ulaşılması, daha güçlü, sentetik glukokortikoidlerin kullanılabileceği alternatif tedavi seçeneği sağlar. Prednizolon, orta etkili ve güçlü bir glukokortikoid olup hastalar için hidrokortizona göre uygulaması daha kolay bir doz şeması oluşturur. Bu çalışmada, final-finale yakın boya ulaşmış adölesan konjenital adrenal hiperplazi tanılı hastalarda prednizolon tedavisinin biyokimyasal ve klinik hiperandrojenemi üzerindeki etkisini değerlendirmeyi amaçladık. Gereç ve Yöntemler: 24 yıllık süre boyunca (2000-2024), üçüncü basamak sağlık kuruluşunda konjenital adrenal hiperplazi tanısı ile izlenen ve günlük ilaç kullanım sıklığını azaltmak isteyen veya optimal hidrokortizon dozuna rağmen biyokimyasal/klinik hiperandrojenemisi devam eden hastalar çalışmaya dahil edildi. Final veya finale yakın boya ulaşan ve günde iki doz prednizolon tedavisine geçilen hastaların yeni tedavi ile birlikte puberte gelişimi, gonad işlevleri, klinik ve hormon değişimleri retrospektif olarak incelendi. Bulgular: Çalışmaya ortalama yaşı 16,4±1,5 yıl olan 21 hasta (Karyotip 14’ünde 46,XX, 7’sinde 46,XY) dahil edildi. Karyotipi 46,XX olan olguların dördü erkek yönünde yetiştirilmişti; dolayısıyla toplam 11 hasta (11/21, %52) erkek-yetiştirilmiş, 10 hasta (10/21, %48) kız-yetiştirilmişti. Prednizolon tedavisinden sonra hastaların %71’inde (15/21) normal androjen düzeyi sağlandı. Kız-yetiştirilmiş hastalardan birinde (1/7) normal menstrüel siklus başladı. Pubertal gelişimini tamamlamayan iki erkek-yetiştirilmiş hastadan birinde (1/2, %50) puberte evresinde ilerleme oldu, androstenedion/testosteron oranı yüksek olan üç hastanın tamamında oran (3/3, %100) azaldı, adrenal rest tümörü olan bir hastanın kitlesinde küçülme oldu. Prednizolon tedavisine geçildikten sonra kilo fazlalığı/obezite sıklığında artış olmadı (p>0,05). Sonuç: Prednizolon tedavisi, konjenital adrenal hiperplazi tanılı hastaların önemli bir kısmında Cushingoid belirtilere neden olmadan adrenal androjenlerin normal düzeye gelmesine yardımcı oldu. Ancak gonad işlevlerinin normale gelmesi az sayıda hastada sağlanabildi. Tedavi uyumu kötü olan, hiperandrojenemi düzeltilemeyen ve gonad işlevleri sağlanamayan konjenital adrenal hiperplazi tanılı hastalarda günde tek doz uygulanan daha güçlü glukokortikoid ilaçların kullanımı düşünülebilir.

Anahtar Kelimeler

• Adölesan
• konjenital adrenal hiperplazi
• prednizolon
• gonad işlevleri

Kaynakça

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