Evaluation of serum irisin levels in patients with congenital adrenal hyperplasia receiving supraphysiological doses of hydrocortisone treatment

Introduction: Cortisol is one of the essential hormones for life. It has many effects on carbohydrate, protein, fat, and muscle metabolism. It stimulates adipocyte differentiation by promoting adipogenesis. Classical congenital adrenal hyperplasia (CAH) is a disease associated with a defect in the synthesis of adrenal steroid hormones, occurring in about 1:13,000 to 1:15,000 live births. Depending on the type of enzyme deficiency in its subgroups, there is a deficiency of adrenal hormones and related clinical manifestations. In its treatment, supraphysiological doses of hydrocortisone are used, which can lead to changes in fat and muscle mass. Irisin is an adipomyokine secreted from adipose and muscle tissues. The aim of this thesis is to investigate the levels of irisin in patients with CAH receiving supraphysiological doses of hydrocortisone treatment. Material and Method: A study was conducted at the Department of Pediatric Endocrinology, Pediatric Health and Diseases Division, Bezmialem Vakif University Faculty of Medicine, involving 34 CAH patients aged between 2-18 years and 34 healthy control group children. During the patients check-ups, a venous blood sample was collected in a yellow tube for 17-hydroxyprogesterone (17-OHP) levels and analyzed using the ELISA method. From the patients records, information such as gestational age, chronological age, gender, height, weight, head circumference, and the standard deviation scores (SDS) of these measurements were obtained. Additionally, vital measurements, adrenocorticotropic hormone (ACTH), cortisol, glucose, insulin, 17-OHP, dehydroepiandrosterone sulfate (DHEA-S), androstenedione, plasma renin activity, aldosterone, sodium, potassium, chloride, aspartate aminotransferase, alanine aminotransferase, low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, thyroid-stimulating hormone, and thyroxine levels were recorded for the patients. The data of the groups were compared, and correlation analysis was performed between iris levels and other parameters. Results: The average age of the participants in the CAH patient group was 12,59±3,5, and in the control group, it was 12,22±3,54. In the CAH patient group, 24 (70%) were female and 10 (30%) were male. In the control group, 29 (85%) were female and 5 (15%) were male. The mean treatment dose for the patients was 16,7±4,7 mg/m² of hydrocortisone. Eighteen patients (52,9%) were using astonin. When examining the height standard deviation scores (SDS) values, it was observed that in the CAH patient group, it was -0,27 ± 1,1, and in the control group, it was 0,33 ± 0,99; p= 0,02, indicating a significant difference between the two groups. Irisin levels were 12,98±10,58 in the patient group and 6,97±4,3 in the control group, showing a statistically significantly higher level in the patient group. In our study, no relationship was found between irisin and cortisol, androstenedione, and other laboratory data. Conclusion and Recommendations: In our study, it was determined that the serum irisin level was significantly higher in the CAH patient group. However, no correlation was found with any evaluated parameter. The mechanism by which the irisin molecule, which affects energy expenditure and lipid metabolism, is elevated in CAH patients remains unclear, necessitating further research. The height SDS of CAH patient group under hydrocortisone therapy were significantly lower compared to the control group. Proper monitoring of growth and development in individuals receiving glucocorticoid therapy is crucial, and it is important to manage the disease with the lowest possible steroid dose that can effectively treat the condition. Key words: Congenital Adrenal Hyperplasia, Cortisol, Hydrocortisone, Irisin.