P56 - ECE_2749 - Modified-release hydrocortisone impact on metabolism and hormonal control in patients with congenital adrenal hyperplasia: an observational cohort study

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Abstract Background Congenital adrenal hyperplasia (CAH) is a genetic disorder characterized by impaired cortisol secretion and androgen excess. The mainstay of CAH treatment is glucocorticoid (GC) replacement, necessary to avoid adrenal crises and manage androgen excess. The delicate balance between GC under- and overtreatment is crucial to prevent metabolic and cardiovascular (CV) complications. The new modified-release hydrocortisone (MRHC) formulation improves hormonal control compared to conventional GC; however, there are few data on its metabolic impact. Aim of the Study to evaluate the hormonal control and metabolic impact of MRHC treatment in patients with CAH. Patients and Methods 38 patients with CAH due to 21OH-deficiency (33 patients with classic form and 5 with nonclassic CAH, median age 31years) were included; clinical, metabolic and hormonal data were analyzed at baseline, after 12 and 18 or 24 months after switching to MRHC. At baseline, 15 patients were previously treated with long-acting GC, while 23 with immediate-release or dual-release hydrocortisone. Results During MRHC treatment, hormonal control improved, with a significant reduction in 17-OH-progesterone (median values 418 nmol/L vs 38 nmol/L at 18/24 months, P = .001) and androstenedione levels (19.5 nmol/L vs 8.5 nmol/L, P = .003). Additionally, we observed a decrease in total testosterone levels in women (2.9 nmol/L vs 0.6 nmol/L, P = .001) and a significant increase of the proportion of patients with good disease control (28% at baseline vs 62% at 18/24 months, P = .014). Furthermore, we reported a slight but significant worsening in lipid profile, with increases of total cholesterol (165 mg/dL vs 176 mg/dL, P = .004), and LDL-cholesterol levels (90 mg/dL vs 107 mg/dL, P = .008); in addition, there was also a slight elevation of homocysteine levels (10.2 µmol/L vs 12.1 µmol/L, P = .017). However, after performing a subgroup analysis, we observed that only patients previously treated with immediate or dual-release hydrocortisone had a worsening of lipidic profile; instead, it remained stable in patients who took long-acting GC at baseline. In addition, we noticed a slight improvement of SCORE2 and VAI scores, which were used to evaluate the CV risk profile of our patients. During MRHC treatment no adrenal crises were reported, and it was discontinued only in two cases due to insomnia and polyuria. Conclusions MRHC treatment showed an improvement in hormonal control, while maintaining a good safety profile. Nevertheless, a potential negative effect on metabolic parameters was observed. Although these changes do not appear to affect negatively the CV risk profile, clinicians should carefully assess the overall impact of available therapeutic options to optimally personalize treatment for each patient.

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