Endocrine Abstracts

JOINT867

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 modified-release hydrocortisone (MRHC) formulation seems to improve hormonal control; however, there are few data on its metabolic impact.

Aim of the study: Evaluate the hormonal control and metabolic impact of MRHC treatment in patients with CAH.

Patients and methods: 31 patients with CAH due to 21OH-deficiency (median age 28years) were included; clinical, metabolic and hormonal data were analyzed at baseline and after 6 and 12 months since MRHC switch. At baseline 10 patients were on long half-life GC treatment, 21 on immediate/dual-release hydrocortisone.

Results: During MRHC, there was a significant improvement in hormonal control, with a reduction in 17-OH-progesterone levels (median values: 474 nmol/l vs 61.5 nmol/l at 12 months, P<0.001) and androstenedione levels (22.2 nmol/l vs 10.7 nmol/l, P<0.001). Additionally, was observed a decrease in total testosterone in women (3.1 nmol/l vs 1.4 nmol/l, P=0.001) and an increase in the proportion of patients with good disease control (women 17% at baseline vs 36% at 12 months, P=0.030; men 23% vs 63%, P=0.018). Notably, there was a significant worsening in the lipid profile, with increases in total cholesterol (162 mg/dl vs 176 mg/dl at 12 months, P=0.026), LDL (90 mg/dl vs 104 mg/dl, P=0.009), and homocysteine levels (10.1 μ mol/l vs 12.6 μ mol/l, P=0.044) with only a slight improvement of triglycerides (70 mg/dl vs 59 mg/dl, P=0.006). Moreover, systolic ABP decreased in patients receiving long half-life GC therapy at baseline (125 mmHg vs 121 mmHg at 12 months, P=0.007). When assessing the CV risk profile, we observed a slight improvement in the VAI score, but no changes in the SCORE2, with 5 out of 11 patients remaining at high risk. No adrenal crises were reported and one patient discontinued MRHC due to insomnia.

Conclusions: MRHC was shown to improve hormonal control while maintaining a good safety profile. However, since patients with CAH are known to have a higher CV risk, the worsening of certain parameters should not be underestimated, although the clinical relevance of these findings requires further evaluation. In conclusion, we recommend evaluating the overall impact of available therapies to better tailor treatment for each patient.