Conventional steroids vs. dual-release hydrocortisone on metabolic, cardiovascular, and bone outcomes in adrenal insufficiency: a 10-year study.

OBJECTIVE

Adrenal insufficiency (AI) is characterized by increased mortality compared to general population, mainly due to cardiovascular disease. Conventional glucocorticoid (GC) replacement therapy has a role in determining the increased mortality risk. Primary outcome of the current study was to evaluate the impact of 10 years of conventional GCs and DR-HC on body weight changes in treatment-naive patients with AI. Secondary outcomes were changes from baseline to 5 and 10 years in anthropometric and metabolic profile, insulin sensitivity, cardiovascular, and bone parameters.

DESIGN AND METHODS

We prospectively randomized 42 patients to conventional GCs (cortisone acetate or hydrocortisone) and 44 to DR-HC (1:1). Anthropometric, metabolic, cardiovascular, and bone parameters were evaluated at baseline and after 5 and 10 years of follow-up. This trial is registered at ClinicalTrials.gov NCT06260462.

RESULTS

At 10 years of follow-up, patients with conventional GCs had significantly higher values of BMI (P = .031), waist circumference (P = .047), systolic blood pressure (P = .039), total and LDL cholesterol (P = .041 and P = .042), HbA1c (P = .040), HOMA-IR (P = .006), AUC2h of glucose (P < .001), thickness of the interventricular septum in diastole and of the posterior wall (both P < .001) and significantly lower values of oral disposition index (P = .001) and ISI-Matsuda (P < .001), lumbar spine T score (P = .036), and femoral neck Z score (P = .026), compared to patients treated with DR-HC.

CONCLUSIONS

In patients with treatment-naive AI, 10 years of conventional GC treatment is associated with a worsening of metabolic, insulin-sensitivity, cardiac, and bone outcomes, while DR-HC had no impact on them achieving a lower risk of developing comorbidities.