Dual-release hydrocortisone improves hepatic steatosis in patients with secondary adrenal insufficiency: A real-life study

Background: Conventional glucocorticoid treatment has a significant impact on liver in patients with adrenal insufficiency. Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement in anthropometric and metabolic parameters. We aimed to evaluate the effects of 12-month DR-HC treatment on the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, in patients with secondary adrenal insufficiency (SAI). Methods: A total of 45 patients with hypopituitarism, 22 with hypogonadism, hypothyroidism, ACTH, and GH deficiencies, and 23 with hypogonadism, hypothyroidism, and ACTH deficiency, on replacement therapy for all the pituitary deficiencies, were switched from conventional hydrocortisone to DR-HC. At baseline and after 12 months, glucose and insulin levels, surrogate estimates of insulin sensitivity, and hepatic steatosis were evaluated through ultrasonography and HSI. Results: At diagnosis, ultrasonography documented steatosis in 31 patients (68.8%) while 33 (73.3%) showed high HSI. Hydrocortisone (HC) dose (beta = 1.231, p = 0.010), insulin resistance index (HOMA-IR) (beta = 1.431, p = 0.002), and insulin sensitivity index (ISI)-Matsuda (beta = -1.389, p = 0.034) were predictors of HSI at baseline. After 12 months of DR-HC, a significant decrease in body mass index (BMI) (p = 0.008), waist circumference (WC) (p = 0.010), fasting insulin (p = 0.041), HOMA-IR (p = 0.047), HSI (p < 0.001) and number of patients with HSI > 36 (p = 0.003), and a significant increase in sodium (p < 0.001) and ISI-Matsuda (p = 0.031) were observed. HOMA-IR (beta = 1.431, p = 0.002) and ISI-Matsuda (beta = -9.489, p < 0.001) were identified as independent predictors of HSI at 12 months. Conclusions: In adults with SAI, DR-HC is associated with an improvement in HSI, regardless of the dose used, mainly related to an improvement in insulin sensitivity.