Single-Dose Hydrocortisone Therapy Outperforms Multiple-Dose Glucocorticoid Treatment

Research Findings

Recent studies indicate that a single-dose hydrocortisone therapy is more effective than conventional multiple-dose glucocorticoid therapy for patients with adrenal insufficiency. The research revealed that patients receiving a single dose of hydrocortisone experienced greater weight loss and a more significant reduction in HDL cholesterol compared to those undergoing standard treatment. Additionally, after 24 weeks, pro-inflammatory markers decreased, while CD16+CD14– monocyte levels increased.

Understanding Adrenal Insufficiency

Adrenal insufficiency, commonly referred to as Addison’s Disease, is a significant public health concern, impacting approximately 250 to 450 individuals per million. This condition arises when the adrenal glands fail to produce sufficient steroid hormones, such as cortisol. Symptoms often include weight loss, fatigue, muscle weakness, and low blood pressure. The causes of adrenal insufficiency are categorized into primary and secondary. Primary adrenal insufficiency is often due to adrenal failure, while secondary causes are linked to hypothalamo-pituitary failure.

Glucocorticoid Therapy and Its Challenges

Long-Term Treatment Needs

Adrenal insufficiency has a mortality rate of 1%, necessitating lifelong glucocorticoid replacement therapy for affected individuals. Treatment may require adjustments to address complications like weight gain and metabolic disturbances, such as elevated HbA1c levels, by modifying dosage.

Adverse Effects of Conventional Therapy

Typically, glucocorticoids are administered in small doses throughout the day. However, previous studies have highlighted issues such as bone loss and reduced quality of life among patients on this regimen. Moreover, high doses of glucocorticoids can impair immune function. Multiple dosing may disrupt the body’s natural cortisol rhythm, leading to potential complications.

Study Design

To investigate the impacts of a single-dose hydrocortisone therapy on body weight, metabolic health, and immune function, Isidori and colleagues conducted a 24-week randomized controlled trial across two university hospitals in Naples and Rome. Participants, aged 18 to 80 years with adrenal insufficiency, were transitioned from multiple-dose glucocorticoid therapy. The study involved 46 patients on single-dose hydrocortisone, 43 on standard glucocorticoid therapy, and 25 healthy controls.

Effectiveness of Single-Dose Hydrocortisone

Study Outcomes

At the study’s outset, both treatment groups exhibited higher body mass index (BMI), lipid levels, and inflammatory markers compared to healthy controls. After 24 weeks, those on the single-dose hydrocortisone therapy demonstrated more significant weight loss and lower HDL cholesterol levels than those on standard treatment.

Inflammatory Markers and Immune Response

By the 12-week mark, pro-inflammatory markers in the single-dose hydrocortisone group had decreased, with nearly a 50% reduction by week 24. Additionally, levels of CD16+CD14– monocyte immune cells, typically elevated in healthy individuals, increased in the single-dose group but not in the standard therapy group. Infection rates at 24 weeks were similar between healthy individuals and the single-dose group, though the latter reported slightly more infections. Despite these findings, the incidence of adverse events was comparable between both groups.

Conclusions and Limitations

Study Implications

The findings suggest that single-dose hydrocortisone therapy enhances the quality of life for patients with adrenal insufficiency compared to standard glucocorticoid therapy, as evidenced by improvements in body weight and immune response markers.

Study Limitations

However, the study had limitations, including participant awareness of their treatment type and self-reported infections without medical record verification, which could introduce bias. The observed improvements in immune response markers are specific to adrenal insufficiency, indicating that further research is necessary to explore the broader application of single-dose hydrocortisone therapy.

Reference

Isidori, A. M. et al. Effect of once-daily, modified-release hydrocortisone versus standard glucocorticoid therapy on metabolism and innate immunity in patients with adrenal insufficiency (DREAM): A single-blind, randomized controlled trial. The Lancet Diabetes and Endocrinology (2018). https://doi.org/10.1016/S2213-8587(17)30398-4