Beneficial effects of replacement therapy with modified-release hydrocortisone in patients with adrenal insufficiency

Context Patients with primary adrenal insufficiency (PAI) or congenital adrenal hyperplasia (CAH) receive life-long glucocorticoid (GC) therapy. Daily GC doses are often above the physiological cortisol production rate and can cause long-term morbidities such as osteoporosis. No prospective trial has investigated the long-term effect of different GC therapies on bone mineral density (BMD) in those patients. Objectives To determine if patients on hydrocortisone (HC) or prednisolone show changes in BMD after follow-up of 5.5 years. To investigate if BMD is altered after switching from immediate- to modified-release HC. Design and patients Prospective, observational, longitudinal study with evaluation of BMD by DXA at visit1, after 2.2 ± 0.4 (visit2) and after 5.5 ± 0.8 years (visit3) included 36 PAI and 8 CAH patients. Thirteen patients received prednisolone (age 52.5 ± 14.8 years; 8 women) and 31 patients received immediate-release HC (age 48.9 ± 15.8 years; 22 women). Twelve patients on immediate-release switched to modified-release HC at visit2. Results Prednisolone showed significantly lower Z-scores compared to HC at femoral neck (−0.85 ± 0.80 vs −0.25 ± 1.16, P < 0.05), trochanter (−0.96 ± 0.62 vs 0.51 ± 1.07, P < 0.05) and total hip (−0.78 ± 0.55 vs 0.36 ± 1.04, P < 0.05), but not at lumbar spine, throughout the study. Prednisolone dose decreased by 8% over study time, but no significant effect was seen on BMD. BMD did not change significantly after switching from immediate- to modified-release HC. Conclusions The use of prednisolone as hormone replacement therapy results in significantly lower BMD compared to HC. Patients on low-dose HC replacement therapy showed unchanged Z-scores within the normal reference range during the study period.

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Corticosteroid Replacement Therapy

10.5772/intechopen.98803 ◽

2021 ◽

Author(s):

Michael C. Onyema

Keyword(s):

Clinical Trials ◽

Adrenal Insufficiency ◽

Replacement Therapy ◽

20Th Century ◽

Hormone Replacement ◽

Modified Release ◽

Future Treatment ◽

Release Drug ◽

Treatment Considerations ◽

Special Circumstances

The advent of synthetic corticosteroids in the 20th century provided a vital breakthrough in the management of adrenal insufficiency. In this chapter we review the main indications and guidance for appropriate hormone replacement and also look into the management of therapy during special circumstances. For decades hydrocortisone has remained the cornerstone for glucocorticoid replacement but we explore the alternatives including recently introduced modified-release drug preparations and the future treatment considerations currently undergoing research and pre-clinical trials.

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Comparison of Various Glucocorticoid Replacement Regimens Used in Chronic Adrenal Insufficiency: A Systematic Review

Dubai Diabetes and Endocrinology Journal ◽

10.1159/000508321 ◽

2020 ◽

Vol 26 (2) ◽

pp. 50-68

Author(s):

Nduku Kiko ◽

Atul Kalhan

Keyword(s):

Systematic Review ◽

Adrenal Insufficiency ◽

Replacement Therapy ◽

Clinical Outcomes ◽

Modified Release ◽

Prednisolone Therapy ◽

Glucocorticoid Replacement Therapy ◽

Cv Disease ◽

The Impact

Objective: Patients with adrenal insufficiency require life-long glucocorticoid replacement therapy. Hydrocortisone (15–30 mg/day) and prednisolone (3–7.5 mg/day) are the preferred agents used although there is a lack of consensus among endocrinologists regarding the impact of different steroid regimens on quality of life, bone metabolism, cardiometabolic outcomes, adrenal crisis and infections. We carried out a retrospective systematic review of the literature to compare the efficacy and side effects of various glucocorticoid replacement regimens in patients with chronic adrenal insufficiency. Methods: We searched PubMed, Cochrane Reviews and Google Scholar databases up to March 14, 2019, for studies evaluating various clinical outcomes with glucocorticoid replacement therapy. The abstracts and full studies were appraised and data extracted from the eligible studies. The quality of evidence was evaluated and risk of bias carried out. Results: A total of 47 studies including 9 randomised controlled trials (RCTs) and 38 observational studies were evaluated in this systematic review. Prednisolone therapy was observed to be safe as well as efficacious as hydrocortisone although a higher dose was associated with an increased risk of cardiovascular (CV) disease. A lower hydrocortisone dose (15–20 mg/day) was associated with a reduction of blood pressure and improved clinical outcomes although this observation was based on a solitary RCT. Modified release hydrocortisone was observed to reduce the risk of CV disease based upon results from 2 of the RCTs. However, there was no conclusive evidence of benefit of modified release hydrocortisone and continuous subcutaneous hydrocortisone infusion in improving subjective health status. Conclusion: Prednisolone therapy remains a safe and efficacious alternative to hydrocortisone although there are concerns of dyslipidaemia and CV disease with higher doses. There is limited level I evidence suggestive of a positive effect of modified release hydrocortisone on CV and metabolic outcomes, particularly weight reduction.

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