Improving outcomes in patients with adrenal insufficiency: a review of current and future treatments

Abstract

Introduction:

Adrenal insufficiency is a rare but life-threatening disease. Conventional therapy consists of glucocorticoid replacement using hydrocortisone administered two or three times daily. Although such therapy extends life expectancy, mortality is not normalized, and quality of life remains poor. This failure to restore normal health is thought to be due to the inability of conventional glucocorticoid replacement therapy to normalize total cortisol exposure and to respond to the increased need for glucocorticoids during illness and stress. Also, current management regimens do not restore or replicate the intrinsic circadian rhythm of cortisol secretion.

Areas covered:

This narrative review was based on a PubMed and Medline search of all English-language articles on the safety and efficacy of glucocorticoid replacement therapy in patients with adrenal insufficiency. Based on this search we discuss current treatment strategies in terms of the failure to maintain or normalize metabolism and quality of life in patients with adrenal insufficiency. The rationale for, and technology behind, the development of modified-release preparations of hydrocortisone are described, together with the evidence suggesting that hydrocortisone preparations that mimic the physiological circadian pattern of cortisol release are more effective than conventional glucocorticoid replacement therapies.

Conclusions:

Modified-release hydrocortisone treatments for patients with adrenal insufficiency more closely mimic the physiological circadian pattern of cortisol secretion than conventional twice or thrice daily treatment. The available evidence suggests that these modified-release preparations should improve metabolic outcomes and quality of life.

Keywords::

• Adrenal insufficiency
• Cortisol
• Drug delivery
• Glucocorticoid replacement
• Hydrocortisone

Transparency

Declaration of funding

Editorial assistance was provided with financial support from ViroPharma Ltd.

Declaration of financial/other relationships

G.J. has disclosed that he is a consultant for ViroPharma and AstraZeneca and has received lecture fees from Pfizer. G.J., H.L. and S.S. have disclosed that they have equity interests in Pulsetten AB. M.Q. and P.M.S. have disclosed that they have received fees for consultancy, travel grants and honoraria from ViroPharma.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors thank Dr David Campbell for editorial help in developing the manuscript and collating all author amendments at draft stage.

Notes

*Plenadren is a registered trade name of ViroPharma SPRL, Brussels, Belgium

*;Chronocort is a registered trade name of Diurnal Ltd, Cardiff, UK