Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy

Abstract

SummaryGlucocorticoid replacement therapy in patients with adrenal insufficiency (AI), whether primary (Addison's disease) or secondary (due to hypopituitarism), has been established for some 50 years. The current standard treatment regimen involves twice-or thrice-daily dosing with a glucocorticoid, most commonly oral hydrocortisone. Based on previous small-scale studies and clinical perception, life expectancy with conventional glucocorticoid replacement therapy has been considered normal, with a low incidence of adverse events. Data from the past 10-15 years, however, have shown that morbidity remains high and life expectancy is reduced. The increased morbidity and decreased life expectancy appear to be due to both increased exposure to cortisol and insufficient cortisol coverage during infections and other stress-related events. This is thought to reflect a failure of treatment to replicate the natural circadian rhythm of cortisol release, together with a failure to identify and deliver individualized cortisol exposure and to manage patients adequately when increased doses are required. The resulting over-or under-treatment may result in Cushing-like symptoms or adrenal crisis, respectively. This review summarizes the morbidity and mortality seen in patients receiving the current standard of care for AI and suggests areas for improvement in glucocorticoid replacement therapy.

Transplantation of bovine adrenocortical cells encapsulated in alginate

“…Glucocorticoids are secreted following a circadian rhythm with the highest peak in the morning and the nadir at night. This circadian rhythm is complicated to replicate by current enteral/parenteral replacement therapies with synthetic glucocorticoids, and patients thereby suffer from a poor quality of life and increased mortality (29). Even more challenging is the treatment of adrenal insufficiency in childhood, where daily doses must be additionally adjusted to growth.…”

Systemic High-Dose Corticosteroid Treatment Does Not Improve the Outcome of Ipilimumab-Related Hypophysitis: A Retrospective Cohort Study

“…Since this was a retrospective study, biochemical testing and imaging were not done at fixed, controlled intervals. Replacement dose corticosteroids was defined as a daily dose not higher than 30 mg hydrocortisone or equivalent (16), except in 2 patients who were transiently exposed to 60 mg hydrocortisone for 2–3 days following sick-day guidelines. Systemic high-dose corticosteroid treatment was defined as the administration of corticosteroids at a dose of more than 30 mg hydrocortisone (or equivalent) daily for more than one week during the course of ipilimumab treatment and/or at the time of onset of hypophysitis.…”

Hydrocortisone Dose Influences Pain, Depressive Symptoms and Perceived Health in Adrenal Insufficiency: A Randomized Controlled Trial

“…Current HC dosing schemes are the result of a complex balancing of factors including the endogenous cortisol production as documented in healthy individuals, variation in plasma cortisol in relation to the HC substitution dose, and the risks and benefits of applying (long-term) higher or lower dosing schemes [2,4,5,6]. Health-related quality of life (HRQoL) is another important issue in the individualization of the dosing scheme.…”

“…A few controlled studies have assessed HRQoL in relation to HC dose. All studies were small and applied different HC regimens, often with changes to both timing and dosing [6]. These studies produced variable results, with increases [11], no change [12,13] or decreases [14] in QoL being reported with higher doses of GCs.…”