Endocrine Abstracts

Background: Replicating the physiological cortisol secretion is key in treatment of glucocorticoid insufficient individuals. A sub-optimal replication may explain the impaired quality of life experienced by these individuals. The study investigates fatigue measured by ecological momentary assessments in patients treated with conventional hydrocortisone compared with a once-daily dual-release formula of hydrocortisone (Plenadren) that follows the cortisol physiology more closely.

Methods: The 21-week open-label switch pilot trial included patients with adrenal insufficiency due to hypopituitarism (n = 27). While treated with their usual hydrocortisone regimen, fatigue was assessed four times daily for 20 days using a momentary item version of the Multidimensional Fatigue Inventory. Participants switched treatment to an identical daily dose of Plenadren. The intervention period was 16 weeks and was concluded with repeating the fatigue assessments for 20 days.

Results: On four out of five fatigue subscales, we found statistically significant yet modest treatment effects. Fatigue was reduced 0.7–1.1 points, on a scale ranging from 4–20, when treated with Plenadren compared with conventional hydrocortisone. Changes corresponded to small effect sizes but were below scale-specific minimal important changes. We found larger between-person variances and smaller within-person variances when treated with Plenadren. On an individual level, nine participants (one third) experienced improvements above the minimal important change whereas four participants deteriorated. The method of ecological momentary assessment could furthermore detect a significant diurnal curve of fatigue, and a visual change of the pattern between conventional hydrocortisone and Plenadren.

Conclusion: The Plenadren-related reduction in fatigue was significant but not necessarily of clinical importance when looking at group level. However, there was a large inter-individual treatment effect, why patients with great benefit in quality of life should be identified. Furthermore, the method of ecological momentary assessments was highly suitable for studying fatigue in this patient population.