Effects of standard glucocorticoid replacement therapies on subjective well-being: a randomized, double-blind, crossover study in patients with secondary adrenal insufficiency

Abstract

Objective: For secondary adrenal insufficiency (SAI), established biochemical parameters for dosage control are lacking and no optimal substitution dosage and daily distribution have been determined yet. Therefore, in clinical practice, the individual total dose is often adjusted based on patients' subjective well-being. Design: Effects of three standard glucocorticoid replacement regimens on psychological variables were assessed in patients with SAI based on a randomized double-blind study design. Methods: SAI patients (nZ18) were treated with three different established glucocorticoid replacement regimens in a randomized, double-blind, crossover study (treatment A, hydrocortisone 10 mg-placebo-5 mg-placebo; treatment B, hydrocortisone 10 mg-5 mg-placebo-5 mg; and treatment C, prednisone 5 mg-placebo-placebo-placebo). Following each 4-week replacement regimen, quality of life (SF-36) and emotional distress (brief symptom inventory (BSI)) were assessed along with diurnal changes in current well-being (Bf-S) and alertness (Stanford Sleepiness Scale (SSS)) using validated questionnaires, and additionally compared with patient (patients with pituitary disease and adrenal sufficiency) and healthy control groups. Results: SAI patients showed improvements in physical quality of life (i.e. SF-36 physical function, P!0.05; physical role function, P!0.05) and current well-being (at 1800 h, P!0.05) under treatment A (hydrocortisone 10-0-5-0 mg) compared with the other replacement regimens. Quality of life and current well-being were significantly impaired compared with healthy controls but did not differ from patient controls. Conclusions: Although the observed improvements in psychological parameters were comparatively small, our results indicate beneficial effects of a 10-0-5-0 mg hydrocortisone replacement regimen. Nevertheless, treatment effects were insufficient to restore subjective health compared with healthy controls, indicating the need for improved replacement regimens and supportive psychosocial interventions in SAI patients.

The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients

“…In two cross-sectional studies from Germany including more than 200 patients with both primary and secondary AI, patients on HC doses exceeding 30 mg/day had more severely impaired QoL compared with patients on lower doses (7,8). Our results, showing a dose-related association with measures of QoL, are in accordance with these (7,8) and other previous smaller studies (15,21). The results are also in line with a study on 2424 hypopituitary patients from the KIMS database where the impact of GC replacement on cardiovascular risk factors was analysed (11).…”

“…In a recent survey including Higher GC doses are also associated with more severe impairments of subjective health status in patients with AI (7,8). In a randomised, double-blind, crossover study including 18 patients with secondary AI, treatment with 10C5 mg of hydrocortisone (HC) had more favourable effects on well-being than treatment with either 10C5C 5 mg of HC or 5 mg of prednisolone (15). Also, recent findings suggest that changed GC exposure time profile achieved with a HC dual-release formulation has a beneficial effect on QoL compared with conventional HC replacement (16).…”

Psychological morbidity and impaired quality of life in patients with stable treatment for primary adrenal insufficiency: cross-sectional study and review of the literature

“…Our findings regarding QoL are in line with the results of previous studies on decreased QoL in patients with AI (9,14,36,37) and the self-reported impact of the disease or treatment on subjective health status (38). In addition, Association between hydrocortisone dosage and identity problems.…”

“…In addition, Association between hydrocortisone dosage and identity problems. (11,37,39,40). Accordingly, we found negative effects of high hydrocortisone intake on QoL in patients with PAI.…”

Group 4: Replacement therapy for adrenal insufficiency

“…Finally, Benson et al evaluated the impact on quality of life of 3 different regimens (hydrocortisone 10/0/5/0 vs. hydrocortisone 10/5/0/5 vs. prednisone 5 mg in the morning) in a randomised, double-blind crossover study on 12 patients. After 4 weeks of treatment, there was an improvement in quality of life measures in patients using the first treatment regimen, and more pronounced in the afternoon [24]. In contrast, Alonso et al found no significant difference in quality of life measures when they compared two regimens (20-0-20 mg/day vs. 10-5-5 mg/day) in a three-month prospective crossover study of 12 patients, though the hydrocortisone dosage was elevated in both treated groups [25].…”