Endocrine Abstracts

Background: Secondary adrenal insufficiency is usually treated with hydrocortisone replacement therapy twice or thrice daily in varying doses to mimic the physiological rhythm of cortisol release. However, despite efforts to optimize treatment regimens patients report impaired quality of life (QoL), including important aspects such as fatigue. A possible explanation is a suboptimal imitation of cortisol release resulting in an inadequate substitution at certain times during the day. Such subtle variations are difficult to capture by standard, retrospective QoL questionnaires. The objective of this study was to investigate short-term variability of fatigue in patients with secondary adrenal insufficiency using ecological momentary assessments.

Methods: Thirty-one patients with pituitary insufficiency in steady twice- or thrice-daily hydrocortisone replacement therapy and replacement of other pituitary insufficiencies were included. The majority were males (27/31) with a median age of 63 years (range: 38–76 years). For 20 days participants answered questions about their current fatigue levels four times daily at semi-randomized time points. Questions were administered by a smartphone application and consisted of a momentary version of the Multidimensional Fatigue Inventory (MFI-20). The questionnaire comprised 20 items organized in five scales, each containing four items. Each scale score ranges from 4 to 20, with higher scores indicating more fatigue. Analysis of variance and analysis of temporal patterns were performed using mixed models for repeated measurements.

Results: The response rate of ecological momentary assessments was 80 percent. General Fatigue and Reduced Motivation varied considerably for each participant (within-person variances of 8.9 and 8.8, respectively (Intraclass correlation coefficients (ICC): 0.53 and 0.50, respectively)). Mental and Physical Fatigue showed the most stable within-person patterns (within-person variances of 3.7 and 5.8, respectively (ICC: 0.73 and 0.70, respectively)). A significant diurnal variation of momentary fatigue was shown (P<0.001) with lowest levels in the morning and increasing levels across the day.

Conclusion: Findings indicate that fatigue in patients with secondary adrenal insufficiency varies considerably over short time periods, especially when measuring General Fatigue and Reduced Motivation. Ecological momentary assessment is thus a promising tool for individual profiling to customize timing and dosing of hydrocortisone replacement therapy.