Self-perceived morning well-being and diurnal mood variation. (Left panel) Bar-charts showing each treatment group’s mean scores (with the corresponding S.D.) in the 5 subscales of the Identity-consequence fatigue scale (ICFS). The table underneath presents the p-values of the pairwise comparisons. Ratings of vigour where markedly higher in the subcutaneous-continuous treatment group (SCC) compared to the other modes of hydrocortisone replacement. Moreover, ratings of distraction were significantly lower (i.e. the ability to concentrate was higher) in the SCC compared to the subcutaneous-pulsatile treatment group (SCP). Similarly, with ratings of fatigue. There was no good evidence for an effect of treatment on ICFS ratings related to motivation or activity. To improve clarity, all values have been reversed [5-(ICFS score)]. (Right panel) The diurnal mood variation (100: maximally positive mood, − 100: maximally negative mood) was constructed by subtracting the negative mood ratings from the corresponding positive mood ratings (as estimated by the self-perceived reactivity and well-being items contained in the ecological momentary assessment, see Supplementary Materials and Methods) of days 3 and 4 of each subject and treatment arm. This approach has been suggested by prior research (Basabe et al., 2002). In SCC, mood changes are following the circadian glucocorticoid rhythm, possibly with a small delay. The best mood of the day occurs just before midday. On the contrary, when exposed to a tightly controlled, pulsatile (ultradian) glucocorticoid rhythm (SCP), the diurnal mood variation is dissociated from the hormone’s circadian profile and the best mood of the day occurs in the evening. Finally, when exposed to a non-physiological ultradian glucocorticoid rhythm, characterised by infrequent and inconsistent pulses and minimal glucocorticoid availability over the night sleep (PO), the diurnal mood variation is less pronounced, compared to the other modes of hydrocortisone bioavailability. CI: confidence intervals, PO: oral treatment group, S.D.: standard deviation.