Trial reportScientific reports2026
Different metabolic pathways associated with total cortisol exposure and the cortisol time profile: a randomized crossover trial.
Trial report in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
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Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Excess cortisol exposure and disruption of its circadian pattern have both been linked to adverse health outcomes; however, whether distinct metabolic signatures differentiate total cortisol exposure from cortisol secretion dynamics remains unclear. This study aimed to identify metabolites and metabolic pathways uniquely associated with total cortisol exposure and/or variation of the cortisol time profile. In a randomized, 12-week, cross-over trial 18 adults with primary adrenal insufficiency (AI) received the same total daily dose of hydrocortisone (HC) administered as a once-daily (OD) dual-release tablet and conventional HC tablets 3 times daily (TID). Serum and urine samples were collected during 24h in-house standardized pharmacokinetic sampling days and metabolites were detected using liquid and gas chromatography-mass spectrometry (LC-MS and GC-MS). Total cortisol exposure was quantified as the area under the serum cortisol concentration-time curve and variability in the cortisol time profile was assessed by calculating the lag–1 autocorrelation from serum cortisol concentrations over 24 hours. Compared with OD dosing, TID administration resulted in a 20% higher total cortisol exposure and a greater variability in the cortisol time profile. In total, 2406 metabolites were detected. Pathway analysis of serum metabolites uniquely correlated with total cortisol exposure were involved in amino acid metabolism - including arginine, tryptophan and glutamate pathways - as well as glycerolipid metabolism. In contrast, metabolites uniquely associated with variability of the cortisol time profile were mapped to primary bile acid biosynthesis and cysteine-methionine metabolism. We identified distinct groups of metabolites and metabolic pathways that specifically correlate with either overall serum cortisol exposure or variability in its time profile, indicating that cortisol dose exposure and the circadian dynamics may exert independent metabolic and regulatory effects in humans, with potential implications for personalized hydrocortisone therapy.
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