• Freek J H Sorgdrager, Jorien Werumeus Buning, Elske H Bos, André P Van Beek, and Ido P Kema.
• Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, RB Groningen, Netherlands.
• J. Clin. Endocrinol. Metab. 2018 Sep 1; 103 (9): 3411-3419.

ContextHydrocortisone (HC) treatment influences health-related quality of life (HRQOL) in secondary adrenal insufficiency (AI). Glucocorticoids regulate tryptophan metabolism through the kynurenine pathway, which modulates mood and energy homeostasis.ObjectiveThis study investigated whether tryptophan metabolism mediated the effect of HC dose on HRQOL in patients with secondary AI.Design, Setting, And PatientsForty-seven patients with secondary AI participated in this double-blind randomized controlled cross-over trial in the University Medical Center Groningen.InterventionPatients were treated for two 10-week periods with a daily HC dose of 0.2 to 0.3 mg/kg and 0.4 to 0.6 mg/kg body weight, respectively.Main Outcome MeasuresDiary data and questionnaires were used to assess HRQOL. Tryptophan, kynurenine and 3-hydroxykynurenine were measured in serum and dialyzed plasma and the kynurenine-to-tryptophan ratio (Kyn/Trp ratio) ratio was calculated.ResultsA higher dose HC was associated with increased levels of tryptophan (95% CI for mean difference 0.37 to 12.5, P = 0.038), reduced levels of kynurenine (95% CI, -0.49 to -0.10, P = 0.004) and 3-hydroxykynurenine (95% CI, -10.6 to -2.35, P = 0.003), and a reduced Kyn/Trp ratio (95% CI, -0.84 to -0.50, P < 0.001). The Kyn/Trp ratio mediated the effect of a higher dose HC on fatigue (P = 0.041) and physical functioning (P = 0.005).ConclusionMetabolism of tryptophan through the kynurenine pathway is reduced after a 10-week treatment with a higher dose HC and plays a role in the effect of HC on fatigue and physical functioning in patients with secondary AI.

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