Hydrocortisone Affects Fatigue and Physical Functioning Through Metabolism of Tryptophan: A Randomized Controlled Trial

Freek J. H. Sorgdrager, Jorien Werumeus Buning, Elske H. Bos, André P. Van Beek, Ido P. Kema

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Abstract

Context: Hydrocortisone (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.

Objective: This study investigated whether tryptophan metabolism mediated the effect of HC dose on HRQOL in patients with secondary AI.

Design, Setting and Patients: Forty-seven patients with secondary AI participated in this double-blind randomized controlled cross-over trial in the University Medical Center Groningen.

Intervention: Patients were treated for two 10-week periods with a daily HC dose of 0.2 - 0.3 mg and 0.4 - 0.6 mg/kg body weight, respectively.

Main outcome measures: Diary 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 (kyn/trp) ratio was calculated.

Results: A higher dose HC was associated with increased levels of tryptophan (95% CI for mean difference 0.37 to 12.5, p= .038), reduced levels of kynurenine (95% CI -0.49 to -0.10, p= .004) and 3-hydroxykynurenine (95% CI -10.6 to -2.35, p= .003) and a reduced kyn/trp ratio (95% CI -0.84 to -0.50, p < .001). The kyn/trp ratio mediated the effect of a higher dose HC on fatigue (p = .041) and physical functioning (p = .005).

Conclusion: Metabolism 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.

Original languageEnglish
Pages (from-to)3411-3419
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume103
Issue number9
Early online date2-Jul-2018
DOIs
Publication statusPublished - Sep-2018

Keywords

  • QUALITY-OF-LIFE
  • ADRENAL INSUFFICIENCY
  • KYNURENINE PATHWAY
  • ADDISONS-DISEASE
  • DEPRESSION SCALE
  • HOSPITAL ANXIETY
  • BRAIN
  • HEALTH
  • BLOOD
  • GLUCOCORTICOIDS

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