The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure

Research output: Contribution to journalArticle

Authors

  • Lucy Ann Behan
  • Mark J Hannon
  • Christopher J Thompson
  • Robert D Murray
  • Nicola Crabtree
  • Beverly A Hughes
  • Amar Agha
  • Paul M Stewart

Abstract

CONTEXT: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy.

OBJECTIVE: To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.

DESIGN AND PATIENTS: We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE.

SETTING: Endocrine Centres within University Teaching Hospitals in the UK and Ireland.

MAIN OUTCOME MEASURES: Urinary corticosteroid metabolite profile and body composition assessment.

RESULTS: In study A, when patients were divided into three groups - patients not receiving HC and patients receiving HC≤20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5α-THF/THE ratios when compared to controls.

CONCLUSIONS: In ACTH-deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.

Details

Original languageEnglish
Pages (from-to)583-93
Number of pages11
JournalEuropean Journal of Endocrinology
Volume173
Issue number5
Early online date11 Aug 2015
Publication statusPublished - Nov 2015