HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) All Versions of this Article: EJE-09-0315v1 161/3/375    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sigurjonsdottir, H. Articles by Walker, B. Search for Related Content PubMed PubMed Citation Articles by Sigurjonsdottir, H. Articles by Walker, B.

Lack of regulation of 11β-hydroxysteroid dehydrogenase type 1 during short term manipulation of growth hormone in patients with hypopituitarism

H Sigurjonsdottir, Medicine, University of Gothenburg, Gothenburg, Sweden
R Andrew, Centre for Cardiovascular Science, University of Edinburgh,, Edinburgh , United Kingdom
R Stimson, Centre for Cardiovascular Science, University of Edinburgh,, Edinburgh , United Kingdom
G Johannsson, Medicine, University of Gothenburg, Gothenburg, Sweden
B Walker, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, United Kingdom

Correspondence: Brian Walker, Email: b.walker{at}ed.ac.uk

Objective: Evidence from long-term clinical studies measuring urinary steroid ratios suggests that growth hormone (GH) administered for longer than 2 months down-regulates 11β-HSD1, thereby reducing cortisol regeneration in liver and adipose tissue. We aimed to measure acute effects of GH on 11β-HSD1 in liver and adipose tissue in vivo, including using a stable isotope tracer.

Design: Observational study of GH withdrawal and re-introduction in patients with hypopituitarism.

Methods: 12 men with benign pituitary disease causing GH and ACTH deficiency on stable replacement therapy for >6 months were studied after GH withdrawal for 3 weeks, and after either placebo or GH injections were re-introduced for a further 3 weeks. We measured cortisol kinetics during d4-cortisol infusion, urinary cortisol/cortisone metabolite ratios, liver 11β-HSD1 by appearance of plasma cortisol after oral cortisone, and 11β-HSD1 mRNA levels in subcutaneous adipose biopsies.

Results: GH withdrawal and re-introduction had no effect on d3-cortisol appearance, urinary cortisol/cortisone metabolite ratios, initial appearance of cortisol after oral cortisone, or adipose 11β-HSD1 mRNA. GH withdrawal increased plasma cortisol 30-180 minutes after oral cortisone, increased d4-cortisol clearance, and decreased relative excretion of 5-reduced cortisol metabolites.

Conclusions: In this setting, GH did not regulate 11β-HSD1 rapidly in vivo in humans. Altered cortisol metabolism with longer term changes in GH may reflect indirect effects on 11β-HSD1. These data do not suggest that glucocorticoid replacement doses need to be increased immediately after introducing GH therapy to compensate for reduced 11β-HSD1 activity, although dose adjustment may be required in the longer term.