Document Detail

Effects of growth hormone replacement on cortisol metabolism in hypopituitary patients treated with cortisone acetate.
MedLine Citation:
PMID:  11465341     Owner:  NLM     Status:  MEDLINE    
Growth hormone (GH) replacement may inhibit 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) activity, resulting in diminished conversion of cortisone to cortisol. Moreover, GH replacement may lower bioavailability of hydrocortisone tablets. Therefore, substitution therapy with cortisone acetate could be disadvantageous during GH replacement. We conducted a randomized, placebo-controlled GH replacement (1 to 2 U GH/day) study during 6 months, followed by a 6-month open extension study (2U GH/day). Twelve men and 12 women with GH deficiency, of whom 17 received cortisone acetate (25 to 37.5 mg/day), participated. Eight patients were randomized to placebo initially. At baseline, after 6 and 12 months, urinary cortisol and cortisone metabolites were measured. No changes in urinary cortisol metabolites were observed after 6 months placebo (n=8). After 6 months GH the urinary (tetrahydrocortisol+allotetrahydrocortisol)/tetrahydrocortison ratio ((THF+alloTHF)/THE ratio) was unaltered in cortisone acetate treated patients (n = 17) and in patients with intact adrenal function (n = 7), whereas after 12 months GH the (THF + alloTHF)/THE ratio decreased only in cortisone acetate treated patients (1 dropout, n=9). Urinary THF and alloTHF were higher in cortisone acetate treated patients than in patients with intact adrenal function before GH and remained so after 12 months GH (p < 0.05 to p < 0.01). The sum of cortisol + cortisone metabolites did not change after GH in either group. The urinary free cortisol/free cortisone ratio, presumably reflecting renal 11betaHSD2 activity, tended to decrease in cortisone acetate treated patients (p<0.07 and p<0.05 after 6 and 12 months GH, respectively), as well as in patients with intact adrenal function (p<0.05 and a decrease in five/six patients after 6 and 12 months GH, respectively). In conclusion, these results suggest that GH replacement decreases 11betaHSD1 activity, which becomes manifest in patients receiving cortisone acetate substitution therapy. 11betaHSD2 activity is unaltered or may even be increased. It is unlikely that the bioavailability of conventional doses of cortisone acetate is impaired after GH replacement.
J A Beentjes; M N Kerstens; R P Dullaart
Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Scandinavian journal of clinical and laboratory investigation     Volume:  61     ISSN:  0036-5513     ISO Abbreviation:  Scand. J. Clin. Lab. Invest.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-07-23     Completed Date:  2001-12-12     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0404375     Medline TA:  Scand J Clin Lab Invest     Country:  Norway    
Other Details:
Languages:  eng     Pagination:  277-86     Citation Subset:  IM    
Department of Endocrinology, University Hospital Groningen, The Netherlands.
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MeSH Terms
11-beta-Hydroxysteroid Dehydrogenase Type 1
Cortisone / administration & dosage*,  analogs & derivatives*,  pharmacokinetics
Human Growth Hormone / administration & dosage*
Hydrocortisone / urine*
Hydroxysteroid Dehydrogenases / metabolism
Hypopituitarism / drug therapy*,  metabolism*
Middle Aged
Water / metabolism
Reg. No./Substance:
12629-01-5/Human Growth Hormone; 50-04-4/cortisone acetate; 50-23-7/Hydrocortisone; 53-06-5/Cortisone; 7732-18-5/Water; EC 1.1.-/Hydroxysteroid Dehydrogenases; EC Dehydrogenase Type 1; EC protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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