Document Detail

Modulation of cortisol metabolism during treatment of acromegaly is independent of body composition and insulin sensitivity.
MedLine Citation:
PMID:  15004437     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: The set point of cortisol-cortisone conversion is shifted in the direction of cortisone by the inhibition of the activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) during adult GH replacement and in active acromegaly. Additionally, both fat mass and insulin may modulate 11beta-HSD1 and are both influenced by changes in GH status. This study examined the relative direct contribution of GH/IGF1 in modulating cortisol metabolism. METHODS: Overall cortisol/cortisone conversion (ratio of urine 11-hydroxy-/11-oxo-cortisol metabolites; Fm/Em), insulin sensitivity (homeostatic model assessment; HOMA %S) and fat mass (DXA) were examined in parallel in 6 patients (mean age 53 years, range 42-76; 4 males, 2 females) with previously untreated active acromegaly during 6 months of therapy with Sandostatin LAR (20-30 mg i.m. 4 weekly). All but 1 patient had normal ACTH reserve. RESULTS: At baseline, Pearson correlation demonstrated an inverse relationship between serum GH (mean of a 5-point day curve) and Fm/Em (r = -0.83, p = 0.04) and a trend towards an inverse relationship between HOMA %S and Fm/Em (r = -0.79, p = 0.06) but no other patterns were evident. During the course of treatment, serum GH decreased from 9.9 +/- 6.4 (mean +/- SD) to 3.5 +/- 3.1 ng/ml (p < 0.01) and serum IGF-1 from 785 +/- 268 to 431 +/- 156 ng/ml (p < 0.005). Fm/Em increased from 0.52 +/- 0.1 to 0.75 +/- 0.08 (p < 0.03) consistent with increased 11beta-HSD1 activity. There were no significant changes in truncal fat percentage (33.0 +/- 9.0 vs. 33.0 +/- 8.2) or insulin sensitivity (HOMA %S: 37.1 +/- 8.6 vs. 52.8 +/- 33.7). CONCLUSIONS: Modulation of cortisol metabolism during treatment of active acromegaly is dependent on changes in GH/IGF-1 status and is not influenced by any individual change in body composition or insulin sensitivity.
Giovanni V Frajese; Norman F Taylor; Paul J Jenkins; G Michael Besser; John P Monson
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Publication Detail:
Type:  Journal Article     Date:  2004-03-02
Journal Detail:
Title:  Hormone research     Volume:  61     ISSN:  0301-0163     ISO Abbreviation:  Horm. Res.     Publication Date:  2004  
Date Detail:
Created Date:  2004-04-15     Completed Date:  2004-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0366126     Medline TA:  Horm Res     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  246-51     Citation Subset:  IM    
Copyright Information:
Copyright 2004 S. Karger AG, Basel
Department of Endocrinology, St Bartholomew's Hospital, King's College Hospital, London, UK.
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MeSH Terms
11-beta-Hydroxysteroid Dehydrogenase Type 1 / metabolism
Acromegaly / blood,  drug therapy*,  metabolism*,  pathology
Adipose Tissue / pathology
Delayed-Action Preparations
Human Growth Hormone / blood
Hydrocortisone / metabolism*
Insulin / metabolism
Insulin-Like Growth Factor I / metabolism
Middle Aged
Octreotide / administration & dosage,  therapeutic use*
Osmolar Concentration
Reg. No./Substance:
0/Delayed-Action Preparations; 11061-68-0/Insulin; 12629-01-5/Human Growth Hormone; 50-23-7/Hydrocortisone; 67763-96-6/Insulin-Like Growth Factor I; 83150-76-9/Octreotide; EC Dehydrogenase Type 1

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