The effects of growth hormone deficiency and replacement on glucocorticoid exposure in hypopituitary patients on cortisone acetate and hydrocortisone replacement
Swords, F.M., Carroll, P.V., Kisalu, J., Wood, P.J., Taylor, N.F. and Monson, J.P. (2003) The effects of growth hormone deficiency and replacement on glucocorticoid exposure in hypopituitary patients on cortisone acetate and hydrocortisone replacement. Clinical Endocrinology (Oxf), 59, (5), 613-620. (doi:10.1046/j.1365-2265.2003.01894.x).
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Objective 11?-hydroxysteroid dehydrogenase type 1 (11?HSD1) converts inactive cortisone to active cortisol. 11?HSD1 activity is increased in GH deficiency and inhibited by GH and IGF-I in acromegaly. However it is not known whether these changes in cortisol metabolism exert significant effects during hydrocortisone therapy, and the effect has not been studied in patients taking cortisone acetate. We have studied the effect of GH induced 11?HSD1 inhibition in hypopituitary adults with severe GH deficiency to determine whether this inhibition has a different magnitude of effect when patients are taking different forms of glucocorticoid replacement therapy.
Design, patients and measurements We have taken the ratio of 11-hydroxy/11-oxo cortisol metabolites (Fm/Em), an established measure of net 11?HSD activity to reflect the likely balance of cortisol to cortisone exposure in tissues expressing 11?HSD1, principally the liver and adipose tissue. We recruited 10 hypopituitary adults all on established glucocorticoid replacement therapy, but who were not receiving GH. Patients were treated with their standard hydrocortisone therapy for one week and an equivalent dose of cortisone acetate in its place for one week in random order. Serial serum cortisol assessments and urine steroid profiles were performed on each treatment. All patients were then established on GH therapy for at least three months before the two-week cycle was repeated. Fm/Em was also measured in a control population (20F, 20M).
Results Prior to GH, the ratio Fm/Em was greater with hydrocortisone compared with cortisone acetate replacement (1·17 ± 0·28 and 0·52 ± 0·09 respectively, P < 0·001) or with normal subjects (normal males: 0·81 ± 0·24, females 0·66 ± 0·14). Following GH replacement Fm/Em fell in patients on hydrocortisone and cortisone acetate (Pre-GH: 0·84 ± 0·40, Post-GH: 0·70 ± 0·34, P < 0·05) confirming the inhibition of 11?HSD1 by GH/IGF-I. Conversely, the ratio of urinary free cortisol/cortisone did not change indicating unchanged 11?HSD2 activity. Mean circulating cortisol also fell in all subjects after GH. This effect was greater during cortisone acetate treatment (?18·7%, P < 0·0001), than during hydrocortisone replacement (?10·9%, P < 0·05).
Conclusions Our data suggest that tissue exposure to glucocorticoid is supra-physiological in hypopituitary patients with untreated GH deficiency taking hydrocortisone replacement therapy. This situation is ameliorated by GH replacement therapy. However, local and circulating cortisol concentrations are more vulnerable to the inhibitory effect of GH on 11?HSD1 in patients taking cortisone acetate, such that serum cortisol assessments should be made in patients taking cortisone acetate after GH therapy to ensure that glucocorticoid replacement remains adequate.
|Digital Object Identifier (DOI):||doi:10.1046/j.1365-2265.2003.01894.x|
|Keywords:||therapy, aged, prospective studies, metabolism, middle aged, humans, deficiency, population, activity, comparative study, endocrinology, cortisone, hydrocortisone|
|Subjects:||R Medicine > RG Gynecology and obstetrics
Q Science > QR Microbiology
|Divisions :||University Structure - Pre August 2011 > School of Medicine > Developmental Origins of Health and Disease
University Structure - Pre August 2011 > School of Medicine > Community Clinical Sciences
University Structure - Pre August 2011 > School of Medicine
|Accepted Date and Publication Date:||
|Date Deposited:||08 Sep 2008|
|Last Modified:||31 Mar 2016 12:42|
|RDF:||RDF+N-Triples, RDF+N3, RDF+XML, Browse.|
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