Modulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients.
Affiliation
Department of Endocrinology, Christie Hospital, Manchester, United Kingdom.Issue Date
2000-04
Metadata
Show full item recordAbstract
11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) functions as a net reductase converting cortisone to cortisol. GH inhibits 11beta-HSD1, resulting in a shift in cortisol metabolism favoring cortisone, an observation that may have significance in patients with ACTH deficiency who are unable to compensate for such changes. We have studied the effect of three doses of GH replacement (0.17, 0.33, and 0.5 mg each given for 12 weeks in ascending order) on cortisol metabolism in nine patients, aged 62-70 yr, with hypopituitarism who were receiving fixed doses of oral hydrocortisone. Serum insulin-like growth factor I levels rose in a dose-dependent manner over the course of the study. Fat mass decreased significantly at 24 weeks (P = 0.02), a change that was maintained at 36 weeks. Fasting serum insulin levels did not change significantly over the course of the study. The ratio of urine cortisol to cortisone metabolites (Fm/Em) fell significantly at 12 weeks (GH dose, 0.17 mg/day) from 1.32 (0.91-2.20) at baseline to 1.08 (0.89-2.11) (P < 0.05). Although it did not fall further as the dose of GH was increased, the reduction in the Fm/Em ratio persisted at 24 weeks (GH dose, 0.33 mg/day), 1.09 (0.8-2.11) (P < 0.05 vs. baseline), and 36 weeks (GH dose, 0.5 mg/day), 1.19 (0.82-2.31) (P < 0.05 vs. baseline). The Fm/Em ratio did not correlate with serum insulin-like growth factor I, fat mass, or fasting insulin levels at any time during the study. This study confirms the inhibitory effect of GH on 11beta-HSD1 but has shown that the effect occurs maximally at very low GH doses and is not mediated indirectly by change in circulating insulin. Patients with partial or total ACTH deficiency, in whom cortisol replacement is suboptimal, may be at risk of the clinical manifestations of cortisol deficiency when they are commenced on GH therapy.Citation
Modulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients. 2000, 85 (4):1727-30 J. Clin. Endocrinol. Metab.Journal
The Journal of Clinical Endocrinology and MetabolismDOI
10.1210/jc.85.4.1727PubMed ID
10770221Type
ArticleLanguage
enISSN
0021-972Xae974a485f413a2113503eed53cd6c53
10.1210/jc.85.4.1727
Scopus Count
Collections
Related articles
- Growth hormone, insulin-like growth factor-I and the cortisol-cortisone shuttle.
- Authors: Stewart PM, Toogood AA, Tomlinson JW
- Issue date: 2001
- The effects of growth hormone deficiency and replacement on glucocorticoid exposure in hypopituitary patients on cortisone acetate and hydrocortisone replacement.
- Authors: Swords FM, Carroll PV, Kisalu J, Wood PJ, Taylor NF, Monson JP
- Issue date: 2003 Nov
- The effect of growth hormone replacement therapy on cortisol-cortisone interconversion in hypopituitary adults: evidence for growth hormone modulation of extrarenal 11 beta-hydroxysteroid dehydrogenase activity.
- Authors: Gelding SV, Taylor NF, Wood PJ, Noonan K, Weaver JU, Wood DF, Monson JP
- Issue date: 1998 Feb
- Growth hormone replacement inhibits renal and hepatic 11 beta-hydroxysteroid dehydrogenases in ACTH-deficient patients.
- Authors: Walker BR, Andrew R, MacLeod KM, Padfield PL
- Issue date: 1998 Aug
- Modulation of cortisol metabolism during treatment of acromegaly is independent of body composition and insulin sensitivity.
- Authors: Frajese GV, Taylor NF, Jenkins PJ, Besser GM, Monson JP
- Issue date: 2004