Modulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85469
Title:
Modulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients.
Authors:
Toogood, Andy; Taylor, N F; Shalet, Stephen M; Monson, J P
Abstract:
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.
Affiliation:
Department of Endocrinology, Christie Hospital, Manchester, United Kingdom.
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 Metabolism
Issue Date:
Apr-2000
URI:
http://hdl.handle.net/10541/85469
DOI:
10.1210/jc.85.4.1727
PubMed ID:
10770221
Type:
Article
Language:
en
ISSN:
0021-972X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorToogood, Andyen
dc.contributor.authorTaylor, N Fen
dc.contributor.authorShalet, Stephen Men
dc.contributor.authorMonson, J Pen
dc.date.accessioned2009-11-05T17:19:14Z-
dc.date.available2009-11-05T17:19:14Z-
dc.date.issued2000-04-
dc.identifier.citationModulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients. 2000, 85 (4):1727-30 J. Clin. Endocrinol. Metab.en
dc.identifier.issn0021-972X-
dc.identifier.pmid10770221-
dc.identifier.doi10.1210/jc.85.4.1727-
dc.identifier.urihttp://hdl.handle.net/10541/85469-
dc.description.abstract11 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.en
dc.language.isoenen
dc.subject.mesh11-beta-Hydroxysteroid Dehydrogenases-
dc.subject.meshAdipose Tissue-
dc.subject.meshAdrenocorticotropic Hormone-
dc.subject.meshBody Composition-
dc.subject.meshCortisone-
dc.subject.meshFasting-
dc.subject.meshFemale-
dc.subject.meshHormone Replacement Therapy-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshHydrocortisone-
dc.subject.meshHydroxysteroid Dehydrogenases-
dc.subject.meshHypopituitarism-
dc.subject.meshInsulin-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.titleModulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital, Manchester, United Kingdom.en
dc.identifier.journalThe Journal of Clinical Endocrinology and Metabolismen
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