SFE2001 Poster Presentations Steroids (13 abstracts)
MODULATION OF CORTISOL METABOLISM DURING TREATMENT OF ACROMEGALY IS INDEPENDENT OF BODY COMPOSITION AND INSULIN SENSITIVITY
JP Monson 2 , PJ Jenkins 2 , NF Taylor 1 , P Yeo 2 , PV Carroll 2 , C Camacho-Hubner 2 , K Noonan 2 , L Perry 2 & GM Besser 2
1JP Monson, PJ Jenkins, P Yeo, PV Carroll, C Camacho-Hubner, K Noonan, L Perry, GM Besser; Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE; 2NF Taylor, King's College Hospital, London SE5 9PJ.
Cortisol metabolism is modulated by inhibition of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta HSD1) during GH replacement (Weaver et al, Clin Endocrinol, 1994, 41, 639; Gelding et al, Clin Endocrinol, 1998, 48, 153) and in active acromegaly (Moore et al, J Clin Endocrinol Metab, 1999, 84, 4172). 11 beta HSD1 activity is also influenced by both fat mass and insulin. To determine the relative contribution of GH/IGF-I to alteration in cortisol metabolism we have examined, in parallel, 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) in 6 patients (mean age 53 yrs, range 42-76; 4 males; all patients had normal ACTH reserve) with previously untreated active acromegaly during 6 months of therapy with Sandostatin LAR TM (20-30 mg IM 4 weekly). Pearson correlation demonstrated trends towards inverse relationships at baseline for mean GH and Fm/Em (R= -0.83, p=0.04) and HOMA%S and Fm/Em (R= -0.79, P=0.06) but no other patterns were evident. During treatment, serum GH (mean of day curve) decreased from 29.6 ±19.2 (mean±SD) to 10.4 ± 9.2 mU/L (P<0.01) and serum IGF-I from 785.0±268.3 to 430.8±156.3 ng/mL (P<0.005). Fm/Em increased from 0.52±0.1 to 0.75±0.08 (P<0.03) consistent with increased 11 beta HSD1 activity. There were no significant changes in % truncal fat (29.3±15.5 vs 33.0±8.2) or insulin sensitivity (HOMA%S: 37.1±8.6 vs 52.8±33.7). We conclude that modulation of cortisol metabolism during treatment of active acromegaly is dependent on changes in GH/IGF-I status and occurs independently of any individual change in body composition or insulin sensitivity. Supported by Novartis Pharmaceuticals
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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