BSPED2009 Poster Presentations (1) (38 abstracts)
Increased Hypothalamic-pituitary-adrenal axis (HPAA) activity after childhood bone marrow transplantation (BMT) with total body irradiation (TBI) results in chronic hypercortisolaemia associated with obesity
Nikki Davis 1 , Ruth Elson 1 , Claire Stewart 2 , Andrew Moss 2 , Wolf Woltersdorf 1 , Jacqueline Cornish 1 , Michael Stevens 1 & Elizabeth Crowne 1
1Bristol Royal Hospital for Children, Bristol, UK; 2Manchester Metropolitan University, Manchester, UK.
Introduction: Data on the impact of TBI on the HPAA are limited. This study investigates the HPAA in BMT-survivors and non-BMT controls using overnight serum cortisol profiles and midnight/9am ACTH levels.
Subjects (N=35): N=14, child (7), adult (7) controls, N=21 child (7), adult (14) BMT-survivors (TBI dose 12.0-14.4Gy). None had had treatment with corticosteroids in the last year.
Method: Subjects rested for 3 h after venous cannulation, then blood samples were taken every 20 min between 9pm–9am. Subjects slept at their usual time and waking time was recorded. Body composition was measured by DEXA. Cortisol profiles were analysed using Cluster and Autodeconvolution software.
Results: Median (range) age at and time since BMT were 5.8 (0.2–16.0) yrs and 3.5 (1.2–19.3) yrs respectively. Peak cortisol was higher in BMT-survivors (183 vs 143 nmol/l, P=0.048) and in females compared to males across the groups (215 vs 138 nmol/l, P<0.000). % body fat was also higher in females (36.7 vs 24.3, P=0.003) and correlated with area under the curve (AUC) (r=0.335, P=0.05) and peak cortisol (r=0.467, P=0.005). Covariate analysis showed female gender was the main determinant of peak cortisol (P=0.002). Trough cortisol levels (AUC 9-11.40pm) were higher in BMT-survivors (75.4 vs 26.9 nmol/l/min, P<0.05) and females versus males (83.0 vs 40.0 nmol/l/min, P<0.05). Covariate analysis identified BMT as the main determinant of trough levels (P<0.05). There was no difference in time of awakening, CAR, AUC, time of peak, or ACTH levels between BMT-survivors and controls. Time from BMT correlated with trough cortisol levels (r=0.478, P=0.03).
Discussion: Therefore age, gender, adiposity and BMT all influenced HPAA activity. Gender and adiposity were pre-eminent factors for peak cortisol whereas BMT influenced raised trough levels. This may relate to TBI or to chronic stress altering HPAA feedback regulation.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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