Tools
Tools
Russell, Georgina, Kalafatakis, Konstantinos, Durant, Claire, Marchant, Nicola, Thakrar, Jamini, Thirard, Russell, King, Jade, Bowles, Jane, Upton, Thomas, Thai, Ngoc Jade, Brooks, Jonathan C.W. 
ORCID: https://orcid.org/0000-0003-3335-6209, Wilson, Aileen, Phillips, Kirsty, Ferguson, Stuart, Grabski, Meryem, Rogers, Chris A., Lampros, Theodoros, Wilson, Sue, Harmer, Catherine, Munafo, Marcus and Lightman, Stafford L.
(2024)
Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency:The PULSES trial.
Journal of Internal Medicine, 295 (1).
pp. 51-67.
ISSN 0954-6820
Preview |
PDF (Journal of Internal Medicine - 2023 - Russell - Ultradian hydrocortisone replacement alters neuronal processing emotional)
- Published Version
Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
Background: Primary adrenal insufficiency (PAI) mortality and morbidity remain unacceptably high, possibly arising as glucocorticoid replacement does not replicate natural physiology. A pulsatile subcutaneous pump can closely replicate cortisol's circadian and ultradian rhythm. Objectives: To assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism. Methods: A 6-week randomised, crossover, double-blinded and placebo-controlled feasibility study of usual dose hydrocortisone in PAI administered as either pulsed subcutaneous or standard care in Bristol, United Kingdom (ISRCTN67193733). Participants were stratified by adrenal insufficiency type. All participants who received study drugs are included in the analysis. The primary outcome, the facial expression recognition task (FERT), occurred at week 6. Results: Between December 2014 and 2017, 22 participants were recruited – 20 completed both arms, and 21 were analysed. The pump was well-tolerated. No change was seen in the FERT primary outcome; however, there were subjective improvements in fatigue and mood. Additionally, functional magnetic resonance imaging revealed differential neural processing to emotional cues and visual stimulation. Region of interest analysis identified the left amygdala and insula, key glucocorticoid-sensitive regions involved in emotional ambiguity. FERT post hoc analysis confirmed this response. There were four serious adverse events (AE): three intercurrent illnesses requiring hospitalisation (1/3, 33.3% pump) and a planned procedure (1/1, 100% pump). There was a small number of expected AEs: infusion site bruising/itching (3/5, 60% pump), intercurrent illness requiring extra (3/7, 42% pump) and no extra (4/6, 66% pump) steroid. Conclusions: These findings support the administration of hormone therapy that mimics physiology.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by the Medical Research Council, DPFS grant, MR/J012548/1 and the Above and Beyond Charities UHBristol, 04/2014-15. CJH was supported by the Oxford Health NIHR Biomedical Research Centre. |
| Uncontrolled Keywords: | fmri,glucocorticoid replacement therapy,primary adrenal insufficiency,ultradian,internal medicine ,/dk/atira/pure/subjectarea/asjc/2700/2724 |
| Faculty \ School: | Faculty of Social Sciences > School of Psychology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 26 Jan 2024 02:15 |
| Last Modified: | 30 Apr 2024 09:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/94268 |
| DOI: | 10.1111/joim.13721 |
Downloads
Downloads per month over past year
Actions (login required)
 |
View Item |