SFEBES2026 Oral Communications Adrenal and Cardiovascular (6 abstracts)
Replacing the early morning cortisol rise reduces fatigue and improves qol in adrenal insufficiency: a double-blind study
Aled Rees 1 , Alessandro Prete 2 , Verena Theiler-Schwetz 2 , Wiebke Arlt 3 , Irina-Oana Chifu 4 , Birgit Harbeck 5,6 , Catherine Napier 7 , John Newell-Price 8 , Nicole Reisch 9 , Günter Stalla 10 , Helen Coope 11 , John Porter 11 , Jo Quirke 11 & Richard Ross 8
1Cardiff University, Cardiff, United Kingdom; 2University of Birmingham, Birmingham, United Kingdom; 3MRC Laboratory of Medical Sciences, London, United Kingdom; 4University Hospital of Würzburg, Würzburg, Germany; 5Amedes MVZ Hamburg, Hamburg, Germany; 6University Hospital of Hamburg, Hamburg, Germany; 7Newcastle University, Newcastle, United Kingdom; 8University of Sheffield, Sheffield, United Kingdom; 9Ludwig-Maximilians-Universität München, Munich, Germany; 10Medicover Neuroendocrinology Munich, Munich, Germany; 11Neurocrine UK, Cardiff, United Kingdom
Background: Replacement therapy with immediate-release hydrocortisone in adrenal insufficiency (AI) fails to restore the early morning cortisol rise, and patients suffer from fatigue and an impaired quality of life (QoL). Plenadren, a once daily dual-release hydrocortisone, only replaces daytime cortisol levels whilst Chronocort, a twice daily delayed-release and sustained absorption hydrocortisone, replaces the cortisol circadian rhythm with an early morning rise in cortisol. Using Plenadren and Chronocort, we tested the hypothesis that waking with physiological cortisol levels will reduce fatigue and improve QoL.
Methods: Double-blind, double-dummy, two-period, two-sequence crossover, randomised study comparing 4 weeks’ treatment with 25 mg Chronocort versus 25 mg Plenadren. Inclusion criteria were primary AI with morning pre-dose cortisol < 50 nmol/l. The primary endpoint was the difference in 07:00 h cortisol after 4 weeks of treatment. Key secondary outcome was the Multidimensional Assessment of Fatigue (MAF) score after 4 weeks. Other secondary and exploratory outcomes included AddiQoL, PROMIS 7b, SF36, EQ-5D-5L, GAD-7 and PHQ-9.
Results: Of 49 evaluable participants, 92% achieved a physiological 07:00 h cortisol >140 nmol/l with Chronocort compared with 4% on Plenadren, with median serum cortisol of 417 vs 6 nmol/l, (P < 0.0001). The disease specific questionnaire AddiQoL (P = 0.03), the fatigue questionnaire PROMIS 7b (P = 0.02), SF36 physical functioning (P = 0.03) and EQ-5D-5L QoL (P = 0.02) showed significant benefit for Chronocort compared to Plenadren. The MAF score was not significantly different between the two treatments; however, a sensitivity analysis showed that in the first period, before crossover, Chronocort reduced the MAF Score (P = 0.008) compared to Plenadren. Anxiety with GAD-7 scale showed no difference but the PHQ-9 depression scale revealed a significant difference in favour of Chronocort (P = 0.017). The safety profiles were similar for both treatments.
Conclusions: Chronocort provides physiological waking cortisol levels and is associated with reduced fatigue and improved QoL compared to Plenadren in AI patients.
Volume 117
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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