Evidence map›Paper›PMID 37857352›Full record

Trial reportJournal of internal medicine2024

Ultradian hydrocortisone replacement alters neuronal processing, emotional ambiguity, affect and fatigue in adrenal insufficiency: The PULSES trial.

Georgina Russell, Konstantinos Kalafatakis, Claire Durant, Nicola Marchant, Jamini Thakrar, Russell Thirard, Jade King, Jane Bowles, Thomas Upton, Ngoc Jade Thai and 11 more

Erratum issuedOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of internal medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Extended-release Hydrocortisone Formulations-Is There a Clinically Meaningful Benefit?The Journal of clinical endocrinology and metabolism · 2025
    Review
  9. Article
  10. Clinical Endocrinology-Time for a Reset?Journal of the Endocrine Society · 2024
    Article
  11. Review
  12. Article
  13. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 11 institutions in 5 countries.

Georgina RussellLaboratories of Integrative Neuroscience and Endocrinology, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-1299-4116
Konstantinos KalafatakisLaboratories of Integrative Neuroscience and Endocrinology, Bristol Medical School, University of Bristol, Bristol, UK.
Claire DurantDepartment of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
Nicola MarchantLaboratories of Integrative Neuroscience and Endocrinology, Bristol Medical School, University of Bristol, Bristol, UK.
Jamini ThakrarLaboratories of Integrative Neuroscience and Endocrinology, Bristol Medical School, University of Bristol, Bristol, UK.
Russell ThirardBristol Trials Centre, Bristol Medical School, University of Bristol, Bristol, UK.
Jade KingUniversity Hospital Bristol and Weston NHS Foundation Trust, Bristol, UK.
Jane BowlesLaboratories of Integrative Neuroscience and Endocrinology, Bristol Medical School, University of Bristol, Bristol, UK.
Thomas UptonLaboratories of Integrative Neuroscience and Endocrinology, Bristol Medical School, University of Bristol, Bristol, UK.
Ngoc Jade ThaiClinical Research and Imaging Centre, University of Bristol, Bristol, UK.
Jonathan C W BrooksSchool of Psychology, University of East Anglia, Norwich, UK.
Aileen WilsonClinical Research and Imaging Centre, University of Bristol, Bristol, UK.
Kirsty PhillipsUniversity Hospital Bristol and Weston NHS Foundation Trust, Bristol, UK.
Stuart FergusonSchool of Medicine, University of Tasmania, Hobart, Tasmania, Australia.
Meryem GrabskiDivision of Psychology and Language Sciences, UCL, London, UK.
Chris A RogersBristol Trials Centre, Bristol Medical School, University of Bristol, Bristol, UK.
Theodoros LamprosDepartment of Informatics and Telecommunications, Human-Computer Interaction Laboratory, University of Ioannina, Arta, Greece.
Sue WilsonDepartment of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.
Catherine HarmerDepartment of Psychiatry, Oxford University and Oxford Health NHS Foundation Trust, Oxford, UK.
Marcus MunafoMRC Integrative Epidemiology Unit, School of Psychological Science, University of Bristol, Bristol, UK.
Stafford L LightmanLaboratories of Integrative Neuroscience and Endocrinology, Bristol Medical School, University of Bristol, Bristol, UK.
University of Bristol · GBUniversity Hospitals Bristol NHS Foundation Trust · GBAt Bristol · GBImperial College London · GBNorth Bristol NHS Trust · GBOxford Health NHS Foundation Trust · GBQueen Mary University of London · GBUniversity College London · GBUniversity of East Anglia · GBUniversity of Ioannina · GRUniversity of Tasmania · AU

Funding

Medical Research Council MR/J012548/1
6 · The paper itself

Abstract

backgroundPrimary 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.

objectivesTo assess the effect of pump therapy on quality of life, mood, functional neuroimaging, behavioural/cognitive responses, sleep and metabolism.

methodsA 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.

resultsBetween 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.

conclusionsThese findings support the administration of hormone therapy that mimics physiology.

Indexed as

Adrenal InsufficiencyHydrocortisoneFatigueFeasibility StudiesGlucocorticoidsHumansQuality of LifeUltradian RhythmGlucocorticoidsHydrocortisonefMRIglucocorticoid replacement therapyprimary adrenal insufficiencyultradian

Identifiers

PMID37857352
PMCPMC10952319
OpenAlexW4387782759

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.