Abstract
Background
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Adrenal crisis is the leading cause of death in patients with adrenal insufficiency, and prevention requires immediate parenteral hydrocortisone administration.
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However, most patients do not receive their home emergency hydrocortisone injection.
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Our [this] study aimed to investigate barriers and enablers to using emergency hydrocortisone injections in managing adrenal crises.
Methods
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This mixed-methods* observational study utilized an online survey distributed through two U.S.-based patient advocacy groups.
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A total of 688 respondents completed the survey, including 485 (70%) parents/caregivers of individuals with adrenal insufficiency and 203 (30%) adults with adrenal insufficiency.
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Qualitative free-text responses were analyzed using thematic content analysis, with subsequent quantification of identified barriers and enablers to administering parenteral hydrocortisone during adrenal crises.
* Mixed methods research combines elements of both quantitative and qualitative analyses to answer the research question. A mixed methods approach can provide a more comprehensive understanding as it merges the benefits of both approaches.
Results
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Over 60% of patients with adrenal insufficiency had required parenteral hydrocortisone for an adrenal crisis, yet fewer than 20% managed to self-inject.
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Thirteen barriers and nine enablers were identified across three thematic domains: device factors, external factors, and emotional factors.
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Key barriers included the complexity of the multi-step hydrocortisone injection process (81%), injection-related anxiety and lack of confidence (18%), challenges accessing the correct hydrocortisone formulation or equipment (38%), and inadequate support for managing adrenal crises (29%).
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Key enablers included the effectiveness of hydrocortisone (14%), the convenience of the combined powder-and-diluent hydrocortisone vial (36%), and patient education (4%).
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Notably, 97% of participants expressed a preference for a hydrocortisone autoinjector to enhance self-injection capabilities.
Conclusions
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Effective adrenal crisis management requires comprehensive, evidence-based interventions across patient, healthcare, and societal levels.
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This should include the development of user-friendly hydrocortisone delivery devices, individualized patient education, healthcare system reforms, and public awareness.
Summary publications of this study
Researchgate - full text, 20 min read
Citation – Llahana S, Anthony J, Sarafoglou K, Geffner ME and Ross R (2025) Patient and caregiver experiences with hydrocortisone injections in adrenal crisis: a mixed-methods cross-sectional study. Front. Endocrinol. 16:1544502. doi: 10.3389/fendo.2025.1544502
Keywords – adrenal insufficiency, adrenal crisis, parenteral glucocorticoid therapy, hydrocortisone injection, self-management, congenital adrenal hyperplasia
Received – 13 December 2024; Accepted – 27 March 2025; Published – 22 April 2025.
Link to published version – https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1544502/full
doi – https://doi.org/10.3389/fendo.2025.1544502
Title – Patient and caregiver experiences with hydrocortisone injections in adrenal crisis: a mixed-methods cross-sectional study.
Copyright – Copyright © 2025 Llahana, Anthony, Sarafoglou, Geffner and Ross. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Correspondence- Sofia Llahana, Sofia.Llahana@citystgeorges.ac.uk
Authors –†These authors share first authorship
ORCID Sofia Llahana, orcid.org/0000-0002-3606-5370
Kyriakie Sarafoglou, orcid.org/0000-0002-5741-3629
Mitchell E. Geffner, orcid.org/0000-0002-0384-3287
Richard Ross, orcid.org/0000-0001-9222-9678
Disclaimer/Publisher’s note – All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Data availability statement – The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement – This study was conducted in collaboration with and disseminated via two US-based Patient Advocacy Groups, adhering to their ethical standards for patient engagement. As the survey was entirely anonymous, no identifiable data were collected, and participation was voluntary, with completion implying informed consent. Given these factors, the study did not involve any interventions or collection of sensitive data that would necessitate formal ethics review under applicable guidelines. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements because the survey was conducted anonymously, ensuring that individual responses could not be identified. Completion of the survey served as implied consent to participate in the study. Additionally, participants confirmed their eligibility through a self-reported checklist before proceeding with the survey. These measures ensured that ethical standards were upheld without the need for written informed consent.
Author Contributions SL: Conceptualization, Formal Analysis, Methodology, Resources, Software, Validation, Visualization, Writing – original draft, Writing – review & editing. JA: Conceptualization, Data curation, Investigation, Methodology, Project administration, Resources, Validation, Writing – original draft, Writing – review & editing. KS: Methodology, Validation, Visualization, Writing – review & editing. MG: Methodology, Validation, Visualization, Writing – review & editing. RR: Methodology, Supervision, Validation, Visualization, Writing – review & editing.
Funding – The author(s) declare that financial support was received for the research and/or publication of this article. SL is funded by the National Institute for Health Research (NIHR) under its HEE/NIHR ICA Clinical Lecturer Personal Development Award scheme, Grant NIHR301286.
Acknowledgments – We would like to thank Adrenal Insufficiency United (AIU) and CARES (Congenital Adrenal Hyperplasia Research, Education, and Support) Foundation for their support in designing this study and disseminating the survey to their members.
Conflict of interest – SL has received consulting and invited speaker fees from Recordati, Ipsen, and Neurocrine Pharmaceuticals. JA is Founder and Chief Strategy Officer for SOLUtion Medical which is developing injector products for adrenal crisis treatment. KS serves as a consultant for Neurocrine Biosciences, Spruce Biosciences, Crinetics Pharmaceuticals, Adrenas Therapeutics; Alexion Pharmaceuticals, Novo Nordisk and Eton Pharmaceuticals on behalf of University of Minnesota Medical School, but does not receive personal income for these activities. MG receives consulting fees from Adrenas, Aeterna Zentaris, Ascendis, Eton Pharmaceuticals, Novo Nordisk, Neurocrine Biosciences, Pfizer, Spruce Biosciences, Theratechnologies Inc., and Tolmar; and royalties from McGraw-Hill and UpToDate. RR is a consultant to Neurocrine Biosciences.
Supplementary material – The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fendo.2025.1544502/full#supplementary-material
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