1 – Adrenal Crisis & Experiences with Emergency Injections

Journal article published in 2025 - People With Adrenal Insufficiency Who Are in Adrenal Crisis Are Frequently Unable to Self-Administer Rescue Injections

Journal article published in Endocrine Practice. 31 (2025) 625-630

Journal title: People with Adrenal Insufficiency who are in Adrenal Crisis are Frequently Unable to Self-Administer Rescue Injections.

Running title: Failed Emergency Injections in Adrenal Crisis

Authors: Whitaker J. Hover, Aiden D. Krein, Julia Kallet, BS, Gregory L. Kinney, PhD, Phyllis W. Speiser, MD, Selma F. Witchel, MD, Diane Donegan, MD, Alexandra Ahmet, MD, Julia Anthony, MS, Sofia Llahana, MSc, Susan L. Majka, RN, JD, Michal F. Slovick, MD, Joshua D. Stilley, MD, Paul L. Margulies, MD, Michael McDermott, MD, Erin A. Foley, MPH, Elizabeth A. Regan, MD, PhD.

doi: https://doi.org/10.1016/j.eprac.2025.02.017

Original full text journal article - 20 min read

Acknowledgment, affiliations, references , contact info are outlined in a section below.

Note: Abstract, highlights and clinical relevance reflect verbiage from the full text journal article and publications with Science Direct and NIH - links are listed in a section below. Bullet points are added to maximize clarity of the research.

Highlights

  • Adrenal crisis is treatable variety of shock that is an ongoing risk for persons with adrenal insufficiency, and if not treated effectively can result in death or multisystem organ failure.
  • Emergency care may not be immediately available due to location of an acute injury or other precipitating factors leading to an adrenal crisis.
  • An emergency intramuscular or subcutaneous injection of cortisol by the patient or a caregiver is recommended by current treatment guidelines in order to manage or halt an evolving adrenal crisis.
  • Patient education regarding the risk of adrenal crisis and the recommended responses, including detailed teaching for emergency injections, is needed and should be reinforced annually.

Clinical relevance

  • Patients in an adrenal crisis were often sick or confused, and failed to successfully complete a needed emergency injection, resulting in worse outcomes.

  • Not all adrenal insufficiency patients were provided with prescriptions for injection kits (syringes, cortisol for injection, and diluent if needed).

  • More than half of patients had never practiced an injection.

  • Those who had previous practice with injections had greater success in an emergency situation.

About this study - Abstract

Objectives

  • Individuals with adrenal insufficiency (AI) are at risk of acute adrenal crisis and death, particularly during illness or trauma, and may require rapid treatment with parenteral glucocorticoid such as hydrocortisone (HC) to manage a crisis.

  • Current guidelines recommend timely self-injection in an evolving crisis.

  • Little is known about the patient experience with emergency injections.

  • We (study) surveyed people with adrenal insufficiency regarding success with emergency injections.

Methods

  • In 2022 a survey was conducted through the National Adrenal Diseases Foundation website of individuals with AI or their caregivers about experience with managing an adrenal crisis.

  • They reported on adrenal crisis events that required an emergency cortisol injection and the success or failure of the injection, context of the event and reasons for failure,

Results

  • Nearly half (41%) of adrenal insufficient patients were unable to self-administer an emergency glucocorticoid injection, citing effects of their crisis-associated illness and confusion as major barriers.

  • Failed injections led to bad outcomes (sicker, need for hospitalization, or death) in 36% of cases.

Conclusions

  • Effective, timely, management of an impending adrenal crisis can prevent progression to hospitalization, multisystem failure requiring intensive care unit care, and death.
  • Reliance solely on patient self-injection may result in worse outcomes.

  • Treating physicians should include patient education about injections and specific practical instruction in the technique, as well as the potential need for assistance in a crisis.
  • US Food and Drug Administration approval of a glucocorticoid autoinjector, greater engagement with Emergency Medical Services clinicians, hospital emergency staff, and other health care professionals, is key for future success in managing adrenal crises.

Key words – adrenal crisis – emergency injections – hypotension – adrenal insufficiency – auto injectors – education

Access full journal article to learn more about the participants
Who participanted in this study - p. 627
Comments by participants about managing an adrenal crisis - p. 628

Comprehensive redesign of care

  • A redesign of adrenal crisis care needs to address the spectrum of abilities and situations for patients and caregivers, and also address the severity of crisis, location of event, available resources, and patient response to initial treatment.

  • Education about the condition and its treatment is central to this process for all stake- holders.

  • Stakeholders in the redesign process should include en- docrinologists, patient educators, patients, caregivers, emergency physicians, primary care providers, insurers, biopharmaceutical manufacturers, EMS clinicians, hospital and emergency room staff (including nurses), and hospital quality assessment staff.
  • We [researchers] have identified patient/caregiver difficulty with emergency injections, lack of consistent protocols for EMS clinicians, lack of knowledge across the emergency care system about the critical need for rapid treatment, and some apparent reluctance on the part of physicians to use a safe and effective treatment..
  • The finding that patients and caregivers, as well as treating endocrinologists, often opt for pre- hospital emergency injections instead of immediate referral to hospital and emergency room care reflects both the importance of a rapid response to a crisis and also the real experiences of failed current care systems.
Comprehensive redesign of care obtained from last section in journal article (1st paragraph, p. 630). Bullet points are added to maximize clarity of the research.

Publications of this article

Science Direct-abstract/summary - 4 min read
National Jewish Health-summary overview - 4 min read
NIH-abstract/summary - 4 min read
Full text journal article - 20 min read
Abstract, highlights and clinical relevance reflect verbiage from the full text journal article and publications with Science Direct and NIH. Bullet points are added to maximize clarity of the research.

See full text journal article for table re: demographics and responses from participants.

Citation – People With Adrenal Insufficiency Who Are in Adrenal Crisis Are Frequently Unable to Self-Administer Rescue Injections

Hover, Whitaker J. et al. Endocrine Practice , Volume 31, Issue 5, 625 – 630

Original Article – Endocrine Practice , Volume 31, Issue 5, 625 – 6

Publication history – Received November 20, 2024; Revised February 22, 2025; Accepted February 25, 2025; Published online March 3, 20

doi –  10.1016/j.eprac.2025.02.017

Title – People with Adrenal Insufficiency who are in Adrenal Crisis are Frequently Unable to Self- Administer Rescue Injections

Authors – Whitaker J, Hover;1* Aiden D, Krein;1* (*co-first authors), Julia Kallet, BS1, Gregory L. Kinney PhD2, Phyllis W. Speiser MD3, Selma F. Witchel MD4, Diane Donegan MD5, Alexandra Ahmet MD6, Julia Anthony MS7, Sofia Llahana MSc8, Susan L. Majka RN, JD9, Michal F. Slovick MD10, Joshua D. Stilley MD11, Paul L. Margulies MD12, Michael McDermott MD13, Erin A. Foley MPH14, Elizabeth A. Regan MD, PhD15

Author Affiliations – 

1 Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, Colorado
2 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado
3 Division of Pediatric Endocrinology, Cohen Children’s Medical Ctr of NY, Zucker School of Medicine at Hofstra-Northwell, Hempstead, New York 4 UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania
5 Department of Endocrinology, Mayo Clinic, Rochester, Minnesota
6 Division of Endocrinology, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Canada
7 Founder and Chief Strategy Officer, Solution Medical, Philadelphia, Pennsylvania
8 School of Health & Psychological Sciences, City St George’s, University of London, London, United Kingdom
9 Secretary, Board of Directors, National Adrenal Diseases Foundation, Newton, Massachusetts
10 Mosaic Family Health, Fox Valley Family Medicine Residency, Medical College of Wisconsin, Appleton, Wisconsin
11 Department of Emergency Medicine, University of Missouri, Columbia, Missouri
12 Medical Director, National Adrenal Diseases Foundation, Newton, Massachusetts
13 Department of Endocrinology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado
14 Co-President, Board of Directors, National Adrenal Diseases Foundation, Newton, Massachusetts
15 Division of Rheumatology, Department of Medicine, National Jewish Health, Denver, Colorado

Author Contributions – W.J.H. and A.D.K. are coefirst authors.

Disclosure –Julia Anthony is Founder and Chief Strategy Officer for Solution Medical which is developing injector products for adrenal crisis treatment.

Acknowledgment – We acknowledge the National Adrenal Diseases Foundation (NADF) and Ms Lori Engler, co-president of the board of directors for the NADF, for her work in developing the patient survey.

 

References

  1. BornsteinSR,AllolioB,ArltW,etal.Diagnosisandtreatmentofprimaryadrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364e389. https://doi.org/10.1210/jc.2015-1710

  2. Rushworth RL, Torpy DJ, Falhammar H. Adrenal crisis. New Engl J Med. 2019;381(9):852e861. https://doi.org/10.1056/NEJMra1807486

  3. Rushworth RL, Chrisp GL, Bownes S, Torpy DJ, Falhammar H. Adrenal crises in adolescents and young adults. Endocrine. 2022. https://doi.org/10.1007/ s12020-022-03070-3

  4. Rushworth RL, Torpy DJ, Falhammar H. Adrenal crises in older patients. Lancet Diabetes Endocrinol. 2020;8(7):628e639. https://doi.org/10.1016/S2213- 8587(20)30122-4

  5. Ahmet A, Gupta A, Malcolm J, Constantacos C. Approach to the patient: pre- venting adrenal crisis through patient and clinician education. J Clin Endocrinol Metab. 2023;108(7):1797e1805. https://doi.org/10.1210/clinem/dgad003

  6. Hahner S, Spinnler C, Fassnacht M, et al. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015;100(2):407e416. https://doi.org/10.1210/ jc.2014-3191

  7. Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010;162(3):597e602. https://doi.org/10.1530/EJE-09-0884

  8. Puar TH, Stikkelbroeck NM, Smans LC, Zelissen PM, Hermus AR. Adrenal crisis: still a deadly event in the 21st century. Am J Med. 2016;129(3):339.e1-9. https://doi.org/10.1016/j.amjmed.2015.08.021

  9. Worth C, Vyas A, Banerjee I, et al. Acute illness and death in children with adrenal insufficiency. Front Endocrinol (Lausanne). 2021;12:757566. https:// doi.org/10.3389/fendo.2021.757566

  10. R A language and environment for statistical computing. R Foundation for sta- tistical computing; 2010.

  11. Burger-Stritt S, Kardonski P, Pulzer A, Meyer G, Quinkler M, Hahner S. Man- agement of adrenal emergencies in educated patients with adrenal insuffi- ciency-A prospective study. Clin Endocrinol. 2018;89(1):22e29. https://doi.org/ 10.1111/cen.13608

  12. Vijayaraghavan R. Autoinjector device for rapid administration of drugs and antidotes in emergency situations and in mass casualty management. J Int Med Res. 2020;48(5). https://doi.org/10.1177/0300060520926019

  13. Burger-Stritt S, Eff A, Quinkler M, et al. Standardised patient education in ad- renal insufficiency: a prospective multi-centre evaluation. Eur J Endocrinol. 2020;183(2):119e127. https://doi.org/10.1530/EJE-20-0181

  14. Gargya A, Chua E, Hetherington J, Sommer K, Cooper M. Acute adrenal insuf- ficiency: an aide-memoire of the critical importance of its recognition and prevention. Intern Med J. 2016;46(3):356e359. https://doi.org/10.1111/ imj.12998

  15. White KG. A retrospective analysis of adrenal crisis in steroid-dependent pa- tients: causes, frequency and outcomes. BMC Endocr Disord. 2019;19(1):129. https://doi.org/10.1186/s12902-019-0459-z

  16. ChrispGL,QuartararoM,TorpyDJ,FalhammarH,RushworthRL.Useofmedical identification jewellery in children and young adults with adrenal insufficiency in Australia. Endocrine. 2021. https://doi.org/10.1007/s12020-020-02595-9

  17. Beun JG, Burman P, Kampe O, et al. Doctors, teach your adrenal insufficiency patients well: provide them with a European Emergency Card. Endocr Connect. 2023;12(1). https://doi.org/10.1530/EC-22-0345

  18. Betterle C, Presotto F, Furmaniak J. Epidemiology, pathogenesis, and diagnosis of Addison’s disease in adults. J Endocrinol Invest. 2019;42(12):1407e1433. https://doi.org/10.1007/s40618-019-01079-6

  19. White K, Arlt W. Adrenal crisis in treated Addison’s disease: a predictable but under-managed event. Eur J Endocrinol. 2010;162(1):115e120. https://doi.org/ 10.1530/EJE-09-0559

 

Highlights

  • Adrenal crisis is treatable variety of shock that is an ongoing risk for persons with adrenal insufficiency, and if not treated effectively can result in death or multisystem organ failure.
  • Emergency care may not be immediately available due to location of an acute injury or other precipitating factors leading to an adrenal crisis.
  • An emergency intramuscular or subcutaneous injection of cortisol by the patient or a caregiver is recommended by current treatment guidelines in order to manage or halt an evolving adrenal crisis.
  • Patient education regarding the risk of adrenal crisis and the recommended responses, including detailed teaching for emergency injections, is needed and should be reinforced annually.

Clinical relevance

  • Patients in an adrenal crisis were often sick or confused, and failed to successfully complete a needed emergency injection, resulting in worse outcomes.

  • Not all adrenal insufficiency patients were provided with prescriptions for injection kits (syringes, cortisol for injection, and diluent if needed).

  • More than half of patients had never practiced an injection.

  • Those who had previous practice with injections had greater success in an emergency situation.

About this study - Abstract

Objectives

  • Individuals with adrenal insufficiency (AI) are at risk of acute adrenal crisis and death, particularly during illness or trauma, and may require rapid treatment with parenteral glucocorticoid such as hydrocortisone (HC) to manage a crisis.

  • Current guidelines recommend timely self-injection in an evolving crisis.

  • Little is known about the patient experience with emergency injections.

  • We (study) surveyed people with adrenal insufficiency regarding success with emergency injections.

Methods

  • In 2022 a survey was conducted through the National Adrenal Diseases Foundation website of individuals with AI or their caregivers about experience with managing an adrenal crisis.

  • They reported on adrenal crisis events that required an emergency cortisol injection and the success or failure of the injection, context of the event and reasons for failure,

Results

  • Nearly half (41%) of adrenal insufficient patients were unable to self-administer an emergency glucocorticoid injection, citing effects of their crisis-associated illness and confusion as major barriers.

  • Failed injections led to bad outcomes (sicker, need for hospitalization, or death) in 36% of cases.

Conclusions

  • Effective, timely, management of an impending adrenal crisis can prevent progression to hospitalization, multisystem failure requiring intensive care unit care, and death.
  • Reliance solely on patient self-injection may result in worse outcomes.

  • Treating physicians should include patient education about injections and specific practical instruction in the technique, as well as the potential need for assistance in a crisis.
  • US Food and Drug Administration approval of a glucocorticoid autoinjector, greater engagement with Emergency Medical Services clinicians, hospital emergency staff, and other health care professionals, is key for future success in managing adrenal crises.

Key words – adrenal crisis – emergency injections – hypotension – adrenal insufficiency – auto injectors – education

About the participants

Who participated in this study

See Table in full text journal article - p. 627

Participants' share comments about experiences in managing an adrenal crisis.

See comments in full text journal article - p. 628

Access full text journal article.

In essence...

Comprehensive redesign of care

  • An adrenal crisis is a serious event that may require an emergency injection

  • Over 50% (58%) of participants/caregivers indicated a need for an emergency cortisol injection and 36% reported difficulty administering the shot.

  • Auto injectors are needed to maximize care in cases of emergency.
  • Future research should include rapid injector development to help patients and caregivers.

Publications of this article

Science Direct-abstract/summary - 4 min read
National Jewish Health-summary overview - 4 min read
NIH-abstract/summary - 4 min read
Full text journal article - 20 min read
Abstract, highlights and clinical relevance reflect verbiage from the full text journal article and publications with Science Direct and NIH. Bullet points are added to maximize clarity of the research.

See full text journal article for table re: demographics and responses from participants.

Citation – People With Adrenal Insufficiency Who Are in Adrenal Crisis Are Frequently Unable to Self-Administer Rescue Injections

Hover, Whitaker J. et al. Endocrine Practice , Volume 31, Issue 5, 625 – 630

Original Article – Endocrine Practice , Volume 31, Issue 5, 625 – 6

Publication history – Received November 20, 2024; Revised February 22, 2025; Accepted February 25, 2025; Published online March 3, 20

doi –  10.1016/j.eprac.2025.02.017

Title – People with Adrenal Insufficiency who are in Adrenal Crisis are Frequently Unable to Self- Administer Rescue Injections

Authors – Whitaker J, Hover;1* Aiden D, Krein;1* (*co-first authors), Julia Kallet, BS1, Gregory L. Kinney PhD2, Phyllis W. Speiser MD3, Selma F. Witchel MD4, Diane Donegan MD5, Alexandra Ahmet MD6, Julia Anthony MS7, Sofia Llahana MSc8, Susan L. Majka RN, JD9, Michal F. Slovick MD10, Joshua D. Stilley MD11, Paul L. Margulies MD12, Michael McDermott MD13, Erin A. Foley MPH14, Elizabeth A. Regan MD, PhD15

Author Affiliations – 

1 Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, National Jewish Health, Denver, Colorado
2 Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado
3 Division of Pediatric Endocrinology, Cohen Children’s Medical Ctr of NY, Zucker School of Medicine at Hofstra-Northwell, Hempstead, New York 4 UPMC Children’s Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania
5 Department of Endocrinology, Mayo Clinic, Rochester, Minnesota
6 Division of Endocrinology, Department of Pediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Canada
7 Founder and Chief Strategy Officer, Solution Medical, Philadelphia, Pennsylvania
8 School of Health & Psychological Sciences, City St George’s, University of London, London, United Kingdom
9 Secretary, Board of Directors, National Adrenal Diseases Foundation, Newton, Massachusetts
10 Mosaic Family Health, Fox Valley Family Medicine Residency, Medical College of Wisconsin, Appleton, Wisconsin
11 Department of Emergency Medicine, University of Missouri, Columbia, Missouri
12 Medical Director, National Adrenal Diseases Foundation, Newton, Massachusetts
13 Department of Endocrinology, University of Colorado Denver Anschutz Medical Campus, Aurora, Colorado
14 Co-President, Board of Directors, National Adrenal Diseases Foundation, Newton, Massachusetts
15 Division of Rheumatology, Department of Medicine, National Jewish Health, Denver, Colorado

Author Contributions – W.J.H. and A.D.K. are coefirst authors.

Disclosure –Julia Anthony is Founder and Chief Strategy Officer for Solution Medical which is developing injector products for adrenal crisis treatment.

Acknowledgment – We acknowledge the National Adrenal Diseases Foundation (NADF) and Ms Lori Engler, co-president of the board of directors for the NADF, for her work in developing the patient survey.

 

References

  1. BornsteinSR,AllolioB,ArltW,etal.Diagnosisandtreatmentofprimaryadrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101(2):364e389. https://doi.org/10.1210/jc.2015-1710

  2. Rushworth RL, Torpy DJ, Falhammar H. Adrenal crisis. New Engl J Med. 2019;381(9):852e861. https://doi.org/10.1056/NEJMra1807486

  3. Rushworth RL, Chrisp GL, Bownes S, Torpy DJ, Falhammar H. Adrenal crises in adolescents and young adults. Endocrine. 2022. https://doi.org/10.1007/ s12020-022-03070-3

  4. Rushworth RL, Torpy DJ, Falhammar H. Adrenal crises in older patients. Lancet Diabetes Endocrinol. 2020;8(7):628e639. https://doi.org/10.1016/S2213- 8587(20)30122-4

  5. Ahmet A, Gupta A, Malcolm J, Constantacos C. Approach to the patient: pre- venting adrenal crisis through patient and clinician education. J Clin Endocrinol Metab. 2023;108(7):1797e1805. https://doi.org/10.1210/clinem/dgad003

  6. Hahner S, Spinnler C, Fassnacht M, et al. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015;100(2):407e416. https://doi.org/10.1210/ jc.2014-3191

  7. Hahner S, Loeffler M, Bleicken B, et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. Eur J Endocrinol. 2010;162(3):597e602. https://doi.org/10.1530/EJE-09-0884

  8. Puar TH, Stikkelbroeck NM, Smans LC, Zelissen PM, Hermus AR. Adrenal crisis: still a deadly event in the 21st century. Am J Med. 2016;129(3):339.e1-9. https://doi.org/10.1016/j.amjmed.2015.08.021

  9. Worth C, Vyas A, Banerjee I, et al. Acute illness and death in children with adrenal insufficiency. Front Endocrinol (Lausanne). 2021;12:757566. https:// doi.org/10.3389/fendo.2021.757566

  10. R A language and environment for statistical computing. R Foundation for sta- tistical computing; 2010.

  11. Burger-Stritt S, Kardonski P, Pulzer A, Meyer G, Quinkler M, Hahner S. Man- agement of adrenal emergencies in educated patients with adrenal insuffi- ciency-A prospective study. Clin Endocrinol. 2018;89(1):22e29. https://doi.org/ 10.1111/cen.13608

  12. Vijayaraghavan R. Autoinjector device for rapid administration of drugs and antidotes in emergency situations and in mass casualty management. J Int Med Res. 2020;48(5). https://doi.org/10.1177/0300060520926019

  13. Burger-Stritt S, Eff A, Quinkler M, et al. Standardised patient education in ad- renal insufficiency: a prospective multi-centre evaluation. Eur J Endocrinol. 2020;183(2):119e127. https://doi.org/10.1530/EJE-20-0181

  14. Gargya A, Chua E, Hetherington J, Sommer K, Cooper M. Acute adrenal insuf- ficiency: an aide-memoire of the critical importance of its recognition and prevention. Intern Med J. 2016;46(3):356e359. https://doi.org/10.1111/ imj.12998

  15. White KG. A retrospective analysis of adrenal crisis in steroid-dependent pa- tients: causes, frequency and outcomes. BMC Endocr Disord. 2019;19(1):129. https://doi.org/10.1186/s12902-019-0459-z

  16. ChrispGL,QuartararoM,TorpyDJ,FalhammarH,RushworthRL.Useofmedical identification jewellery in children and young adults with adrenal insufficiency in Australia. Endocrine. 2021. https://doi.org/10.1007/s12020-020-02595-9

  17. Beun JG, Burman P, Kampe O, et al. Doctors, teach your adrenal insufficiency patients well: provide them with a European Emergency Card. Endocr Connect. 2023;12(1). https://doi.org/10.1530/EC-22-0345

  18. Betterle C, Presotto F, Furmaniak J. Epidemiology, pathogenesis, and diagnosis of Addison’s disease in adults. J Endocrinol Invest. 2019;42(12):1407e1433. https://doi.org/10.1007/s40618-019-01079-6

  19. White K, Arlt W. Adrenal crisis in treated Addison’s disease: a predictable but under-managed event. Eur J Endocrinol. 2010;162(1):115e120. https://doi.org/ 10.1530/EJE-09-0559

 
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