Doctors, teach your adrenal insufficiency patients well: provide them with a European Emergency Card!

News, , ,

Abstract

Adrenal insufficiency is a life-threatening condition requiring chronic glucocorticoid replacement therapy, as well as stress adaptation to prevent adrenal crises. To increase patients’ self-sustainability, education on how to tackle an adrenal crisis is crucial. All patients should carry the European Emergency Card.

Correspondence should be addressed to J G Beun: COOR@BijnierNET.nl

Johan G. Beun1, Pia Burman2, Olle Kämpe34, Eisten S. Husebye56, Stephanie Hahner7, Jette Kristensen8, Alida Noordzij1, and Per Dahlqvist9

1 AdrenalNET, The Netherlands
2 Department of Endocrinology, Skåne University Hospital, Lund University, Sweden
3 Department of Medicine (Solna), Centre for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
4 Department of Endocrinology, Diabetes and Metabolism, Karolinska University Hospital, Stockholm, Sweden
5 Department of Clinical Science, University of Bergen, Bergen, Norway
6 Department of Medicine, Haukeland University Hospital, Bergen, Norway
7 Division of Endocrinology and Diabetes, University Hospital of Wuerzburg, Germany
8 Addison Foreningen i Danmark, Denmark
9 Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

The authors thank ENDO-ERN and especially Prof. Alberto Pereira Arias for allowing them to publish this manuscript in the Endocrine Connections. AdrenalNET thanks the editors Mrs Iotova, Mr Bertherat and Mr Mastorakos for their support during production.

The number of individuals in Europe with primary and secondary adrenal insufficiency (AI) is estimated to be 20–50 per 100,000 (1). AI is characterised by adeficit in synthesis and release of cortisol, with symptoms including tiredness, weakness, loss of energy, weight loss, nausea, vomiting, abdominal pain, and muscle and joint pain. Patients with primary AI typically also crave for salt and are hyperpigmented, due to concurrent deficiency of aldosterone and increasedadrenocorticotropic hormone. Once diagnosed, chronic, daily replacement with glucocorticoids is essential. An adequate hormone replacement dose is consideredto be a total of 15–25 mg hydrocortisone (or cortisone acetate 20–35 mg per day) in adults in two to three daily doses, and 8 mg/m2 body surface/day in children divided over three to four doses (2). Patients with primary AI typically also require fludrocortisone, 0.05–0.2 mg daily. However, in situations of illness or severe stress, the ordinary replacement doses do not suffice. Therefore, patients with AI should be empowered byregular education on the use of sick day rules and emergency equipment. To avoid an adrenal crisis in situations of severe stress and/or illness, sick day rulesinclude doubling or tripling the ordinary daily glucocorticoid dose, distributed evenly over the day (1). In addition, in the event of an adrenal crisis, patients have to betreated without delay with i.v. or i.m. hydrocortisone and, equally important, with i.v. physiological salt solution (3). A patient with adrenal insufficiency needs tobe vigilant in case of food poisoning or any gastrointestinal upset since gastroenteritis is the most common cause of adrenal crisis (3).

Figure 1 The European Emergency Card is now available in 18 European countries.

Box 1
The European Emergency Card was based on an idea by Per Dahlqvist and Olle Kämpe, i.e. a uniform, well-designed, credit card-size plastic emergency card, with short and clear instructions in native language and English, intended to be well-recognised anywhere. Until then all hospitals and all countries had their own elaborate card, often in paper, which was not suited for an adrenal crisis emergency situation. The new card was designed by Johan Dahlqvist andimplemented as standard national cards in Sweden in 2011 and in Norway in 2012.

In a 2014 meeting in Bergen of the European Patient Support Groups for Addison’s disease, Eystein Husebye recommended that the organisations promote the card in their individual countries, in order to create a standard emergency card in all of Europe. The Danish/Dutch Addison organisations thereafter made contact with Pia Burman, chair of the European Society of Endocrinology (ESE) Clinical Committee. A uniform emergency card, based on the Swedish version, was developed and made available for all European patients suffering from adrenal insufficiency. The project was endorsed by ESE and ECAS (the EuropeanCouncil of Affiliated Societies), and the card disseminated across many European countries (Fig. 1 and 2). The first publication of the European Emergency Card was in 2015 (6). Inquiries and interest in adopting the card have been made from endocrinologists and patient support groups in several countries outsideEurope, and we believe a global uniform emergency card would increase recognisability even further; this is a long-term goal of the project.

The European Emergency Card – one version for adults and one version for children – is credit card-sized and provides instructions in English on one side and in the national language on the other side. These instructions describe how bystanders should act if a patient shows this card (Fig. 3 and 4). The message on the card is clear: treat this patient immediately with i.v. hydrocortisone and saline, independent of the underlying cause. There is, to our knowledge, no formalscientific evidence demonstrating that a uniform emergency card like this reduces adrenal crises with poor outcome; however, current guidelines recommend thatall patients with AI are equipped with an emergency card, based on expert opinion and best practice statements (2).

The European Emergency Card is currently supplied by AdrenalNET – https://adrenals.eu/emergency-card/

Figure 2 Since 2015, 150,000 adult cards and 50,000 paediatric cards have been distributed in 18 European countries.

For the patient to feel safe and to be able to prevent an  adrenal  crisis,  education  is  essential.  Patients should  be  provided  with  equipment  for  self-injection of hydrocortisone, and a medical alert card/European Emergency Card to inform physicians and other health professionals of the patient’s condition andhow to manage an acute adrenal crisis. Furthermore, the patients’ families, perhaps also neighbours, friends and colleagues at work, should be familiar with the disease and how to act in the event of an emergency. Besides the patient’s endocrinologist, endocrine nurses are invaluable resources for providing patienteducation.

In recent years, several important steps have been taken to improve self-management. In 2016, the Dutch AdrenalNET  (network  for  adrenal  gland patients, carers and healthcare practitioners) published stress instructions to prevent adrenal crises, which were later adopted by the European Society ofEndocrinology and the European Reference Netwerk on rare endocrine conditions (Endo-ERN) (4). In addition, emergency injection ‘kits’ have been made available for patients (5) and a uniform European Emergency Card was developed (6) (Box 1, Fig. 3).

Figure 3 European Emergency Card (credit card size); (A) adult edition, (B) paediatric edition.

AdrenalNET also developed e-learning courses for nurses. Currently, these courses are available in Dutch, English and Danish at https:// screenlearning.net/en/. Translation to other languages is ongoing. Other countries have developed courses for physicians (Germany) and education groups for patients and relatives (The Netherlands, Germany, Norway and Sweden) (7).

Figure 4 Emergency Keycard (54 × 28.5 mm); (A) adult edition, (B) paediatric edition.

Nonetheless, in a prospective study of more than 400 adult patients with AI, a prevalence of 8.3 adrenal crises per 100 patient-years was observed, with a mortality rate of 0.5 per 100 patient-years (8). A national study showed that adrenal crises were a major  cause  of  premature death in  patients  with  secondary  hypocortisolism  due to pituitary disease (9). A recent study  observed  one death due to an adrenal crisis per 300 patient-years in children and young adults with AI (10). Thus, there are still unmet needs in education  and  self-management. This is emphasised by results from a recentsurvey in 24 European countries (11), revealing that only 48% of the responders (n = 183) had access to guidelines on management of an adrenal crisis in their own language. Injectable hydrocortisone and emergency cards are still not available in all European countries (Box 2, Fig. 5).

Figure 5 – Injectable cortisone

So, there is still work to be done. Inour view, education has to start as soon as the patient is diagnosed. Patients have to be informed on how to adapt glucocorticoid doses in stressful situations.

Moreover, it is important  to  convince  the  patient that an adrenal crisis is potentially life-threatening, and that the patient should not hesitate to use emergency injections or contact a physician. If necessary, this information  has  to  be  repeated  over  and  over  again.In addition, it also appears to be important to  inform some doctors that a well-educated and well instructed patient will not misuse the emergency injection. Thus,continued efforts are needed to provide easily accessible and correct information  to  enhance  awareness  of  AI and crisis management, for  example,  in  social media and periodic courses to healthcare providers. We recommend that all patients with AI always carry the European Emergency Card. A well-known medical alert card  increases  the  chances  of  the  patient’s  medical condition being recognised. Hopefully, these measures should help the patient to get  adequate  treatment  fast and avoidpreventable deaths from adrenal crises.

Box 2
Injectable hydrocortisone is available in only 85% of responding European countries (alternative names Hydrocortisone, Solucortef, Flebocortid, Actocortina, Corhydron). A few countries have methylprednisolone instead (e.g. Bulgaria and Spain).

INJECTABLE HYDROCORTISONE IS NOT AVAILABLE IN 15% OF RESPONDING EUROPEAN COUNTRIES (11).

References

  1. Nowotny H, Ahmed SF, Bensing S, Beun JG, Brösamle M, Chifu I, van der Grinten HC, Clemente M, Falhammar H, Haner S, et Therapy options for adrenal insufficiency and recommendations for themanagement of adrenal crisis. Endocrine 2021 71 586–594. (https:// doi.org/10.1007/s12020-021-02649-6)
  2. Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, Husebye ES, Merke DP, Murad MH, Strataski CA, et Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society clinical practice guideline. Journal of Clinical Endocrinology and Metabolism 2016 101 364–389. (https://doi. org/10.1210/jc.2015-1710)
  3. Husebye ES, Pearce SH, Krone NP & Kampe Adrenal insufficiency.Lancet 2021 397 613–629. (https://doi.org/10.1016/S0140-6736(21)00136-7)
  4. Endo-ERN. Guidelines on taking hydrocortisone to prevent an Addison’s Amsterdam, Netherlands: Endo-ERN, 2019. (available at: https:// endo-ern.eu/wp-content/uploads/2019/03/20190312-Stressinstructie-addisoncrisis-hydrocortison-ENG-Endo-ERN-approved.pdf)
  5. BijnierNET/AdrenalNET. Short instruction: emergency injection in an adrenal crisis. (available at: https://adrenals.eu/stress-instructions/ emergency-injection/)
  6. Quinkler M, Dahlqvist P, Husebye ES & Kampe A European Emergency Card for adrenal insufficiency can save lives. European Journal of Internal Medicine 2015 26 75–76. (https://doi.org/10.1016/j.ejim.2014.11.006)
  7. Repping-Wuts HJ, Stikkelbroeck NM, Noordzij A, Kerstens M & Hermus A glucocorticoid education group meeting: an effective strategy for improving self-management to prevent adrenal crisis.European Journal of Endocrinology 2013 169 17–22. (https://doi. org/10.1530/EJE-12-1094)
  8. Hahner S, Ross RJ, Arlt W, Bancos I, Burger-Stritt S, Torpy DJ, Husebye ES & Quinkler M. Adrenal insufficiency. Nature Reviews. Disease Primers 2021 7 (https://doi.org/10.1038/s41572-021-00252-7)
  9. Burman P, Mattsson AF, Johannsson G, Hoybye C, Holmer H, Dahlqvist P, Berinder K, Engström BE, Ekman B, Erfurth EM, et Deaths among adult patients with hypopituitarism: hypocortisolism during acute stress, and de novo malignant brain tumors contribute to an increased mortality. Journal of Clinical Endocrinology and Metabolism 2013 98 1466–1475. (https://doi.org/10.1210/jc.2012-4059)Worth C, Vyas A, Banerjee I, Lin W, Jones J, Stokes H, Komlosy N, Ball S & Clayton Acute illness and death in children with adrenal insufficiency. Frontiers in Endocrinology (Lausanne) 2021 12 757566.(https://doi.org/10.3389/fendo.2021.757566)
  10. Van‘t Westeinde A, Noordzij A, Beun JG, Kristensen J, Brösamle M, Dal Maso G, Lazzerini A, Reisch N & Lajic S. Access to Medical Treatment for Adrenal Insufficiency in Europe. Presented at the European Congress of Endocrinology 2022, Milan, 2022.

Declaration of interest
None of the authors have any conflict of interest that could be perceived as prejudicing the impartiality of this work.

Funding
This work did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Acknowledgements
The authors owe many thanks to Marten Dooper and Jacob van den Hoek who helped enormously to produce this article.

Received in final form 19 October 2022
Accepted 3 November 2022
Accepted Manuscript published online 3 November 2022

https://ec.bioscientifica.com
https://doi.org/10.1530/EC-22-0345