Adrenal insufficiency is a term used for patients who are unable to produce enough of their own steroid (cortisol). Patients with adrenal insufficiency fall into three main groups:
- Primary adrenal insufficiency is usually caused by a problem with the adrenal cortex. The commonest cause in the UK is Addison’s disease, an autoimmune adrenalitis.
- Secondary adrenal insufficiency is the result of pituitary dysfunction leading to reduced ACTH production. This may occur because of pituitary tumours, post-pituitary surgery or radiation to the pituitary.
- Patients with tertiary adrenal insufficiency develop cortisol deficiency due to problems with their hypothalamic-pituitary axis (HPA). A common cause is suppression of the HPA axis because of prolonged, supra-physiological doses of glucocorticoid treatment. Any patients taking an equivalent daily dose of 5mg of prednisolone for 4 weeks or more are potentially at risk1.
Physiological stress, such as illness, leads to significant requirement for cortisol, which helps the body coordinate an effective metabolic and haemodynamic response. In all types of adrenal insufficiency, patients may not be able to sufficiently increase cortisol to respond to the stressful event. This can cause a life-threatening scenario termed an ‘adrenal crisis’. Adrenal crises can occur in any individual with adrenal insufficiency and requires urgent, emergency treatment.
Presentation
Adrenal insufficiency itself is more common than an adrenal crisis and can present to GPs with non-specific symptoms including fatigue, feeling lightheaded, nausea, vomiting and abdominal pain2. Typical biochemical abnormalities to look out for are hyponatraemia (as well as hyperkalaemia in primary adrenal insufficiency). Patients can also have hypotension and/or hypoglycaemia2.
In an adrenal crisis, typically triggered by missed doses, illness or recent surgery, patients are more unwell. Haemodynamic collapse with shock and profound hypotension is common and these patients require emergency treatment. When assessing patients known to have, or at risk of adrenal insufficiency (e.g. prolonged steroid courses), GPs should have a low threshold to treat these patients if there are any concerns about an adrenal crisis3.
Management of adrenal crisis
Treatment of a crisis focuses on providing urgent steroid replacement, without waiting for investigation or tests. The advice, available on the NHS emergency steroid card, is immediate administration of 100mg of hydrocortisone given IM or IV. Patients should be supplied with this hydrocortisone and taught how to administer it themselves; this education is usually carried out in secondary care but annual checks both in terms of understanding and also that the medication is in-date is important. Thereafter, urgent transfer to hospital for ongoing IV hydrocortisone (50mg IV 6 hourly), fluid replacement and treatment of possible precipitants is essential. This advice remains unchanged in patients with suspected or confirmed Covid-19 with possible adrenal crisis. All patients suspected to have an adrenal crisis should be provided with emergency treatment (described above) and immediately transferred to hospital for further treatment and investigations.
Management of adrenal insufficiency
More typically, patients will present to their GP relatively well with symptoms of possible adrenal insufficiency. If this is clinically suspected then they should still be referred to the local endocrine specialists, despite the Covid-19 situation. Ideally following discussion with local specialists, they should be commenced on hydrocortisone treatment (typically 10mg in the morning, 10mg at lunchtime and 5mg mid-afternoon or if already on long term steroids, advised not to reduce this below an equivalent daily dose of prednisolone 5mg. The usual investigation for adrenal insufficiency is a short synacthen test, and if appropriate these will be undertaken by the endocrine team in hospital, even during current restrictions.
Prevention
Prevention of an adrenal crisis is essential and can avoid unnecessary hospital admission and death. Sick-day ‘double-dosing’ rule education in primary and secondary care is a key element of this. Patients need education on double-dosing of their steroids during significant intercurrent illness, invasive procedures and surgery. Ensuring patients are up to date with this education and timely reinforcement of this information is, again, important in preventing a crisis.
Patients with confirmed adrenal insufficiency should be provided with education and provision for emergency IM injection of hydrocortisone in the event of developing vomiting/diarrhoea, which is likely to warrant admission to hospital for IV steroids and IV fluids, until able to eat and drink safely.
Empowering patients with this knowledge, and understanding the risks associated with inadequate steroid replacement, is the most effective measure to prevent adrenal crises.
Patients with adrenal insufficiency should be provided with the recently developed NHS steroid emergency card, which reinforces this information and helps at risk patients to access timely emergency treatment.
Covid-19
There is some evidence for higher steroid requirements in Covid-19 compared to other illnesses. Recent Covid-19 specific guidance advice has been published for patients with potential adrenal insufficiency and suspected or confirmed Covid-19 infection.
Dr Rebecca C Sagar is a specialist registrar, diabetes & endocrinology, Leeds Teaching Hospitals NHS Trust and Dr Afroze Abbas is a consultant endocrinologist, Leeds Teaching Hospitals NHS Trust
Further guidance
- Society of Endocrinology guidance: https://www.endocrinology.org/clinical-practice/clinical-guidance/adrenal-crisis/
- NHS emergency steroid card: https://www.endocrinology.org/media/3563/new-nhs-emergency-steroid-card.pdf
- EJE Covid-19 and adrenal insufficiency guidance: https://eje.bioscientifica.com/view/journals/eje/aop/eje-20-0361/eje-20-0361.xml
References
1 Arlt W, Baldeweg SE, Pearce SHS, Simpson HL. Endocrinology in the time of COVID-19: Management of adrenal insufficiency. Eur J Endocrinol 2020
2 Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism 2016; 101: 364-89
3 Arlt W, Society for Endocrinology Clinical C. SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients. Endocr Connect 2016; 5: G1-G3
READERS' COMMENTS [2]
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fantastic article
This is a very useful, to the point refresher