Adrenal Crisis Guidelines (Adults)

Publication: 01/10/2019  --
Last review: 01/01/1900  
Next review: 03/10/2022  
Clinical Guideline
CURRENT 
ID: 6141 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2019  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Adrenal Crisis Guidelines (Adults)

 

Summary of Guideline

Adrenal crisis is a life-threatening emergency that can occur in patients with adrenal insufficiency.

Pertinent aspects of history and examination

Patients with adrenal crises frequently present with non-specific symptoms, and therefore there should be a high degree of suspicion in individuals with adrenal insufficiency who present acutely.

Most commonly, patients with adrenal crisis feel ‘generally unwell’ with severe fatigue/lethargy, dizziness, nausea, vomiting, diarrhea, abdominal pain and/or hypotension. Drowsiness and coma are late features.

Biochemically, patients may have hyponatraemia, hyperkalaemia (in primary adrenal failure only), hypoglycaemia (mainly in children) and/or AKI secondary to dehydration. In patients with type 1 diabetes, adrenal insufficiency may present with recurrent hypoglycaemia.  

Key diagnostic criteria

There is no consensus on diagnostic criteria as symptoms are non-specific. Patients are often more unwell than would be expected from their intercurrent / precipitating illness (i.e. infections). Hypotension and cardiovascular collapse is a frequent feature.

If adrenal crisis is suspected clinically, treatment should be given WITHOUT DELAY. It is safer to treat and reassess later if there is any doubt whether an adrenal crisis may be occurring.

Investigations required

Treatment should not be delayed by investigations, but should be initiated immediately if adrenal crisis is suspected.

U&Es, FBC, Glucose and venous blood gas should be done in all patients.

Investigations in to the precipitating cause should be undertaken (i.e. cultures for an infective source)

In patients not known to have adrenal insufficiency, take paired sample of cortisol and ACTH before hydrocortisone is administered. ACTH samples must be sent to the laboratory immediately in a red bag and received within 20 minutes of collection.

Treatment

Treatment with steroids and fluids should be commenced immediately, and hypoglycaemia corrected where necessary.

1.    Hydrocortisone Treatment:

  • Give initial Hydrocortisone 100 mg IV (or IM) bolus followed by either:
  • Hydrocortisone 200 mg  over 24 hours as a continuous intravenous infusion (dilute with Glucose 5% or Sodium Chloride 0.9%) (Preferably)  OR
  • Hydrocortisone 50 mg IV (or IM) every 6 hours

2.    IV Sodium chloride 0.9%:

  • Give 1 L 0.9% sodium chloride in the first hour.
  • Subsequent fluids administration depends on clinical assessment of volume status.
  • Be Cautious in patients with heart failure, chronic kidney disease and elderly as they are at risk of fluid overload. So, careful monitoring is recommended in these patients.
  • Be cautious in patients with secondary adrenal insufficiency. Excess fluids can cause rapid correction of hyponatraemia. Please contact endocrinology early for advice.

3.    Additional Treatment:

  • Treat precipitating cause if present (e.g. antibiotics for infection)
  • Treat Hypoglycaemia if present.
  • Consider referral to ICU if patient remains hypotensive despite initial treatment.

4.    Monitor bloods to avoid too rapid correction of hyponatraemia when present. Check U&Es at baseline, 2 hours, four hours later and then 6 hourly during the first 24 hours

5. Refer to Endocrinology for review and patient education to help avoid re-admission

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Background

Adrenal crisis is a life-threatening emergency that can occur in patients with adrenal insufficiency.

Frequency:

In retrospective studies, it’s estimated that 30-44% of patients with chronic adrenal insufficiency will have at least one adrenal crisis in their lifetime 1–4. At least one-fifth of patients with chronic adrenal insufficiency will have more than one adrenal crisis4

Adrenal crises occur at a rate of 6-12 cases per 100 patient years. The risk of adrenal crisis in patients with adrenal insufficiency in any given year is estimated to be 1:12. 5  

Morbidity and Mortality:

Patients with Addison’s disease have 2-fold increase in all-cause mortality in comparison with the normal population. Mortality is significantly greater in the subset of patients with Addison’s disease and type-1 diabetes mellitus. Although cardiovascular and malignant diseases are the most common causes of death, 12.6% and 7.1% of deaths are attributed to endocrine causes and adrenal insufficiency, respectively.6  In Norwegian study, adrenal failure was the second common cause of death (15%) after cardiovascular disease (39%).7

In a prospective study, adrenal crisis resulted in death and ICU admission in 6.3% and 13.6% of patients, respectively.1

Level of Evidence: B

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Diagnosis

Patients At Risk:

1.    All patients with known chronic adrenal insufficiency (e.g. Addison’s disease, Congenital adrenal hyperplasia, hypopituitarism)

It’s well known that some of patients with adrenal insufficiency never develop adrenal crisis while others develop more than one adrenal crisis. Some studies showed that longer duration of the disease, history of mental health disorders and previous history of adrenal crisis are risk factors of development of adrenal crisis in patients with chronic adrenal insufficiency 1,2

2.    Patients on long-term steroid (e.g. rheumatoid arthritis, polymyalgia rheumatic, etc.)

Chronic exogenous steroid exposure (>4 weeks) suppress hypothalamo-pituitary-adrenal axis and therefore it can cause adrenal insufficiency. This applies to all routes (oral, parenteral, topical, inhaled, intra-articular). 8,9

3.    Adrenal crisis can be the first presentation of adrenal insufficiency. Patients with known autoimmune disease are at increased risk.

Precipitating factors:

At least half of adrenal crisis are precipitated by infections, especially gastroenteritis. Other precipitating factors are surgery, exercise, cessation of glucocorticoids and emotional stress. In 9% of crisis, the precipitating factor is unknown. 1,4,10 

Clinical Presentation: 1,8 

Presentation is frequently non-specific. Patients are often more unwell than would be expected from their intercurrent / precipitating illness (i.e. Infections). Hypotension and cardiovascular collapse is a frequent feature.

General: Fatigue/tiredness, muscle cramps, fever

GI: Nausea, Vomiting, Diarrhoea, Abdominal pain (might mimic peritonitis) 

CVS: Postural Hypotension (Drop in SBP >20 mmHg), Hypotension (SBP <90 mmHg), Dizziness, Hypovolaemia

CNS: Confusion, Coma (late)

Biochemical: Hyponatraemia, AKI (due to hypovolaemia), Hyperkalaemia (in primary adrenal insufficiency), Hypoglycaemia (mainly in children)

Level of Evidence: B

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Investigations 8, 11

Diagnostic tests should never delay the prompt start of life-saving treatment in suspected adrenal crisis;

Basic tests (all patients): FBC, U&Es, Capillary blood glucose, venous blood gas.

Investigation of the precipitating cause (i.e. cultures for infection)

If adrenal crisis is suspected in patients not already known to have adrenal insufficiency:

Take paired sample of cortisol and ACTH before starting hydrocortisone (if this will not delay the hydrocortisone treatment).

Formal confirmation of diagnosis can be safely carried out after clinical recovery

Level of Evidence: C

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Management 5, 8, 9, 11, 12

1.    Hydrocortisone Treatment:

  • Give initial Hydrocortisone  100 mg IV (or IM) bolus followed by either :
  • Hydrocortisone 200 mg  over 24 hours as a continuous intravenous infusion(dilute with Glucose 5% or Sodium Chloride 0.9% ) (Preferably) OR
  • Hydrocortisone 50 mg  IV (or IM) every 6 hours

2.    IV Sodium chloride 0.9%:

  • Give 1 L 0.9% sodium chloride in the first hour.
  • Subsequent fluids administration depends on clinical assessment of volume status.
  • Patients with heart failure, chronic kidney disease and elderly are at risk of fluid overload. So, careful monitoring is recommended in these patients.
  • Be cautious in patients with secondary adrenal insufficiency. Excess fluids can cause rapid correction of hyponatraemia. Please contact endocrinology early for advice.   

3.    Treat Hypoglycaemia if present.

4.    Additional Treatment:

  • Treat precipitating cause if present (e.g. antibiotics for infection)
  • Consider referral to ICU if patient remains hypotensive or oliguric despite initial treatment.

5.    Monitoring

  • Clinical: blood pressure, pulse, volume status, urine output
  • Biochemical: urea and electrolytes (especially Na+ and K+) at baseline, 2 hours, 4 hours later, and thereafter 6 hourly during the first 24 hours, particularly where hyponatraemia is present.

6.    Recovery

  • Once the patient is clinically stable, reduce dose of glucocorticoids over 24-72 hours to their maintenance dose, dependent upon the precipiatant.
  • In patients with primary adrenal insufficiency, fludrocortisone should be commenced once the daily dose of hydrocortisone is less than 40 mg

7.    Refer to Endocrinologist (bleep 4710)

  • For education, emergency steroid injection teaching, medic alert bracelets or pendants.
  • To establish precipitating cause.

8.    Prevention of Adrenal Crisis:

Patients with adrenal insufficiency should be educated about sick-day rules:

  • Sick Day Rule 1: During illness with systemic features (i.e. fever, general malaise), or that requires bed rest and/or antibiotics, the patient needs to increase the daily oral glucocorticoid dose 2-3 fold for 2-3 days, or longer if symptoms have yet to improve.
  • Sick Day Rule 2: In case of vomiting/diarrhoea, administer hydrocortisone IM injection (using provided emergency hydrocortisone injection kit) and attend A&E immediately

Level of Evidence: C 

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Provenance

Record: 6141
Objective:

To improve the diagnosis and management of adrenal crisis in adults.
To provide evidence-based recommendations for appropriate diagnosis, investigation and management of adrenal crisis in adults.
To reduce morbidity and mortality caused by adrenal crisis in adults.

Clinical condition:

Adrenal Crisis

Target patient group: All patients with adrenal insufficiency/adrenal crisis
Target professional group(s): Secondary Care Doctors
Adapted from:

Evidence base

References:

  1. Hahner, S. et al. High Incidence of Adrenal Crisis in Educated Patients With Chronic Adrenal Insufficiency: A Prospective Study. The Journal of Clinical Endocrinology & Metabolism 100, 407–416 (2015).
  2. Omori, K., Nomura, K., Shimizu, S., Omori, N. & Takano, K. Risk factors for adrenal crisis in patients with adrenal insufficiency. Endocr. J. 50, 745–752 (2003).
  3. Braatvedt, G. D., Newrick, P. G. & Corrall, R. J. Patients’ self administration of hydrocortisone. BMJ 301, 1312 (1990).
  4. Hahner, S. et al. Epidemiology of adrenal crisis in chronic adrenal insufficiency: the need for new prevention strategies. European Journal of Endocrinology 162, 597–602 (2010).
  5. Allolio, B. EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Adrenal crisis. European Journal of Endocrinology 172, R115–R124 (2015).
  6. Bergthorsdottir, R., Leonsson-Zachrisson, M., Odén, A. & Johannsson, G. Premature Mortality in Patients with Addison’s Disease: A Population-Based Study. J Clin Endocrinol Metab 91, 4849–4853 (2006).
  7. Erichsen, M. M. et al. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. European Journal of Endocrinology 160, 233–237 (2009).
  8. Arlt, W. & Allolio, B. Adrenal insufficiency. The Lancet 361, 1881–1893 (2003).
  9. Bancos, I., Hahner, S., Tomlinson, J. & Arlt, W. Diagnosis and management of adrenal insufficiency. The Lancet Diabetes & Endocrinology 3, 216–226 (2015).
  10. White, K. & Arlt, W. Adrenal crisis in treated Addison’s disease: a predictable but under-managed event. European Journal of Endocrinology 162, 115–120 (2010).
  11. Arlt, W. & the Society for Endocrinology Clinical Committee. SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients. Endocrine Connections 5, G1–G3 (2016).
  12. Husebye, E. S. et al. Consensus statement on the diagnosis, treatment and follow-up of patients with primary adrenal insufficiency. Journal of Internal Medicine 275, 104–115 (2014).

 

Evidence levels:

A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs

B. Robust experimental or observational studies

C. Expert consensus.

D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

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