7. Acute Adrenal Insufficiency, Addisonian Crisis or Adrenal Crisis

An adrenal crisis is a potentially life-threatening medical emergency that requires immediate medical attention and management in a hospital or emergency department. 

An adrenal crisis is caused by an extreme or sudden physical or emotional stress such as surgery, trauma, accident or an acute infection. It can occur frequently in people who already receive standard replacement therapy but can also be the first presentation of adrenal insufficiency.

People with chronic adrenal insufficiency cannot produce cortisone as a response to stress.
While a fixed daily dose of hydrocortisone should be sufficient to maintain all bodily functions under normal circumstances, it may not be high enough to cover acute stress situations. Therefore any stress that, for a healthy person, seems minor or easily manageable (e.g. a stomach bug), requires taking additional hydrocortisone (also called “stress dosing” or may otherwise potentially lead to an adrenal crisis. 
The threshold to progressing to an adrenal crisis differs from person to person and situation to situation.

7.1. Incidence

Retrospective studies consistently show that 5 – 10 % of all people with known and treated adrenal insufficiency will experience at least one adrenal crisis per year. 1 in 200 of those patients will die from an adrenal crisis.

There is an uneven distribution in the occurrence of crises, as some people do not experience a single adrenal crisis for decades, while others do so recurrently. However, the incidence of an adrenal crisis increases with age, especially above 50 years of age.  

Incidence of an adrenal crisis among diagnosed people
The largest analysis so far was conducted via postal survey by the UK Addison’s Disease Self Help Group. The results from 841 participants from the UK, Canada, Australia and New Zealand indicate an incidence of eight crises per 100 patient years (or 8% of patients per year).
A recent Australian study identified an increase in adrenal crisis hospital admission rates over 13 years. It suggested that people with adrenal insufficiency today are at a greater risk because they have less of a “cushion” of cortisol with a standard daily dose of approx. 20-25 mg hydrocortisone compared with the old-fashioned standard dose of 30 mg. However, taking more hydrocortisone than necessary over a long time can increase the susceptibility to infection and thereby increase the risk of adrenal crisis. Therefore it seems sensible to take daily doses as low as possible and stress dose when needed rather than over-replacing on a continuous basis.

7.2. Symptoms of Adrenal Crisis

In addition to the symptoms of the triggering cause (e.g. stomach or respiratory flu, accident), typical symptoms of an adrenal crisis are:

• Severe drop in blood pressure causing dizziness, lightheadedness and possibly loss of consciousness (patient is in danger of hypovolaemic shock)
• Nausea and vomiting
• Confusion and lethargy
• Muscle weakness, joint pains, cramps, headaches

Many people with secondary adrenal insufficiency do not present with electrolyte abnormalities when in crisis due to their still functioning aldosterone production.
Some even experience an increase of blood pressure before the expected sudden drop: The results from the 2017 AADAI Member and Community Surveys indicate that number to be around 20%.
The onset of measurable serum electrolyte abnormalities in patients with primary adrenal insufficiency depends on how quickly the crisis progresses. For instance, it will be faster for patients with an acute gastrointestinal event than those experiencing an injury. 

7.3. Causes and Development

The most frequent causes of adrenal crises in people with already diagnosed chronic adrenal insufficiency are infections, particularly gastroenteritis (“stomach flu” with diarrhoea and vomiting), pneumonia / lower respiratory tract infections and urinary tract infections. In addition surgery, strenuous exercise, emotional stress and accidents can contribute and lead to an adrenal crisis.

The development of an adrenal crisis usually takes several hours. However, a survey of 37 patients who had experienced a crisis showed a substantial variation, with the median time from first symptoms to contacting health professionals being 135 minutes with a range of 5 minutes to 7 days.

7.4. Treatment and Development

Treatment of an adrenal crisis should not be delayed under any circumstances.

Every person diagnosed with adrenal insufficiency should carry an emergency kit
and know how to give him- or herself an intra muscular (IM) or sub cutaneous (SC) injection of Solu-Cortef in case medical attention is delayed or his or her condition is deteriorating quickly.

Hospital or emergency department treatment is simple and highly effective, consisting of immediate intravenous administration of 100 mg hydrocortisone and rapid rehydration with normal saline infusion, followed by 100mg IV or IM every 6 hours (as per NSW emergency protocols) or continuous hydrocortisone infusion of 200mg over 24 hours until the patient stabilises. 
(Usually, mineralocorticoid replacement (in primary adrenal insufficiency) is not necessary if the daily hydrocortisone dose is > 50mg.)

This treatment usually brings rapid improvement. After the patient has improved and can take fluids and medications by mouth the amount of hydrocortisone is decreased until a maintenance dose is achieved. 
The length of hospitalisation may be hours to days and will depend on the severity of the crisis and any underlying precipitating factors, such as infection, as well as overall health.

Unfortunately, some cases are fatal due to delayed treatment, especially in previously undiagnosed persons.

7.5. Reducing the Risk of Adrenal Crisis: Knowledge is Key

Not all triggers for an adrenal crisis (such as accidents) can be prevented.

To reduce the risk of an adrenal crisis,
people with diagnosed adrenal insufficiency should

• never stop taking their medication 
• know, recognise and act upon symptoms of under-replacement 
• regularly review their stress dose/sick day management plan (🡺 Stress dosing, sick day management)
• follow up with an endocrinologist on an annual basis 
• get the flu vaccine each year
• maintain hydration and electrolytes especially in hot weather

To be prepared to deal with the onset of an adrenal crisis,
people with diagnosed adrenal insufficiency (and their relatives/friends) should know:

• and recognise the symptoms of the beginning of an adrenal crisis. (This is easier said than done; It has been commonly reported that people who are in general well informed about their condition fail to recognise the signs in themselves.) 
• what circumstances may trigger an adrenal crisis and therefore require stress dosing (fever, diarrhoea, vomiting, flu or cold, injury, medical procedures / surgery).
• how (and when) to give an emergency injection
• when to notify medical staff about their condition (e.g. before undergoing planned or emergency surgical or invasive diagnostic procedures)

To ensure that emergency personnel recognise the condition as quickly as possible
people with diagnosed adrenal insufficiency should:

• wear a medical alert bracelet 
• carry a medical treatment letter from their endocrinologist
• carry an emergency kit with Solu-Cortef, syringes and needles

Check out the one-page info sheets under the tab “Newly Diagnosed?”. We suggest to print and keep them handy and to review them regularly.
– Emergency/Adrenal Crisis (one page instruction sheet)
– How to Prevent an Adrenal Crisis: Beware of symptoms and react quickly
– How to Give Yourself an Emergency Injection

> NEXT CHAPTER

> CHAPTER OVERVIEW
Anatomy/Physiology | Types of Adrenal Insufficiency | Symptoms | Testing/Diagnosis | Treatment | Stress dosing/Sick day Management | Adrenal Crisis | Quality of Life and Risks | Other Conditions and Drugs | Long-term Management | Suggested Reading | Literature/References

Author: Gisela Spallek, MD PhD
Edited by Maria Stewart, Director of AIC and deputy editor Des Rolph, Associate Director of AIC