Adrenal Crisis Prehospital Management

An adrenal crisis is a life-threatening emergency caused by insufficient cortisol production, often seen in patients with adrenal insufficiency. Cortisol is essential for managing stress, blood pressure, glucose metabolism, and immune regulation. When the body’s demand for cortisol exceeds its supply, the patient is at risk of shock, organ failure, and death. Early recognition and management in the prehospital setting are crucial to prevent these severe outcomes.

Adrenal Crisis Incidence

Primary adrenal insufficiency, where the adrenal glands are unable to produce cortisol, affects approximately 3,400 individuals in the UK, and 1 in 20,000 people in Western Europe.

Secondary adrenal insufficiency, which occurs when the pituitary gland cannot produce enough ACTH to stimulate cortisol production by the adrenal glands, is more prevalent, affecting 150 to 280 people per million.

Adrenal Crisis Pathophysiology

Understanding the pathophysiology of adrenal crisis requires examining the different causes of adrenal insufficiency, which can be categorised into primary, secondary, and tertiary forms of adrenal insufficiency.

The hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in cortisol production:

1. Hypothalamus: Releases corticotropin-releasing hormone (CRH) in response to stress or low cortisol levels.
2. Pituitary Gland: CRH stimulates the pituitary to release adrenocorticotropic hormone (ACTH).
3. Adrenal Cortex: ACTH prompts the adrenal glands to produce cortisol, which helps regulate vascular tone, glucose metabolism, inflammation, and stress.

Disruptions at any level of the HPA axis can lead to adrenal insufficiency, which is needed during periods of physiological stress, culminating in adrenal crisis.

Primary adrenal insufficiency occurs when there is direct impairment of the adrenal glands, leading to insufficient production of cortisol and often aldosterone. Common causes include:

• Addison’s Disease: An autoimmune endocrine disorder where the adrenal glands are destroyed or cease to function.
• Congenital Adrenal Hyperplasia (CAH): A genetic condition that impairs adrenal gland function, leading to cortisol deficiency.
• Surgery or Trauma: Surgical removal of or injury to the adrenal glands can also result in adrenal insufficiency.

In primary adrenal insufficiency, both cortisol and aldosterone production are impaired. The loss of aldosterone results in sodium loss, potassium retention, and dehydration, which exacerbates hypotension and contributes to the development of shock.

Secondary adrenal insufficiency arises when the pituitary gland fails to produce sufficient ACTH, reducing stimulation of the adrenal glands and leading to cortisol deficiency. Common causes include:

• Pituitary Disease: Pituitary tumours, infections, or damage to the pituitary gland can impair ACTH production.
• Hypothalamic or Pituitary Tumours: Tumours affecting the hypothalamus or pituitary gland, as well as the treatments for these (surgery or radiotherapy), can lead to ACTH deficiency.
• Brain Injury: Trauma to the brain may disrupt the function of the pituitary gland, leading to reduced ACTH secretion and subsequent cortisol insufficiency.

In secondary adrenal insufficiency, aldosterone production is generally preserved because it is regulated by the renin-angiotensin system rather than by ACTH. However, cortisol deficiency alone is sufficient to trigger adrenal crisis in times of stress.

Tertiary adrenal insufficiency results from chronic suppression of the hypothalamus, leading to a reduction in CRH production and subsequent decreased ACTH release. The most common cause of tertiary adrenal insufficiency is prolonged use of steroids. Key factors include:

• Prolonged Steroid Use: Patients who have taken high doses or multiple courses of steroids, or have used steroids for extended periods or through multiple routes (e.g., oral, inhaled, or topical), may experience suppression of the HPA axis.
• Steroid Withdrawal: The abrupt cessation of steroids can result in an adrenal crisis because the adrenal glands may have reduced or ceased natural cortisol production due to long-term steroid use.

In tertiary adrenal insufficiency, as with secondary, aldosterone production is typically unaffected, but the body’s inability to produce sufficient cortisol in times of stress can still precipitate an adrenal crisis.

Pathophysiology Features of Adrenal Crisis

Regardless of whether adrenal insufficiency is primary, secondary, or tertiary, the lack of cortisol has several critical effects:

Hypotension and Shock
Cortisol is essential for maintaining vascular tone and sensitivity to vasoconstrictors like adrenaline. In the absence of cortisol, blood vessels lose this responsiveness, leading to severe hypotension and potentially refractory shock, particularly when unresponsive to fluid resuscitation alone.

Hypoglycaemia
Cortisol plays a key role in gluconeogenesis (glucose production in the liver). In adrenal crisis, cortisol deficiency impairs this process, resulting in hypoglycaemia, which may cause confusion, lethargy, seizures, or coma.

Electrolyte Imbalances
In primary adrenal insufficiency, aldosterone deficiency leads to hyponatraemia (low sodium levels due to sodium loss) and hyperkalaemia (high potassium levels). These imbalances worsen hypotension and can result in life-threatening arrhythmias. Secondary and tertiary adrenal insufficiency usually preserve aldosterone production, but cortisol deficiency alone can still cause significant clinical deterioration.

Dehydration
The loss of sodium and the resulting volume depletion exacerbate dehydration, compounding hypotension and leading to a higher risk of shock.

Metabolic Acidosis
Dehydration, hypoperfusion, and electrolyte disturbances can lead to metabolic acidosis, further impairing cellular function and driving the patient towards multi-organ dysfunction.

Immunosuppression and Inflammation
Cortisol modulates immune and inflammatory responses. Without cortisol, there is an uncontrolled inflammatory response, which can worsen underlying conditions (e.g., infection) and contribute to a vicious cycle of deterioration.

Neurological and Psychiatric Symptoms
Altered mental status is common in adrenal crisis, ranging from confusion and agitation to seizures or coma. These symptoms are often due to hypoglycaemia, electrolyte disturbances, or hypotension-induced cerebral hypoperfusion.

Steroids Encountered in the Prehospital Setting

While there are many types of steroids, the two most commonly encountered in the prehospital setting are corticosteroids and anabolic-androgenic steroids.

Corticosteroids are naturally occurring hormones produced by the adrenal glands, located above the kidneys. They are essential for managing stress, maintaining blood pressure and blood glucose levels, and regulating immune function and inflammation. The pituitary gland produces adrenocorticotropic hormone (ACTH), which stimulates the adrenal glands to produce cortisol.

Synthetic corticosteroids are commonly prescribed to treat conditions associated with inflammation or immune dysregulation. These include:

• Rheumatoid arthritis
• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Lupus and autoimmune disorders
• Multiple sclerosis
• Inflammatory bowel diseases (e.g., Crohn’s disease)
• Skin conditions (e.g., eczema)
• Endocrine disorders (e.g., adrenal insufficiency, pituitary disorders)

Anabolic steroids are synthetic drugs that mimic testosterone, the primary male hormone. These are occasionally prescribed to treat conditions like delayed puberty, muscle loss due to chronic illness (e.g., cancer, AIDS), or to support masculinisation in transgender men.

However, anabolic steroids are more often abused for muscle gain and enhanced athletic performance. They are commonly referred to by slang terms like “roids,” “gear,” and “juice.” Anabolic steroids can be taken orally or injected. Although physical withdrawal from anabolic steroids can cause uncomfortable symptoms such as depression, aggression, headaches, and hypotension, it is rarely life-threatening.

Signs & Symptoms of Adrenal Crisis

Adrenal crisis, a life-threatening condition, presents with a range of non-specific symptoms and signs that can rapidly worsen if not treated promptly.

Severe Fatigue and Lethargy: Patients may experience extreme tiredness, drowsiness, confusion, and, in severe cases, may progress to coma.

Hypotension and Circulatory Collapse: Low blood pressure is a hallmark of adrenal crisis, often with postural hypotension (a ≥20 mmHg drop in blood pressure when moving from lying to standing), causing dizziness, fainting, and, in extreme cases, hypovolaemic shock.

Gastrointestinal Symptoms: Abdominal pain is common, often with tenderness and guarding. Patients may also experience nausea, vomiting, and diarrhoea, particularly in cases of primary adrenal insufficiency.

Fever: A raised body temperature may indicate infection or the body’s stress response, both of which can precipitate an adrenal crisis.

History of Weight Loss and Skin Pigmentation: In patients with primary adrenal insufficiency (e.g., Addison’s disease), there may be a history of progressive weight loss and increased skin pigmentation over the course of weeks or months, due to elevated ACTH levels stimulating melanocytes.

Underlying Acute Conditions: It’s crucial to assess for any acute illness or stressors that may have triggered the adrenal crisis, such as infection, trauma, or surgery.

Prehospital Management Of Adrenal Crisis

An adrenal crisis is a medical emergency requiring prompt recognition and intervention. The management of an adrenal crisis should follow an ABCDE approach and includes immediate administration of corticosteroids and observations.

Pulse

Measure and record the pulse rate to assess for tachycardia, a common sign of shock.

Respiratory Rate

Measure and record the respiratory rate, as adrenal crisis can lead to respiratory distress.

Oxygen Saturation

Measure oxygen saturations using pulse oximetry. Administer oxygen if hypoxia is present to maintain saturation above 94%.

Blood Pressure and Postural Hypotension

Measure and record blood pressure, as patients are likely to be hypotensive. Check for postural hypotension (a significant drop in BP when moving from supine to standing). If necessary, administer IV fluids before attempting to move the patient to prevent a profound BP drop.

Blood Glucose

Measure and record blood glucose levels to check for hypoglycaemia, a key feature of adrenal crisis. If hypoglycaemia is present, administer 5% dextrose as a supplement to normal saline.

Temperature

Measure and record body temperature to detect fever, which could indicate infection as a precipitating cause.

ECG

Monitor with a 12-lead ECG if indicated, especially if there are signs of electrolyte imbalance or abnormal cardiac rhythms (refer to the Cardiac Rhythm Disturbance guidelines).

For patients in adrenal crisis or suspected adrenal insufficiency, administer IV or IM hydrocortisone (100 mg).

If the patient is on long-term steroid therapy or presents with symptoms of shock, nausea, vomiting, or acute abdominal symptoms, administer hydrocortisone even if adrenal insufficiency is only suspected. Pregnant women with Addison’s disease in labour should also receive hydrocortisone. If in doubt about adrenal insufficiency, administer hydrocortisone as a precaution.

Hospital Conveyance

IV fluids or hypoglycaemia management.

Further assessment/management of any underlying condition precipitating the adrenal crisis.

Community Management and Referral

Patients with mild illness or injury who have successfully followed their treatment plan (increasing steroid doses as per medical advice) and present with stable physiological parameters may be managed in the community. Close monitoring is advised.

For patients on replacement steroids, ensure that their treatment plan for illness or injury (which often involves increasing their maintenance steroid dose) is followed. However, more significant illnesses or injuries may require additional doses or hospital referral.

Key Points

Bibliography

Joint Royal Colleges Ambulance Liaison Committee, & Association of Ambulance Chief Executives. (2022). JRCALC Clinical Guidelines 2022. Class Professional Publishing

NHS (2019). Overview – Addison’s disease. NHS. https://www.nhs.uk/conditions/addisons-disease

NHS (2023). Steroids. NHS. https://www.nhs.uk/conditions/steroids