Overview
Adrenal Crisis
1. Clinical Overview
Summary
Adrenal crisis is a life-threatening emergency caused by acute cortisol deficiency. It most commonly occurs in patients with known adrenal insufficiency (primary or secondary) when physiological stress (infection, surgery, trauma) exceeds the body's cortisol supply, or when glucocorticoid replacement is interrupted. It can also occur de novo in critical illness (e.g., Waterhouse-Friderichsen syndrome). The condition presents with cardiovascular collapse, hypoglycaemia, hyponatraemia, and hyperkalaemia. Immediate treatment with intravenous hydrocortisone saves lives — do not wait for investigation results before treating.
Key Facts
- Definition: Acute, severe cortisol deficiency causing circulatory collapse
- Incidence: 5-10 adrenal crises per 100 patient-years in known adrenal insufficiency
- Mortality: 0.5% per crisis episode; higher if delayed treatment
- Classic Triad: Hypotension + Hypoglycaemia + Hyponatraemia (± Hyperkalaemia)
- Key Management: IV Hydrocortisone 100mg stat — do NOT wait for cortisol results
- Critical Point: Every patient with adrenal insufficiency should carry emergency injection kit
- Key Investigation: Random cortisol (taken before treatment if possible, but don't delay treatment)
Clinical Pearls
"Treat First, Test Later": In suspected adrenal crisis, give IV hydrocortisone 100mg immediately. Do not wait for investigation results. A saved blood sample can confirm diagnosis later.
Sick Day Rules: All patients with adrenal insufficiency must know sick day rules — double oral hydrocortisone dose for fever, illness, minor surgery. For vomiting/diarrhoea, give injection.
Refractory Hypotension: If shock is refractory to fluids and vasopressors, always consider adrenal crisis — it responds rapidly to steroids if this is the cause.
Why This Matters Clinically
Adrenal crisis is potentially fatal but rapidly reversible with appropriate treatment. The key is to maintain a high index of suspicion — particularly in patients on long-term steroids, those with known adrenal insufficiency, or critically ill patients with unexplained shock. Delayed treatment leads to cardiovascular collapse and death. Prevention through patient education (sick day rules, emergency injection) is crucial.
2. Epidemiology
Incidence & Prevalence
- Incidence of adrenal crisis: 5-10 episodes per 100 patient-years in known adrenal insufficiency
- Prevalence of adrenal insufficiency: Primary (Addison's) 100-140 per million; Secondary 150-280 per million
- Iatrogenic: Millions on chronic steroids at risk if unaware of need for stress dosing
- Trend: Increasing due to wider use of glucocorticoids and survival of pituitary/adrenal disease patients
Demographics
| Factor | Details |
|---|---|
| Age | Any age; peak for Addison's disease 30-50 years |
| Sex | Female:Male = 2:1 for autoimmune Addison's |
| Ethnicity | Autoimmune Addison's more common in Northern European populations |
| Setting | 50% occur at home; 30% in hospital; 20% in transit |
Risk Factors
Non-Modifiable:
- Known primary adrenal insufficiency (Addison's disease)
- Known secondary adrenal insufficiency (pituitary disease)
- Bilateral adrenalectomy
- History of pituitary surgery or radiotherapy
- Autoimmune polyglandular syndrome (Type 1 or 2)
Modifiable/Precipitating:
| Risk Factor | Mechanism | Prevention |
|---|---|---|
| Infection (most common) | Increased cortisol demand | Sick day rules |
| Gastrointestinal illness (vomiting/diarrhoea) | Cannot absorb oral steroids | IM/IV emergency injection |
| Surgery/trauma | Stress response requires cortisol | Perioperative steroid cover |
| Stopping steroids abruptly | HPA axis suppression | Gradual taper |
| Non-adherence to replacement | No cortisol supply | Education, support |
| Anticoagulation | Risk of adrenal haemorrhage | Monitoring |
| Pregnancy | Increased metabolic demand | Dose adjustment in 3rd trimester |
| Hot weather/dehydration | Volume depletion compounds crisis | Increase fluids, sick day awareness |
Special Populations at Risk:
- Patients on long-term steroids (>3 weeks at supraphysiological doses)
- Post-adrenalectomy patients (unilateral — contralateral suppression; bilateral — absolute deficiency)
- Pituitary tumour patients (pre- or post-surgery)
- Patients receiving checkpoint inhibitor immunotherapy (immune-related hypophysitis)
- Critically ill patients in ICU (relative adrenal insufficiency)
Common Precipitants
| Precipitant | Frequency |
|---|---|
| Gastrointestinal illness | 35-40% |
| Other infections | 20-25% |
| Non-adherence/insufficient dose | 15-20% |
| Perioperative/procedures | 10-15% |
| Emotional stress | 5-10% |
| Unknown | 5-10% |
3. Pathophysiology
Mechanism
Step 1: Cortisol Deficiency
- Cortisol is essential for the stress response, maintaining vascular tone, glucose homeostasis, and permitting catecholamine action
- Deficiency can be: Primary (adrenal), Secondary (pituitary), or Tertiary (hypothalamic/steroid withdrawal)
Step 2: Loss of Glucocorticoid Effects
- Vascular: Loss of vascular reactivity to catecholamines → refractory hypotension
- Metabolic: Impaired gluconeogenesis → hypoglycaemia
- Inflammatory: Exaggerated inflammatory response
- Cardiac: Direct myocardial effects → reduced contractility
Step 3: Loss of Mineralocorticoid Effects (Primary Adrenal Insufficiency)
- Aldosterone deficiency (only in primary, not secondary)
- Sodium wasting → hyponatraemia, volume depletion
- Potassium retention → hyperkalaemia (can cause arrhythmias)
Step 4: Precipitant Overwhelms Capacity
- Stress (infection, surgery, trauma) massively increases cortisol demand
- Insufficient cortisol reserve is exceeded
- Cardiovascular collapse ensues
Classification
| Type | Mechanism | Aldosterone | ACTH Level |
|---|---|---|---|
| Primary (Addison's) | Adrenal gland destruction | Low (mineralocorticoid deficiency) | High (no feedback) |
| Secondary | Pituitary ACTH deficiency | Normal (renin-angiotensin intact) | Low |
| Tertiary | Long-term steroid use suppressing HPA axis | Normal | Low |
| Critical Illness-Related | Relative insufficiency in severe illness | Variable | Variable |
Special Syndromes
| Syndrome | Cause | Features |
|---|---|---|
| Waterhouse-Friderichsen Syndrome | Bilateral adrenal haemorrhage in meningococcal sepsis | Purpuric rash, DIC, profound shock |
| Sheehan Syndrome | Postpartum pituitary necrosis | Failure to lactate, then panhypopituitarism |
| Adrenal Haemorrhage | Anticoagulation, trauma, sepsis | Abdominal/flank pain, adrenal mass |
4. Clinical Presentation
Symptoms
Classic Presentation:
Atypical Presentations:
Signs
Red Flags
[!CAUTION] Red Flags — Immediate action required if:
- Known adrenal insufficiency + fever, vomiting, or any acute illness → Give emergency injection immediately
- Refractory hypotension despite fluids and vasopressors → Consider adrenal crisis (empirical hydrocortisone)
- Hypotension + hypoglycaemia + hyponatraemia → Classic triad — treat as adrenal crisis
- Purpuric rash + shock → Waterhouse-Friderichsen syndrome (meningococcal + adrenal haemorrhage)
- Recent steroid withdrawal + acute illness → Tertiary adrenal crisis
- Bilateral adrenal masses on imaging → Adrenal haemorrhage or metastases
Severe fatigue and weakness (100%)
Common presentation.
Nausea and vomiting (90%)
Common presentation.
Abdominal pain (70-80%)
Common presentation.
Confusion or altered consciousness (50-70%)
Common presentation.
Dizziness/syncope (60%)
Common presentation.
Muscle cramps (40%)
Common presentation.
5. Clinical Examination
Structured Approach
General:
- Consciousness level (may be confused, drowsy, or comatose)
- Signs of shock: Cool peripheries, prolonged capillary refill, weak pulse
- Hydration status: Skin turgor, mucous membranes
Specific Findings:
- Vital signs: Hypotension (often profound), tachycardia, fever or hypothermia
- Skin: Hyperpigmentation (palmar creases, buccal mucosa, scars) — suggests chronic primary AI
- Abdomen: May have tenderness (can mimic acute abdomen)
- Look for precipitant: Signs of infection (pneumonia, UTI, cellulitis)
Special Tests
| Test | Purpose | Finding | Notes |
|---|---|---|---|
| BM (bedside glucose) | Screen for hypoglycaemia | <4 mmol/L (or <70 mg/dL) | Treat immediately |
| ECG | Assess for hyperkalaemia | Peaked T waves, widened QRS | May need calcium gluconate |
| Capillary blood gas | Acid-base, electrolytes | Metabolic acidosis, hyponatraemia, hyperkalaemia | Rapid results |
| Blood pressure | Confirm shock | SBP <90 mmHg | May not respond to fluids alone |
6. Investigations
First-Line (Bedside)
- Blood glucose — hypoglycaemia is common
- ECG — hyperkalaemia changes (peaked T waves, widened QRS, arrhythmias)
- Blood pressure — document hypotension
- Capillary blood gas — rapid electrolytes, pH
Laboratory Tests
| Test | Expected Finding | Purpose |
|---|---|---|
| Random cortisol (take before treatment if possible) | <100 nmol/L virtually diagnostic; <300 nmol/L in stressed patient highly suggestive | Confirms diagnosis retrospectively |
| Sodium | Low (hyponatraemia) | Mineralocorticoid effect |
| Potassium | High (hyperkalaemia) — especially primary AI | Mineralocorticoid effect |
| Glucose | Low (hypoglycaemia) | Glucocorticoid effect |
| Urea/Creatinine | Elevated (prerenal AKI from dehydration) | Volume status |
| ACTH | High in primary AI; low in secondary | Differentiates cause (take before steroids) |
| Full blood count | Eosinophilia, lymphocytosis (AI); neutrophilia (infection) | Look for precipitant |
| Blood cultures | Positive if infective cause | Identify source |
| Lactate | Elevated in shock | Tissue hypoperfusion |
Imaging
| Modality | Findings | Indication |
|---|---|---|
| Chest X-ray | Infection (pneumonia), small heart | Precipitant; cardiac size |
| CT Abdomen | Adrenal enlargement, haemorrhage, calcification, metastases | If suspected adrenal pathology |
| MRI Pituitary | Pituitary adenoma, Sheehan's, apoplexy | Suspected secondary AI |
Diagnostic Criteria
Diagnosis is clinical in emergency — treat first!
Supportive findings:
- Random cortisol <100 nmol/L (virtually diagnostic)
- Random cortisol <300 nmol/L in acutely stressed patient (highly suggestive)
- Electrolyte triad: Hyponatraemia + Hyperkalaemia + Hypoglycaemia
- Clinical response to hydrocortisone (both diagnostic and therapeutic)
Definitive diagnosis (once stable):
- Short Synacthen Test (SST): 0.25mg IV cosyntropin, measure cortisol at 0 and 30/60 min; peak <550 nmol/L confirms AI
- ACTH level: High = primary; Low = secondary/tertiary
7. Management
Management Algorithm
Acute/Emergency Management
[!IMPORTANT] DO NOT DELAY TREATMENT for investigations. Adrenal crisis is rapidly fatal if untreated.
Immediate Actions (Time-Critical):
- IV Hydrocortisone 100mg STAT (IM if no IV access) — do not wait for cortisol result
- IV 0.9% Saline 1L rapidly (over 30-60 min) — repeat as needed; typical deficit 3-4L
- Check and correct hypoglycaemia — IV dextrose if BM low
- Monitor — continuous cardiac monitoring for hyperkalaemia; BP, HR, GCS
Ongoing Treatment (First 24 hours):
- Hydrocortisone 50-100mg IV/IM every 6-8 hours
- Continued IV saline (guided by fluid status)
- Monitor electrolytes 4-6 hourly
- Identify and treat precipitant (antibiotics if infection)
Conservative Management
- Identify and treat precipitant (most commonly infection)
- Supportive care: Oxygen if hypoxic, temperature management
- NPO if vomiting — parenteral steroids essential while NPO
Medical Management
| Drug | Dose | Route | Notes |
|---|---|---|---|
| Hydrocortisone (emergency) | 100mg stat, then 50-100mg 6-8 hourly | IV or IM | First-line; has both glucocorticoid and mineralocorticoid activity at high doses |
| Dexamethasone (alternative) | 4mg stat | IV | Use if diagnosis uncertain (doesn't interfere with cortisol assay); no mineralocorticoid effect |
| 0.9% Sodium Chloride | 1L stat, then as needed | IV | Address volume deficit; may need 3-4L in first 24h |
| Dextrose 10% | 200-500mL | IV | For hypoglycaemia |
| Fludrocortisone | 100-200mcg daily | PO | Add once switched to oral; for mineralocorticoid replacement in primary AI |
Transition to Oral (Once Stable):
- Switch to oral hydrocortisone when tolerating oral intake
- Restart usual replacement dose; consider temporarily increased dose during recovery
- Add fludrocortisone if primary adrenal insufficiency
Specialist Referral
- All patients should be reviewed by Endocrinology
- ICU if persistent hypotension, multi-organ failure, or ventilatory support needed
- Haematology if DIC/adrenal haemorrhage
Disposition
- Admit all adrenal crisis patients — minimum 24-48 hours observation
- ICU/HDU if: Persistent shock, multi-organ dysfunction, need for inotropes
- Discharge criteria: Stable on oral steroids, tolerating oral intake, precipitant controlled, education given
- Follow-up: Endocrinology within 2 weeks; reinforce sick day rules
8. Complications
Immediate (Minutes-Hours)
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Cardiovascular collapse/death | 0.5% per episode | Profound hypotension, cardiac arrest | Aggressive resuscitation, hydrocortisone |
| Hyperkalaemia-induced arrhythmia | 5-10% (primary AI) | Bradycardia, VT/VF | Calcium gluconate, insulin-dextrose, dialysis |
| Hypoglycaemic coma | 10-20% | Altered consciousness, seizures | IV dextrose |
| Aspiration | 5% | If vomiting with reduced GCS | Airway protection |
Early (Days)
- Persistent hypotension requiring ongoing support
- Electrolyte abnormalities during correction
- Identification of precipitant (may require ongoing antibiotics etc.)
- Fluid overload (if aggressive resuscitation in cardiac compromise)
Late (Weeks-Months)
- Recurrent crises: 30-50% of patients have recurrent episodes
- Mortality from subsequent crisis: Risk increases with each episode
- Psychological impact: Anxiety, fear of recurrence
- Underlying cause progression: If metastatic disease etc.
9. Prognosis & Outcomes
Natural History
Untreated adrenal crisis is fatal within hours due to cardiovascular collapse. With prompt treatment, recovery is usually rapid — hypotension improves within hours. Most patients survive if treated quickly.
Outcomes with Treatment
| Variable | Outcome |
|---|---|
| Survival with prompt treatment | >9% |
| Mortality per crisis | 0.5-1% (higher if delayed treatment) |
| Time to BP improvement | Usually 2-6 hours after hydrocortisone |
| Time to full recovery | 24-72 hours typically |
| Risk of recurrent crisis | 30-50% of patients will have another |
Prognostic Factors
Good Prognosis:
- Rapid recognition and treatment
- Known adrenal insufficiency (aware patient)
- Single precipitant identified and treated
- Young, otherwise healthy patient
- Access to medical care
Poor Prognosis:
- Delayed presentation or diagnosis
- Undiagnosed adrenal insufficiency (first presentation as crisis)
- Waterhouse-Friderichsen syndrome
- Multi-organ failure
- Underlying malignancy
- Recurrent non-adherence
10. Evidence & Guidelines
Key Guidelines
- Society for Endocrinology Emergency Guidance: Emergency management of acute adrenal insufficiency (2020) — UK consensus guidance; emphasises immediate hydrocortisone, fluid resuscitation, precipitant management. Society for Endocrinology
- Endocrine Society Clinical Practice Guideline: Diagnosis and treatment of primary adrenal insufficiency (2016) — Comprehensive US guideline covering prevention, sick day rules, emergency management. PMID: 26760044
- European Guideline on Adrenal Insufficiency (2013, updated 2021) — ESE/EE guidance on replacement therapy, monitoring, crisis prevention.
Landmark Trials
Adrenal Crisis Prevention Study (Germany, multiple publications) — Hahner et al. demonstrated that most crises are preventable with education and emergency supplies.
- Key finding: Patients with emergency hydrocortisone injection kits have fewer hospital admissions for crisis
- Clinical Impact: All adrenal insufficient patients should have emergency injection kit
Critical Illness Corticosteroid Therapy (CORTICUS, 2008) — Studied hydrocortisone in septic shock broadly. While not specifically about adrenal crisis, it informed understanding of adrenal function in critical illness.
- 499 patients with septic shock
- No mortality benefit from steroids overall; faster shock reversal
- PMID: 18184957
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| Immediate IV hydrocortisone in crisis | Expert Consensus | Universal agreement; too dangerous to trial placebo |
| IV crystalloid resuscitation | Expert Consensus | Standard shock management |
| Sick day rules education | 2b | Observational studies show reduced crises |
| Emergency injection kit provision | 2b | Reduces hospital admissions |
| Fludrocortisone replacement in primary AI | 1b | Randomised data |
11. Patient/Layperson Explanation
What is Adrenal Crisis?
Adrenal crisis happens when your body doesn't have enough of a hormone called cortisol. Cortisol is essential for dealing with stress like illness, surgery, or injury. Without enough cortisol, your body can't cope, leading to dangerously low blood pressure, low blood sugar, and problems with salt balance.
Why does it happen?
Your adrenal glands (small glands above your kidneys) make cortisol. If these glands don't work properly, or if the brain signals that control them are disrupted, you may not make enough cortisol. Common reasons include:
- Addison's disease: Your immune system attacks your adrenal glands
- Long-term steroid tablets: Taking steroids suppresses your own cortisol production; if stopped suddenly, you have none
- Pituitary problems: The brain doesn't send the signal to make cortisol
- Severe infections: Can cause sudden adrenal failure (very rare)
How is it treated?
- Emergency injection: If you have adrenal insufficiency and become unwell, you (or someone with you) need to give an injection of hydrocortisone into your muscle immediately.
- Hospital treatment: IV steroids, IV fluids (saline drip), and treating any infection or other trigger.
- Rapid recovery: Most people feel much better within hours of receiving the steroid injection.
What to expect
- If treated quickly, recovery is usually complete within 1-3 days
- You'll need to stay in hospital for monitoring
- Before discharge, doctors will make sure you understand "sick day rules"
- You should always carry a steroid emergency card and wear a medical alert bracelet
Sick Day Rules — KNOW THESE
- For minor illness/fever: Double your usual steroid tablet dose
- If vomiting or severe illness: You MUST give the emergency injection (you can't absorb the tablets)
- Before surgery or procedures: Tell your doctors — you need extra steroids
- Always carry: Emergency injection kit, steroid card, medical alert jewellery
When to seek help
- If you have adrenal insufficiency and develop fever, vomiting, diarrhoea, or feel very unwell — take action immediately
- If someone with known adrenal problems collapses or becomes confused — give their emergency injection and call 999
- Urgent: Very low blood pressure, confusion, or collapse = medical emergency
12. References
Primary Guidelines
- Arlt W, Society for Endocrinology Clinical Committee. Society for Endocrinology Endocrine Emergency Guidance: Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients. Endocr Connect. 2016;5(5):G1-G3. PMID: 27935815
- Bornstein SR, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. PMID: 26760044
Key Trials
- Hahner S, et al. High incidence of adrenal crisis in educated patients with chronic adrenal insufficiency: a prospective study. J Clin Endocrinol Metab. 2015;100(2):407-416. PMID: 25419882
- Sprung CL, et al. Hydrocortisone therapy for patients with septic shock (CORTICUS). N Engl J Med. 2008;358(2):111-124. PMID: 18184957
- Smans LC, et al. The incidence of adrenal crisis in referred patients with adrenal insufficiency: a Dutch multicenter study. Eur J Endocrinol. 2016;175(2):119-126. PMID: 27185869
Further Resources
- Addison's Disease Self Help Group (UK): www.addisonsdisease.org.uk
- Society for Endocrinology: www.endocrinology.org
- National Adrenal Diseases Foundation (US): www.nadf.us
- NHS: Addison's disease
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists. This content does not constitute medical advice for individual patients.