Acute Adrenal Insufficiency: Addisonian Crisis in the Emergency Setting

Acute adrenal insufficiency – clinically referred to as Addisonian crisis or adrenal crisis – is one of those emergencies that is regularly recognized too late in acute care medicine. Mortality with delayed treatment is alarmingly high, while the treatment itself is remarkably simple: rapid hydrocortisone administration can be lifesaving. The problem almost never lies in the therapy but in making the diagnosis. Precisely because the symptoms are nonspecific and overlap with sepsis, shock of other etiologies, or gastrointestinal diseases, valuable time is lost. This article gives you a structured overview of the pathophysiology, at-risk patients, clinical recognition, immediate treatment, and management of typical accompanying complications.

Pathophysiology: Why the Body Decompensates

The adrenal glands produce three essential hormone groups: glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and androgens. Cortisol is essential for the body's stress response, maintenance of vascular tone, glucose homeostasis, and immune system modulation.

In primary adrenal insufficiency (Addison's disease), the adrenal cortex itself is destroyed – most commonly by autoimmune mechanisms, less frequently by infection (e.g., tuberculosis), hemorrhage (Waterhouse-Friderichsen syndrome), or metastases. Here, both cortisol and aldosterone are lost, making the clinical presentation particularly dramatic.

In secondary/tertiary adrenal insufficiency, the problem lies at the pituitary or hypothalamic level. ACTH is absent, and cortisol production ceases. Aldosterone production remains largely intact (regulated by the RAAS), which is why electrolyte disturbances may be less pronounced. By far the most common cause of the secondary form is abrupt discontinuation of exogenous glucocorticoid therapy – iatrogenic adrenal insufficiency.

The Mechanism of the Crisis

Under normal conditions, the body increases cortisol production three- to fivefold during stress (infection, trauma, surgery). When this reserve capacity is absent, the following occurs:

• Hemodynamic instability: Cortisol is essential for catecholamine action on blood vessels. Without cortisol, arterioles barely respond to norepinephrine – resulting in catecholamine-refractory shock.
• Hypoglycemia: Cortisol promotes gluconeogenesis. Without cortisol, blood glucose drops, especially in children and during sepsis.
• Hyponatremia: Due to ADH excess (loss of cortisol-mediated inhibition) and, in primary insufficiency, due to aldosterone deficiency.
• Hyperkalemia: Primarily in primary insufficiency due to absent aldosterone action at the distal tubule.
• Metabolic acidosis: A combination of hypoperfusion and renal dysfunction.

Identifying At-Risk Patients

The crucial clinical skill is not the therapy but thinking of the diagnosis in the first place. The following patient groups carry an increased risk:

• Known adrenal insufficiency (primary or secondary) on replacement therapy – any intercurrent illness can trigger a crisis if the dose is not adjusted.
• Patients on chronic glucocorticoid therapy (prednisolone ≥ 5 mg/day or equivalent for more than 3–4 weeks): The hypothalamic-pituitary-adrenal (HPA) axis is suppressed.
• Recently discontinued steroid therapy: The HPA axis can take months to recover.
• High-dose inhaled corticosteroids: Rare but documented – especially in children.
• Pituitary surgery or traumatic brain injury: Secondary insufficiency due to pituitary damage.
• Bilateral adrenal hemorrhage: In the setting of anticoagulation, sepsis (especially meningococcal), antiphospholipid syndrome.
• Patients on immunotherapy: Checkpoint inhibitors (e.g., nivolumab, ipilimumab) can cause hypophysitis or adrenalitis – an increasingly relevant problem in oncology.

Typical Triggers of a Crisis

In patients with known adrenal insufficiency, the following situations trigger decompensation:

• Febrile infection (most common trigger)
• Vomiting/diarrhea (oral replacement is not absorbed)
• Surgery and anesthesia without stress dose adjustment
• Trauma
• Extreme emotional stress
• Forgetting or self-discontinuation of replacement therapy

Clinical Presentation: Recognizing the Warning Signs

Adrenal crisis is a clinical chameleon. Its symptoms overlap with numerous other emergencies, making the differential diagnosis challenging. The classic triad – hypotension, hyponatremia, and hypoglycemia – is typical but not always completely present.

Cardinal Symptoms and Clinical Findings

• Hemodynamics: Profound hypotension (systolic often < 90 mmHg), tachycardia, shock – characteristically failing to respond to volume resuscitation and vasopressors.
• Gastrointestinal: Nausea, vomiting, diffuse abdominal pain (may mimic an acute abdomen), diarrhea.
• Neurological: Confusion, somnolence progressing to coma, seizures (especially with hypoglycemia/hyponatremia).
• General: Profound weakness, myalgias, fever (possible even without infection due to absent cortisol effects).
• Skin signs in primary insufficiency: Hyperpigmentation (palmar creases, oral mucosa, scars) due to ACTH excess – this sign can be highly suggestive but is absent in secondary insufficiency.

Laboratory Clues

• Hyponatremia (often 120–130 mmol/L)
• Hyperkalemia (in primary insufficiency, often 5.5–7.0 mmol/L)
• Hypoglycemia (blood glucose often < 60 mg/dL)
• Metabolic acidosis
• Elevated creatinine (prerenal acute kidney injury)
• Eosinophilia, lymphocytosis (rarely used diagnostically but a helpful clue)
• Serum cortisol: A random cortisol < 3 µg/dL (< 83 nmol/L) during a stress situation is virtually diagnostic. Values < 15 µg/dL (< 414 nmol/L) are highly suspicious, as values > 18–20 µg/dL would be expected during acute stress.

Important: Blood sampling for cortisol (and ideally ACTH) should be performed before hydrocortisone administration – but therapy must never be delayed for this. When in doubt: inject first, diagnose later.

Immediate Treatment: The Algorithm

Treatment of adrenal crisis is time-critical and follows a clear protocol. The principle is: Hydrocortisone – Volume – Glucose – Monitoring.

Step 1: Hydrocortisone Bolus

• Hydrocortisone 100 mg IV as a bolus – immediately, without waiting for laboratory results.
• Followed by: Hydrocortisone 50 mg IV every 6–8 hours or alternatively as a continuous infusion of 200 mg/24 h via syringe pump.
• In children: Hydrocortisone 2 mg/kg IV as a bolus (max. 100 mg), then 1–2 mg/kg every 6–8 hours.

Why hydrocortisone? Hydrocortisone has both glucocorticoid and mineralocorticoid activity. At stress doses (> 50 mg/day), the mineralocorticoid effect is sufficient – additional fludrocortisone is not necessary in the acute phase.

Dexamethasone as an alternative: If hydrocortisone is unavailable, dexamethasone 4 mg IV can be administered. Advantage: It does not interfere with cortisol measurement in the laboratory. Disadvantage: No mineralocorticoid activity – fludrocortisone may need to be added once oral intake is possible.

Step 2: Aggressive Volume Resuscitation

• Normal saline (NaCl 0.9%) 1000 mL in the first hour, then guided by clinical response.
• Often 2–3 liters are needed in the first few hours.
• Caution: With concurrent hypoglycemia, additionally infuse 5% or 10% dextrose (see below).
• Overly rapid sodium correction in the setting of pre-existing hyponatremia carries the risk of osmotic demyelination syndrome (central pontine myelinolysis). Sodium correction should not exceed 8–10 mmol/L in 24 hours.

Step 3: Treat Hypoglycemia

• Check blood glucose immediately and at frequent intervals (every 30–60 minutes in the acute phase).
• If blood glucose < 60 mg/dL: 40% dextrose 20–50 mL IV as a bolus (equivalent to 8–20 g of glucose).
• Maintenance: 5% dextrose infusion, target blood glucose > 100 mg/dL.
• Hydrocortisone alone often rapidly improves hypoglycemia – nonetheless, glucose supplementation should not be omitted.

Step 4: Manage Hyperkalemia

Hyperkalemia in adrenal crisis is primarily treated by hydrocortisone administration and volume resuscitation. In severe cases (potassium > 6.5 mmol/L or ECG changes), standard emergency measures apply:

• Calcium gluconate 10% – 10 mL IV over 2–3 minutes (myocardial protection; does not lower potassium)
• Insulin 10 IU + 40% dextrose 50 mL IV (potassium shift into cells – Caution: hypoglycemia risk is already elevated!)
• Salbutamol 10–20 mg nebulized (additive potassium-lowering effect)
• Sodium bicarbonate 50 mmol IV for concurrent severe acidosis (pH < 7.1)

Important: Do not supplement potassium, even if the serum sodium level is low! Let the hydrocortisone take effect first and monitor electrolytes closely.

Step 5: Search for the Trigger and Causal Treatment

In parallel with stabilization, the precipitating cause must be identified:

• Search for a source of infection (blood cultures, urine culture, chest X-ray, CT if indicated)
• If sepsis is suspected: empiric antibiotics per local guidelines
• Medication history: Was steroid therapy discontinued? Checkpoint inhibitor therapy?
• Imaging: CT/MRI of the adrenals if hemorrhage is suspected, pituitary MRI if a secondary cause is suspected

Differential Diagnoses: What Else to Consider

Adrenal crisis can mimic the following conditions – and vice versa:

Differential Diagnosis	Distinguishing Feature
Septic shock	Similar presentation, but cortisol is typically elevated; Caution: relative adrenal insufficiency in sepsis
Anaphylaxis	Acute onset, urticaria/angioedema, bronchospasm
Acute abdomen	Absence of peritoneal signs, improvement after hydrocortisone
Diabetic ketoacidosis	Hyperglycemia instead of hypoglycemia, ketonuria
Myxedema coma	Hypothermia, bradycardia; Caution: can coexist with adrenal crisis
Intoxication	History, toxicology screening

Clinical pearl: In any catecholamine-refractory shock of unclear etiology, adrenal crisis should be considered. A trial dose of hydrocortisone 100 mg IV has a low threshold, minimal side effects, and is potentially lifesaving. When in doubt, give it.

Special Situations

Perioperative Stress Dosing

Patients with known adrenal insufficiency or a suppressed HPA axis require adjusted perioperative hydrocortisone dosing:

• Minor procedures (e.g., arthroscopy): Hydrocortisone 25 mg IV at induction
• Moderate procedures (e.g., cholecystectomy): Hydrocortisone 50 mg IV at induction, then 25 mg every 8 hours for 24–48 hours
• Major procedures (e.g., laparotomy, cardiac surgery): Hydrocortisone 100 mg IV at induction, then 50 mg every 8 hours, tapering over 2–3 days to maintenance dose

Relative Adrenal Insufficiency in Sepsis

In septic shock, an inadequate cortisol response can occur despite structurally intact adrenal glands. Based on current evidence, in septic shock that persists despite adequate volume resuscitation and vasopressor therapy, administration of hydrocortisone 50 mg IV every 6 hours (200 mg/day) is recommended. This therapy does not serve as replacement in the strict sense but rather aims at hemodynamic stabilization.

Adrenal Crisis in Children

Children are particularly vulnerable to hypoglycemia. Hydrocortisone dosing is weight-based (2 mg/kg bolus, max. 100 mg). Blood glucose monitoring must be performed at frequent intervals. Glucose bolus in children: 10% dextrose – 2–5 mL/kg IV.

Prevention: The Best Crisis Management

A substantial proportion of adrenal crises are preventable. The following measures are essential:

• Patient education: Every patient with adrenal insufficiency must know the sick-day rules – double or triple the oral hydrocortisone dose during fever or vomiting.
• Emergency ID: A steroid emergency card and emergency medication (hydrocortisone for self-injection) should be carried at all times.
• Emergency kit: Hydrocortisone 100 mg for subcutaneous or intramuscular self-injection – patients and family members should be trained in its use.
• No abrupt discontinuation of steroids: Tapering schedules must be followed consistently.
• Perioperative communication: Document in the anesthesia record and on the surgical safety checklist.

Summary: Take-Home Messages

1. Thinking of it is half the battle. Any catecholamine-refractory shock and any unexplained hypotension with hyponatremia should prompt consideration of adrenal crisis.
2. Hydrocortisone 100 mg IV immediately – do not wait for laboratory results.
3. Aggressive volume resuscitation with normal saline (NaCl 0.9%), blood glucose monitoring, correct hypoglycemia.
4. Hyperkalemia is primarily improved by hydrocortisone and volume; standard emergency treatment for ECG changes.
5. Search for the trigger in parallel with stabilization – infection is the most common precipitant.
6. Prevention: Steroid emergency card, sick-day rules, emergency kit, perioperative stress dosing.

Practical Training

Adrenal crisis is a prime example of an emergency that occurs rarely but requires immediate and targeted intervention. Precisely because making the diagnosis is the real challenge, you benefit enormously from practicing such scenarios in a realistic simulation environment. In the emergency training courses at Simulation Tirol, rare but life-threatening conditions like adrenal crisis are practiced in scenario-based simulations – from recognizing the warning signs to immediate treatment to structured team management. Find out more at simulation.tirol/notfalltraining.