Key Facts

Adrenal crisis is an under-recognised emergency that carries significant mortality if not treated promptly. It should be considered in any patient with unexplained hypotension, particularly those with a history of steroid use or known adrenal insufficiency.

Epidemiology

Primary adrenal insufficiency (Addison's disease) has a prevalence of approximately 100-140 per million in the UK. However, adrenal crisis due to secondary causes (chronic steroid therapy, pituitary disease) is far more common. Approximately 5-10 crises per 100 patient-years occur in those with known adrenal insufficiency. Adrenal crisis is the cause of death in approximately 6-15% of patients with Addison's disease.

Aetiology

Primary adrenal insufficiency:

• Autoimmune adrenalitis (Addison's disease) — 80% in UK; may be part of autoimmune polyendocrine syndrome
• TB — most common cause worldwide
• Adrenal haemorrhage (Waterhouse-Friderichsen syndrome — meningococcal sepsis)
• Metastases, infiltration (lymphoma, amyloid)

Secondary adrenal insufficiency (most common overall):

• Chronic corticosteroid therapy (>5mg prednisolone >3 weeks) — HPA axis suppression
• Pituitary disease (tumour, surgery, apoplexy, Sheehan's syndrome)

Pathophysiology

Cortisol is essential for maintaining vascular tone, gluconeogenesis, and the stress response. In adrenal insufficiency, the adrenal glands cannot produce adequate cortisol. During physiological stress (infection, surgery, trauma), cortisol requirements increase dramatically. Without this cortisol surge, cardiovascular collapse occurs. In primary disease, aldosterone deficiency also contributes (hyponatraemia, hyperkalaemia, dehydration).

Acute Presentation

• Severe hypotension (refractory to fluids/vasopressors until steroids given)
• Shock, tachycardia, peripheral vasoconstriction
• Nausea, vomiting, abdominal pain (may mimic acute abdomen)
• Confusion, reduced consciousness
• Fever (may be triggered by intercurrent infection)

Chronic Features (May Be Present)

• Hyperpigmentation (primary only — ACTH-driven; buccal mucosa, skin creases, scars)
• Weight loss, fatigue, anorexia
• Postural hypotension
• Salt craving (aldosterone deficiency)

Red Flags

• Hypotension not responding to fluids — give IV hydrocortisone
• Patient on long-term steroids presenting with acute illness — stress dose required
• Hyponatraemia + hyperkalaemia + hypoglycaemia — classic triad
• Post-surgical patient on chronic steroids who becomes hypotensive — adrenal crisis until proven otherwise

Bedside

• Blood glucose: Hypoglycaemia (impaired gluconeogenesis)
• Blood pressure: Severe hypotension
• ECG: Hyperkalaemia changes (peaked T waves, wide QRS)
• Temperature: Hypothermia or fever (infection trigger)

Bloods

• Random cortisol: Take BEFORE giving hydrocortisone if possible (but do NOT delay treatment) — cortisol <100 nmol/L in acute illness is diagnostic; <300 is suspicious
• ACTH: Elevated in primary (>100 pg/mL), low/normal in secondary
• U&Es: Hyponatraemia, hyperkalaemia, raised urea
• Blood glucose: Hypoglycaemia
• FBC: Eosinophilia (cortisol normally suppresses eosinophils)
• TFTs: Coexisting hypothyroidism (autoimmune polyendocrine syndrome)
• Calcium: Hypercalcaemia may occur

Imaging

• CT adrenals: Haemorrhage, calcification (TB), metastases
• MRI pituitary: If secondary cause suspected

Special Tests

• Short Synacthen test: Definitive test for adrenal insufficiency — measure cortisol at 0 and 30 min after 250mcg tetracosactide IV; cortisol <550 nmol/L at 30 min = adrenal insufficiency
• Adrenal autoantibodies (21-hydroxylase): For autoimmune Addison's

Non-pharmacological

• Do NOT delay treatment for investigations — adrenal crisis is a clinical diagnosis
• IV access: Immediately

Pharmacological

Acute treatment:

• Hydrocortisone 100mg IV immediately (or IM if no IV access)
• 0.9% NaCl: 1L rapid bolus, then guided by clinical response and electrolytes
• 50% glucose IV: If hypoglycaemic (50mL)
• Continue hydrocortisone 50mg IV/IM 6-hourly until stable (usually 24-48h)
• Then convert to oral hydrocortisone (20mg morning, 10mg afternoon) and titrate
• If primary adrenal insufficiency — add fludrocortisone 50-200mcg OD when oral intake established (not needed acutely as high-dose hydrocortisone has mineralocorticoid activity)

Hyperkalaemia management (if K⁺ >6.0):

• Calcium gluconate 10% 30mL IV (cardioprotection)
• Insulin 10 units + 25g glucose IV
• Salbutamol 10mg nebulised
• Hydrocortisone will also help (promotes renal K⁺ excretion)

Treat precipitant:

• Antibiotics if infection suspected
• Investigate and treat underlying trigger

Referral Criteria

• All adrenal crises — endocrinology review
• New diagnosis — investigation for cause (Synacthen test, ACTH, adrenal antibodies)
• Patient education — sick day rules, emergency injection technique, MedicAlert, steroid card

• With prompt treatment: Rapid recovery expected; most patients stabilise within hours
• Without treatment: Fatal — cardiovascular collapse
• Mortality from adrenal crisis: ~0.5% per crisis episode; ~6-15% of Addison's patients die from adrenal crisis over their lifetime
• Prevention: Patient education (sick day rules), steroid emergency card, MedicAlert bracelet, IM hydrocortisone kit
• Long-term: Lifelong replacement required for primary adrenal insufficiency; regular endocrine follow-up

Sick Day Rules for Adrenal Insufficiency

Steroid Replacement in Adrenal Insufficiency