• Most common cause is secondary adrenal failure (hypothalamic-pituitary disease with inadequate ACTH or long-term corticosteroid therapy), where mineralocorticoid production is generally preserved

Symptoms and signs

• Lethargy
• Nausea
• Weight loss
• Hypoglycaemia

Indicators of severe adrenal insufficiency

• Hyponatraemia
• Hypoglycaemia
• Hypotension - systolic BP <90 mmHg, diastolic BP <50 mmHg
• Tachycardia - with no obvious cause

Primary adrenal failure

• Hypotension (postural/sustained)
• Pigmentation (palmar/buccal/scars/pressure areas)
• Vitiligo

Secondary adrenal failure

• Pallor
• Loss of pubic/axillary hair (because of co-existing secondary hypogonadism)

Risk factors

Primary adrenal failure

• Auto-immune disease (diabetes/hypothyroidism/pernicious anaemia)
• TB
• Metastases, especially from carcinoma of lung

Secondary adrenal failure

• Withdrawal of oral (or potent topical or inhaled) corticosteroids
• Pituitary surgery/radiotherapy

• FBC
• U&E
• Blood glucose

Check for severe adrenal insufficiency

• Does patient have indicators of severe adrenal insufficiency?
  
  • hyponatraemia
  • hypoglycaemia
  • hypotension - systolic BP <90 mmHg, diastolic BP <50 mmHg
  • tachycardia - with no other reason to explain it

If indicators of severe adrenal insufficiency present

• As severely ill, obtain blood sample for serum cortisol (gold top) and plasma ACTH (purple top bottle on ice) before hydrocortisone is given but treatment must not await result
  • if urgent cortisol required, inform biochemistry laboratory

If no indicators of severe adrenal insufficiency present

• As not severely ill, perform short tetracosactide (Synacthen^®) test (SST) (serum cortisol before, then 30 min after tetracosactide 250 microgram IV/IM)
  
  • adrenal failure excluded by basal or peak (30 min) serum cortisol >550 nmol/L during SST
• If Synacthen^® test not available, 0900 hr serum cortisol preferred but random cortisol can be taken to prevent delay in treatment
  
  • adrenal failure confirmed by 0900 hr serum cortisol <150 nmol/L
  • random cortisol (any time of the day) during period of severe stress (e.g. sepsis, myocardial infarction) <500 nmol/L

Adrenal failure suspected

• Send gold top and EDTA (purple) blood bottles for markers of pituitary function:
• Cortisol
• FSH/LH
• testosterone (males)
• TSH/FT4
• growth hormone (GH)
• insulin-like growth factor 1 (IGF-1)
• prolactin
• If adrenal insufficiency strongly suspected, send EDTA (purple) top blood bottle for adrenocorticotropic hormone (ACTH)
• All of hormone tests can be measured in gold top blood bottle except ACTH which needs EDTA (purple) top bottle

Results in primary adrenal failure only

• Hyperkalaemia
• Raised urea

• If severely ill:
• hydrocortisone 100 mg as slow IV bolus, followed by 50 mg by slow IV bolus 6-hrly or 200 mg infusion in glucose 5% over 24 hr
• sodium chloride 0.9% 1 L by IV infusion over 30-60 min, followed by 3-4 L IV over next 24 hr
• If hypoglycaemic, give simultaneous infusion of:
• glucose 20% 100 mL by IV infusion over 30 min, followed by glucose 10% 1 L by IV infusion over 12 hr. Monitor blood glucose and change to glucose 20% if 10% inadequate
• glucagon is unhelpful in this situation

• Admit to endocrinology ward
• When improving and tolerating oral fluid:
• hydrocortisone 20 mg oral 8-hrly
• refer to endocrinology team for advice on maintenance dosage (usually 20 mg in morning and 10 mg in afternoon - no later than 1800 hr)
• if diagnosis in doubt, seek advice from endocrinology team about substituting dexamethasone 1 mg oral 8-hrly for hydrocortisone and perform SST within three days. If on oral hydrocortisone (maintenance dose 20 mg in morning and 10 mg in afternoon), afternoon dose can be omitted and SST carried out between 0800-0900 next day
• after the test and while awaiting result, revert to maintenance dose
• In primary adrenal failure:
• add fludrocortisone 50-100 microgram oral daily
• request adrenal autoantibodies
• arrange chest and abdominal X-rays
• if TB suspected, request CT scan of adrenals
• If secondary adrenal failure suspected, refer to endocrinology team

• U&E daily
• Lying and standing BP twice daily, looking for orthostatic hypotension

• Patients must carry 'Steroid card' and wear 'Medic Alert bracelet'
• Patients must understand need for:
• lifelong hydrocortisone
• doubling the daily dose for the duration of any intercurrent illness
• parenteral hydrocortisone if vomiting (supply with ampoule of hydrocortisone 100 mg to keep in fridge for use by paramedics in emergency)
• Refer to endocrinology for follow-up