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Endocrinology & Metabolic

Addison's Disease

Primary adrenal insufficiency: the cortex fails, so cortisol and usually aldosterone are lost together, and any physiological stress can tip a stable patient into adrenal crisis.

In a nutshell

Primary adrenal insufficiency: cortisol and usually aldosterone are lost, giving fatigue, weight loss, postural hypotension, hyperpigmentation, hyponatraemia and hyperkalaemia. If adrenal crisis is suspected, give hydrocortisone 100 mg intramuscularly or intravenously immediately and 1 litre of 0.9% sodium chloride intravenously over 30 minutes.

Classic presentation

A 35-year-old with months of fatigue, weight loss and salt craving, tanned palmar creases, postural dizziness, sodium 126 mmol/L and potassium 6.1 mmol/L, now vomiting after a flu-like illness.

Key points

  • Exogenous glucocorticoid is the commonest cause of adrenal insufficiency overall. Suspect it after more than 4 weeks of treatment by any route, or more than 3 weeks under 16.
  • The physiological equivalent total daily dose is hydrocortisone 15 mg to 25 mg, prednisolone 3 mg to 5 mg, or dexamethasone 0.5 mg.
  • Short Synacthen test: cortisol before and 30 minutes after 250 micrograms tetracosactide (brand name Synacthen). The licence calls a rise of 200 nmol/L, to above 500 nmol/L, normal.
  • Do not test cortisol while the person takes oral glucocorticoids at physiological equivalent doses or above. Wait 4 weeks after an intramuscular or intra-articular injection.
  • Stop oral oestrogen 6 weeks before a cortisol test: it raises cortisol binding globulin and falsely elevates the result.
  • Testing during glucocorticoid withdrawal: pause prednisolone 24 hours, hydrocortisone 12 hours or dexamethasone 72 hours before the sample.
  • Postural hypotension here means a fall of 20 mmHg or more in blood pressure from lying to standing, and it is one of the earliest signs.
  • Addison's disease is rare and usually presents between the ages of 30 and 50. Autoimmune adrenalitis is the commonest adult cause in the UK.

First-line investigation

An 8 am to 9 am serum cortisol: below 150 nmol/L needs endocrinology referral, 150 to 300 nmol/L is uncertain and repeated, above 300 nmol/L makes it very unlikely.

Management

Adrenal crisis: treat, then think

  • Hydrocortisone 100 mg intramuscularly or intravenously, immediately, on suspicion alone. Anyone can give the intramuscular dose, including the patient from their own kit. No overdose risk.1,6,2
  • 1 litre of 0.9% sodium chloride intravenously over 30 minutes, then more guided by haemodynamics and electrolytes until stable. Monitor blood pressure, heart rate, electrolytes and glucose.1,2
  • 999 ambulance to hospital, no referral needed. Check capillary glucose and an ECG. Treat hyperkalaemia in parallel, using the UK Kidney Association thresholds.1,4

Keep it running until the gut works

  • Hydrocortisone 200 mg over 24 hours by continuous intravenous infusion in glucose 5%, or 50 mg intramuscularly or intravenously every 6 hours.1,6
  • 100 mg every 6 hours in severe obesity. Continue until haemodynamically stable and absorbing oral glucocorticoids. Identify and treat the precipitant, and refer to endocrinology.6,1
  • Then at least 40 mg oral hydrocortisone daily in 2 to 4 divided doses, or at least 10 mg oral prednisolone daily, until the cause resolves.1

Lifelong replacement

  • Hydrocortisone 15 mg to 25 mg total daily dose orally, in 2 to 4 divided doses in primary disease and 2 to 3 in secondary or tertiary. Larger dose in the morning.1
  • If multiple daily doses do not suit: prednisolone 3 mg to 5 mg daily, or modified-release hydrocortisone. Never give routine replacement by pump or injection.1
  • Primary disease also needs fludrocortisone: initially 50 micrograms total daily dose orally, adjusted to response up to 300 micrograms. Never give a mineralocorticoid in secondary or tertiary disease.1
  • Monitor fludrocortisone with lying and standing blood pressure and electrolytes, and consider renin. Above 300 micrograms daily was off-label in August 2024.1

Sick-day rules, with the numbers

  • Significant physiological stress: at least 40 mg oral hydrocortisone daily in 2 to 4 divided doses, or at least 10 mg prednisolone daily, until the illness resolves.1
  • Already on 10 mg prednisolone daily or more? No extra dose needed. Split the usual total daily dose into 2 equal doses instead.1
  • Vomits within 30 minutes of a dose: repeat at double the dose once vomiting settles. Vomits again within 30 minutes: intramuscular hydrocortisone, then the emergency department.1
  • Severely unwell in hospital or in intensive care: 200 mg intravenous hydrocortisone over 24 hours, or 50 mg intramuscularly or intravenously 4 times a day.1
  • Severe mental health crisis: consider sick-day dosing, and 100 mg intramuscular hydrocortisone if oral treatment is impossible. Hyperemesis gravidarum: 100 mg intramuscularly at once, then admit.1
  • For surgery and invasive procedures NICE sets no dose of its own and points to Woodcock et al, tables 1 and 2.1

The kit and the two cards

  • Kit: one vial of hydrocortisone, sodium phosphate 100 mg/1 mL premixed or sodium succinate 100 mg powder with water for injection, two blue needles, two 2 mL syringes.1
  • Plus written instructions with diagrams and steroid emergency cards. Train the person and their carers, and check expiry dates. Never stop glucocorticoids abruptly.1,4
  • NHS Steroid Emergency Card: primary adrenal insufficiency; hypopituitarism needing replacement; prednisolone 5 mg daily or equivalent for 4 weeks or more, across all routes.6,7,3
  • Card also for prednisolone 40 mg daily or equivalent for over 1 week, repeated short oral courses, or a course within 1 year of stopping long-term therapy.6,3
  • The blue steroid treatment card is different: for people on glucocorticoids for non-endocrine conditions who are at risk of tertiary insufficiency.1

Review

  • Ask about adherence, how often emergency doses were needed, sick-day understanding and previous crises. Watch for under-replacement (weight loss, nausea, fatigue) and over-replacement (weight gain, hypertension, fractures).1
  • Measure lying and standing blood pressure, electrolytes, HbA1c (glycated haemoglobin) and lipids, with bone density once in the 5 years after diagnosis.1

Exam traps

  • Never wait for a cortisol result or a Synacthen test before treating a suspected crisis. There is no overdose risk and the diagnosis survives treatment.
  • Hyperpigmentation may be invisible on black or brown skin. Ask about a change in colour and look at the buccal mucosa and surgical scars.
  • Hyperkalaemia points to primary disease. Aldosterone is preserved in secondary and tertiary insufficiency, so those patients must not be given a mineralocorticoid.
  • NICE makes no short Synacthen test recommendation and sets no peak cortisol cut-off. The threshold is assay-dependent and comes from your own laboratory.
  • Vomiting after a hydrocortisone tablet is an absorption emergency. After the second failed dose the route changes, not the tablet.
  • NICE uses hydrocortisone 15 mg to 25 mg daily for routine replacement; the BNF lists 20 mg to 30 mg. Follow the endocrine plan.
  • The cortisol thresholds hold only for an 8 am to 9 am sample on a modern immunoassay in someone not taking glucocorticoids.
  • Do not carry out routine cortisol day series to check hydrocortisone dosing.
  • Call 999 even after a successful self-administered emergency injection: the patient still needs hospital.

Illustrations

Adrenal cortex hormone lossDiagram of the adrenal cortex zones showing combined loss of cortisol, aldosterone and androgen production in autoimmune Addison's disease.PassFinals · original
Generalised hyperpigmentation in Addison's diseaseHistorical clinical illustration showing the diffuse bronze facial pigmentation associated with primary adrenal insufficiency.Fæ, Wikimedia Commons · CC-BY-4.0
Short Synacthen test result patternGraph comparing a normal brisk cortisol rise after synthetic ACTH against the blunted response seen in adrenal insufficiency.PassFinals · original

Key sources

  1. NICE, Adrenal insufficiency: identification and management (NG243. Section 1.2 and table 1 (when to suspect, cortisol thresholds), section 1.3 and table 2 (replacement, emergency kits), section 1.4 (physiological stress, pregnancy), section 1.5 (psychological stress), sections 1.6 and 1.7 (adrenal crisis), section 1.8 and box 1 (monitoring), section 1.9 (glucocorticoid withdrawal))Published 28 Aug 2024 | Updated 18 Dec 2024
  2. Society for Endocrinology endocrine emergency guidance: Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients (Endocrine Connections, September 2016, reviewed 2019 with no changes. Hydrocortisone 100 mg bolus then 200 mg per 24 hours, the 24-hour fluid volume, the 20 mmHg postural drop and the short Synacthen protocol)Published 1 Sept 2016
  3. Specialist Pharmacy Service and Society for Endocrinology, Exogenous steroids treatment in adults: adrenal insufficiency and adrenal crisis, who is at risk and how should they be managed safely (March 2021, endorsed by the Society for Endocrinology and the British Association of Dermatologists. Which glucocorticoid exposures suppress the axis, and who needs a Steroid Emergency Card)Published 10 Mar 2021
  4. NHS, Addison's disease (Patient-facing overview: who it affects, causes, the emergency injection kit, the steroid emergency card, and when to call 999)Updated 19 Sept 2025
  5. Synacthen Ampoules 250 micrograms, Summary of Product Characteristics, electronic medicines compendium (Section 4.2, the 30-minute Synacthen diagnostic test: dose, route, sampling times and the normal-response threshold)Updated 18 Dec 2024
  6. BNF, Hydrocortisone (Adrenal crisis in steroid-dependent patients with adrenal insufficiency, adult indication: initial 100 mg dose, 200 mg per 24 hours by continuous infusion diluted in glucose 5%, 50 mg every 6 hours as an alternative, 100 mg every 6 hours in severe obesity. For routine Addison's replacement it lists 20 to 30 mg daily in 2 divided doses. Also the Royal College of Physicians and Society for Endocrinology Steroid Emergency Card criteria. Open access, but the page does not render to automated tools; verbatim extract at reports/textbook-source-packs/batch02/hydrocortisone.md)
  7. NHS England, National Patient Safety Alert: Steroid Emergency Card to support early recognition and treatment of adrenal crisis in adults (NatPSA/2020/005/NHSPS. Four deaths and four critical care admissions from omitted steroid in a two-year reporting period, and the actions required of prescribers and providers)Published 13 Aug 2020 | Updated 31 Oct 2024
  8. BNF, Fludrocortisone acetate (Consulted for dosing in hepatic or renal impairment, pregnancy and breastfeeding, as NICE NG243 table 2 directs. Open access, but the page does not render to automated tools)

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.