What is Addison's disease?

Addison's disease (primary adrenal insufficiency, PAI) is failure of the adrenal cortex to produce adequate cortisol and aldosterone — most commonly from autoimmune destruction (~80% of cases in HICs; anti-21-hydroxylase antibodies). In LMICs: tuberculosis is the leading cause (bilateral adrenal destruction). Other causes: bilateral adrenal haemorrhage (Waterhouse-Friderichsen syndrome — meningococcal sepsis); metastatic cancer; sarcoidosis; adrenoleukodystrophy. Secondary AI (from pituitary failure) and tertiary AI (from hypothalamic failure or exogenous steroids) are distinct entities with different management.

What are the symptoms?

Symptoms develop insidiously over months to years: profound fatigue and weakness (most common); anorexia; nausea; weight loss; postural hypotension (dizziness on standing — from aldosterone deficiency); HYPERPIGMENTATION (bronze/brown — sun-exposed areas, mucosal surfaces, scars, skin creases — pathognomonic of PRIMARY AI only); salt craving; hyponatraemia; hyperkalaemia; hypoglycaemia; menstrual irregularity; depression. Hyperpigmentation is the key diagnostic clue — often the reason the correct diagnosis is finally made.

How is Addison's treated?

Lifelong hormone replacement: Cortisol: hydrocortisone 10mg on waking + 5mg at lunch + 5mg mid-afternoon (total ~15-25mg/day). Split to mimic diurnal variation. Modified-release hydrocortisone (Plenadren) once-daily — may offer metabolic advantages. Aldosterone: fludrocortisone 50-200μg once daily (morning). Monitor: sodium/potassium normal + renin upper normal + no postural hypotension. DHEA: 25-50mg daily — particularly benefits women (fatigue, sexual function, wellbeing) — ESE guidelines suggest consideration.

What are sick day rules?

Sick day rules are the critical patient-management protocol for increased cortisol demand: Mild illness (cold, low fever): double usual hydrocortisone. Significant illness (fever >38°C, infection, trauma): triple usual dose. Vomiting/diarrhoea (cannot absorb oral): emergency hydrocortisone 100mg IM injection kit immediately → then attend hospital for IV hydrocortisone + fluid resuscitation. If in doubt: inject. Sick day rules failure is the most common cause of preventable adrenal crisis.

How does GMJ News cover Addison's disease?

GMJ News covers adrenal crisis (100mg IV hydrocortisone immediately), hyperpigmentation as primary AI diagnostic clue, Short Synacthen test, ACTH distinguishing primary from secondary AI, sick day rules and emergency injection kit, APS-2 autoimmune associations, anti-21OH antibodies, hydrocortisone split dosing, fludrocortisone monitoring, surgical stress dosing, exogenous steroid-induced AI (most common cause globally), pregnancy management, and TB as dominant LMICs cause.

Home › Topics › Addison’s Disease

Addison’s Disease

GMJ News knowledge hub · last reviewed September 2026 · Georgian Medical Journal

Summary Statistics Glossary GMJ news FAQ Documents Organizations Research

Addison’s disease (primary adrenal insufficiency — PAI) — caused by autoimmune destruction of the adrenal cortex (approximately 80% of cases in HICs), tuberculosis (the leading cause in LMICs) or other rarer causes — results in deficiency of both cortisol and aldosterone, producing a characteristic clinical syndrome of fatigue, postural hypotension, hyperpigmentation (“tanned skin in all seasons” — from ACTH cross-reacting with MSH receptors), hyponatraemia and hyperkalaemia that, untreated, can progress to the life-threatening adrenal crisis (Addisonian crisis): cardiovascular collapse, profound hypoglycaemia and death (WHO). The short Synacthen test (synthetic ACTH 250μg IM/IV → cortisol <430 nmol/L at 30 or 60 minutes = adrenal insufficiency) is the standard diagnostic test, and every patient must carry a steroid emergency card and be trained in sick day rules (double or triple hydrocortisone dose during illness, fever or surgery) because adrenal crisis can occur from any physiological stress if replacement is not increased.

Key messages

Adrenal crisis — 100mg IV hydrocortisone immediately — do not wait

Adrenal crisis: sudden life-threatening cortisol deficiency — precipitated by physiological stress in a patient with adrenal insufficiency. Features: cardiovascular collapse; vomiting; hypoglycaemia; hyponatraemia; hyperkalaemia; altered consciousness. Treatment: IMMEDIATE hydrocortisone 100mg IV bolus → 200mg/24h continuous IV OR 50mg IM/IV 6-hourly + 1L normal saline. Do not delay for investigations — treat clinically if suspected.

Hyperpigmentation — pathognomonic for PRIMARY adrenal insufficiency

In primary AI: ACTH rises (lost negative cortisol feedback) → cross-reacts with MSH receptors → increased melanin → hyperpigmentation (bronze/brown in sun-exposed areas, mucosal surfaces — gums, tongue, buccal mucosa — and areas of friction). Pathognomonic for PRIMARY AI. Secondary AI (pituitary ACTH deficiency): no hyperpigmentation — pallor instead. The hyperpigmentation distinguishes Addison's disease from secondary/tertiary AI.

Short Synacthen test — the diagnostic gold standard

SST: synthetic ACTH (tetracosactide) 250μg IM or IV → cortisol at 0, 30, 60 minutes. Peak cortisol <430 nmol/L = adrenal insufficiency. SST does not distinguish primary from secondary AI (both may fail). Distinguish: serum ACTH (high in primary; low/normal in secondary) + aldosterone + renin.

Sick day rules — the patient-held emergency plan

Every AI patient must carry: (1) Steroid emergency card (and/or MedicAlert bracelet); (2) Written sick day rules: fever >37.5°C, vomiting, diarrhoea, or any intercurrent illness → DOUBLE or TRIPLE hydrocortisone dose; persistent vomiting/inability to absorb oral medication → SELF-INJECT 100mg hydrocortisone IM immediately (or attend hospital). For surgery → parenteral stress dosing. Sick day rules failure is the most common precipitant of preventable adrenal crisis.

Autoimmune Addison's — APS-2 and annual monitoring

Approximately 80% of Addison's in HICs is autoimmune (anti-21-hydroxylase antibodies positive in ~80%). Associated conditions: autoimmune thyroid disease (Hashimoto's/Graves' — most common, ~25%); type 1 DM; coeliac disease; premature ovarian insufficiency; vitiligo; pernicious anaemia. APS-2 (Schmidt's syndrome): Addison's + autoimmune thyroid + T1DM. Annual monitoring: TFTs; FBC (pernicious anaemia); coeliac antibodies.

Replacement therapy — hydrocortisone + fludrocortisone

Hydrocortisone split dosing to mimic diurnal cortisol: typically 10mg on waking + 5mg at lunch + 5mg mid-afternoon (total 15-25mg/day). Do not take too late — disrupts sleep. Modified-release hydrocortisone (Plenadren, Chronocort): once-daily, mimics dawn cortisol surge. Fludrocortisone: 50-200μg once daily for aldosterone deficiency — monitor sodium, potassium, lying/standing BP, renin.

Key statistics

~80%

of Addison's disease in HICs is autoimmune (anti-CYP21A2 antibodies)

ESE 2021

leading cause of Addison's disease globally (LMICs) — bilateral adrenal destruction

WHO

430 nmol/L

peak cortisol threshold (SST 30 or 60 min) — below = adrenal insufficiency

ESE/Endocrine Society

100mg IV

hydrocortisone IMMEDIATELY for adrenal crisis — do not delay for investigations

ESE/Endocrine Society

15-25mg

typical daily hydrocortisone replacement dose (split to mimic diurnal rhythm)

ESE 2021

Steroid card

mandatory for every AI patient — carry at all times; inject 100mg IM if vomiting

ESE/Society for Endocrinology

Addison's disease — primary vs secondary adrenal insufficiency: key differences

Source: ESE/Endocrine Society. ACTH distinguishes primary (high) from secondary (low); hyperpigmentation only in primary AI.

Glossary of key terms

HPA axis and AI types
EndocrinologyHypothalamic-pituitary-adrenal (HPA) axis: CRH (hypothalamus) → ACTH (anterior pituitary) → cortisol (adrenal cortex zona fasciculata). Primary AI (Addison's): adrenal gland destroyed → low cortisol + aldosterone → no negative feedback → ACTH rises. Secondary AI (hypopituitarism): pituitary ACTH deficiency → low cortisol → ACTH low. Tertiary AI: hypothalamic CRH deficiency OR exogenous corticosteroid suppression (most common cause of AI globally).

Anti-21-hydroxylase antibodies
Immunology/EndocrinologyAnti-CYP21A2 (anti-21-hydroxylase) antibodies present in ~80% of autoimmune Addison's. Can be detected years before clinical AI develops ("pre-clinical autoimmune adrenalitis phase"). Patients at risk (autoimmune thyroid, T1DM): annual 9am cortisol + ACTH. If 9am cortisol <130 nmol/L or borderline → SST. Anti-21OH-positive patients: ~20% develop clinical AI per decade.

Surgical stress dosing
Anaesthesia/EndocrinologyAI patients cannot mount normal surgical cortisol stress response. Stress dosing protocol (Society for Endocrinology): Minor (GA <45min, LA, dental): 25-50mg IV at induction + usual maintenance. Moderate (hip replacement, appendicectomy, laparoscopic cholecystectomy): 50mg IV at induction + 25mg 6-hourly × 24h + resume oral when tolerating. Major (cardiac, major abdominal): 100mg IV at induction + 50mg 6-hourly × 72h + taper to oral. Always inform anaesthetic and surgical teams.

Electrolytes in Addison's
BiochemistryAldosterone deficiency → reduced sodium retention + reduced potassium excretion → hyponatraemia (typically 125-135 mmol/L; severe in acute crisis) + hyperkalaemia (arrhythmia risk). Cortisol deficiency → impaired free water excretion → dilutional hyponatraemia contribution. Hypoglycaemia: reduced gluconeogenesis + enhanced insulin sensitivity → especially severe in children and acute crisis. Combination hyponatraemia + hyperkalaemia + hypoglycaemia in an unwell patient = Addison's until proven otherwise.

Exogenous steroid-induced AI (tertiary AI)
Pharmacology/EndocrinologyMost common cause of AI globally: long-term supraphysiological corticosteroids (prednisolone, dexamethasone, high-dose inhaled/topical corticosteroids) → HPA suppression → adrenal atrophy. Risk: ≥5mg prednisolone/day for >3 months. HPA recovery after stopping: weeks to months. Risk of adrenal crisis if: steroids abruptly withdrawn; physiological stressor occurs during recovery. Sick day rules, steroid card and SST testing apply equally to steroid-induced AI.

Pregnancy and Addison's
Obstetrics/EndocrinologyPregnancy increases cortisol requirements: hydrocortisone dose typically needs to increase 20-40% in third trimester (cortisol-binding globulin rises → free cortisol may decrease). Labour and delivery: stress dosing (100mg IM/IV at onset of active labour + 50mg 6-hourly during labour). Post-partum: careful taper. Neonatal HPA monitoring not required if mother on physiological replacement doses. Addison's typically does not worsen in pregnancy when well-managed.