Addison’s Disease (Adrenal Insufficiency)

Deficiency of cortisol (± aldosterone).

Causes

Primary (the adrenal gland itself — cortisol and aldosterone deficient):

• Autoimmune destruction of the adrenal cortex (~70%; female 10:1)
• Infection (TB, HIV), adrenal haemorrhage (acute stress/hypotension)
• Iron overload; infiltration (amyloidosis, lymphoma); adrenal surgery; genetic

Secondary (pituitary/ACTH — cortisol deficient, aldosterone preserved):

• Suppression by long-term corticosteroid therapy (the commonest cause overall)
• Previously treated Cushing’s syndrome; hypopituitarism; Sheehan syndrome (postpartum pituitary infarction)

Murtagh triad — fatigue + abdominal pain (± anorexia/nausea/vomiting) ± skin pigmentation.

Clinical features

Lethargy/weakness, anorexia/nausea, diarrhoea/abdominal pain, weight loss, dizziness/syncope, and skin hyperpigmentation (mouth, palmar creases — from ACTH, so primary only). Signs: hyperpigmentation, dehydration, postural hypotension.

Investigations

• Biochemistry: ↑K⁺, ↓Na⁺; low morning (8–9 am) plasma cortisol — <140 nmol/L with ACTH >2× the upper limit of normal is highly likely to be primary adrenal insufficiency, and >365 nmol/L makes it highly unlikely.
• Short Synacthen (ACTH stimulation) test — the mainstay: baseline cortisol, then synthetic ACTH, then cortisol at 30–60 min; Addison’s fails to respond. Withhold steroids on the day of the test.
• Adrenal (adrenocortical) antibodies — present in ~2/3 of autoimmune cases.
• For a suspected autonomous/secondary picture, a dexamethasone suppression test and aldosterone:renin ratio (off interfering antihypertensives — can switch to verapamil/hydralazine/moxonidine) help characterise the axis.

Management

Specialist-guided lifelong replacement:

• Glucocorticoid — hydrocortisone (e.g. 12 mg mane / 8 mg nocte).
• Mineralocorticoid — fludrocortisone ~100 microgram daily (titrate to BP, K⁺, Na⁺ and plasma renin in the upper-normal range).
• Sick-day rules — increase glucocorticoid during illness (individualised, e.g. hydrocortisone 20 mg TDS for 2–3 days, then taper). Monitor BMD 2-yearly.

Addisonian crisis

An acute deficiency from increased demand (infection, trauma, surgery) or abrupt steroid cessation.

• Presentation: nausea/vomiting, abdominal pain, weakness/drowsiness → coma; hypotension → shock.
• Biochemistry: hypoglycaemia, hyponatraemia, hyperkalaemia, hypercalcaemia, raised urea/creatinine.
• Management: IV fluids + IV hydrocortisone 100 mg stat, then 50 mg 6-hourly; hospital admission.