Addison's Disease

🔍 When to Suspect

Persistent fatigue, unexplained weight loss, muscle weakness, and hyperpigmentation, especially with a history of autoimmune disease or unexplained hypotension, salt craving, or hypoglycaemia

From the full topic in The Ocean Library: Addison's Disease

🧭 When to suspect Addison's disease

Addison's disease (primary adrenal insufficiency) is autoimmune destruction of the adrenal cortex, producing a deficiency of cortisol and aldosterone. The presentation is insidious and the symptoms are non-specific, so the diagnosis is notoriously delayed – many patients see more than one clinician before it is considered, and around half are only diagnosed after presenting in adrenal crisis, which can be rapidly fatal.

Suspect it in anyone with unexplained hyperpigmentation, or with no other explanation for persistent fatigue, unexplained weight loss, muscle weakness, nausea or vomiting, salt craving, dizziness or postural symptoms, hyponatraemia or hyperkalaemia. In children also think of hypoglycaemia, faltering growth, early puberty, hypotensive crisis and prolonged neonatal jaundice. Hyperpigmentation favours skin creases, recent scars and the buccal mucosa – but may not be visible on black or brown skin, so ask whether the person has noticed a change in their skin colour.

Raise your index of suspicion further in people with other autoimmune disease (type 1 diabetes, autoimmune thyroid disease, vitiligo, pernicious anaemia, coeliac disease, premature ovarian insufficiency), those who have recently stopped glucocorticoids (taken for > 4 weeks if aged 16 and over, or > 3 weeks if under 16), and those on opioids, checkpoint inhibitors, antifungals or antiretrovirals. The two clinical skills that matter are: suspect it early and check an 8–9 am cortisol, and never miss an adrenal crisis.

Addison's disease is rare – affecting roughly 1 in 10,000 people (around 110–140 per million) – but can occur at any age, is about 1.8× more common in women, and most often presents between 30 and 50 years.

🧠 Clinical pearl Starting levothyroxine in someone with unrecognised Addison's can precipitate an adrenal crisis: thyroid hormone increases the metabolic clearance of cortisol, unmasking the deficiency. If a patient with co-existing autoimmune disease deteriorates rather than improves after levothyroxine is started, think adrenal insufficiency – and in dual deficiency, replace glucocorticoid before thyroid hormone.

Source: NICE NG243 · BJGP 2015

---