Addison Disease (Adrenal Insufficiency)

Related Subjects: |Adrenal Physiology |Addisons Disease |Phaeochromocytoma |Adrenal Adenomas |Adrenal Cancer |Cushing Syndrome |Cushing Disease |Congenital Adrenal hyperplasia |Primary hyperaldosteronism (Conn's syndrome) |ACTH |McCune Albright syndrome

⚠️ Diagnostic tests must NEVER delay treatment of a suspected adrenal crisis. 💉 Immediate IV hydrocortisone is lifesaving and safe, even if the diagnosis is not yet confirmed. 📊 Each year ~8% of patients with Addison’s Disease experience adrenal crisis, usually needing an emergency IM hydrocortisone injection.

🚑 Initial Emergency Management (Pigmented, Hypotensive)

• 🫁 ABC, secure IV access, send bloods: U&E, glucose, cortisol, ACTH
• 💧 Start IV fluids: 1 L 0.9% Saline over 6 h; treat any hypoglycaemia
• 🧪 If stable → do short Synacthen test before steroids
• 💊 If unstable → give Hydrocortisone 100 mg IV stat, then q6–8h
• 📈 Titrate fluids & steroids to BP/HR and clinical response
• 📞 Refer to Endocrine team → convert to oral replacement once stable
• 🧾 Common causes: abrupt steroid withdrawal, Addison’s disease, congenital adrenal hyperplasia, hypopituitarism, acute illness

💊 Patients on ≥5 mg prednisolone (or equivalent) for >4 weeks are at risk of adrenal atrophy and crisis during acute illness, surgery or trauma.

📖 Introduction

• Rare: 0.8–1 per 100,000
• Loss of cortisol + mineralocorticoid can be insidious or life-threatening
• Look for hypotension + pigmentation + hypoglycaemia → always screen if suspected

🧬 Aetiology

• Cortisol & aldosterone essential for life
• Demand ↑ during stress (infection, trauma)
• ACTH drives cortisol; RAAS drives aldosterone
• Loss of adrenal medulla = surprisingly no sequelae

🧾 Types

• Primary – adrenal failure (Addison’s)
• Secondary – pituitary ACTH deficiency
• Tertiary – abrupt withdrawal of chronic steroids or treatment of Cushing’s

🔎 Causes

• Autoimmune adrenalitis (Addison’s)
• Infection: TB, HIV, CMV, meningococcal sepsis (Waterhouse-Friderichsen)
• Infiltration: sarcoid, amyloid
• Vascular: adrenal infarction, haemorrhage
• Drugs: ketoconazole, rifampicin, metyrapone
• Neoplastic: metastases (lung, breast, lymphoma)
• Congenital adrenal hyperplasia
• Rare syndromes: Wolman’s, Schilder’s

🩺 Clinical Features

• Fatigue, weight loss, anorexia, diarrhoea
• 🟤 Hyperpigmented palmar creases, buccal mucosa (primary)
• GI: vomiting, abdominal pain
• Acute crisis: shock, postural hypotension, tachycardia, hypoglycaemia
• Secondary causes: pale skin, pituitary features (hypogonadism, visual loss)
• Loss of body hair in women, vitiligo

🧪 Investigations

• FBC: lymphocytosis, eosinophilia
• Electrolytes: ↓Na⁺, ↑K⁺, metabolic acidosis
• Glucose: ↓, Creatinine: ↑ (pre-renal)
• Morning cortisol & ACTH, short Synacthen test
• Adrenal antibodies (21-hydroxylase)
• TFTs, plasma renin/aldosterone
• Imaging: CXR (TB, small heart), Adrenal CT/MRI

💉 Management of Acute Crisis

• IV access + send urgent bloods
• 1 L 0.9% Saline stat over 2 h
• 50 ml 50% dextrose if hypoglycaemic
• Hydrocortisone 100 mg IV stat, then 50–100 mg IV/IM q6h or infusion (200 mg/24h)
• Treat underlying infection or trigger
• Primary disease: glucocorticoid + mineralocorticoid
• Secondary disease: glucocorticoid only

🏥 Long-Term Replacement

• Hydrocortisone 20–30 mg/day in divided doses (e.g. 15 mg AM, 5 mg PM)
• Double dose if unwell (“sick day rules”)
• ± Fludrocortisone 50–200 mcg OD (if mineralocorticoid deficient)
• All patients carry steroid card + emergency hydrocortisone injection kit

🛡️ Sick Day Rules

• Rule 1: Double oral glucocorticoid during febrile illness needing antibiotics/bed rest
• Rule 2: IM/IV hydrocortisone during vomiting, surgery, trauma
• Teach self-injection + provide emergency kit
• Wear medical alert bracelet + carry steroid emergency card

References

• Leicester UHL Adrenal Crisis Guideline
• Emergency Management of Acute Adrenal Insufficiency
• Addison’s Disease UK – Adrenal Crisis Emergency