A 38-year-old woman from rural Maharashtra presents with progressive fatigue, weight loss, and hyperpigmentation over 6 months. Investigations reveal hyponatraemia (Na⁺ 125 mEq/L), hyperkalaemia (K⁺ 6.2 mEq/L), and elevated ACTH (180 pg/mL). A diagnosis of Addison disease is made. Which of the following is NOT a recognised feature or finding in primary adrenal insufficiency?

Explanation

## Addison Disease: Clinical and Biochemical Features ### Overview Primary adrenal insufficiency (Addison disease) results from destruction or dysfunction of the adrenal cortex, leading to deficiency of cortisol, aldosterone, and adrenal androgens. The pathophysiology and clinical manifestations are well-characterised. ### Electrolyte and Hormonal Abnormalities **Key Point:** The hallmark electrolyte disturbance in Addison disease is **hyponatraemia with hyperkalaemia** — a combination that is pathognomonic for primary adrenal insufficiency. | Feature | Mechanism | Finding | |---------|-----------|----------| | Hyponatraemia | Loss of aldosterone → ↓ Na⁺ reabsorption in collecting duct; also ADH elevation | Na⁺ typically 120–130 mEq/L | | Hyperkalaemia | Loss of aldosterone → ↓ K⁺ secretion in collecting duct | K⁺ typically 5.5–6.5 mEq/L | | Elevated ACTH | Loss of negative feedback from cortisol | ACTH > 100 pg/mL (often > 200) | | Elevated plasma renin | Hypovolaemia + loss of aldosterone feedback | Renin activity markedly elevated | | **Suppressed aldosterone** | Primary adrenal failure | Aldosterone < 5 ng/dL, often undetectable | **High-Yield:** The combination of **elevated renin + suppressed aldosterone** is diagnostic of primary adrenal insufficiency and distinguishes it from secondary insufficiency (where renin is low). ### Metabolic and Haematological Features 1. **Hypoglycaemia** - Loss of cortisol impairs gluconeogenesis and glycogenolysis - Fasting hypoglycaemia is common - Impaired response to glucagon (cortisol is required for glucagon's effect) 2. **Eosinophilia and Relative Lymphocytosis** - Cortisol normally suppresses eosinophils and lymphocytes - Loss of cortisol → eosinophilia (up to 5–10% of WBC) - Relative lymphocytosis (up to 40–50% of WBC) ### Why Hypertension and Alkalosis Are NOT Features **Warning:** Hypertension and metabolic alkalosis are **NOT** seen in Addison disease. Instead: - **Hypotension** (not hypertension) is characteristic — due to loss of both cortisol (needed for vascular tone) and aldosterone (needed for intravascular volume) - **Metabolic acidosis** (not alkalosis) may occur — due to renal hypoperfusion and accumulation of organic acids - Hyperkalaemia itself can cause acidosis (K⁺ shifts out of cells in exchange for H⁺ moving in) **Clinical Pearl:** A patient presenting with hyponatraemia, hyperkalaemia, and **hypotension** should immediately raise suspicion for Addison disease. Hypertension would suggest a different diagnosis (e.g., primary hyperaldosteronism, Cushing syndrome). ### Summary Table: Addison Disease vs. Cushing Syndrome | Finding | Addison Disease | Cushing Syndrome | |---------|-----------------|------------------| | Blood pressure | Hypotension | Hypertension | | Na⁺ | Low | Normal or high | | K⁺ | High | Low | | Metabolic pH | Acidosis | Alkalosis | | Eosinophils | Elevated | Suppressed | | ACTH | High (primary) | Low (secondary) | **Key Point:** The correct answer is **hypertension and metabolic alkalosis** — these are features of **Cushing syndrome** (cortisol excess), not Addison disease (cortisol deficiency).