Which of the following laboratory findings is characteristic of primary adrenal insufficiency (Addison disease)?

Explanation

## Laboratory Diagnosis of Primary Adrenal Insufficiency **Key Point:** Primary adrenal insufficiency is characterized by **elevated ACTH with low cortisol** due to loss of negative feedback from the failing adrenal gland. ### Pathophysiology of ACTH–Cortisol Axis in Addison Disease ```mermaid flowchart TD A[Hypothalamus secretes CRH]:::action --> B[Anterior pituitary secretes ACTH]:::action B --> C{Adrenal cortex intact?}:::decision C -->|Yes| D[Cortisol secretion ↑]:::outcome D --> E[Negative feedback to hypothalamus & pituitary]:::action E --> F[ACTH suppressed]:::outcome C -->|No - Addison Disease| G[Cortisol secretion ↓]:::urgent G --> H[Loss of negative feedback]:::urgent H --> I[ACTH rises compensatorily]:::urgent I --> J[High ACTH + Low Cortisol]:::outcome ``` ### Laboratory Findings in Addison Disease | Parameter | Primary Adrenal Insufficiency | Secondary Adrenal Insufficiency | Normal | |-----------|-------------------------------|----------------------------------|--------| | **Cortisol (8 AM)** | Low (<5 µg/dL) | Low (<5 µg/dL) | 10–20 µg/dL | | **ACTH** | **High (>100 pg/mL)** | Low or normal (<50 pg/mL) | 10–50 pg/mL | | **Aldosterone** | Low | Normal or low | Variable | | **Renin** | High | Normal or low | Normal | | **Sodium** | Low (hyponatremia) | Low (hyponatremia) | 135–145 mEq/L | | **Potassium** | High (hyperkalemia) | Normal | 3.5–5.0 mEq/L | **High-Yield:** The **elevated ACTH with low cortisol** is the diagnostic hallmark of primary adrenal insufficiency. This pattern distinguishes it from secondary/tertiary insufficiency (low ACTH, low cortisol). ### Diagnostic Approach **Mnemonic:** **ACTH-UP** — In primary insufficiency, ACTH goes UP while cortisol goes DOWN. 1. **Baseline 8 AM cortisol** — If <5 µg/dL, highly suggestive of insufficiency. 2. **ACTH level** — High (>100 pg/mL) confirms primary; low/normal confirms secondary. 3. **Short ACTH stimulation test (250 µg IV)** — No rise in cortisol (remains <18 µg/dL at 30–60 min) confirms primary insufficiency. 4. **Electrolytes** — Hyponatremia + hyperkalemia support primary (aldosterone deficiency). **Clinical Pearl:** The combination of **hyponatremia + hyperkalemia + high ACTH + low cortisol** is virtually pathognomonic for primary adrenal insufficiency.