A 48-year-old woman with newly diagnosed hypertension (BP 162/104 mmHg) is found to have a serum potassium of 2.8 mEq/L and serum sodium of 148 mEq/L on initial labs. She denies diuretic use. Which investigation is most appropriate to confirm the suspected diagnosis?

## Diagnostic Approach to Primary Aldosteronism **Key Point:** The clinical triad of **hypertension + hypokalemia + hypernatremia** without diuretic use is classic for primary aldosteronism (Conn syndrome). The **plasma aldosterone-to-renin ratio (ARR)** is the screening test of choice, but specific conditions must be met for accurate measurement. **High-Yield:** Plasma aldosterone and PRA must be measured in the **morning (8–10 AM) after 30 minutes of upright posture** to maximize aldosterone secretion and minimize renin suppression, ensuring optimal sensitivity and specificity for screening. ### Why This Investigation? **Standardized Screening Protocol:** 1. **Timing:** Morning measurement (8–10 AM) captures peak aldosterone levels 2. **Posture:** 30 minutes upright posture (sitting or standing) stimulates renin and aldosterone physiologically 3. **Calculation:** ARR = Plasma aldosterone (ng/dL) ÷ PRA (ng/mL/hr) 4. **Cutoff:** ARR >20–30 suggests primary aldosteronism (varies by lab); suppressed PRA (<1 ng/mL/hr) is confirmatory **Clinical Pearl:** Hypokalemia (K⁺ <3.5 mEq/L) in a hypertensive patient without diuretic use is a **red flag for hyperaldosteronism**. Hypokalemia causes metabolic alkalosis and increases risk of arrhythmias, making early diagnosis critical. ### Diagnostic Algorithm for Primary Aldosteronism ```mermaid flowchart TD A[HTN + Hypokalemia + Hypernatremia]:::outcome --> B[Measure plasma aldosterone & PRA<br/>Morning, after 30 min upright posture]:::action B --> C{ARR > 20-30?<br/>PRA suppressed?}:::decision C -->|Yes| D[Confirmatory test:<br/>Saline suppression test]:::action C -->|No| E[Primary aldosteronism<br/>unlikely]:::outcome D --> F{Aldosterone<br/>suppressed <4 ng/dL?}:::decision F -->|No| G[Primary aldosteronism<br/>confirmed]:::outcome F -->|Yes| H[Aldosterone suppression<br/>excludes diagnosis]:::outcome G --> I[Adrenal imaging:<br/>CT or MRI]:::action I --> J{Unilateral adenoma?}:::decision J -->|Yes| K[Adrenalectomy or<br/>MRA therapy]:::action J -->|No| L[Bilateral hyperplasia:<br/>Spironolactone/eplerenone]:::action ``` ### Comparison of Diagnostic Tests | Test | Timing/Conditions | Interpretation | Role | |---|---|---|---| | **Plasma aldosterone & PRA** | Morning, 30 min upright | ARR >20–30; PRA <1 ng/mL/hr | **Screening test** | | **Saline suppression test** | IV 1 L normal saline over 4 hrs | Aldosterone >4 ng/dL = diagnostic | **Confirmatory test** | | **Captopril challenge** | 25 mg PO, measure at 60 min | ARR remains >20–30 | Alternative confirmatory | | **Adrenal CT/MRI** | After biochemical confirmation | Unilateral adenoma vs. bilateral | **Localization** | | **Adrenal vein sampling** | Specialized centers | Aldosterone gradient >4:1 | Gold standard for lateralization | **Mnemonic:** **RAAS** — **R**enin-aldosterone **A**ssay **A**t **S**tandardized time (morning, upright posture). [cite:Harrison 21e Ch 297; KD Tripathi 8e Ch 12]