## Investigation of Choice for Primary Aldosteronism Screening **Key Point:** The aldosterone-to-renin ratio (ARR) is the gold standard screening test for primary aldosteronism in patients with resistant hypertension and spontaneous hypokalemia. ### Rationale for Correct Answer In primary aldosteronism, there is **autonomous aldosterone secretion** independent of the renin-angiotensin system. This results in: - **High PAC** (typically >15 ng/dL) - **Suppressed plasma renin activity (PRA)** (typically <1 ng/mL/hr) - **ARR > 20–30** (varies by lab; ARR >20 is highly suggestive) The ARR effectively identifies the pathognomonic pattern: **high aldosterone with low renin**. **High-Yield:** ARR is the **first-line screening test** for primary aldosteronism. A positive ARR (>20–30) mandates confirmatory testing (saline suppression test, captopril challenge, or fludrocortisone suppression test) before imaging. ### Investigation Algorithm ```mermaid flowchart TD A[Resistant HTN + Hypokalemia]:::outcome --> B[Measure ARR<br/>PAC and PRA]:::action B --> C{ARR > 20-30?}:::decision C -->|Yes| D[Confirmatory test<br/>Saline suppression or<br/>Captopril challenge]:::action C -->|No| E[Primary aldosteronism<br/>unlikely]:::outcome D --> F{Aldosterone<br/>suppressed?}:::decision F -->|No| G[Adrenal imaging<br/>CT ± AVS]:::action F -->|Yes| H[Secondary cause<br/>or false positive]:::outcome G --> I[Subtype classification<br/>Adenoma vs. hyperplasia]:::outcome ``` **Clinical Pearl:** Hypokalemia in the setting of resistant hypertension is a red flag for primary aldosteronism and warrants ARR screening. The combination of **high BP, low K+, and suppressed renin** is virtually diagnostic. **Tip:** Ensure patient is **off spironolactone and ACE inhibitors/ARBs for 4–6 weeks** before ARR measurement to avoid false negatives, as these drugs suppress aldosterone and elevate renin, respectively. [cite:Harrison 21e Ch 297]
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