A 48-year-old woman with resistant hypertension (BP 165/105 mmHg on triple therapy) and hypokalemia (K⁺ 3.1 mEq/L) is suspected to have primary aldosteronism. Plasma aldosterone is elevated at 18 ng/dL (normal <15), and plasma renin activity is suppressed at 0.3 ng/mL/hr (normal 0.6–1.6). Which investigation is most appropriate to confirm the diagnosis?

## Diagnosis: Primary Aldosteronism (Suspected) The clinical triad—resistant hypertension, hypokalemia, and elevated aldosterone-to-renin ratio (ARR = 18/0.3 = 60, normal <20)—is highly suggestive of primary aldosteronism. The next step is **confirmatory testing** before subtype localization. ## Confirmatory Test: Saline Suppression Test **Key Point:** The **0.9% saline suppression test** is the gold-standard confirmatory test for primary aldosteronism. - **Protocol:** Infuse 0.9% NaCl 500 mL/hr for 4 hours (total 2 L) - **Interpretation:** - **Aldosterone >10 ng/dL after suppression** = confirms primary aldosteronism - **Aldosterone <5 ng/dL after suppression** = excludes primary aldosteronism - **5–10 ng/dL** = indeterminate **High-Yield:** Saline suppression is the **most specific** confirmatory test because it directly tests the kidney's ability to suppress aldosterone in response to sodium loading and volume expansion. ## Why Saline Suppression Over Captopril? | Test | Mechanism | Sensitivity | Specificity | Use | |------|-----------|-------------|------------|-----| | Saline suppression | Volume expansion → ↓ renin → ↓ aldosterone | 90% | 95% | **Gold standard for confirmation** | | Captopril challenge | ACE inhibition → ↑ renin → ↓ aldosterone | 85% | 80% | Alternative; less specific | **Clinical Pearl:** Captopril test is less reliable because some aldosterone-producing adenomas can show paradoxical aldosterone rise with ACE inhibition. Saline suppression is more physiologically sound and reproducible. ## Investigation Sequence for Primary Aldosteronism ```mermaid flowchart TD A[Resistant HTN + hypokalemia]:::outcome --> B[Measure ARR: aldosterone/renin]:::action B --> C{ARR > 20?}:::decision C -->|Yes| D[Saline suppression test]:::action D --> E{Aldosterone > 10 ng/dL after 2L saline?}:::decision E -->|Yes| F[Primary aldosteronism confirmed]:::outcome E -->|No| G[Diagnosis excluded]:::outcome F --> H[CT or MRI to localize]:::action H --> I{Unilateral adenoma?}:::decision I -->|Yes| J[Adrenal venous sampling for confirmation]:::action I -->|No| K[Bilateral hyperplasia - medical management]:::action ``` ## When to Use Adrenal Venous Sampling **Key Point:** Adrenal venous sampling (AVS) is **NOT** a confirmatory test; it is a **subtype localization** test used AFTER primary aldosteronism is confirmed. AVS determines whether the aldosterone excess is from a unilateral adenoma (surgical candidate) or bilateral hyperplasia (medical management).