A 48-year-old woman from Mumbai with a 10-year history of hypertension is found to have a blood pressure of 142/92 mmHg despite being on amlodipine 5 mg daily. Her physician suspects secondary hypertension and orders investigations. Plasma renin activity (PRA) is low (0.3 ng/mL/hr; normal 0.6–1.6), and serum aldosterone is elevated at 18 ng/dL (normal 4–10). Serum potassium is 3.2 mEq/L (normal 3.5–5.0). What is the most likely diagnosis?

Explanation

## Diagnosis of Primary Hyperaldosteronism (Conn Syndrome) ### Clinical Presentation & Key Findings **Key Point:** The **suppressed plasma renin activity (PRA) with elevated aldosterone** is the diagnostic hallmark of **primary hyperaldosteronism**. This distinguishes it from secondary causes where renin would be elevated. ### Diagnostic Algorithm for Hypertension with Hypokalemia ```mermaid flowchart TD A[Hypertension + Hypokalemia]:::outcome --> B{Check PRA & Aldosterone}:::decision B -->|High renin, High aldosterone| C[Secondary Hyperaldosteronism]:::outcome B -->|Low renin, High aldosterone| D[Primary Hyperaldosteronism]:::action C --> E[Renovascular HTN or Renal disease]:::outcome D --> F[Aldosterone-secreting adenoma or bilateral hyperplasia]:::outcome B -->|Normal PRA, Normal aldosterone| G[Essential HTN or other secondary cause]:::outcome ``` ### Biochemical Profile in This Patient | Parameter | This Patient | Normal | Primary Hyperaldosteronism | Secondary Hyperaldosteronism | |-----------|--------------|--------|---------------------------|------------------------------| | **PRA** | 0.3 (LOW) | 0.6–1.6 | **SUPPRESSED** | Elevated | | **Aldosterone** | 18 (HIGH) | 4–10 | **ELEVATED** | Elevated | | **K⁺** | 3.2 (LOW) | 3.5–5.0 | **LOW** | Variable | | **BP** | 142/92 | <120/80 | Elevated | Elevated | **High-Yield:** The **aldosterone-to-renin ratio (ARR)** is the screening test. ARR = 18 ÷ 0.3 = **60** (normal <30). Ratio >30 is highly suggestive of primary hyperaldosteronism. ### Pathophysiology of Conn Syndrome 1. **Aldosterone-secreting adenoma** (or bilateral adrenal hyperplasia) produces aldosterone **independently** of renin 2. **Aldosterone effects:** - ↑ Sodium reabsorption in collecting duct → ↑ blood volume → ↑ BP - ↑ Potassium excretion → **hypokalemia** - ↑ H⁺ excretion → metabolic alkalosis 3. **Feedback suppression:** High blood volume and sodium → **suppresses renin secretion** → low PRA **Clinical Pearl:** The **suppressed renin in the face of hypokalemia and hypertension** is the key distinguishing feature. In secondary hyperaldosteronism (e.g., RAS, cirrhosis), renin would be elevated as it is the **driver** of aldosterone secretion. ### Confirmatory Tests - **Aldosterone suppression test:** Saline loading (2 L normal saline IV over 4 hrs) → aldosterone should suppress to <5 ng/dL in normal subjects but remains elevated (>10 ng/dL) in primary hyperaldosteronism - **Imaging:** CT/MRI adrenal to identify adenoma vs. bilateral hyperplasia - **Adrenal vein sampling:** Gold standard to lateralize aldosterone production **Mnemonic:** **SUPPRESSED RENIN + ELEVATED ALDOSTERONE = PRIMARY (Aldosterone-producing adenoma)** [cite:Harrison Principles of Internal Medicine 21e Ch 298; Endocrinology: An Integrated Approach Ch 8]