What is the approach to managing secondary hypertension?

Approach to Secondary Hypertension

The evaluation and management of secondary hypertension requires systematic screening for specific causes in patients with clinical features suggesting underlying etiologies, followed by targeted diagnostic testing and cause-specific treatment. 1

When to Suspect Secondary Hypertension

Secondary hypertension should be considered in patients with:

• Onset of hypertension before age 30 or after age 50 1, 2
• Severe or resistant hypertension (BP >140/90 mmHg despite three optimal-dose medications including a diuretic) 3, 1
• Sudden deterioration in previously controlled BP 1
• Target organ damage disproportionate to hypertension duration 1
• Specific clinical features suggesting secondary causes:
  • Hypokalemia (primary aldosteronism)
  • Abdominal bruits (renovascular disease)
  • Snoring, daytime sleepiness (obstructive sleep apnea)
  • Cushingoid features (Cushing's syndrome)
  • Diminished femoral pulses (coarctation of aorta) 1, 4

Diagnostic Approach

Initial Evaluation

1. Comprehensive physical examination focusing on:

   • Blood pressure in both arms and legs (coarctation)
   • Abdominal bruits (renovascular disease)
   • Cushingoid features (moon facies, striae, central obesity)
   • Fundoscopic examination for retinopathy
   • Thyroid examination 3, 1

2. Basic laboratory screening:

   • Complete blood count
   • Comprehensive metabolic panel (including electrolytes, creatinine, eGFR)
   • Urinalysis
   • 12-lead ECG 1

Targeted Diagnostic Testing

Based on clinical suspicion, order specific tests:

Suspected Cause	Recommended Screening Test
Primary aldosteronism	Aldosterone-to-renin ratio
Renovascular hypertension	Renal Doppler ultrasound, CT/MR angiography
Pheochromocytoma	24h urinary/plasma metanephrines
Obstructive sleep apnea	Overnight polysomnography
Renal parenchymal disease	Renal ultrasound, urinalysis, eGFR
Cushing's syndrome	24h urinary free cortisol, dexamethasone suppression
Thyroid disease	TSH
Hyperparathyroidism	PTH, calcium, phosphate
Coarctation of aorta	Echocardiogram, CT angiogram [1]

Important Diagnostic Considerations

• Medication interference: Beta-blockers, NSAIDs, and alpha-2 agonists can cause false positives in aldosterone-renin testing, while ACE inhibitors, ARBs, and diuretics can cause false negatives 1
• Confirmation testing: For primary aldosteronism, a positive screening test should be followed by confirmatory testing (saline suppression test or 24-hour urinary aldosterone on high-sodium diet) 5
• Ambulatory BP monitoring: Essential to rule out white-coat hypertension and confirm true resistant hypertension 3, 1

Management Approach

Cause-Specific Treatment

1. Primary aldosteronism:

   • Unilateral disease: Adrenalectomy
   • Bilateral disease: Mineralocorticoid receptor antagonists (spironolactone, eplerenone) 1, 5

2. Renovascular hypertension:

   • Fibromuscular dysplasia: Renal angioplasty
   • Atherosclerotic disease: Optimal CV risk management with consideration of stenting 1

3. Obstructive sleep apnea:

   • CPAP therapy
   • Weight loss
   • Mandibular advancement devices 1, 6

4. Pheochromocytoma:

   • Surgical removal after adequate alpha-blockade
   • Alpha-blockers must be initiated before beta-blockers 1

Pharmacological Management

For resistant hypertension while addressing the underlying cause:

1. Optimize current regimen:

   • Maximize diuretic therapy (consider loop diuretics for eGFR <30 ml/min/1.73m²)
   • Ensure medication adherence 3, 1

2. Add fourth-line agents:

   • Spironolactone (first choice for resistant hypertension)
   • Alternative options: amiloride, doxazosin, eplerenone, clonidine, or beta-blockers 1

3. Consider beta-blockers for persistent hypertension secondary to increased sympathetic tone 3

Lifestyle Modifications

Essential adjunctive measures include:

• Weight loss (5-10% reduction)
• Sodium restriction (<1,500 mg/day)
• Regular physical activity (150+ minutes/week)
• DASH diet pattern
• Alcohol moderation 1

Follow-up and Monitoring

• Regular BP monitoring (home and office)
• Periodic assessment of target organ damage
• Monitor for medication side effects, particularly hyperkalemia and renal function
• Target BP should be 120-129 mmHg systolic if tolerated 1

Common Pitfalls to Avoid

• Overlooking secondary causes in resistant hypertension (affects 5-10% of hypertensive patients) 4, 2
• Failing to withdraw interfering medications before hormonal testing 1
• Premature discontinuation of antihypertensive medications after treating the secondary cause, as residual hypertension is common 6
• Initiating beta-blockers before alpha-blockers in pheochromocytoma (can precipitate hypertensive crisis) 1
• Not considering medication-induced hypertension (NSAIDs, oral contraceptives, decongestants, etc.) 7, 2

Remember that even after successful treatment of secondary causes, blood pressure rarely returns completely to normal due to vascular remodeling or concomitant essential hypertension, highlighting the importance of early detection and comprehensive management 6.