What is the recommended work-up and treatment for a patient with secondary hypertension?

Secondary Hypertension Work-up and Treatment

Screening for primary aldosteronism by renin and aldosterone measurements should be considered in all adults with confirmed hypertension (BP ≥ 140/90 mmHg), as secondary hypertension may be present in up to 10-20% of hypertensive patients. 1

Diagnostic Approach to Secondary Hypertension

Initial Evaluation

• Comprehensive screening is recommended for young adults (<40 years) with hypertension 1
• For patients with resistant hypertension, referral to specialized hypertension centers should be considered 1
• Objective evaluation of medication adherence (directly observed treatment or detecting prescribed drugs in blood/urine) should be considered in patients with apparent resistant hypertension 1

Laboratory and Diagnostic Tests

1. Basic tests for all hypertensive patients:

   • Blood tests: Sodium, potassium, serum creatinine, eGFR, fasting glucose, lipid profile 1, 2
   • Urine tests: Dipstick urinalysis, albumin-to-creatinine ratio 1, 2
   • 12-lead ECG to detect atrial fibrillation, left ventricular hypertrophy 1, 2

2. Specific tests based on suspected secondary causes:

Suspected Cause	Recommended Screening Test
Primary aldosteronism	Aldosterone-to-renin ratio [2]
Renovascular hypertension	Renal Doppler ultrasound, CT/MR angiography [2]
Pheochromocytoma	24h urinary/plasma metanephrines [2]
Obstructive sleep apnea	Overnight polysomnography [2]
Renal parenchymal disease	Renal ultrasound, urinalysis, eGFR [2]
Cushing's syndrome	24h urinary free cortisol, dexamethasone suppression [2]
Thyroid disease	TSH [2]
Hyperparathyroidism	PTH, calcium, phosphate [2]
Coarctation of aorta	Echocardiogram, CT angiogram [2]

When to Suspect Secondary Hypertension

• Age of onset <30 years (especially before puberty) 3
• Resistant hypertension (BP uncontrolled despite 3 medications) 3
• Malignant or accelerated hypertension 3
• Acute rise in BP from previously stable readings 3
• Presence of hypokalemia (suggesting aldosteronism) 4
• Renal bruit (suggesting renal artery stenosis) 5
• Increase in serum creatinine ≥50% after starting ACE inhibitor/ARB therapy 3
• Recurrent flash pulmonary edema 3

Treatment of Secondary Hypertension

General Approach

1. Treat the underlying cause while maintaining BP control 2
2. Continue antihypertensive therapy during diagnostic workup 2
3. Refer to specialists (endocrinologists, nephrologists, vascular surgeons) for complex cases 2

Specific Treatments Based on Etiology

Primary Aldosteronism

• Unilateral disease: Consider adrenalectomy 2
• Bilateral disease: Mineralocorticoid receptor antagonists (spironolactone 25-100 mg daily) 2, 6
• Monitor serum potassium and renal function 6

Renovascular Hypertension

• Fibromuscular dysplasia: Consider renal angioplasty 2
• Atherosclerotic disease: Medical therapy with optimal CV risk management 2
• RAS blockers (ACE inhibitors or ARBs) are effective but monitor for renal function deterioration 7

Pheochromocytoma

• Surgical removal after adequate alpha-blockade 2
• Alpha-blockers must be initiated before beta-blockers to prevent hypertensive crisis 2

Obstructive Sleep Apnea

• CPAP therapy and weight loss 2
• Mandibular advancement devices may be considered 2

Resistant Hypertension

Recommended treatment includes:

1. Reinforcement of lifestyle measures, especially sodium restriction 1

2. Addition of low-dose spironolactone (25 mg daily) to existing treatment 1

3. If intolerant to spironolactone, consider:

   • Eplerenone 1
   • Amiloride 1
   • Higher dose thiazide/thiazide-like diuretic 1
   • Loop diuretic 1
   • Addition of bisoprolol or doxazosin 1

4. For truly resistant cases, consider catheter-based renal denervation if performed at a medium-to-high volume center 1

Monitoring and Follow-up

• Regular BP monitoring (home and office) 2
• If moderate-to-severe CKD is diagnosed, repeat measurements of serum creatinine, eGFR, and urine ACR at least annually 1
• Monitor for medication side effects, particularly hyperkalemia and renal function deterioration 2
• Evaluate for target organ damage periodically 2

Important Considerations

• Early detection and treatment are crucial to prevent irreversible target organ damage 2
• The prevalence of secondary hypertension varies by age group: most common in children (renal disease), young adults (fibromuscular dysplasia in women), and older adults (atherosclerotic renal artery stenosis) 4
• Secondary hypertension is often underdiagnosed, with prevalence potentially as high as one-third of referred patients and up to half of those with difficult-to-treat hypertension 8
• Medication adherence should always be assessed before extensive workup for secondary causes 1