How is secondary hypertension diagnosed and managed?

Secondary Hypertension: Diagnosis and Management

Secondary hypertension, which accounts for approximately 10% of all hypertension cases, requires targeted screening and specific treatment approaches to address the underlying causes and reduce cardiovascular morbidity and mortality. 1

When to Suspect Secondary Hypertension

• Early onset (<20 years) or late onset (>50 years) hypertension
• Severe hypertension (>180/110 mmHg) or resistant hypertension (BP >140/90 mmHg despite three optimal-dose medications including a diuretic)
• Sudden deterioration in previously controlled BP
• Target organ damage disproportionate to hypertension duration
• Specific clinical features suggesting secondary causes
• Poor response to conventional therapy 2, 3

Diagnostic Approach

Initial Evaluation

• Comprehensive history focusing on:

  • Duration and previous levels of high blood pressure
  • Symptoms suggesting secondary causes
  • Intake of substances that raise BP (liquorice, cocaine, NSAIDs, oral contraceptives, steroids)
  • Family history of hypertension or related disorders 2

• Physical examination targeting:

  • Features of Cushing syndrome (truncal obesity, purple striae)
  • Skin stigmata of neurofibromatosis (pheochromocytoma)
  • Enlarged kidneys (polycystic kidney disease)
  • Abdominal bruits (renovascular hypertension)
  • Precordial murmurs (aortic coarctation)
  • Diminished femoral pulses (aortic coarctation) 2

Laboratory Investigations

• Basic screening tests:
  • Blood tests: electrolytes, creatinine, eGFR, fasting glucose, lipid profile, TSH, calcium
  • Urinalysis and urinary albumin-to-creatinine ratio
  • 12-lead ECG 2, 1

Specialized Tests for Specific Causes

Suspected Cause	Recommended Screening Test
Primary aldosteronism	Aldosterone-to-renin ratio
Renovascular hypertension	Renal Doppler ultrasound, CT/MR angiography
Pheochromocytoma	24h urinary/plasma metanephrines and normetanephrines
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 [2]

Management Strategies for Common Secondary Causes

Primary Aldosteronism

• Diagnosis: Elevated aldosterone-to-renin ratio (ARR)
• Treatment options:
  • Unilateral disease: Adrenalectomy
  • Bilateral disease: Mineralocorticoid receptor antagonists (spironolactone, eplerenone) 2, 1
• Medication considerations:
  • Many medications affect ARR testing (see table below)
  • Ideally withdraw interfering medications 2-4 weeks before testing 2

Renovascular Hypertension

• Diagnosis: Renal Doppler ultrasound, CT/MR angiography
• Treatment approach:
  • Fibromuscular dysplasia (<40 years): Renal angioplasty without stenting
  • Atherosclerotic disease (>60 years): Optimal CV risk management, consider stenting for flash pulmonary edema or acute kidney injury 2, 1
• Medical therapy: RAS blockers with caution (monitor for acute kidney injury) 1

Obstructive Sleep Apnea

• Diagnosis: Overnight polysomnography (AHI >5 confirms diagnosis)
• Treatment options:
  • Weight loss (primary intervention)
  • CPAP therapy
  • Mandibular advancement devices 2, 1
• BP pattern: Often shows non-dipping or reverse-dipping on 24h monitoring 2

Pheochromocytoma/Paraganglioma

• Diagnosis: Plasma or 24h urinary metanephrines and normetanephrines
• Treatment: Surgical removal after adequate alpha-blockade
• Medication preparation: Alpha-blockers must be initiated before beta-blockers to prevent hypertensive crisis 2, 1

Drug-Induced Hypertension

• Common culprits: NSAIDs, oral contraceptives, sympathomimetics, steroids, immunosuppressants
• Management: Discontinue or substitute offending agent when possible 1, 4

Approach to Resistant Hypertension

1. Rule out pseudo-resistance:

   • Confirm medication adherence
   • Exclude white-coat hypertension with 24h ABPM
   • Ensure proper BP measurement technique 1

2. Optimize current regimen:

   • Maximize diuretic therapy
   • Consider loop diuretics for eGFR <30 ml/min/1.73m² 1

3. Add fourth-line agent:

   • Spironolactone (first choice)
   • Alternatives: amiloride, doxazosin, eplerenone, clonidine, beta-blockers 1

4. Consider specialist referral for:

   • Renal denervation evaluation
   • Complex cases requiring multidisciplinary management 1

Important Considerations

• Despite treating the underlying cause, BP rarely returns completely to normal due to vascular remodeling or concomitant essential hypertension 5
• Early detection and treatment are crucial to prevent irreversible vascular changes 5
• Medications affecting aldosterone-renin testing should be carefully managed:
  • False positives: Beta-blockers, NSAIDs, alpha-2 agonists
  • False negatives: ACE inhibitors, ARBs, diuretics 2

Treatment Goals

• Target BP should be 120-129 mmHg systolic if tolerated 1
• Single-pill combinations improve adherence 1
• Regular monitoring of BP (home and office) and periodic assessment of target organ damage are essential 1