What are the secondary causes of hypertension and how are they managed?

Secondary Causes of Hypertension and Their Management

Secondary hypertension affects approximately 5-10% of all hypertensive patients and requires specific evaluation and targeted treatment to potentially cure or significantly improve blood pressure control.

Common Secondary Causes

Renal Causes

• Renal parenchymal disease: Presents with history of urinary tract infections, obstruction, hematuria, urinary frequency, nocturia, or family history of polycystic kidney disease 1
• Renovascular disease: Prevalence 5-34% in resistant hypertension; presents with abrupt onset or worsening hypertension, flash pulmonary edema, or early-onset hypertension (especially fibromuscular dysplasia in women) 1
  • Management: Renal artery revascularization shows limited benefit over medical therapy for atherosclerotic disease, but may be considered in specific cases 1

Endocrine Causes

• Primary aldosteronism: Affects 8-20% of resistant hypertension cases; presents with hypokalemia (spontaneous or diuretic-induced), muscle cramps/weakness, or family history of early-onset hypertension 1

  • Screening: Plasma aldosterone-to-renin ratio under standardized conditions 1
  • Management: Adrenalectomy for unilateral disease; mineralocorticoid receptor antagonists for bilateral disease 1

• Pheochromocytoma: Uncommon but dangerous; presents with episodic symptoms (headaches, palpitations, sweating), labile hypertension 1

  • Management: Surgical removal after appropriate alpha-blockade 1

• Other endocrine causes: Cushing's syndrome, hyperparathyroidism, thyroid disorders (hyper/hypothyroidism), and acromegaly 1

Sleep Disorders

• Obstructive sleep apnea: Present in 25-50% of resistant hypertension cases; associated with snoring, daytime sleepiness, obesity, and non-dipping nocturnal BP pattern 1
  • Management: Weight loss, CPAP therapy (especially for moderate to severe cases with AHI >15) 1
  • CPAP improves BP control and can resolve resistant hypertension 1

Drug and Substance-Induced Hypertension

• Medications: NSAIDs, oral contraceptives, decongestants, stimulants, corticosteroids, immunosuppressants (cyclosporine/tacrolimus), erythropoiesis-stimulating agents 1
• Substances: Alcohol (heavy intake), caffeine, nicotine, cocaine, amphetamines, herbal supplements 1
• Management: Discontinuation or dose reduction of offending agent when possible 1

Other Causes

• Aortic coarctation: More common in children but can present in adults; check for radio-femoral delay and BP difference between arms and legs 1
• Genetic causes: Liddle's syndrome, glucocorticoid-remediable aldosteronism 1

Clinical Clues Suggesting Secondary Hypertension

• Age of onset <30 years (especially before puberty) 1, 2
• Severe or resistant hypertension (BP remains >140/90 mmHg despite optimal doses of ≥3 antihypertensive medications including a diuretic) 1
• Abrupt onset or sudden deterioration of previously controlled hypertension 1
• Hypertensive urgency or emergency 1
• Onset of diastolic hypertension in older adults 1
• Target organ damage disproportionate to duration or severity of hypertension 1
• Presence of clinical features specific to secondary causes 1

Diagnostic Approach

1. Basic screening for all suspected cases:

   • Thorough history and physical examination focusing on specific clinical clues 1
   • Basic blood biochemistry (sodium, potassium, creatinine, eGFR) 1
   • Urinalysis, fasting blood glucose or HbA1c 1
   • Thyroid function tests (TSH) 1
   • ECG 1

2. Targeted screening based on clinical suspicion:

   • For primary aldosteronism: Plasma aldosterone-to-renin ratio under standardized conditions 1
   • For renovascular disease: Renal ultrasound, followed by duplex Doppler, MRA, or CT angiography 1
   • For obstructive sleep apnea: Berlin Questionnaire, Epworth Sleepiness Score, polysomnography 1
   • For pheochromocytoma: Plasma or 24-hour urinary metanephrines 1

Management Principles

1. Treat the underlying cause:

   • Renovascular disease: Medical therapy is first-line for atherosclerotic disease; consider revascularization for specific cases 1
   • Primary aldosteronism: Adrenalectomy for unilateral disease; mineralocorticoid receptor antagonists for bilateral disease 1
   • Obstructive sleep apnea: CPAP therapy for moderate-severe cases (AHI >15); weight loss and sleep hygiene for mild cases 1
   • Drug-induced: Discontinue or modify offending medications 1

2. Optimize antihypertensive therapy while addressing the underlying cause:

   • Use appropriate agents based on the specific secondary cause 1
   • For resistant hypertension, consider adding spironolactone (25mg daily) as fourth-line agent 2
   • Monitor for drug interactions and adverse effects, particularly with ACE inhibitors in renovascular disease 3

3. Lifestyle modifications:

   • Sodium restriction (<1500 mg/day) is particularly important in salt-sensitive patients 1
   • Limit alcohol consumption (excessive intake contributes to resistant hypertension) 1
   • Weight loss for obese patients, especially those with sleep apnea 1

Special Considerations

• Referral to specialists is recommended for complex cases or when specialized testing/treatment is needed 1, 2
• Monitor for residual hypertension even after treating the secondary cause, as vascular remodeling may have occurred 4
• ACE inhibitors and ARBs require careful monitoring in suspected renovascular disease, as they may cause acute kidney injury 3
• Young patients (<30 years) with hypertension warrant thorough evaluation for secondary causes even with normal initial screening 2

Common Pitfalls to Avoid

• Missing white coat hypertension: Confirm diagnosis with 24-hour ambulatory BP monitoring 2
• Inadequate medication review: Always check for substances that can elevate BP, including OTC medications 1
• Premature discontinuation of antihypertensive therapy: Even after treating secondary causes, many patients require continued antihypertensive therapy 4
• Overlooking non-adherence: Verify medication adherence before extensive workup for secondary causes 2
• Failure to recognize multiple causes: Secondary hypertension may have more than one contributing factor 1