When should secondary hypertension be suspected?

When to Suspect Secondary Hypertension

Secondary hypertension should be suspected in patients with early-onset hypertension (<30 years of age), resistant hypertension, sudden deterioration in blood pressure control, hypertensive urgency/emergency, or when strong clinical clues suggest a secondary cause. 1, 2

Key Clinical Scenarios Warranting Investigation

• Early-onset hypertension (<30 years of age), particularly in the absence of typical risk factors like obesity, metabolic syndrome, or family history 1, 2
• Resistant hypertension (uncontrolled BP despite optimal doses of ≥3 antihypertensive drugs, including a diuretic) 1
• Abrupt onset or worsening of previously controlled hypertension 1, 2
• Hypertensive urgency or emergency 1
• Target organ damage disproportionate to the duration or severity of hypertension 2
• Specific clinical features suggestive of secondary causes (discussed below) 1, 2

Common Secondary Causes and Their Clinical Clues

1. Renal Parenchymal Disease (1-2% prevalence) 1, 2

• History of urinary tract infections, obstruction, hematuria
• Urinary frequency and nocturia
• Family history of polycystic kidney disease
• Elevated serum creatinine or abnormal urinalysis
• Physical finding: Abdominal mass (in polycystic kidney disease) 1, 2

2. Renovascular Disease (5-34% prevalence) 1, 2

• Abrupt onset or worsening hypertension
• Flash pulmonary edema (atherosclerotic disease)
• Early-onset hypertension, especially in women (fibromuscular dysplasia)
• Physical finding: Abdominal systolic-diastolic bruit 1, 2

3. Primary Aldosteronism (8-20% prevalence) 1, 2

• Resistant hypertension
• Hypokalemia (spontaneous or diuretic-induced)
• Muscle cramps or weakness
• Incidentally discovered adrenal mass
• Physical finding: Arrhythmias (with hypokalemia), especially atrial fibrillation 1, 2

4. Obstructive Sleep Apnea (25-50% prevalence) 1, 3

• Snoring, fitful sleep, breathing pauses during sleep
• Daytime sleepiness
• Obesity
• Non-dipping nocturnal BP pattern
• Physical findings: Obesity, large neck circumference 1, 2

5. Drug/Substance-Induced Hypertension 2, 4

• Temporal relationship between medication use and BP elevation
• Common culprits: NSAIDs, oral contraceptives, decongestants, stimulants, corticosteroids, erythropoietin, cyclosporine 2, 4

Diagnostic Approach

Initial Screening

• Thorough history and physical examination
• Basic blood biochemistry (including serum sodium, potassium, eGFR)
• Thyroid function tests (TSH)
• Dipstick urinalysis 1, 2

Further Investigations Based on Clinical Suspicion

• Renal disease: Renal ultrasound 1
• Renovascular disease: Renal duplex Doppler ultrasound, CT or MR angiography 1, 2
• Primary aldosteronism: Plasma aldosterone/renin ratio under standardized conditions 1, 2
• Obstructive sleep apnea: Home sleep apnea testing or overnight polysomnography 1
• Pheochromocytoma: Plasma or 24-hour urinary fractionated metanephrines 2, 5

Important Considerations

• Secondary hypertension affects 5-10% of the general hypertensive population but may be present in up to 30% of referred patients and 50% of those with difficult-to-treat hypertension 6, 5
• In patients with resistant hypertension, exclude pseudoresistant hypertension (poor adherence, white coat effect, improper BP measurement) and drug/substance-induced hypertension before extensive workup 1, 4
• Consider using 24-hour ambulatory BP monitoring to confirm the diagnosis of hypertension and rule out white coat hypertension 6, 5
• Even after treating the underlying cause, BP may not return to normal due to concomitant essential hypertension or irreversible vascular remodeling, highlighting the importance of early detection 6, 7
• Referral to a specialist center with appropriate expertise and resources should be considered for suspected secondary hypertension cases 1, 2

Pitfalls to Avoid

• Delaying investigation in young patients with hypertension, as secondary causes are more common in this population 1, 7
• Failing to consider medication-induced hypertension, particularly NSAIDs, which are widely used 4, 7
• Overlooking obstructive sleep apnea, which is one of the most common secondary causes, especially in patients with resistant hypertension 2, 3
• Not considering secondary hypertension in elderly patients, where atherosclerotic renal artery stenosis, renal failure, and thyroid disorders are common causes 7