What causes secondary hypertension?

Causes of Secondary Hypertension

Secondary hypertension is caused by specific, identifiable, and potentially correctable underlying conditions that affect approximately 10% of all hypertensive patients. 1, 2

Common Causes of Secondary Hypertension

Renal Causes

• Renal parenchymal disease (1-2% prevalence)

  • Clinical indicators: Urinary tract infections, obstruction, hematuria, urinary frequency, nocturia, analgesic abuse, family history of polycystic kidney disease, elevated creatinine, abnormal urinalysis 1
  • Physical findings: Abdominal mass (polycystic kidney disease), skin pallor
  • Screening: Renal ultrasound

• Renovascular disease (5-34% prevalence)

  • Clinical indicators: Resistant hypertension, abrupt onset/worsening hypertension, flash pulmonary edema, early-onset hypertension (especially in women with fibromuscular dysplasia) 1
  • Physical findings: Abdominal systolic-diastolic bruit, bruits over carotid or femoral arteries
  • Screening: Renal Duplex Doppler ultrasound, MRA, abdominal CT

Endocrine Causes

• Primary aldosteronism (8-20% prevalence in resistant hypertension)

  • Clinical indicators: Resistant hypertension, hypokalemia (spontaneous or diuretic-induced), muscle cramps/weakness, incidentally discovered adrenal mass, family history of early-onset hypertension 1
  • Physical findings: Arrhythmias (especially atrial fibrillation with hypokalemia)
  • Screening: Plasma aldosterone/renin ratio under standardized conditions
  • Confirmatory tests: Sodium loading test, adrenal CT scan, adrenal vein sampling

• Pheochromocytoma (uncommon)

  • Clinical indicators: Episodic headaches, sweating, palpitations, anxiety
  • Screening: Plasma free metanephrines or 24-hour urinary metanephrines 3

• Cushing's syndrome (uncommon)

  • Clinical indicators: Central obesity, moon face, buffalo hump, purple striae
  • Screening: Late-night salivary cortisol or overnight dexamethasone suppression test 3

• Thyroid disorders

  • Hyperthyroidism: Heat intolerance, weight loss, tachycardia
  • Hypothyroidism: Cold intolerance, weight gain, bradycardia
  • Screening: Thyroid-stimulating hormone (TSH) levels 1

Sleep Disorders

• Obstructive sleep apnea (25-50% prevalence in resistant hypertension)
  • Clinical indicators: Resistant hypertension, snoring, fitful sleep, breathing pauses, daytime sleepiness 1
  • Physical findings: Obesity, Mallampati class III-IV, loss of normal nocturnal BP fall
  • Screening: Berlin Questionnaire, Epworth Sleepiness Score, overnight oximetry
  • Confirmatory test: Polysomnography

Vascular Causes

• Aortic coarctation (uncommon)
  • Clinical indicators: Early-onset hypertension, upper/lower extremity BP differential
  • Physical findings: Weak femoral pulses, systolic murmur
  • Screening: Echocardiography, CT angiography 4

Drug and Substance-Related Causes

• Medications:

  • NSAIDs and COX-2 inhibitors
  • Oral contraceptives
  • Sympathomimetics (decongestants, diet pills)
  • Corticosteroids
  • Erythropoietin
  • Cyclosporine and tacrolimus
  • Antidepressants (MAOIs, SNRIs)
  • Anticancer therapies (VEGF inhibitors, tyrosine kinase inhibitors) 1

• Substances:

  • Alcohol (heavy consumption)
  • Illicit drugs (cocaine, amphetamines)
  • Herbal supplements (ephedra, ma huang) 1

• Dietary factors:

  • Excessive sodium intake (>10g/day)
  • Licorice (glycyrrhizic acid) 1

Clinical Indicators for Secondary Hypertension Evaluation

1. Age-related factors:

   • Onset before age 30 (especially before puberty)
   • New onset after age 50 4, 5

2. Hypertension characteristics:

   • Resistant hypertension (BP >140/90 mmHg despite three optimal-dose medications including a diuretic)
   • Malignant or accelerated hypertension
   • Sudden deterioration in previously controlled BP
   • Hypertensive emergency 1, 3

3. Laboratory abnormalities:

   • Unprovoked hypokalemia
   • Elevated creatinine
   • Abnormal urinalysis 1

4. Response to therapy:

   • Poor response to conventional therapy
   • Acute rise in creatinine (>50%) after starting ACE inhibitors or ARBs (suggests renovascular disease) 5

Diagnostic Approach

1. Basic screening for all hypertensive patients:

   • Complete blood count
   • Fasting blood glucose or HbA1c
   • Serum electrolytes (sodium, potassium)
   • Renal function (creatinine, eGFR)
   • Lipid profile
   • Thyroid-stimulating hormone
   • Urinalysis
   • 12-lead ECG 1, 3

2. Targeted testing based on clinical suspicion:

   • For suspected primary aldosteronism: Aldosterone-to-renin ratio
   • For suspected renovascular disease: Renal Duplex Doppler ultrasound
   • For suspected sleep apnea: Sleep study (polysomnography)
   • For suspected pheochromocytoma: Plasma or urinary metanephrines 3

Management Principles

1. Treat the underlying cause:

   • Primary aldosteronism: Mineralocorticoid receptor antagonists or adrenalectomy for unilateral disease
   • Renovascular disease: Medical therapy (preferred for atherosclerotic disease), angioplasty for fibromuscular dysplasia
   • Sleep apnea: CPAP therapy, weight loss
   • Drug-induced: Discontinue or substitute offending agent 1

2. Specialist referral when appropriate:

   • Endocrinology for hormonal causes
   • Nephrology for renal causes
   • Sleep medicine for sleep apnea
   • Vascular surgery for renovascular disease or coarctation 3

Pitfalls and Caveats

1. Avoid missing secondary causes in high-risk patients:

   • Young patients (<30 years)
   • Patients with resistant hypertension
   • Patients with suggestive clinical or laboratory findings 1, 5

2. Consider drug-induced hypertension before extensive workup:

   • Review all medications, including OTC and herbal supplements
   • Anticancer therapies can cause significant hypertension in 80-90% of patients 1

3. Recognize that multiple factors may contribute to hypertension:

   • Secondary causes may coexist with primary hypertension
   • Multiple secondary causes may be present simultaneously 6

4. Be aware that secondary causes are more common in:

   • Resistant hypertension (up to 20% have primary aldosteronism)
   • Severe hypertension (>180/110 mmHg)
   • Hypertension with target organ damage disproportionate to duration 1