What are the common causes of secondary hypertension?

Common Causes of Secondary Hypertension

Renal parenchymal disease is the most common cause of secondary hypertension, followed by renovascular disease, primary aldosteronism, and obstructive sleep apnea. 1

Most Frequent Causes by Prevalence

Renal Parenchymal Disease (Most Common)

• Affects 1-2% of all adults with hypertension, making it the leading cause of secondary hypertension 2, 3
• Clinical clues include history of recurrent urinary tract infections, urinary obstruction, hematuria, increased urinary frequency or nocturia, chronic analgesic abuse, or family history of polycystic kidney disease 2, 3
• Physical examination may reveal palpable abdominal masses (suggesting polycystic kidneys) or generalized pallor from chronic kidney disease 2
• Renal ultrasound is the first-line diagnostic test, providing anatomical data on kidney size, cortical thickness, urinary tract obstruction, and renal masses 1, 2

Renovascular Disease (Second Most Common)

• Prevalence is approximately 2% in the general hypertensive population, but increases dramatically to 5-34% in patients with resistant hypertension 1, 2
• Suspect this diagnosis with abrupt onset or worsening of hypertension, flash pulmonary edema, or early-onset hypertension especially in women (suggesting fibromuscular dysplasia) 3, 4
• In younger adults (<30 years), fibromuscular dysplasia is the predominant renovascular cause 2
• Atherosclerotic renal artery stenosis typically presents after age 50 years 5

Primary Aldosteronism

• Affects 8-20% of patients with resistant hypertension, making it a critical diagnosis in this population 2, 3, 4
• Clinical features include resistant hypertension, spontaneous or diuretic-induced hypokalemia (though normal potassium does not exclude the diagnosis), muscle cramps or weakness, incidentally discovered adrenal mass, or family history of early-onset hypertension or stroke 3, 4
• The European Society of Cardiology 2024 guidelines now recommend measuring plasma aldosterone-to-renin ratio in all adults with confirmed hypertension (Class IIa recommendation) 4

Obstructive Sleep Apnea

• Prevalence is 25-50% in patients with resistant hypertension 3, 4
• Identifying features include snoring, fitful sleep, breathing pauses during sleep, daytime sleepiness, obesity, Mallampati class III-IV airway, and loss of normal nocturnal blood pressure fall (non-dipping pattern) 3, 4

Less Common but Important Causes

Drug-Induced Hypertension

• Review all medications before pursuing expensive workup, including NSAIDs, oral contraceptives, decongestants, stimulants, and herbal supplements 3
• Heavy alcohol intake (≥30 drinks per week) significantly increases risk of treatment-resistant hypertension 3

Pheochromocytoma/Paraganglioma

• Uncommon but dangerous, presenting with episodic symptoms (headaches, palpitations, sweating), labile hypertension, and pallor 3, 4
• Screen with 24-hour urinary catecholamines or metanephrines 3

Cushing Syndrome

• Clinical features include weight gain, moon facies, buffalo hump, purple striae, and proximal muscle weakness 3
• Screen with 24-hour urinary free cortisol or overnight dexamethasone suppression test 3

Thyroid Disorders

• Hyperthyroidism causes isolated systolic hypertension; hypothyroidism causes diastolic hypertension 3
• Screen with thyroid-stimulating hormone 3

Aortic Coarctation

• Suspect in young patients with hypertension and diminished or delayed femoral pulses 3, 5
• Confirm with echocardiogram or CT/MR angiography 3

Clinical Red Flags Requiring Screening

Screen for secondary hypertension when any of the following are present: 3, 4

• Age of onset <30 years (or <40 years per ESC 2024 guidelines) 4, 5
• Resistant hypertension (BP >140/90 mmHg despite ≥3 antihypertensive drugs including a diuretic) 3, 6
• Severe hypertension (>180/110 mmHg) or accelerated/malignant hypertension 3, 6
• Abrupt onset or sudden deterioration of previously controlled hypertension 1, 3
• Hypertensive urgency or emergency 3
• Target organ damage disproportionate to duration or severity of hypertension 3
• Unprovoked hypokalemia 3

Diagnostic Approach Algorithm

Initial Screening (All Suspected Cases)

• Thorough medication review to exclude drug-induced causes 3
• Serum creatinine with eGFR calculation 2
• Urinalysis with albumin-to-creatinine ratio 2
• Serum electrolytes (sodium, potassium) 3, 4
• Fasting blood glucose or HbA1c 4
• Thyroid-stimulating hormone 3
• 12-lead ECG 4

Targeted Testing Based on Clinical Suspicion

• For primary aldosteronism: Plasma aldosterone-to-renin ratio, followed by confirmatory testing (saline suppression test), then CT adrenal imaging 3, 4
• For renovascular disease: Renal ultrasound with Doppler, followed by CT or MR renal angiography 3, 4
• For obstructive sleep apnea: Polysomnography or home sleep apnea testing 3
• For pheochromocytoma: 24-hour urinary catecholamines or metanephrines 3

Critical Pitfalls to Avoid

• Secondary hypertension is often underrecognized, affecting 5-10% of hypertensive patients overall but up to 20% in resistant hypertension 6, 7
• Do not perform expensive imaging studies before completing basic laboratory screening and excluding medication-induced causes 3, 4
• Normal potassium levels do not exclude primary aldosteronism—most patients with primary aldosteronism are normokalemic 4
• Delayed diagnosis leads to vascular remodeling and irreversible target organ damage, resulting in residual hypertension even after treating the underlying cause 4
• Certain antihypertensive medications interfere with aldosterone-to-renin ratio interpretation: mineralocorticoid receptor antagonists raise aldosterone, while beta-blockers and direct renin inhibitors lower renin 4