Secondary Arterial Hypertension

When to Suspect Secondary Hypertension

• Resistant hypertension — BP uncontrolled on ≥3 medications including a diuretic
• Abrupt onset or sudden worsening of previously well-controlled BP
• Age of onset <35–40 years or new hypertension at >70 years
• Disproportionate target-organ damage relative to BP level
• Absence of typical primary HTN risk factors
• Hypertensive emergencies at presentation
• Unprovoked hypokalemia, proteinuria, or LV hypertrophy on workup

Major Causes of Secondary Hypertension

1. Obstructive Sleep Apnea (OSA)

• Affects 15–30% of adult men and 10–15% of adult women

• 50% of adults with OSA have hypertension; >30% of hypertensive adults have OSA

• Mechanism: Intermittent hypoxia → sympathetic activation, RAAS dysregulation, fluid redistribution
• Direct correlation between OSA severity and BP level / treatment resistance
• Clue: Obesity, excessive daytime somnolence, snoring, witnessed apnea
• Treatment: CPAP reduces SBP ~2–4 mmHg on average; benefit is greatest in severe OSA with resistant HTN

2. Renovascular Hypertension / Renal Artery Stenosis

• Cause: Atherosclerosis (older patients) or fibromuscular dysplasia (young women)
• Clue: Abdominal bruit, asymmetric kidney sizes, elevated plasma renin activity, >30% rise in creatinine after starting ACE inhibitor/ARB
• Screening: Duplex renal artery ultrasound, CT/MRI angiography; elevated plasma renin activity
• Treatment: Medical therapy is first-line in most cases. Renal artery stenting provides minimal average benefit (CORAL trial); revascularization reserved for carefully selected patients (bilateral stenosis, recurrent flash pulmonary edema)

3. Primary Aldosteronism (Conn Syndrome)

• Increasingly recognized — may affect up to 5–10% of hypertensive patients; the most common surgically correctable cause
• Mechanism: Autonomous aldosterone excess → sodium retention, hypokalemia, volume expansion, suppressed renin
• Clue: Unprovoked hypokalemia (though many are normokalemic), metabolic alkalosis
• Screening: Aldosterone-to-renin ratio (ARR)
• Confirmatory: Salt loading test, fludrocortisone suppression test
• Imaging: Adrenal CT; adrenal venous sampling (AVS) to lateralize
• Treatment: Unilateral adrenalectomy (adenoma) or mineralocorticoid receptor antagonist — spironolactone/eplerenone (bilateral hyperplasia)

4. Chronic Kidney Disease (CKD)

• Both a cause and consequence of hypertension
• Mechanism: Reduced nephron mass → impaired sodium excretion, RAAS activation, sympathetic activation
• Clue: Anemia, reduced GFR, proteinuria, small or echogenic kidneys on ultrasound
• Management: ACE inhibitors/ARBs (nephroprotective); sodium restriction; loop diuretics if volume overloaded

5. Hypothyroidism

• Mechanism: Reduced cardiac output, increased systemic vascular resistance, impaired renal sodium handling
• Clue: Fatigue, cold intolerance, constipation, bradycardia, elevated TSH
• Screening: TSH
• Treatment: Thyroid hormone replacement normalizes BP

6. Pheochromocytoma / Paraganglioma

• Mechanism: Episodic/sustained catecholamine excess (epinephrine, norepinephrine)
• Classic "5 Ps": Palpitations, Pain (headache), Pressure (high BP), Perspiration, Pallor
• Pattern: Paroxysmal or sustained hypertension; resistant to standard therapy
• Screening: Plasma free metanephrines — test of choice; negative predictive value >98%, minimally affected by medications, continuously elevated (non-cyclic tumour secretion)
• Confirmatory: Clonidine suppression test (if borderline); imaging: CT, MRI, MIBG scan for localization
• Treatment: Alpha-blockade first (phenoxybenzamine or doxazosin), then beta-blockade, then surgical resection

7. Hyperparathyroidism

• Clue: Hypercalcemia (bones, stones, groans, psychic moans), elevated PTH
• Hypercalcemia increases vascular resistance and renal sodium reabsorption
• Screening: Serum calcium, PTH

8. Coarctation of the Aorta

• Congenital narrowing of the aorta (typically distal to left subclavian artery)
• Clue: Upper extremity hypertension with lower extremity hypotension/weak pulses, radio-femoral delay, systolic murmur over the back, rib notching on CXR
• Suspect in young patients with hypertension

9. Drug-Induced / Exogenous Causes

• NSAIDs — sodium retention, prostaglandin inhibition
• Oral contraceptives (estrogen-containing) — RAAS activation
• Sympathomimetics (decongestants, cocaine, amphetamines)
• Corticosteroids / mineralocorticoids
• Cyclosporine / tacrolimus
• Erythropoietin
• Licorice (glycyrrhizin inhibits 11β-HSD2, causing apparent mineralocorticoid excess)

Diagnostic Approach — Summary Table

Key Points

1. Secondary hypertension is potentially curable — identifying the underlying cause matters
2. OSA is the most common secondary cause; pheochromocytoma the rarest but most dangerous
3. Resistant hypertension (≥3 drugs including a diuretic) is the strongest clinical trigger for a secondary workup
4. Plasma free metanephrines is the best screening test for pheochromocytoma
5. Aldosterone:renin ratio is the best screening test for primary aldosteronism
6. Drug history review is mandatory — many common medications elevate BP