How can primary (essential) hypertension be distinguished from secondary hypertension?

Differentiating Primary from Secondary Hypertension

Screen all patients with confirmed hypertension using plasma aldosterone-to-renin ratio (ARR), as secondary causes affect 5-10% of all hypertensive patients and up to 20% of resistant cases, with primary aldosteronism being the most common treatable cause. 1, 2

Clinical Red Flags Requiring Secondary Hypertension Workup

Age and Presentation Patterns:

• Onset before age 30 years, especially without family history of hypertension 1, 2, 3
• Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 drugs including a diuretic) 1, 2
• Abrupt onset or sudden deterioration of previously well-controlled hypertension 1, 2, 4
• Severe hypertension (>180/110 mmHg) or hypertensive emergency 1, 3
• Target organ damage disproportionate to duration or severity of hypertension 1, 2

Specific Symptoms Suggesting Secondary Causes

Primary Aldosteronism (8-20% of resistant hypertension):

• Spontaneous or substantial diuretic-induced hypokalemia 1
• Muscle weakness, tetany, cramps, or arrhythmias 1, 2
• Family history of early-onset hypertension or stroke at young age (<40 years) 1, 2

Renovascular Disease:

• Flash pulmonary edema 1, 2, 4
• Serum creatinine increase ≥50% within one week of starting ACE inhibitor or ARB 2, 4
• Abdominal systolic-diastolic bruit on examination 2, 4
• Severe hypertension with unilateral smaller kidney or kidney size difference >1.5 cm 2, 4

Pheochromocytoma:

• Episodic sweating, palpitations, and frequent headaches 1, 2
• Labile or paroxysmal hypertension 1, 2

Obstructive Sleep Apnea (25-50% of resistant hypertension):

• Snoring, witnessed apneas, and daytime sleepiness 1, 2
• Obesity with neck circumference >40 cm 1, 2
• Non-dipping or reverse-dipping pattern on 24-hour BP monitoring 1, 2, 3

Cushing Syndrome:

• Central obesity with thin extremities, purple striae, easy bruising 1, 5
• Proximal muscle weakness, moon facies, buffalo hump 1, 5

Renal Parenchymal Disease:

• History of urinary tract infections, obstruction, hematuria, or nocturia 2
• Family history of polycystic kidney disease 2

Essential Initial Laboratory Screening

Complete this basic panel before expensive imaging: 2, 5, 6

• Plasma aldosterone-to-renin ratio (ARR) - now recommended for all confirmed hypertension (Class IIa) 1, 5, 6
• Serum electrolytes (sodium, potassium) - hypokalemia strongly suggests primary aldosteronism 1, 5
• Serum creatinine and estimated glomerular filtration rate (eGFR) 1, 5
• Urinalysis with microscopy and urinary albumin-to-creatinine ratio 1, 5
• Fasting blood glucose or HbA1c 1, 5
• Thyroid-stimulating hormone (TSH) 1, 5
• Fasting lipid panel 1, 5
• 12-lead ECG to assess for left ventricular hypertrophy 1, 5

Physical Examination Findings

Cardiovascular Assessment:

• Radio-femoral delay (coarctation of aorta) 1, 2
• Abdominal bruits (renovascular disease) 1, 2
• Jugular venous distension, peripheral edema (flash pulmonary edema pattern) 1

Endocrine/Metabolic Signs:

• Fatty deposits and colored striae (Cushing syndrome) 1, 2
• Enlarged thyroid 1
• Enlarged kidneys on palpation 1, 2

Targeted Confirmatory Testing Based on Clinical Suspicion

For Primary Aldosteronism (if ARR positive - ratio >20 with elevated aldosterone):

• Oral sodium loading test with 24-hour urine aldosterone or IV saline infusion test 1, 5
• Adrenal CT scan for localization after biochemical confirmation 1, 5
• Adrenal vein sampling if surgical intervention considered 1, 2

For Renovascular Disease:

• Renal Duplex Doppler ultrasound as initial imaging 1, 2, 6
• CT or MRI renal angiography for confirmation 1, 2

For Pheochromocytoma:

• 24-hour urinary metanephrines and normetanephrines or plasma free metanephrines 1
• Abdominal/adrenal imaging after biochemical confirmation 2

For Obstructive Sleep Apnea:

• Overnight ambulatory polysomnography (AHI >5 confirms diagnosis; severe if AHI >30) 1, 5, 6

For Cushing Syndrome:

• 24-hour urinary free cortisol or low-dose dexamethasone suppression test 1

Critical Pitfalls to Avoid

Medication Effects on Testing:

• Beta-blockers and direct renin inhibitors lower renin levels, causing false-positive ARR 2
• Mineralocorticoid receptor antagonists raise aldosterone levels 2
• ACE inhibitors and ARBs lower aldosterone and raise renin, causing false-negative ARR 1, 2

Diagnostic Sequence Errors:

• Never perform expensive imaging (CT, MRI, angiography) before completing basic laboratory screening 2, 6
• Avoid screening for pheochromocytoma without specific clinical features (episodic symptoms, labile hypertension) 2

Timing Issues:

• Delayed diagnosis leads to vascular remodeling and residual hypertension even after treating the underlying cause 2, 6
• Secondary hypertension is often underrecognized, maintaining high index of suspicion is essential 5, 7

When to Refer to Specialist

Referral is recommended for: 1, 6

• Positive screening tests requiring confirmatory testing
• Complex cases requiring specialized diagnostic procedures (adrenal vein sampling)
• Surgical intervention being considered (unilateral adrenalectomy for primary aldosteronism)
• Expertise needed in specific forms of secondary hypertension