What initial investigations are recommended for a young adult under 40 with newly diagnosed hypertension to evaluate secondary causes?

Initial Investigations for Young Hypertension

All young adults under 40 with newly diagnosed hypertension should undergo a comprehensive baseline laboratory panel including serum electrolytes, creatinine with eGFR, urinary albumin-to-creatinine ratio, fasting glucose or HbA1c, lipid profile, TSH, and a 12-lead ECG, with the 2024 ESC guidelines now recommending universal aldosterone-to-renin ratio screening in all confirmed hypertensive patients. 1, 2, 3

Why Young Hypertension Demands Heightened Vigilance

Secondary hypertension affects approximately 5-10% of all hypertensive adults but this prevalence rises substantially in younger patients, with up to 10% of hypertensive young adults having an identifiable, potentially reversible cause. 4, 5, 6 The most common etiologies in this age group include:

• Primary aldosteronism (8-20% of resistant cases) 1
• Renovascular disease, particularly fibromuscular dysplasia in young women 1, 7
• Renal parenchymal disease 1
• Coarctation of the aorta 1
• Endocrine disorders (pheochromocytoma, Cushing syndrome) 6

The ESC 2024 guidelines represent a paradigm shift by recommending comprehensive screening for secondary causes in all adults diagnosed before age 40, except obese young adults where obstructive sleep apnea should be prioritized first. 2

Mandatory Baseline Laboratory Panel

Core Metabolic and Renal Assessment

• Serum creatinine and eGFR to detect chronic kidney disease and establish baseline renal function 8, 3
• Serum sodium and potassium – spontaneous or diuretic-induced hypokalemia strongly suggests primary aldosteronism 8, 1, 3
• Urinary albumin-to-creatinine ratio (not dipstick alone) to identify early kidney damage and cardiovascular risk 8, 3

Cardiovascular Risk Stratification

• Fasting glucose or HbA1c to screen for diabetes mellitus, which significantly elevates cardiovascular risk 8, 3
• Fasting lipid profile (total cholesterol, LDL-C, HDL-C, triglycerides) for atherosclerotic risk quantification 8, 3
• Thyroid-stimulating hormone (TSH) to detect hypo- or hyperthyroidism, both reversible causes of hypertension 8, 3

Hematologic Assessment

• Complete blood count (hemoglobin/hematocrit) to detect anemia or other hematologic abnormalities that may affect blood pressure control 8, 3

Cardiac Evaluation

• 12-lead electrocardiogram to identify left ventricular hypertrophy, atrial fibrillation, and ischemic heart disease 8, 3

Universal Aldosterone-Renin Ratio Screening: The New Standard

The 2024 ESC guidelines (Class IIa recommendation) now advise measuring the plasma aldosterone-to-renin ratio (ARR) in all adults with confirmed hypertension, representing a major departure from selective screening approaches. 1, 2 This recommendation reflects the recognition that primary aldosteronism is substantially underdiagnosed and accounts for 8-20% of resistant hypertension cases. 1

Critical Medication Considerations for ARR Testing

• ACE inhibitors and ARBs lower aldosterone and raise renin, potentially causing false-negative results 1
• Beta-blockers and direct renin inhibitors lower renin levels, affecting interpretation 1
• Mineralocorticoid receptor antagonists raise aldosterone levels 1

Targeted Physical Examination Findings

Red-Flag Signs Requiring Immediate Further Investigation

• Radio-femoral pulse delay → coarctation of the aorta; measure thigh blood pressure in all patients ≤30 years 8, 1, 3
• Abdominal systolic-diastolic bruits → renovascular disease 8, 1
• Palpable enlarged kidneys → polycystic kidney disease or renal parenchymal disease 8, 1
• Neck circumference >40 cm → obstructive sleep apnea (present in 25-50% of resistant hypertension) 8, 1
• Central obesity with thin extremities, wide purple striae, easy bruising → Cushing syndrome 8, 1
• Enlarged thyroid gland → thyroid dysfunction 8, 1

When to Proceed to Advanced Imaging

Echocardiography Indications

• Abnormal ECG findings (left ventricular hypertrophy, arrhythmias) 8, 3
• Cardiac symptoms (dyspnea, chest pain, reduced exercise capacity) 1
• Optional but valuable: All newly diagnosed hypertensive patients when resources permit, as echocardiographic findings predict cardiovascular events over 5 years 1

Renal Imaging Indications

Renal Doppler ultrasound should be obtained when: 8, 1

• Moderate-to-severe chronic kidney disease is present
• Renovascular hypertension is suspected (abrupt onset, flash pulmonary edema, ≥50% creatinine rise within one week of starting ACE-inhibitor/ARB)
• Renal parenchymal disease is suspected (recurrent UTIs, hematuria, palpable kidneys)

CT or MR renal angiography for definitive diagnosis of renovascular disease after positive Doppler findings 8, 1

Clinical Red Flags Mandating Secondary Cause Work-Up

Beyond age <40, these features demand immediate investigation: 8, 1, 2, 9, 6, 4

• Resistant hypertension (BP >140/90 mmHg despite optimal doses of ≥3 drugs including a diuretic)
• Severe hypertension (systolic >180 mmHg or diastolic >110 mmHg)
• Abrupt onset or sudden worsening of previously controlled hypertension
• Target organ damage disproportionate to duration or severity of hypertension
• Hypertensive emergency or grade III-IV retinopathy

Confirmatory Testing Based on Initial Screening Results

If ARR is Elevated (>20 with elevated aldosterone and suppressed renin)

• Intravenous saline suppression test or oral sodium-loading test for biochemical confirmation 8, 1
• Adrenal CT imaging for lesion localization 8, 1
• Adrenal vein sampling when surgical intervention is contemplated 8, 1
• Referral to endocrinology or hypertension specialist 8, 1

If Clinical Features Suggest Pheochromocytoma (Episodic Sweating, Palpitations, Headaches)

• 24-hour urinary metanephrines/normetanephrines or plasma free metanephrines 8, 1
• Abdominal/adrenal CT or MRI after biochemical confirmation 8, 1

If Cushing Syndrome is Suspected (Central Obesity, Purple Striae, Easy Bruising)

• Late-night salivary cortisol or 24-hour urinary free cortisol 8, 1
• Low-dose dexamethasone suppression test 1

If Renovascular Disease is Suspected

• Renal Doplex Doppler ultrasound as initial imaging 8, 1
• CT or MR renal angiography for confirmation 8, 1

Common Pitfalls to Avoid

• Do not rely on urine dipstick alone – always order quantitative albumin-to-creatinine ratio, which is more sensitive for early kidney damage 3
• Do not skip the ECG even in young patients – it is essential for detecting left ventricular hypertrophy and arrhythmias 3
• Do not assume primary hypertension based on age alone – secondary causes affect up to 10% of young hypertensive adults 6, 5
• Do not order expensive imaging before completing basic laboratory screening 1
• Do not forget to assess medication adherence before extensive secondary work-up – non-adherence accounts for a large share of apparent resistant hypertension 1
• Do not overlook white-coat hypertension – use ambulatory or home blood pressure monitoring to confirm diagnosis (occurs in 20-30% of apparent resistant cases) 1

Specialist Referral Criteria

Refer to hypertension specialist or endocrinologist when: 8, 1

• Positive screening tests (elevated ARR, abnormal hormonal screens) require confirmatory testing
• Complex procedures such as adrenal vein sampling are needed
• Surgical intervention is being considered (e.g., unilateral adrenalectomy for primary aldosteronism)
• BP remains uncontrolled after ≥6 months of optimal medical therapy