What is the best course of action for a 42-year-old patient with worsening hypertension (HTN), new onset of fatigue, and pitting edema?

Immediate Evaluation for Secondary Hypertension

This 42-year-old patient with worsening hypertension, new-onset fatigue, and pitting edema requires urgent evaluation for secondary causes of hypertension, particularly renal parenchymal disease, primary aldosteronism, and renovascular disease, as these symptoms strongly suggest hypertension-mediated organ damage rather than primary hypertension.

Clinical Red Flags Present

This presentation contains multiple features that distinguish secondary from primary hypertension:

• Age <50 years with worsening hypertension suggests secondary causes rather than the gradual BP rise typical of primary hypertension 1
• New-onset fatigue with pitting edema indicates possible kidney disease or failure, which is explicitly listed as a historical feature favoring secondary hypertension 1
• Sudden worsening of previously controlled hypertension is a key clinical clue suggesting secondary hypertension 2

The combination of edema and fatigue in a relatively young patient with worsening hypertension has a high pretest probability for renal parenchymal disease or primary aldosteronism 1, 2.

Immediate Diagnostic Workup

Essential Laboratory Tests (Obtain Today)

Basic metabolic panel and renal function assessment:

• Serum creatinine with estimated glomerular filtration rate (eGFR) to detect kidney disease 1
• Serum sodium and potassium—hypokalemia suggests primary aldosteronism, which affects 8-20% of resistant hypertension cases 2
• Fasting blood glucose or HbA1c 1
• Complete blood count 1

Screening for primary aldosteronism (critical in this patient):

• Plasma aldosterone-to-renin ratio (ARR) should be obtained as initial screening, as the 2024 ESC guidelines now recommend measuring renin and aldosterone in all adults with confirmed hypertension (Class IIa recommendation) 2
• This is particularly important given the patient's age, worsening hypertension, and potential hypokalemia 2

Urinalysis and urine studies:

• Urinalysis to detect proteinuria, hematuria, or abnormal sediment suggesting renal parenchymal disease 1
• Urinary albumin-to-creatinine ratio to assess kidney damage 1

Additional baseline tests:

• Thyroid-stimulating hormone (TSH) 1
• Lipid profile 1
• Electrocardiogram to assess for left ventricular hypertrophy 1

Physical Examination Priorities

Focus on findings that suggest specific secondary causes:

• Cardiovascular exam: Assess for signs of volume overload (elevated JVP, S3 gallop, pulmonary rales) and check for radio-femoral delay suggesting coarctation 1, 2
• Abdominal exam: Palpate for enlarged kidneys (polycystic kidney disease) and auscultate for renal artery bruits (renovascular disease) 1
• Extremities: Document extent and severity of pitting edema 1
• Blood pressure measurement: Obtain bilateral arm pressures and orthostatic measurements 1

Likely Diagnoses to Consider

Primary Aldosteronism (High Probability)

• Affects 8-20% of patients with resistant hypertension 2
• Presents with hypokalemia, muscle cramps/weakness, or fatigue 2
• The aldosterone-to-renin ratio has high negative predictive value for screening 2
• If ARR is elevated (>20) with elevated aldosterone and suppressed renin, proceed to confirmatory testing with saline infusion test 2

Renal Parenchymal Disease (High Probability)

• History of frequent urination (nocturia implied by fatigue) and edema strongly suggest this diagnosis 1, 2
• Elevated creatinine, reduced eGFR, and proteinuria on urinalysis would confirm 1
• Most common secondary cause of hypertension overall 2

Renovascular Disease (Moderate Probability)

• Abrupt worsening of hypertension in a patient <50 years suggests fibromuscular dysplasia, particularly in women 2
• If initial labs show worsening renal function or if clinical suspicion is high, obtain renal ultrasound with Doppler 2

Immediate Management Approach

Blood Pressure Control

• Do not aggressively lower BP acutely unless there is evidence of hypertensive emergency (BP >180/120 mmHg with acute organ damage) 3, 4
• If BP is <180/120 mmHg without acute symptoms (chest pain, altered mental status, severe headache), this represents hypertensive urgency, not emergency 3, 4
• Initiate or optimize oral antihypertensive therapy 1

For non-Black patients:

• Start with low-dose ACE inhibitor or ARB 1
• Add dihydropyridine calcium channel blocker if needed 1
• Add thiazide-like diuretic as third agent 1

Important caveat: If primary aldosteronism is confirmed, mineralocorticoid receptor antagonists (spironolactone 50-100 mg daily) become the treatment of choice 2

Volume Management

• If significant edema is present with evidence of volume overload, consider loop diuretic (furosemide) for acute symptom relief 5
• Initial dose: 20-40 mg orally once daily, can be increased based on response 5
• Thiazide-like diuretics are preferred for chronic BP control, but loop diuretics are more effective for acute volume overload 3

Critical Next Steps Based on Results

If Creatinine Elevated or eGFR <60 mL/min/1.73m²:

• Renal ultrasound to assess kidney size and rule out obstruction 2
• Consider nephrology referral 2
• Adjust medications based on renal function 1

If Hypokalemia Present (K+ <3.5 mmol/L):

• Strongly suggests primary aldosteronism 2
• Proceed with confirmatory testing (saline suppression test) 2
• If confirmed, obtain adrenal CT imaging for localization 2
• Consider endocrinology referral 2

If Proteinuria Present:

• Quantify with 24-hour urine collection or spot urine protein-to-creatinine ratio 1
• Indicates renal parenchymal disease requiring nephrology evaluation 2

Common Pitfalls to Avoid

• Do not dismiss this as "poorly controlled primary hypertension"—the combination of young age, worsening hypertension, and new symptoms strongly suggests secondary causes 1, 2
• Do not delay aldosterone-renin ratio testing—primary aldosteronism is underdiagnosed and affects up to 20% of resistant hypertension cases 2
• Do not use beta-blockers or direct renin inhibitors before obtaining aldosterone-renin ratio, as these medications interfere with test interpretation 2
• Do not aggressively lower BP in the outpatient setting without ruling out hypertensive emergency—rapid BP reduction can cause cerebral, renal, or coronary ischemia 3, 4
• Do not overlook medication non-adherence or interfering substances (NSAIDs, decongestants, licorice) as potential contributors 1, 2

Follow-Up Timeline

• Recheck labs within 1 week to review results and adjust management 1
• Blood pressure recheck within 2-4 weeks after initiating or adjusting therapy 1
• If secondary cause identified, refer to appropriate specialist (nephrology for renal disease, endocrinology for primary aldosteronism) 2
• Target BP <130/80 mmHg should be achieved within 3 months 1

The key to this patient's management is recognizing that secondary hypertension is present until proven otherwise, obtaining the appropriate screening tests immediately, and avoiding the common error of treating the BP number without identifying the underlying cause 2.