What is the diagnosis and management for a 16-year-old boy with anasarca and pulmonary hypertension, with normal Thyroid-Stimulating Hormone (TSH), Erythrocyte Sedimentation Rate (ESR), and kidney function?

Diagnostic Approach for a 16-Year-Old with Anasarca and Pulmonary Hypertension

This patient requires urgent evaluation for nephrotic syndrome with secondary pulmonary hypertension, despite reportedly normal kidney function tests—specifically, you must obtain a urinalysis with protein quantification (spot urine protein-to-creatinine ratio or 24-hour urine protein) and serum albumin level immediately.

Critical Diagnostic Considerations

The combination of anasarca (severe generalized edema) and pulmonary hypertension in an adolescent with normal TSH, ESR, and "kidney function" creates a diagnostic puzzle that demands specific investigation:

Primary Concern: Nephrotic Syndrome

• Anasarca in a 16-year-old strongly suggests nephrotic syndrome, which can present with normal serum creatinine but massive proteinuria and hypoalbuminemia 1
• Standard "kidney function" tests (creatinine, BUN) may appear normal in nephrotic syndrome because glomerular filtration can be preserved while massive protein loss occurs 1
• You must specifically check: serum albumin, urinalysis with microscopy, spot urine protein-to-creatinine ratio (or 24-hour urine protein), and lipid panel 2

Pulmonary Hypertension Mechanisms in This Context

The pulmonary hypertension could arise through several mechanisms:

• Thromboembolic disease: Nephrotic syndrome creates a hypercoagulable state that can lead to chronic thromboembolic pulmonary hypertension (CTEPH, Group 4) 2
• Volume overload and left heart involvement: Severe fluid retention can cause PH due to left heart disease (Group 2) 2
• Direct renal-cardiac interaction: Elevated right-sided venous pressure from PH increases renal venous pressure, creating a vicious cycle that worsens both anasarca and renal function 1

Essential Diagnostic Workup

Immediate Laboratory Tests

• Serum albumin (expect <2.5 g/dL in nephrotic syndrome causing anasarca) 2
• Spot urine protein-to-creatinine ratio (>3.5 g/day defines nephrotic-range proteinuria) 2
• Complete urinalysis with microscopy (look for oval fat bodies, fatty casts) 2
• Lipid panel (hyperlipidemia accompanies nephrotic syndrome) 2
• NT-proBNP or BNP (elevated levels indicate right ventricular strain and have prognostic value) 2
• Complete blood count (assess for anemia, thrombocytosis from hypercoagulability) 2
• Coagulation studies (PT/INR, aPTT, fibrinogen) if thromboembolic disease suspected 2

Imaging Studies

• Echocardiography with bubble study: Confirms PH severity, assesses right ventricular function, evaluates for structural heart disease or shunts, and screens for congenital heart disease 2
• Ventilation/perfusion (V/Q) scan: Essential to exclude chronic thromboembolic PH (CTEPH), which is highly treatable but requires specific diagnosis 2
• CT angiography of chest: If V/Q scan suggests CTEPH or to evaluate for pulmonary veno-occlusive disease 2
• Chest X-ray: Look for enlarged central pulmonary arteries (right interlobar artery >16 mm in males), cardiomegaly, or underlying lung disease 2

Specialized Testing

• Right heart catheterization: Gold standard for confirming PH (mean PAP ≥25 mmHg) and determining hemodynamic subtype (precapillary vs. postcapillary) 2, 3
• Pulmonary function tests with DLCO: Exclude Group 3 PH from lung disease 2
• Sleep study: Rule out sleep-disordered breathing as contributor 2
• Autoimmune serologies: If not already done—ANA, anti-dsDNA, anti-Scl-70, complement levels (C3, C4) 2
• Hepatitis B/C and HIV testing: Screen for associated causes of both nephrotic syndrome and PAH 2

Differential Diagnosis by PH Classification

Group 1: Pulmonary Arterial Hypertension

• Idiopathic PAH: Rare in this age group but possible 2
• Heritable PAH: Consider BMPR2 mutation testing if family history present 2
• Connective tissue disease-associated PAH: Despite normal ESR, some CTDs present with minimal inflammation 2
• Congenital heart disease: Must be excluded with echocardiography and bubble study 2

Group 2: PH Due to Left Heart Disease

• Volume overload from nephrotic syndrome: Can cause elevated left atrial pressures and secondary PH 2
• Cardiomyopathy: Assess left ventricular function on echocardiography 2

Group 3: PH Due to Lung Disease

• Less likely given normal ESR and clinical presentation, but pulmonary function tests required 2

Group 4: Chronic Thromboembolic PH

• High suspicion given hypercoagulable state from nephrotic syndrome 2
• V/Q scan is mandatory screening test 2

Group 5: PH with Multifactorial Mechanisms

• Chronic kidney disease: Can cause PH even with preserved GFR if significant proteinuria present 1, 3
• Metabolic disorders: Thyroid already checked, but consider other storage diseases 2

Management Priorities

Immediate Actions

• Diuresis with caution: Loop diuretics for anasarca, but monitor renal function closely as aggressive diuresis can worsen prerenal azotemia in the setting of PH 4
• Anticoagulation consideration: If CTEPH confirmed or high suspicion of thromboembolic disease, initiate anticoagulation 2
• Treat underlying nephrotic syndrome: Once biopsy confirms etiology, initiate disease-specific therapy (corticosteroids, immunosuppression) 2

Avoid Common Pitfalls

• Do not assume "normal kidney function" excludes renal disease: Creatinine can be normal in nephrotic syndrome with massive proteinuria 1
• Do not start PAH-specific therapy before complete diagnostic workup: Treatment depends entirely on PH classification 2, 5
• Do not overlook thromboembolic disease: Nephrotic syndrome creates significant thrombotic risk requiring V/Q scanning 2
• Do not use PDE-5 inhibitors empirically: While sildenafil can help in specific PH types and may assist with diuresis in CorPRADA syndrome 4, it is not indicated until PH type is confirmed and is not recommended for chronic use in children 6

Prognosis and Follow-up

• Risk stratification: Use WHO functional class, 6-minute walk distance, NT-proBNP levels, and echocardiographic parameters to assess severity 2
• Multidisciplinary care: Requires nephrology for nephrotic syndrome management and cardiology/pulmonary hypertension specialist for PH evaluation 2, 5
• Mortality considerations: PH in young patients carries significant mortality risk; survival at 5 years depends on underlying cause and response to treatment 7