Causes of Low Albumin and Low Protein in a Teenager
In a teenager with hypoalbuminemia and hypoproteinemia, you must systematically evaluate for protein-losing conditions (nephrotic syndrome, protein-losing enteropathy), inflammatory states, malnutrition, and chronic liver disease, as these represent the most common and clinically significant etiologies affecting morbidity and mortality in this age group.
Primary Diagnostic Categories
Protein-Losing Conditions
- Nephrotic syndrome is a critical consideration in adolescents presenting with low albumin and total protein, characterized by massive urinary protein losses (>3.5 g/day or urine albumin-to-creatinine ratio ≥2,200 mg/g), typically accompanied by edema and hyperlipidemia 1, 2
- Protein-losing enteropathy causes secondary immunodeficiencies with low globulin levels due to gastrointestinal protein losses 2
- Screening should include a random spot urine sample for albumin-to-creatinine ratio, with particular attention to diabetic nephropathy if the patient has type 1 or type 2 diabetes (screening recommended at puberty or age ≥10 years after 5 years of diabetes duration) 1
Inflammatory States
- Inflammation is one of the most common causes of severe hypoalbuminemia, as inflammatory cytokines directly downregulate albumin synthesis in the liver and increase capillary permeability, leading to albumin redistribution 3, 4, 5
- The presence of acute or chronic inflammation limits the specificity of serum albumin as a nutritional marker 1
- Measure C-reactive protein and other inflammatory markers to identify inflammation in patients with low albumin, as elevated CRP negates the positive relationship between serum albumin and protein intake 1, 3
Malnutrition and Inadequate Intake
- Protein-energy malnutrition causes hypoalbuminemia through decreased synthesis rates, though development is slow compared to rapid changes from inflammation or crystalloid dilution 1, 3, 6, 4
- Serum albumin may fall with sustained decrease in dietary protein and energy intake 1, 3
- Assessment should include estimates of dietary and fluid intake (oral, enteral, parenteral), output (urine, gastrointestinal losses), and gastrointestinal symptoms 1
Chronic Liver Disease
- Hepatic dysfunction impairs albumin synthesis and can present with hypoalbuminemia accompanied by elevated globulins (hyperglobulinemia) 7
- Evaluate with complete liver function tests including ALT, AST, alkaline phosphatase, and bilirubin 7
- Consider autoimmune hepatitis (elevated aminotransferases, hypergammaglobulinemia, positive autoantibodies), chronic viral hepatitis, or cirrhosis 7
Systematic Diagnostic Approach
Initial Laboratory Evaluation
- Complete metabolic panel including albumin, total protein, and calculation of albumin/globulin ratio 2
- Urinalysis with urine protein quantification using albumin-to-creatinine ratio to assess for renal protein losses 1, 7
- Complete blood count to evaluate for anemia, infection, inflammation, or other hematological abnormalities associated with immune deficiency 2, 7
- Inflammatory markers (C-reactive protein, ESR) to distinguish inflammation-driven hypoalbuminemia from nutritional causes 1, 3
Secondary Testing Based on Initial Findings
- Serum protein electrophoresis to characterize globulin fraction abnormalities and identify monoclonal gammopathies 7
- Liver function tests if hepatic dysfunction suspected 7
- Stool studies for alpha-1 antitrypsin clearance if protein-losing enteropathy suspected 2
- Nutritional assessment including pre-albumin (shorter half-life, better reflects improving nutritional status than albumin), mid-upper arm circumference, and triceps skinfold thickness 1
Critical Clinical Pitfalls to Avoid
Common Misinterpretations
- Do not assume hypoalbuminemia is solely due to malnutrition when inflammation may be the primary driver, as albumin is a negative acute-phase reactant that decreases during inflammation 3, 4
- Recognize that in hospitalized patients, albumin is most commonly low as part of an acute phase response to inflammation and protein redistribution, so hypoalbuminemia should not be automatically attributed to malnutrition 1
- Orthostatic proteinuria is not uncommon in adolescents and is usually benign; all patients with documented microalbuminuria should have a first morning void immediately on arising to determine if this is the case 1
Non-Nutritional Factors Affecting Albumin
- Hydration status and fluid overload can dilute serum albumin concentration 1, 3, 6
- Peritoneal or urinary albumin losses directly reduce serum levels 1
- Acidemia can affect albumin measurements 1
- Inflammation increases fractional catabolic rate and transfer of albumin out of the vascular compartment 4, 5
Management Priorities
Treat the Underlying Cause
- Focus on treating the underlying cause of hypoalbuminemia rather than the low albumin level itself, as simply administering albumin has not been shown to improve survival or reduce morbidity 3, 4
- For confirmed persistent microalbuminuria in diabetic patients (≥30 mg/g on two of three samples over 6 months), initiate ACE inhibitor therapy even if blood pressure is not elevated, titrated to normalization of albumin excretion 1
- For autoimmune hepatitis, consider immunosuppressive therapy with corticosteroids alone or in combination with azathioprine 7
Nutritional Support
- Provide adequate nutritional support, especially in malnourished patients, with optimization of protein and energy intake 1, 3, 4
- In patients with chronic kidney disease, aim for protein intake of 1.2-1.3 g/kg body weight/day 3
- Address inflammation when present, as it induces anorexia and reduces effective use of dietary protein 4