What are the possible causes of false high procalcitonin (PCT) levels?

False Elevations of Procalcitonin

Procalcitonin can be falsely elevated by non-infectious causes including acute respiratory distress syndrome, chemical pneumonitis, severe falciparum malaria, major surgical trauma (especially abdominal and thoracic), severe burns, electrical injuries, medullary thyroid cancer, and severe viral infections including COVID-19 and influenza. 1, 2, 3

Non-Infectious Medical Conditions

Respiratory and Inflammatory Conditions

• Acute respiratory distress syndrome (ARDS) causes false PCT elevation without bacterial infection present 1, 3
• Chemical pneumonitis may falsely elevate PCT levels 1, 3
• Severe viral illnesses, particularly influenza and COVID-19, can elevate PCT despite absence of bacterial co-infection—approximately 21% of COVID-19 patients show PCT elevation without bacterial pneumonia 2, 3
• Hyperinflammatory states or cytokine storm in COVID-19 may result in higher PCT production than other viral pneumonias 3

Parasitic Infection

• Severe falciparum malaria can cause false PCT elevation 1, 3

Malignancy

• Medullary thyroid cancer with metastases produces PCT directly from tumor cells, causing persistently elevated levels (>100 ng/L) independent of infection status—this represents true PCT production from malignant cells rather than inflammatory response 4
• In these patients, calcitonin levels are also elevated, confirming the thyroid cancer origin rather than sepsis 4

Surgical and Traumatic Causes

Major Surgical Procedures

• Major abdominal surgery causes PCT elevation in 65% of patients without infection, with peak levels occurring on postoperative days 1-2 5
• Major vascular surgery elevates PCT in 27% of patients postoperatively 5
• Thoracic surgery including esophagectomy causes PCT elevation in 41% of patients 5
• Minor aseptic surgery causes PCT elevation in only 21% of patients, significantly less than major procedures 5

Critical timing consideration: PCT elevations from surgical trauma typically peak on postoperative days 1-2 and then rapidly decline based on PCT's 22-35 hour half-life, making "infection monitoring" potentially unreliable during this early window after major surgery 2, 5

Trauma-Related Elevations

• Severe burns cause elevated PCT at admission (mean 2.1 ng/mL), with electrical burns producing particularly high levels (mean 15.7 ng/mL) 6
• Abdominal trauma (particularly liver and gut injuries) significantly increases PCT on day 1 post-trauma (4.04-4.63 ng/mL) compared to other injuries (0.62 ng/mL) 7
• Combined liver/spleen and thorax trauma produces markedly elevated PCT (9.37 ng/mL) 7
• Burn size (TBSA) correlates positively with mean peak PCT levels during later postburn days 6

Shock States

• Cardiogenic and hemorrhagic shock can elevate temperature and potentially PCT independent of infection 8

Technical and Physiological Factors

Renal Function

• PCT levels are markedly influenced by renal function and different techniques of renal replacement therapy 2, 3

Timing Issues

• Early sampling (<6 hours from admission or infection onset) may produce false-negative results, as PCT requires 4 hours to begin rising and 6-8 hours to peak 2, 8

Clinical Interpretation Algorithm

When encountering elevated PCT without clear bacterial infection:

1. Review surgical history: If within 48 hours of major abdominal, thoracic, or vascular surgery, PCT elevation may be trauma-related rather than infectious 5

2. Assess for trauma: Recent severe burns (especially electrical), abdominal trauma, or polytrauma can elevate PCT for 1-2 days post-injury 6, 7

3. Consider viral illness: In patients with influenza or COVID-19, PCT may be elevated without bacterial co-infection 2, 3

4. Evaluate for ARDS or chemical pneumonitis: These conditions can falsely elevate PCT 1, 3

5. Check thyroid cancer history: Patients with medullary thyroid cancer and metastases may have persistently elevated PCT (>100 ng/L) with concurrent calcitonin elevation 4

6. Assess renal function: Impaired renal function or renal replacement therapy affects PCT clearance 2, 3

Important Caveats

• Do not delay empiric antibiotic therapy in critically ill patients while investigating false elevation causes if bacterial infection is clinically suspected 8
• Serial PCT measurements are more valuable than single readings—a 50% rise from previous value suggests true bacterial infection, while declining levels suggest non-infectious cause or treatment response 3, 8
• CRP lacks specificity for distinguishing these false elevations and remains elevated longer than PCT in both infectious and non-infectious conditions 1, 5