What causes hyperprocalcitoninemia (elevated procalcitonin levels)?

From the Guidelines

Hyperprocalcitoninemia is primarily caused by bacterial infections.

Causes of Hyperprocalcitoninemia

• Bacterial infections, such as bacterial meningitis 1 and community-acquired bacterial coinfections 1, are a major cause of elevated procalcitonin levels.
• The inflammatory response triggered by bacterial infections leads to an increase in procalcitonin production, making it a useful biomarker for differentiating between bacterial and viral infections 1.
• However, it's essential to note that hyperinflammatory status or cytokine storm, such as that induced by SARS-CoV-2 infection, can also result in higher procalcitonin production, potentially limiting its role in differentiating between viral and bacterial infections 1.
• Other factors, such as the timing of procalcitonin sampling, can also impact its accuracy, with early sampling (within 6 hours of admission) potentially leading to false negative results 1.
• In general, a low procalcitonin level at initial presentation has a high negative predictive value for ruling out bacterial coinfections, while an initially high level may not provide additional value beyond traditional clinical criteria or laboratory data 1.

From the Research

Causes of Hyperprocalcitoninemia

• Hyperprocalcitoninemia, or elevated procalcitonin levels, can be caused by various factors, including:
  • Bacterial infections, as procalcitonin is a biomarker whose serum concentrations are elevated in response to systemic inflammation caused by bacterial infection and sepsis 2, 3, 4
  • Severe viral infections, as procalcitonin rises during pure viral infection in proportion to disease severity and is not suppressed by interferon signalling 5
  • Medullary thyroid cancer metastases, which can synthesize procalcitonin, leading to elevated levels 6
• It is essential to note that procalcitonin levels can be influenced by various factors, and elevated levels do not always indicate a bacterial infection 6, 4

Factors Influencing Procalcitonin Levels

• Disease severity: procalcitonin levels rise in proportion to disease severity, regardless of the underlying cause 5
• Inflammatory cytokines: procalcitonin production is linked to inflammatory cytokines such as TNF and IL-6 3
• Interferon signalling: contrary to previous assumptions, interferon signalling does not suppress procalcitonin synthesis 5

Clinical Interpretation of Procalcitonin Results

• Procalcitonin results should be interpreted in the context of the patient's clinical presentation and other laboratory findings 4
• Elevated procalcitonin levels should prompt further investigation to determine the underlying cause, as they can be influenced by various factors 6, 4