Procalcitonin

Procalcitonin is normally produced by thyroid C-cells as a precursor to calcitonin, but during bacterial infection, it is produced by many extrathyroidal tissues (liver, lungs, adipocytes, monocytes) in response to bacterial endotoxins and inflammatory cytokines (IL-6, TNF-alpha, IL-1beta). Unlike calcitonin, this infection-induced PCT is not cleaved to active calcitonin and accumulates in serum. Interferon-gamma (released during viral infections) suppresses PCT production, which explains why PCT preferentially rises in bacterial rather than viral infections—making it more specific than CRP for bacterial etiology. Clinical uses include: (1) Sepsis diagnosis and severity assessment—levels often correlate with the extent of bacterial infection and can help distinguish sepsis from SIRS of non-infectious origin; (2) Antibiotic stewardship—serial PCT measurements can guide decisions to start, continue, or discontinue antibiotics, particularly in respiratory tract infections and ICU settings (based on PCT-guided algorithms studied in trials like ProHOSP and ProACT); (3) Prognosis—persistently elevated or rising PCT levels suggest poor prognosis or treatment failure. Normal levels are typically <0.05 ng/mL; levels >0.5 ng/mL suggest possible bacterial infection, and levels >2 ng/mL suggest high likelihood of severe bacterial infection/sepsis. Limitations include false elevations in trauma, major surgery, burns, cardiogenic shock, and certain cancers (medullary thyroid carcinoma, small cell lung cancer), as well as false negatives in localized infections without systemic involvement. It should be interpreted in clinical context alongside other markers (CRP, WBC, lactate) rather than as a standalone diagnostic test.