Procalcitonin: Definition, Test, Clinical Information, Reference Values, Diagnostic Applications and Precautions

It is a protein that consists of 116 amino acids.

It is the precursor peptide of calcitonin, a hormone synthesized by the parafollicular C cells of the thyroid and participates in calcium homeostasis.

Procalcitonin arises from endopeptidase-cleaved preprocalcitonin.

Procalcitonin is a peptide released into the bloodstream in response to bacterial toxins, leading to rapidly elevated serum levels in patients with bacterial infections.

Procalcitonin has recently received increased attention as a valuable measure to differentiate between acute bacterial infection and other inflammatory and febrile syndromes.

Studies have shown that elevated serum levels of procalcitonin have significantly higher infection specificity than erythrocyte sedimentation rate and C-reactive protein.

Procalcitonin has been extensively studied as a clinical tool to decide when to start and stop antibacterial agents in patients with pneumonia and has also shown promise in differentiating between infectious and noninfectious causes of fever after orthopedic surgery.


For all these reasons, it remains an intriguing clinical tool for use in fever patients with an autoimmune disease who commonly take immunosuppressive medications and are at increased risk of infection.

Typically produced in the C cells of the thyroid gland, procalcitonin generally cleaves into calcitonin, Katalin, and an N-terminal residue.

Under normal circumstances, procalcitonin is not released into the bloodstream; however, during severe plasma infection, levels can increase dramatically.

Interestingly, this does not lead to an increase in plasma calcitonin levels or activity. At this time, the exact site of procalcitonin production and its pathophysiological role during sepsis remains uncertain.

Procalcitonin test

This test is helpful for:

  • Diagnosis of bacteremia and septicemia in adults and children (including newborns).
  • Diagnosis of kidney involvement in urinary tract infection in children.
  • Diagnosis of bacterial infection in neutropenic patients.
  • Diagnosis, risk stratification, and monitoring of septic shock.
  • Diagnosis of secondary systemic disease after surgery and severe trauma, burns, and multi-organ failure.
  • Differential diagnosis of bacterial versus viral meningitis.
  • Differential diagnosis of acquired bacterial versus viral pneumonia.
  • We are monitoring the therapeutic response to antibacterial therapy.

Clinical information

Procalcitonin is processed into an N-terminal 57 amino acid peptide. The expression of this group of peptides is generally limited to thyroid C cells and, to a small extent, to other neuroendocrine cells.

Calcitonin is the only hormonally active of these peptides. It is secreted by C cells in response to hypercalcemia. It inhibits bone resorption by osteoclasts, minimizing oscillations in serum calcium and calcium loss.

During severe systemic inflammation, particularly bacterial infection, tissue-specific control of calcitonin-related peptide expression is disrupted, and many tissues secrete ProCT and CCP-1 (collectively referred to as procalcitonin) in large quantities. Calcitonin levels do not change.

Noninfectious inflammatory stimuli must be extremely severe to result in procalcitonin elevations, making it a more specific marker for severe infections than most inflammatory markers (cytokines, interleukins, and acute phase reactants).

Procalcitonin elevations are more sustained than most other markers and occur in neutropenic patients. This reduces the risk of false-negative results.

Procalcitonin becomes detectable within 2 to 4 hours after a triggering event and peaks in 12 to 24 hours.

Procalcitonin secretion is very similar to the severity of the inflammatory lesion, with higher levels associated with more severe disease and decreasing levels with resolution of the disease.

In the absence of a continuous stimulus, procalcitonin is cleared with a half-life of 24 to 35 hours, making it suitable for serial monitoring.

Finally, the dependence of sustained procalcitonin elevations on ongoing inflammatory stimuli allows the identification of secondary septic events under conditions that can lead to noninfectious procalcitonin elevations, such as cardiac surgery, severe trauma, severe burns, and multiple organ failure.

Procalcitonin levels should fall at a predictable rate without secondary infection.

Reference values

The reference value for PCT in adults and children older than 72 hours is 0.15 ng / mL or less.

In children younger than 72 hours: less than 2.0 ng/ml at birth increases to 20 ng / ml at 18-30 hours of age, then falls to 0.15 ng/ml at 72 hours.


General considerations

In children older than 72 hours and adults, levels less than 0.15 ng/ml make a diagnosis of significant bacterial infection unlikely.

Procalcitonin between 0.15 and 2.0 ng / mL does not exclude infection because localized infections (without systemic signs) can be associated with low levels.

Levels greater than 2.0 ng / mL suggest systemic bacterial infection/sepsis or severe localized bacterial infection, such as pneumonia, meningitis, or peritonitis.

They can also occur after severe noninfectious inflammatory stimuli, such as severe burns, severe trauma, acute multi-organ failure, or significant abdominal or cardiothoracic surgery.

In cases of noninfectious elevations, procalcitonin levels should begin to drop after 24 to 48 hours.

Autoimmune diseases, chronic inflammatory processes, viral infections, and mild localized bacterial infections rarely lead to more than 0.5 ng / mL of procalcitonin elevations.

Diagnostic Applications

Based on the current consensus in the literature, we have:

Diagnosis of bacteremia in neonates: after birth

Procalcitonin values ​​increase from birth until reaching maximum values ​​at 24 hours of life and gradually decrease at 48 hours.

Therefore, during the first 72 hours of life, different reference ranges will apply to newborns at other times of age.

Procalcitonin levels in newborns suffering from early sepsis are significantly higher than in uninfected newborns when using reference ranges for hours of age.

Adult levels should be applied 72 hours or more after birth.

  • Diagnosis of kidney involvement in pediatric urinary tract infections.
  • In children with urinary tract infections, a procalcitonin level greater than 0.5 ng/ml has a sensitivity of 70% to 90% and a specificity of 80% to 90% for kidney involvement.
  • Procalcitonin responses in neutropenic patients.

These responses are similar to patients with average neutrophil counts and functions, and the cutoff points discussed in the general considerations above should be used.

In the appropriate clinical setting, procalcitonin levels greater than 2.0 ng/ml on the first day of admission to the intensive care unit represent a high risk of progression to severe sepsis and septic shock.

Procalcitonin levels less than 0.5 ng / ml on the first day of admission to the intensive care unit represent a low risk of progression to severe sepsis and septic shock.

The reported sensitivity and specificity for the diagnosis of sepsis vary between 60% and 100%, depending on the underlying and coexisting diseases and the patient populations studied. The higher the procalcitonin level, the worse the prognosis.

A procalcitonin level of less than 0.5 ng/ml makes bacterial meningitis very unlikely. Most patients with bacterial meningitis will have procalcitonin levels more significant than ten times this level.

With successful antibiotic therapy, procalcitonin levels should drop with a half-life of 24 to 35 hours.


Severe trauma, severe burns, multiple organ failure, or major surgery can cause procalcitonin elevations without sepsis. After removal of the noxious stimulus, procalcitonin should start to drop.

Untreated end-stage renal disease patients may have procalcitonin levels greater than 0.15 ng/ml in the absence of infection or severe inflammation.

Within three hemodialysis treatments, this should fall into the normal reference range. End-stage renal failure patients on stable hemodialysis or peritoneal dialysis treatments have procalcitonin levels similar to healthy adults with normal kidney function.

Patients with medullary thyroid carcinoma or, very rarely, islet cell tumors can have significant elevations in procalcitonin in the absence of sepsis. In some instances, these levels can exceed 10,000 ng / mL.

For unknown reasons, some babies and children may have procalcitonin levels of 0.15 ng / mL to 0.50 ng / mL.

There is a low but definite possibility of false-positive results in patients with heterophile antibodies, as with all immunometric assays. Therefore, test results that do not fit the clinical picture should be discussed with the laboratory.

A hook effect can occur at concentrations above 2,500 ng/ml (extremely rare), resulting in a measured procalcitonin concentration lower than the samples.

This can complicate the interpretation of serial procalcitonin measurements in rare patients with extremely high procalcitonin levels.

A retest should be ordered after sample dilution if this is clinically suspected.