Procalcitonin
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Procalcitonin (PCT), a protein that consists of 116 amino acids, is the peptide precursor of calcitonin, a hormone that is synthesized by the parafollicular C cells of the thyroid and involved in calcium homeostasis. Procalcitonin arises from endopeptidase-cleaved preprocalcitonin.
The reference value of procalcitonin in adults and children older than 72 hours is 0.15 ng/mL or less.
Reference values have not been established in infants younger than 72 hours.
In healthy adults, the reference range of procalcitonin is below the level of detection. [1]
The half-life of procalcitonin is 25-30 hours (not significantly altered in individuals with renal dysfunction). [2]
Conditions associated with mildly elevated serum procalcitonin (PCT) levels (0.15-2 ng/mL) include the following:
Localized mild-to-moderate bacterial infection
Noninfectious systemic inflammatory response
Untreated end-stage renal failure
Conditions associated with elevated serum procalcitonin levels (>2 ng/mL) include the following:
Severe localized bacterial infection (eg, severe pneumonia, meningitis, peritonitis)
Severe noninfectious inflammatory stimuli (eg, major burns, severe trauma, acute multiorgan failure, major abdominal or cardiothoracic surgery)
Medullary thyroid carcinoma (may exceed 10,000 ng/mL)
In neonates aged less than 72 hours, a procalcitonin level of more than 1 ng/mL at birth, 100 ng/mL or more at age 24 hours, and 50 ng/mL or more at age 48 hours suggests serious bacterial infection.
In children with urinary tract infection, a procalcitonin level of more than 0.5 ng/mL suggests renal involvement.
Specifics for procalcitonin (PCT) collection and panels are as follows:
Specimen type: Blood serum
Container: Vacutainer, red top
Collection method: Venipuncture
Specimen volume: 0.5 mL
Related tests include complete blood cell (CBC) count, C-reactive protein (CRP), blood culture, and cerebrospinal fluid (CSF) analysis.
Procalcitonin (PCT), a protein that consists of 116 amino acids, is the peptide precursor of calcitonin, a hormone that is synthesized by the parafollicular C cells of the thyroid and involved in calcium homeostasis. Procalcitonin arises from endopeptidase-cleaved preprocalcitonin.
Procalcitonin is also produced by the neuroendocrine cells of the lung and intestine and is released as an acute-phase reactant in response to inflammatory stimuli, especially those of bacterial origin. This raised procalcitonin level during inflammation is associated with bacterial endotoxin and inflammatory cytokines. [1, 2] Increased levels of serum procalcitonin in response to viral infections and noninfectious inflammatory stimuli such as autoimmune disease and chronic inflammatory processes are much less pronounced, rarely exceeding 0.5 ng/mL. [3, 4] Procalcitonin released as an acute-phase reactant does not result in increased serum calcitonin levels.
The physiological importance and regulation of procalcitonin production is not well understood. Several hypotheses suggest that procalcitonin may be involved in metabolism of calcium, cytokine network, and modulation of nitric oxide (NO) synthesis, as well as pain-relieving effects. [5] No enzymes in the plasma break down procalcitonin. Therefore, if procalcitonin enters the circulation, it remains unchanged, with a half-life of around 30 hours, with no evidence that serum procalcitonin binds to cellular receptors of calcitonin or any specific procalcitonin receptors. [5]
Studies have shown that, in patients with sepsis, higher procalcitonin levels are associated with a greater risk of progression to severe sepsis and septic shock, worsening the survival prognosis. Local bacterial infections and abscesses do not significantly raise procalcitonin levels. [4, 6, 7] Procalcitonin levels fall with successful treatment of severe bacterial infection and severe noninfectious inflammatory stimuli. Persistent or recurrent procalcitonin elevation in the latter setting should prompt suspicion of secondary infection.
Indications for serum procalcitonin measurement include the following:
To aid in the diagnosis and risk stratification of bacterial sepsis [8, 9]
To aid in the diagnosis of renal involvement in children with urinary tract infection
To aid in distinguishing bacterial from viral infections, including meningitis [10]
To monitor therapeutic response to antibacterial therapy and reduce antibiotic exposure [11, 12, 13, 14, 15]
To aid in the diagnosis of systemic secondary infection after surgery and in severe trauma, burns, and multiorgan failure [16]
To aid diagnosis of infected necrosis and associated systemic complications in acute pancreatitis [17]
Proposed applications of serum procalcitonin measurement include the following:
To aid the choice and timing of the initiation of antibiotic treatment (Procalcitonin Algorithm)
To assist with elucidating prognosis of severe localized infections (eg, pneumonia) [18]
To aid with elucidating prognosis of critically ill patients with systemic infection
Predicting the need of antibiotic treatment in sepsis and to shorten the duration of antibiotics required [19]
Use as independent predictor of graft failure late after renal transplantation [20]
Procalcitonin versus C-reactive protein
CRP is the most common laboratory marker used in the clinical setting to evaluate systemic inflammatory response to an infectious agent. It is routinely used as a diagnostic, predictor, and monitoring marker in patients with acute sepsis. Several recent comparison studies have aimed to determine the use of PCT in conjunction with CRP or independent of it in the setting of severe bacterial infections.
Procalcitonin is a more useful diagnostic inflammation parameter than CRP in patients with pediatric neutropenic fever, both in estimating the severity of infection and the duration and origin of the fever. [21]
Procalcitonin is a more reliable parameter than other markers in the diagnosis of bacterial sepsis, allowing better differentiation among sepsis-related fatalities. [22]
Procalcitonin is a useful early diagnostic marker for detection of bacteremia in febrile neutropenia and has better diagnostic value than CRP. [23]
Procalcitonin levels may also be elevated in medullary thyroid carcinoma [24] and small-cell lung carcinoma, [24] paralytic/vascular ileus [21] exhibiting paraneoplastic production, and renal failure. [24]
Procalcitonin, although useful in bacterial sepsis, has no value in the assessment of fungal or viral infections and shows no response to intracellular microorganisms (ie, Mycoplasma) or in local infections with no systemic response.
Similar to CRP, clinical conditions associated with high baseline procalcitonin levels include burns, major surgery, and systemic inflammatory processes.
To date, the use of procalcitonin, both as an indicator of severe infection and predictor of antibiotic choices/duration, has been center-specific, with insufficient data from multicenter/multinational studies to support its use as a routine laboratory marker in clinical practice.
Dandona P, Nix D, Wilson MF, Aljada A, Love J, Assicot M. Procalcitonin increase after endotoxin injection in normal subjects. J Clin Endocrinol Metab. 1994 Dec. 79(6):1605-8. [Medline].
Meisner M, Dresden-Neustadt SK. UNI-MED. Procalcitonin-Biochemistry and Clinical Analaysis. 1st edition. 2010.
Meili M, Müller B, Kulkarni P, Schütz P. Management of patients with respiratory infections in primary care: procalcitonin, C-reactive protein or both?. Expert Rev Respir Med. 2015 Oct. 9 (5):587-601. [Medline].
Ryu JA, Yang JH, Lee D, Park CM, Suh GY, Jeon K, et al. Clinical Usefulness of Procalcitonin and C-Reactive Protein as Outcome Predictors in Critically Ill Patients with Severe Sepsis and Septic Shock. PLoS One. 2015. 10 (9):e0138150. [Medline].
Maruna P, Nedelnikova K, Gurlich R. Physiology and Genetics of Procalcitonin. Physiol. Res. 2000. 49 (Suppl. 1):57-61.
Eberhard OK, Haubitz M, Brunkhorst FM, Kliem V, Koch KM, Brunkhorst R. Usefulness of procalcitonin for differentiation between activity of systemic autoimmune disease (systemic lupus erythematosus/systemic antineutrophil cytoplasmic antibody-associated vasculitis) and invasive bacterial infection. Arthritis Rheum. 1997 Jul. 40(7):1250-6. [Medline].
Yu Y, Li XX, Jiang LX, Du M, Liu ZG, Cen ZR, et al. Procalcitonin levels in patients with positive blood culture, positive body fluid culture, sepsis, and severe sepsis: a cross-sectional study. Infect Dis (Lond). 2015 Sep 4. 1-7. [Medline].
Harbarth S, Holeckova K, Froidevaux C, Pittet D, Ricou B, Grau GE. Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis. Am J Respir Crit Care Med. 2001 Aug 1. 164(3):396-402. [Medline].
Simon L, Gauvin F, Amre DK, Saint-Louis P, Lacroix J. Serum procalcitonin and C-reactove protein levels as markers of bacterial infection: a systematic review and meta-analysis. Clinical Infectious Diseases. 2004. 39:206-17.
Gendrel D, Raymond J, Assicot M, Moulin F, Iniguez JL, Lebon P. Measurement of procalcitonin levels in children with bacterial or viral meningitis. Clin Infect Dis. 1997 Jun. 24(6):1240-2. [Medline].
Christ-Crain M, Jaccard-Stolz D, Bingisser R, Gencay MM, Huber PR, Tamm M. Effect of procalcitonin-guided treatment on antibiotic use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial. Lancet. 2004 Feb 21. 363(9409):600-7. [Medline].
Christ-Crain M, Stolz D, Bingisser R, Müller C, Miedinger D, Huber PR. Procalcitonin guidance of antibiotic therapy in community-acquired pneumonia: a randomized trial. Am J Respir Crit Care Med. 2006 Jul 1. 174(1):84-93. [Medline].
Stolz D, Christ-Cain M, Bissinger R, Leuppi J, Miedinger D, Muller C, et al. Antibiotic treatment of exacerbations of COPD: A randomized, controlled trial comparing procalcitonin-guidance with standard therapy. Chest. 2007. 13:9-19.
Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med. 2008 Mar 1. 177(5):498-505. [Medline].
Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C. Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010 Feb 6. 375(9713):463-74. [Medline].
Uzzan B, Cohen R, Nicolas P, Cucherat M, Perret GY. Procalcitonin as a diagnostic test for sepsis in critically ill adults and after surgery or trauma: a systematic review and meta-analysis. Crit Care Med. 2006 Jul. 34(7):1996-2003. [Medline].
Rau B, Steinbach G, Gansauge F, Mayer JM, Grünert A, Beger HG. The potential role of procalcitonin and interleukin 8 in the prediction of infected necrosis in acute pancreatitis. Gut. 1997 Dec. 41(6):832-40. [Medline].
Hedlund J, Hansson LO. Procalcitonin and C-reactive protein levels in community-acquired pneumonia: correlation with etiology and prognosis. Infection. 2000 Mar-Apr. 28(2):68-73. [Medline].
Lila Bouadma MD, Charles-Edouard Luyt MD, FlorenceTubach MD, et al. for the PRORATA trial group Use of procalcitonin to reduce patients’ exposure to antibiotics in intensive care units (PRORATA trial): a multicentrerandomised controlled trial. The Lancet. 2000. 375(9713):463-74.
Algeciras-Schimnich A, Preissner CM, Theobald JP, Finseth MS, Grebe SK. Procalcitonin: a marker for the diagnosis and follow-up of patients with medullary thyroid carcinoma. J Clin Endocrinol Metab. 2009 Mar. 94(3):861-8. [Medline].
Secmeer G, Devrim I, Kara A, Ceyhan M, Cengiz B, Kutluk T. Role of procalcitonin and CRP in differentiating a stable from a deteriorating clinical course in pediatric febrile neutropenia. J Pediatr Hematol Oncol. 2007 Feb. 29(2):107-11. [Medline].
Schrag B, Roux-Lombard P, Schneiter D, Vaucher P, Mangin P, Palmiere C. Evaluation of C-reactive protein, procalcitonin, tumor necrosis factor alpha, interleukin-6, and interleukin-8 as diagnostic parameters in sepsis-related fatalities. Int J Legal Med. 2012 Jul. 126(4):505-12. [Medline].
Kim DY, Lee YS, Ahn S, Chun YH, Lim KS. The usefulness of procalcitonin and C-reactive protein as early diagnostic markers of bacteremia in cancer patients with febrile neutropenia. Cancer Res Treat. 2011 Sep. 43(3):176-80. [Medline].
Maruna P, Frasko R, Gurlich R. Plasma procalcitonin in patients with ileus. Relations to other inflammatory parameters. Physiol Res. 2008. 57(3):481-6. [Medline].
Jiun-Lih Jerry Lin, MBBS, MS(Orth) Clinical Associate Lecturer, MD Program Research Supervisor, Sydney Medical School, University of Sydney; Orthopaedic Registrar, Mona Vale Hospital, Australia
Disclosure: Nothing to disclose.
Swee Leong Yap, MBBS Surgical Hospital Medical Officer, Western Health, Australia
Disclosure: Nothing to disclose.
Eric B Staros, MD Associate Professor of Pathology, St Louis University School of Medicine; Director of Clinical Laboratories, Director of Cytopathology, Department of Pathology, St Louis University Hospital
Eric B Staros, MD is a member of the following medical societies: American Medical Association, American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology
Disclosure: Nothing to disclose.
Procalcitonin
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