Introduction
The composition of the human body is beyond astonishing. There exist divisions and subdivisions in the roles assigned to each organ which, at times, are complex and linked to each other. Hormones like calcitonin have a vital role in the maintenance of healthy life. Calcitonin is a hormone produced by the thyroid glands and is involved in the homeostasis of minerals such as calcium and phosphorus. Calcitonin in its inactive form exists as procalcitonin. Procalcitonin production occurs at the following:
- Parafollicular cells (C cells) of the thyroid gland
- Neuroendocrine cells of the lung and the intestine
Thus, procalcitonin is the peptide precursor of the hormone Calcitonin. It is essentially a protein with 116 amino acids formed when the endopeptidase enzyme cleaves the pre-procalcitonin. Over the years, procalcitonin has been studied as a significant biomarker simply because of its specific functions in the human body that help in suggesting the advent and progression of many diseases.
This article briefly discusses the role of procalcitonin in the human body.
What exactly does procalcitonin do?
To your surprise, procalcitonin essentially has nothing to contribute to the functions of the human body. However, it does stand as an essential diagnosing parameter due to its connection with the hormone calcitonin.
Procalcitonin is produced in the body by Thyroid C cells. Gene CALC-1 on chromosome number 11 is the site of procalcitonin synthesis in the DNA. The obtained mRNA product, i.e., Pre-procalcitonin, is subjected to breakage by the enzyme endopeptidase. This enzyme-generated cleavage results in 3 different molecules having different numbers of amino acids in their structure. These molecules are:
- N-terminal procalcitonin having 57 amino acids
- Kata Calcitonin with 21 amino acids
- calcitonin in its active form having 32 amino acids.
Typically, all the procalcitonin is expected to be converted into the active calcitonin that is used in bodily functions. This implies that procalcitonin could conversely help the body by providing more calcitonin. However, in the case of healthy individuals, the levels of procalcitonin are supposed to be very low. If it is found to be more, it could suggest some abnormalities associated with any disease condition.
Altered production of procalcitonin in diseases condition
High levels of procalcitonin could indicate prevailing inflammation in the body. Also, during an inflammatory condition, procalcitonin production employs two alternative mechanisms. There are essentially two pathways, direct and indirect.
- Normal pathway:
The activation of the CALC-1 gene is conducted by various factors such as elevated levels of calcium, glucagon, glucocorticoids, etc. This pathway involves thyroid glands, and the route for Procalcitonin production is the thyroid C cells majorly and endocrine cells to a lesser extent. Also, this leads to the production of calcitonin at the end stage and releasing it into the bloodstream. - Direct pathway:
In the Direct pathway, the metabolites that induce the CALC-1 gene are essentially lipopolysaccharide and other toxic microbial substances. The Procalcitonin produced via this pathway is a result of underlying inflammation. In this pathway, the route for procalcitonin production would be adipocytes and other parenchyma tissues of the body. - Indirect pathway:
The only difference between direct and indirect pathways is that the augmentation of this groute results from various inflammatory mediators such as IL-6 (Interleukin), TNF alpha (Tumor Necrotic Factor), etc.
It is also important to note that severe bacterial infection called septicemia involves high procalcitonin production.
Role of procalcitonin in diagnosing diseases
- Specificity
Procalcitonin is regarded as one of the valuable diagnostic parameters when the cause of the diseased condition is a bacterial species. Specificity in the diagnosis is something procalcitonin provides totally. Though other inflammatory markers such as CRP (C Reactive Protein) have been established, thus, the measure of procalcitonin levels becomes vital anytime the suspicion is towards bacterial infection. And that’s because CRP stands as an insufficient marker at diagnosing or distinguishing between bacterial infection over infection of non-bacterial origin. - Definite elevation and decrease
The procalcitonin levels increase immediately within just 6 to 12 hours in the initial phase of the bacterial infection. Also, the levels increase consistently for about 2 to 4 hours, followed by the advent of sepsis. Sepsis is a worldwide health concern marked by whole-body inflammation in response to microbial infection, which results in organ dysfunction. In hospitalized patients, it’s becoming a common problem. By screening biomarkers with diagnostic value, early and differential identification of sepsis is crucial to minimize unnecessary use of antimicrobial drugs and optimal use of antibiotic therapies. Procalcitonin thus acts as a biomarker for sepsis identification. When the host’s immune system responds well, or proper treatment is introduced, the levels of procalcitonin are found to decrease almost up to 50% within 24 hours. This indicates that procalcitonin could be regarded as a definite biomarker to monitor disease progression or therapy. - Early detection
Tests such as blood, urine, and sputum cultures are used to determine the presence of bacterial infection in the body. One of the most crucial things essential in curing any disease is the prompt diagnosis. Prompt and efficient diagnosis are the key elements that help physicians decide on a definite therapy. The serum procalcitonin levels help the medical practitioners instantly know if the inflammatory response is of bacterial origin or not. Further, early detection reduces the chances of the microbes residing longer and becoming resistant. Also, it helps to prevent the infected individual from being exposed to more antibiotic therapies.
Exceptions
The serum procalcitonin levels are found to help incredibly well at finding the origin of infection. However, there are a few limitations for us to acknowledge before we draw some severe conclusions about it. High levels of procalcitonin were also found in some non-infectious conditions such as burns, carcinomas, etc. Apart from this, falsely elevated procalcitonin levels were also seen in patients with a chronic kidney disorder.
Conclusion
Procalcitonin helps detect bacterial infection and its severity level in the human body. However, it is certainly worth mentioning that there is still a need for some meticulous research in this context. Moreover, there is no harm in utilizing procalcitonin as a diagnostic marker unless a practitioner knows its limitation in the clinical setting.
References:
- Procalcitonin (PCT) [Internet]. Medscape.com. 2021 [cited 2022 Feb 3]. Available from: https://emedicine.medscape.com/article/2096589-overview
- Rowland T, Hilliard H, Barlow G. Procalcitonin: potential role in diagnosis and management of sepsis. Adv Clin Chem [Internet]. 2015 [cited 2022 Feb 3];68:71–86. Available from: https://www.sciencedirect.com/topics/neuroscience/procalcitonin
- Vijayan AL, Vanimaya, Ravindran S, Saikant R, Lakshmi S, Kartik R, et al. Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy. J Intensive Care [Internet]. 2017;5(1):51. Available from: http://dx.doi.org/10.1186/s40560-017-0246-8
- Cleland DA, Eranki AP. Procalcitonin. In: StatPearls [Internet]. StatPearls Publishing; 2021.
