Extrathyroidal Sources of Procalcitonin
Procalcitonin is produced by neuroendocrine cells of the lung and intestine during systemic bacterial infections, in addition to its normal production by parafollicular C-cells of the thyroid gland. 1
Primary Extrathyroidal Production Sites
During systemic inflammation and bacterial infection, PCT is synthesized by parenchymal tissues throughout the body, independent of thyroid function:
Major Tissue Sources
- Neuroendocrine cells of the lung - constitutively express PCT and upregulate production during endotoxin exposure 1, 2
- Neuroendocrine cells of the intestine - serve as another primary extrathyroidal source 1
- Liver - demonstrates high PCT concentrations during sepsis (among the highest of all organs) 3
- Kidney - shows elevated PCT tissue levels following LPS stimulation 3
Additional Tissue Sources Identified in Primate Models
Research using baboon sepsis models has documented PCT production in multiple organs following endotoxin exposure 3:
- Adipose tissue
- Ovaries
- Bladder
- Adrenal glands
- Aorta (vascular tissue)
- Colon
- Skin
- Spleen
- Brain
- Pancreas
CT-mRNA expression has been confirmed in liver, lung, kidney, adrenal, colon, skin, spleen, brain, and pancreas tissues, definitively establishing extrathyroidal PCT synthesis. 3
Mechanism of Extrathyroidal Production
When stimulated by bacterial endotoxin, PCT is rapidly produced by parenchymal tissue throughout the body through alternate pathways that are independent of calcitonin synthesis. 2, 3
- Production is triggered by bacterial endotoxin and inflammatory cytokines (TNF, IL-6) 4
- PCT begins to rise 2-4 hours after bacterial exposure, reaching maximum levels at 6-10 hours 1, 5, 3
- This extrathyroidal PCT does not undergo intracellular cleavage to calcitonin and is released directly into circulation 6, 4
Clinical Significance
Extrathyroidal PCT production explains why PCT remains a useful sepsis biomarker even in athyreotic patients (post-thyroidectomy). 3, 6
Important Caveats
- PCT elevation during bacterial sepsis occurs via alternate pathways and is not associated with proportional calcitonin elevation 7
- In contrast, medullary thyroid cancer metastases produce both PCT and calcitonin simultaneously, causing persistently elevated PCT unrelated to infection 7
- PCT values in healthy individuals are normally <0.05 ng/mL, with levels >0.5 ng/mL indicating systemic bacterial infection 1, 5
The widespread distribution of extrathyroidal PCT-producing tissues throughout the body enables PCT to serve as a systemic marker of bacterial infection severity, with production proportional to the extent of inflammatory response. 3, 6