Procalcitonin Studied in the Diagnosis and Monitoring of Thyroid Cancer

Thyroid gland tumour
Thyroid gland tumour, computer illustration.
While calcitonin is considered standard of care for the diagnosis and follow-up of medullary thyroid cancer, researchers may have found a potentially more reliable marker.

Procalcitonin (ProCT) possesses a high level of accuracy for the diagnosis and monitoring of medullary thyroid carcinoma (MTC), suggesting ProCT could replace calcitonin as a standard of care for MTC management, according to study findings published in the Journal of Clinical Endocrinology and Metabolism. Currently, ProCT is only approved by the United States Food and Drug Administration (FDA) as an infectious marker of lower respiratory tract infection and sepsis.

Study authors noted several problems influence calcitonin measurement and clinical reliability in MTC diagnosis and care. “All in all, careful standardized handling of serum samples, accurately defined assay-specific and gender specific reference ranges, and a good knowledge of nonspecific causes of calcitonin increase and disappearance kinetics are required to avoid misdiagnosis,” investigators wrote.

The study results were part of a meta-analysis that included 11 prospective or retrospective studies involving a pooled cohort of 5817 people with nodular thyroid disease.  A total of 336 patients had MTC. Some of the studies in the meta-analysis compared the diagnostic and monitoring accuracy of ProCT with calcitonin.

Across studies, the prevalence of MTC ranged between 0.16% and 60.36%. For ProCT thresholds between 0.06 and 0.50 ng/ml, the summary estimates of sensitivity and specificity were 0.90 (95% CI, 0.71-0.97) and 1.00 (95% CI, 0.85-1.00), respectively.

Additionally, the pooled estimates of positive likelihood ratio (sensitivity/[1-specificity]) and negative likelihood ratio ([1- sensitivity]/specificity) were 288 (95% CI, 5.6-14,929.3) and 0.10 (95% CI, 0.03-0.33), respectively. The pooled area under the curve (AUC) for ProCT was 0.97 (95% CI, 0.95-0.98).

In addition, the positive predictive value for ProCT was 99% and the negative predictive value was 2%. The researchers commented that “this is well in line with previously published data,” demonstrating a 98% to 100% negative predictive value of ProCT for spuriously increased (ie, false positive) CT levels in nonmedullary thyroid diseases.

In terms of limitations of the meta-analysis, the researchers noted that the chosen cutoff values for representing the discriminatory power of ProCT across studies “may have resulted in varying numbers of patients with progressing or remitting MTC confounding the predictive power of the marker.”

Despite this limitation, the researchers concluded that the reported accuracy of ProCT, combined “with the better pre-analytical and analytical characteristics, give it great potential to replace calcitonin as a new standard of care in the management of MTC.”


Giovanella L, Garo ML, Ceriani L, Paone G, Campenni A, D’Aurizio F. Procalcitonin as an alternative tumor marker of medullary thyroid carcinoma. a meta-analysis. J Clin Endocrinol Metab. Published online August 12, 2021. doi:10.1210/clinem/dgab564