Serum calcitonin levels shows more sensitivity than cytopathology for the medullary thyroid cancer diagnosis

Daniela Barros, post graduate student of the Surgical Clinic Program at Ribeirão Preto Medical School, University of São Paulo (FMRP-USP). Ribeirão Preto, SP, Brasil.

Medullary thyroid cancer (MTC) is a neoplasm difficult to diagnose prior to surgery. It represents a well differentiated neuroendocrine carcinoma that affects thyroid C-cells. MTC responds to approximately 5% of malignant thyroid nodules and is an aggressive neoplasm with an estimated 10-year survival rate of 40%-50% (SCHLUMBERGER, M., et al).

MTC is challenging to diagnose preoperatively. According to Trimboli and cols. (2014), although cervical ultrasound is not specific for the diagnosis of this neoplasm, the latter can exhibit signs such as hypoechogenicity and microcalcifications, which suggest a higher risk of malignancy (TRIMBOLI, P., et al, 2014).

The few studies that analyzed ultrasound images of MTC patients found that the traditional risk factors used to characterize papillary thyroid carcinoma (PTC) are similar to those for MTC (WELLS, SA Jr., et al).

Fine-needle aspiration biopsy (FNAB) is a safe and useful procedure to detect MTC. However, the accuracy of cytopathology in detecting MTC is lower than in the case of PTC. In a meta-analysis that examined 15 papers, the accuracy of FNAB to diagnose MTC in patients with suspicious nodules was less than 50% (TRIMBOLI, P., et al, 2015).

Figure 1 MTC cytological presentation examples in FNAB. (A) Bethesda III: Large clusters of polygonal and triangular cells. (B) Bethesda VI: abundant amyloid substance in the extracellular space with polygonal and triangular tumor cells. Image:OLIVEIRA, D. H. A. et al.

Therefore, FNAB has a high diagnostic value for PTC, but its sensitivity for MTC is low. Due to the low sensitivity of FNAB in providing a diagnostic hypothesis of Bethesda V or Bethesda VI for MTC, other methods to investigate this neoplasm should be used to increase sensitivity when a FNAB is not diagnostic. Allelein and cols. (2018) reported that serum CT had a diagnostic sensitivity of 93% for MTC (ALLELEIN, S., et al).

The low cure rate once the disease spreads beyond the thyroid gland supports the use of serum CT screening in the early diagnosis of MTC in patients with thyroid nodules. Although this practice is the standard of care at some centers in European countries, there has been controversy around its application in the United States (WELLS, SA Jr., et al).

It is very important to find feasible alternatives to increase the preoperative diagnostic accuracy of MTC since some aspects related to preoperative assessment differ from the common surgical approach for nodular thyroid disease. Taking this scenario into consideration, Oliveira, et al. conducted the study “Is there a place for measuring serum calcitonin prior to thyroidectomy in patients with a non-diagnostic thyroid nodule biopsy?” (Arch. Endocrinol. Metab., vol.65 no.1) to verify the cytopathological Bethesda System classification of thyroid nodules FNABs in a group of MTC patients under observation at the Uopeccan (União Oeste Paranaense de Estudos e Combate ao Câncer) and to assess the role of preoperative serum CT levels in the investigation of this neoplasm.

It was identified that Bethesda category III was more prevalent in this group of MTC patients. Serum CT levels were more sensitive than cytopathology for diagnosis of this neoplasm and were able to identify all patients who could not be diagnosed by FNAB. Thus, measuring serum CT levels in the preoperative period is an ideal tool to increase the perioperative safety of thyroidectomy.

The possibility of a preoperative diagnosis of MTC can reduce the surgical morbidity of a second operation for the lymph node dissection of the recurrent chain, in addition to ensuring more safety in the operative act by excluding the presence of concomitant pheochromocytoma (PHEO), since performing TT in patients with undiagnosed PHEO in the setting of multiple endocrine neoplasia type 2 (MEN 2) increases morbidity and the chance of perioperative death (NARANJO, J., et al).

Oliveira, et al. recommend that other centers specialized in thyroid cancer should develop similar studies to assess more robustly the recommendation of measuring preoperative serum CT levels in patients that will undergo thyroidectomy due to suspected lesions for malignancy verified by ultrasound or cytopathological examination resulting in Bethesda category III.


ALLELEIN, S. et al. Measurement of Basal Serum Calcitonin for the Diagnosis of Medullary Thyroid Cancer. Horm Metab Res [online]. 2018, vol. 50, no. 1, pp. 23-8. [viewed 09 April 2021]. Available from:

NARANJO, J., DODD, S., and MARTIN, Y.N. Perioperative management of pheochromocytoma. J Cardiothorac Vasc Anesth [online]. 2017, vol. 31, no. 4, pp. 1427-39. [viewed 09 April 2021]. Available from:

SCHLUMBERGER, M. et al. New therapeutic approaches to treat medullary thyroid carcinoma. Nat Clin Pract Endocrinol Metab [online]. 2008, vol. 4, no. 1, pp. 22-32. [viewed 09 April 2021]. Available from:

TRIMBOLI, P. et al. Detection rate of FNA cytology in medullary thyroid carcinoma: a meta-analysis. Clin Endocrinol (Oxf) [online]. 2015, vol. 82, no. 2, pp. 280-285. [viewed 09 April 2021]. Available from:

TRIMBOLI, P., et al. Medullary thyroid cancer diagnosis: an appraisal. Head Neck [online]. 2014, vol. 36, no. 8, pp. 1216-1223. [viewed 09 April 2021]. Available from:

WELLS, S. A. Jr., et al. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid [online]. 2015, vol. 25, no. 6, pp. 567-610. [viewed 09 April 2021]. Available from:

To read the article, acess

OLIVEIRA, D. H. A. et al. Is there a place for measuring serum calcitonin prior to thyroidectomy in patients with a non-diagnostic thyroid nodule biopsy?. Arch. Endocrinol. Metab. [online]. 2021, vol.65, n.1, pp.40-48 [viewed 09 April 2021]. Available from:

External links

Archives of Endocrinology and Metabolism – AEM:

Diego Henrique Andrade de Oliveira:


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Serum calcitonin levels shows more sensitivity than cytopathology for the medullary thyroid cancer diagnosis [online]. SciELO in Perspective | Press Releases, 2021 [viewed ]. Available from:


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