Marker For Medullary Thyroid Carcinoma Research Articles

Gender and tumor size-specific calcitonin cutoff value for diagnosing MTC in 10,618 patients with thyroid nodule surgery.

Calcitonin is a sensitive marker for medullary thyroid carcinoma (MTC) diagnosis and postsurgical follow-up. This study aimed to define the gender and tumor size-specific calcitonin cutoff values for diagnosing MTC. This retrospective study recruited 95 MTC patients and 10,523 non-MTC patients who underwent thyroid nodule surgery at Zhongshan Hospital between January 2015 and June 2023. Receiver operating characteristic (ROC) curves were used to assess calcitonin cutoff values for diagnosing MTC. Calcitonin levels in non-MTC patients were influenced by gender, CKD stage and age, with gender being the highest ranked predictor. In MTC patients, calcitonin levels were associated with tumor diameter, lymph node metastasis, and TNM stage. In the entire study population, calcitonin cutoff values to diagnose MTC were 17.75 pg/mL for males (sensitivity: 97.60%, specificity: 99.40%) and 7.15 pg/mL for females (sensitivity: 94.34%, specificity: 99.22%). In patients with a thyroid nodule diameter ≤10 mm, the calcitonin cutoff values to diagnose MTC were 17.50 pg/mL for males (sensitivity: 95.00%, specificity: 99.27%) and 7.15 pg/mL for females (sensitivity: 90.91%, specificity: 99.04%). In patients with a thyroid nodule diameter >10 mm, the calcitonin cutoff values to diagnose MTC were 104.80 pg/mL for males (sensitivity: 100.00%, specificity: 100.00%) and 32.60 pg/mL for females (sensitivity: 96.77%, specificity: 100.00%). We have identified the gender and tumor size-specific cutoff values for the diagnosis of MTC. Cutoff values based on gender and tumor diameter may help to improve the accuracy of preoperative diagnosis of MTC, which is worth to be verified by future studies.

Progress and controversy on the extent of surgery for medullary thyroid carcinoma based on calcitonin levels

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor originating from the parafollicular cells (C cells) of the thyroid gland, classified as sporadic and hereditary. Calcitonin (Ctn) secreted by the C cells is a specific serological marker for MTC, which is of great value in diagnosis, treatment and postoperative management of MTC. The effect of chemoradiotherapy and 131I therapy on MTC is limited, with surgery being the primary therapy. Given the aggressive nature and relatively poor prognosis of MTC, the reasonable surgical extent is crucial for improving cure rate and prognosis of patients. However, there are still some controversies regarding the extent of surgery for MTC. This article elaborates on the research progress and controversies of serum Ctn levels in assisting the evaluation of the extent of surgery for MTC.

Experimental Study of Interference in Calcitonin Testing: A Case Report and Literature Review.

Calcitonin (CT) is a sensitive serum marker of medullary thyroid carcinoma usually detected via immunoassays; however, its levels are easily disturbed by several endogenous factors. The study aimed to discuss a case of suspected interference resulting in aberrant CT values and review previous reports of CT interference. A female patient visited our clinic with a physical ultrasound examination showing a slightly enlarged thyroid gland with small nodules. She had elevated CT levels, inconsistent with the clinical presentation and other findings. We evaluated the results by retesting using the same platform, platform validation, multiplex dilution, Polyethylene Glycol (PEG) precipitation, heterophilic blocking tubes, and RET gene analysis. Retesting CT using the same platform confirmed the high value obtained. However, serial dilution of the sample produced nonlinear results, suggesting some interference. While PEG precipitation did not significantly reduce the CT level, incubating the sample in HBTs normalized the CT value, indicating interference from heterophilic antibodies. Gene sequencing revealed no RET mutations. In cases where elevated CT levels are inconsistent with clinical presentations and other findings, the laboratory technicians should communicate with clinicians, analyze the reasons for the inconsistent results, and use different methods to verify the results. Accurate testing provides realistic and reliable data for doctors and patients and helps to avoid unnecessary procedures.

Serum Biochemical Markers for Medullary Thyroid Carcinoma: An Update.

Medullary thyroid carcinoma (MTC), a rare malignancy, requires early diagnosis for optimal patient outcomes. An important aspect of MTC diagnosis is the assessment of serum biomarkers. This review aimed to evaluate the use of serum biomarkers in the diagnosis, prognosis, and follow-up of MTC. A thorough search of PubMed covering 1975 to 2022 was conducted to identify English-language articles on MTC serum biomarkers. The review revealed that calcitonin (Ctn) and carcinoembryonic antigen (CEA) remain the most important serum biomarkers for MTC diagnosis and management. Despite limited studies on procalcitonin (PCT), its stability and ability to exclude interference from inflammation make it a valuable potential marker of MTC. Although the positive rate of serum CA19-9 levels in MTC patients was not high, it can be used as an indicator of poor prognosis in advanced MTC. Other serum markers, including chromogranin A, gastrin-releasing peptide precursor, and neurospecific enolase, did not show any unique value in MTC diagnosis and management. Taken together, this review emphasized the importance of serum biomarkers, particularly Ctn and CEA, in the diagnosis and management of MTC. PCT shows promise as a valuable potential marker, whereas CA19-9 can be used as a prognostic indicator of advanced MTC. Further research is needed to validate the significance of these serum biomarkers in MTC and determine the effects of confounding factors on their levels. Clinicians should consider using these markers in MTC diagnosis, prognosis, and follow-up, particularly for patients with advanced disease.

Evaluation of calcitonin measurement in fine needle aspirates in the diagnosis of primary and metastatic medullary thyroid carcinoma

Serum CT represents the tumoral marker of medullary thyroid carcinoma (MTC), and is a main diagnostic tool and follow-up after treatment. Nevertheless, calcitonin levels can be elevated in a number of other situations and does not always distinguish MTC from other clinical circumstances, particularly when elevation remains moderate. Fine needle aspiration biopsy is a widely used examination for the investigation of thyroid nodules and lymph nodes, but its sensitivity for the diagnosis of MTC remains low ranging from 45% to 63%. Calcitonin measurement in fine needle aspiration wash out fluid has been reported as reliable, and is recommended by the experts of American Thyroid Association (ATA) in their 2015 consensus for the management of MTC even if its diagnostic is not standardized yet. Material and methods: Twenty patients with 45 lesions (thyroid nodule and lymph node) were included in this study; calcitonin was performed in each of them, the puncture needles were washed with 1ml of saline solution to obtain to measure Calcitonin in fine needle aspiration washout fluid. Results: After surgery 32 MTC were diagnosed on histology. Receiver operating curve (ROC curve) indicated CT in fine needle aspiration >22.99pg/ml as more accurate cut off value with a sensitivity and specificity of 96.87% and 100%. Calcitonin ratio was evaluated too, the cut off value being>0.64 with a sensitivity of 62.5% and specificity of 100%. Conclusion: Calcitonin in fine needle aspiration wash out fluid constitutes an excellent diagnostic tool of MTC with the use of 22.99pg/ml threshold.

Early calcitonin levels in medullary thyroid carcinoma: Prognostic role in patients without distant metastases at diagnosis.

Calcitonin is the most specific marker for medullary thyroid carcinoma, thus, low detectable calcitonin values after surgery can conceal persistent disease. The present study aimed to explore the prognostic role of pre-operative and early calcitonin levels in patients without distant metastases at diagnosis. A retrospective cohort of patients suffering from medullary thyroid carcinoma was considered (N=55). The final disease status, i.e. complete response (undetectable calcitonin levels and negative radiological assessments) or persistent disease (detectable calcitonin levels and/or positive radiological assessments), was deduced from the last available follow-up. Pre-operative and early calcitonin levels (i.e. six months after surgery) have been correlated to several clinical and histological features, according to the final disease status. Persistent disease patients showed higher pre-operative and early calcitonin values (p=0.028 and p<0.001, respectively), compared to complete response sub-cohort. Cox-regression models show that early detectable calcitonin increases up to 18-fold the risk of persistent disease, independently from tumour size and pre-operative calcitonin levels (p=0.006). Of note, when considering only patients who finally developed distant metastasis, ROC curve analysis shows that an early calcitonin level ≥16 pg/ml predicts the final disease status with a sensitivity of 89% and a specificity of 82% (AUC=0.911, CI95%: 0.819-1000, p<0.001). Calcitonin levels six months after surgery represents an easy and effective predictor of persistent disease for medullary thyroid carcinoma without distant metastasis at diagnosis.

LBODP099 A Young Patient With Undifferentiated And Advanced Medullary Thyroid Carcinoma With Negative RET - CASE REPORT

Abstract A Young Patient With Undifferentiated And Advanced Medullary Thyroid Carcinoma With Negative RET – CASE REPORT INTRODUCTION: Medullary Thyroid Carcinoma (MTC) is a rare and aggressive form of thyroid cancer that arises from C cells, representing 5% of all thyroid malignancy. The biochemical characteristic of MTC is the elevation of serum calcitonin (CTN), which aids in the initial diagnosis and surveillance of this disease. Another important, but less specific marker in the follow-up is the carcinoembryogenic antigen (CEA). Although, it is observed in the Undifferentiated MTC that there is a disproportion between the expected values of CEA and CTN. Case Report A previously healthy 16 years old female patient was hospitalized for the investigation of cervical discomfort, involuntary weight loss and progressive back pain for 9 months. She had a BMI of 14.9kg/cm2, a palpable thyroid nodule measuring approximately 2. 0cm and painful cervical lymph node enlargement. Laboratory tests showed CTN 79.1pg/mL, CEA 4999.42ng/mL added with an independent PTH hypercalcemia. Thyroid US showed a solid nodule with lobulated contours, heterogeneous echotexture, predominantly hypoechogenic, with its longest axis parallel to the skin, measuring approximately 2.4×0.9×0.9 cm, located in the lower middle third of the right thyroid lobe (TI -RADS 4) added to multiple lymph nodes inthe anterior cervical area (in agreement with the neck CT). Regarding the staging Chest CT showed a metastasis suggestive nodulation; Cranial CT, bone scan and total spine MRI showed evidence of several infiltrative nodular formations with heterogeneous enhancement affecting the skullcap, sacrum, iliac bones and multiple vertebral bodies. Sacral bone biopsy was performed giving us the diagnose of a metastatic Medullary Thyroid Carcinoma (MTC). A FineNeedle Aspiration (FNA) of the thyroid nodule and cervical lymph node showed calcitonin levels of 31.1pg/mL added with positive immunohistochemistry for chromogranin,synaptophysin, CD56 and Calcitonin in a focal manner, confirming the hypothesis of Undifferentiated CMT. Genetic testing was performed by next-generation sequencing of the genes ATM, ATR, CDKN2A, EGLN1, FH, HRAS, KIF1B, KMT2D, MAX, MDH2, MERTK, MET, NF1, PIK3CA, RET, SDHA, SDHAF2, SDHB, SDHC, SDHD, TMEM127, TP53 (including promoter), VHL, which results were negative for all pathogenic variants, probably pathogenic or VUS therefore being considered a sporadic MTC. Patient was referred for cervical radiotherapy and started Vandetanib. Conclusion Serum CTN is the main diagnostic and surveillance marker of MTC. CEA is another marker that must be taken into account. We report the case of a young patient diagnosed with metastatic RET negative MTC with disproportionate values of CTN and CEA, which suggests its undifferentiated feature, revealing the importance of joint assessment of these two markers. Presentation: No date and time listed

Procalcitonin as a marker of medullary thyroid carcinoma.

Procalcitonin as a marker of medullary thyroid carcinoma.

Procalcitonin as an Alternative Tumor Marker of Medullary Thyroid Carcinoma.

Calcitonin (CT) measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Procalcitonin (ProCT) has been reported as a promising alternative MTC tumor marker. This study aimed to determine the ProCT diagnostic accuracy in prediction and treatment monitoring of MTC. Electronic databases were searched for observational studies published until May 2021 without language or time restrictions. Studies comparing ProCT and calcitonin accuracy were included. After removing duplicates and exclusion of not-eligible articles, relevant articles were screened independently by 2 reviewers. Eleven studies (4.5% of the identified studies) met the selection criteria. Two reviewers independently extracted data and assessed data quality and validity through QUADAS-2. A meta-analysis was performed on 11 sufficiently clinically and statistically homogeneous studies (n = 5817 patients, 335 MTC patients). Hierarchical summary receiver operating characteristics and bivariate methods were applied. Serum ProCT was found to be a highly accurate test for MTC diagnosis and monitoring. The pooled sensitivity, specificity, positive and negative likelihood ratios, area under the curve, and positive and negative predictive values for ProCT were 0.90 (95% CI: 0.71-0.97), 1.00 (95% CI: 0.85-1.00), 288 (95% CI: 5.6-14 929.3), 0.10 (95% CI: 0.03-0.33), 0.97 (95% CI: 0.95-0.98), 99%, and 2%, respectively. The high accuracy, compounded with favorable analytical characteristics, give ProCT great potential to replace calcitonin as a new standard of care in the management of MTC.

Procalcitonin as an alternative tumor marker of medullary thyroid carcinoma. A meta-analysis

Objective This study aimed to determine the procalcitonin (ProCT) diagnostic accuracy in prediction and treatment monitoring of medullary thyroid carcinoma (MTC). Data sources Electronic databases were searched for observational studies published until May 2021 without language or time restrictions. Study selection Studies comparing ProCT and calcitonin accuracy were included. After removing duplicates and exclusion of not-eligible articles, relevant articles were screened independently by two reviewers. Eleven studies (4.5% of the identified studies) met the selection criteria. Data extraction Two reviewers independently extracted data and assessed data quality and validity through QUADAS-2. Data synthesis A meta-analysis was performed on sufficiently clinically and statistically homogeneous eleven studies (n = 5817 patients, 335 MTC patients). HSROC and bivariate methods were applied. Serum ProCT was found to be a highly accurate test for MTC diagnosis and monitoring. The pooled sensitivity, specificity, positive and negative likelihood ratios, AUC, and positive and negative predictive values for ProCT were 0.90 (95%CI: 0.71-0.97), 1.00 (95%CI: 0.85-1.00), 288 (95%CI: 5.6-14929.3), 0.10 (95%CI: 0.03-0.33), 0.97 (95%CI: 0.95-0.98), 99% and 2%. Conclusions The high accuracy, compounded with favorable analytical characteristics, give ProCT great potential to replace calcitonin as a new standard of care in the management of MTC.

Raman-based cytopathology: an approach to improve diagnostic accuracy in medullary thyroid carcinoma.

Medullary thyroid carcinoma (MTC) is a rare form of thyroid malignancy that can be diagnostically challenging on fine needle aspiration (FNA) cytology. Ancillary tests such as elevated serum or immunohistochemical positive calcitonin have been helpful, yet they can occasionally provide false positive results. In search for an alternative method to improve diagnostic accuracy (DA), we applied hyperspectral Raman spectroscopy to characterize the biochemical composition of single cells from MTC and compared their spectral information to cells from other types of thyroid nodules. Hyperspectral Raman images of 117 MTC single cells from digested tissue were obtained with a line-scan hyperspectral Raman microscope and compared to 127 benign and 121 classic variant of papillary thyroid carcinoma (CVPTC) cells. When principal component analysis and linear discriminant analysis were used to classify the spectral data, MTC cells were differentiated from benign and CVPTC cells with 97% and 99% DA, respectively. In addition, MTC cells exhibited a prominent Raman peak at 1003 cm-1, whose intensity is 84% and 226% greater on average than that observed in benign and CVPTC cells, respectively. When specifically utilizing only this peak as a spectral marker, MTC cells were separated from benign and CVPTC cells with 87% and 95% DA, respectively. As this peak is linked to phenylalanine, which is known to be associated with calcitonin release in thyroid parafollicular cells, the increased intensity further suggests that this Raman peak could potentially be a new diagnostic marker for MTC. Furthermore, preliminary data from MTC cells (n=21) isolated from a simulated FNA procedure provided similar Raman signatures when compared to single cells from digestion. These results suggest that "Raman-based cytopathology" can be used as an adjunct technique to improve the diagnostic accuracy of FNA cytopathology at a single cell level.

Management of medullary thyroid carcinoma

: Medullary thyroid carcinoma (MTC) is a rare malignancy arising from parafollicular C-cells and accounts for 3–10% of all thyroid malignancies. MTC occurs mostly as a sporadic disease, but in at least 30% of cases is hereditary, caused by RET germline mutations. In this setting, different germline RET mutations lead to distinct clinical phenotypes of hereditary MTC such as familial MTC and multiple endocrine neoplasia 2A and 2B. RET genetic screening should be performed in all new discovered cases of MTC since about 4–10% of patients with apparently sporadic MTC have RET germline mutations and therefore an inheritable disease. Calcitonin (CT) is the most reliable marker of MTC for both diagnosis and follow-up after thyroidectomy. In sporadic MTC, a routine determination of CT in patients with nodular goiter has been correlated to a lower rate of advanced tumor stages. Surgery is the only curative treatment. Since the relatively high risk of multifocal and bilateral disease and the early spread to cervical lymph nodes, total thyroidectomy and central neck lymph node dissection is the standard initial treatment. Lateral neck lymph node dissection might be considered according to imaging results and CT levels. The potential benefit of neck reiterative surgery for persistent or recurrent MTC should be balanced against the increased surgical morbidity in a scarred operative field. The treatment of locally advanced MTC that is not amenable to surgery or metastatic MTC benefits of tyrosine kinase inhibitors that have shown some effects on disease progression. External radiotherapy and cytotoxic chemotherapy have demonstrated little benefit. Prognosis strictly depends on stage of disease at diagnosis, with lower survival and cure rate for stage IV disease. The purpose of this review is to describe the management and treatment of patients with MTC, focusing on biochemical and imaging diagnostic tools, preoperative work-up, treatment and prophylactic surgery for hereditary variants.

Procalcitonin as a marker of medullary thyroid carcinoma

Procalcitonin as a marker of medullary thyroid carcinoma

Changes in Serum Calcitonin Concentrations, Incidence of Medullary Thyroid Carcinoma, and Impact of Routine Calcitonin Concentration Monitoring in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL).

Increases in serum calcitonin, a tumor marker for medullary thyroid carcinoma (MTC), have been associated with glucagon-like peptide 1 receptor agonist use in some preclinical studies. We report calcitonin changes in exenatide-treated and placebo-administered participants and MTC incidence in the EXenatide Study of Cardiovascular Event Lowering (EXSCEL) and consider the impact of within-trial calcitonin monitoring. EXSCEL participants were randomized 1:1 to once-weekly exenatide 2 mg or placebo. Serum calcitonin was measured at baseline (with trial medication discontinued if >40 ng/L) and annually thereafter (with trial medication discontinued if ≥50 ng/L). Median calcitonin concentrations were calculated at each time point, and thyroid malignancies were collected prospectively. Data regarding follow-up after an elevated calcitonin were collected retrospectively. At baseline, 52 (30 exenatide and 22 placebo) participants had calcitonin >40 ng/L, and during follow-up an additional 23 participants (15 exenatide and 8 placebo) had calcitonin ≥50 ng/L in the intention-to-treat population. Median calcitonin concentrations were similar between treatment groups at baseline with no increase over time. Confirmed MTC occurred in three participants (2 exenatide and 1 placebo), all of whom had significantly elevated baseline calcitonin values (413, 422, and 655 ng/L). During a median 3.2 years' follow-up, no change in serum calcitonin was seen with exenatide therapy. The three confirmed cases of MTC all occurred in participants with markedly elevated baseline calcitonin levels, measured prior to trial medication administration. Regular calcitonin monitoring identified no additional cases of MTC, suggesting no benefit of routine calcitonin monitoring during exenatide treatment.

CEA as a Marker for Medullary Thyroid Carcinoma in a Patient with Colorectal Cancer

CEA as a Marker for Medullary Thyroid Carcinoma in a Patient with Colorectal Cancer

CALCITONIN REVISITED IN 2020.

Calcitonin (CT) is a polypeptidic hormone specifically secreted by the thyroid parafollicular cells (C cells) and tangentially involved in human phosphocalcic and bone metabolism. CT from other species (e.g. salmon) is more potent than human CT and has limited therapeutic applications. The neoplastic proliferation of C cells leads to medullary thyroid carcinoma (MTC) generally characterized by an increase of CT secretion. Serum CT is therefore the ideal marker for MTC and can confirm its presence at an early stage, as well as the follow up of its remission or progression/relapse/survival after surgery. There are, however, controversies such as the necessity of CT screening in patients with thyroid nodules, or particular situations causing false positive or false negative results. Our minireview also deals with an up-to-date of surgical procedures for MTC, as well as with non-surgical therapy.

Calcitonin Screening in Nodular Thyroid Disease: Is There a Definitive Answer?

Introduction: Calcitonin (Ctn) is a hormone secreted by thyroid “C” cells and is considered an excellent marker for medullary thyroid carcinoma (MTC). However, the use of Ctn to screen patients with nodular thyroid disease (NTD) remains controversial. Objective: The aim of this work was to define the frequency of hypercalcitoninemia among NTD patients followed at a tertiary referral hospital. Methods: A retrospective analysis was made of basal Ctn measurements and corresponding patients’ records between January 2011 and December 2015. Hypercalcitoninemia was defined as > 10 pg/mL. Depending on the Ctn value, three groups were considered: G1, ≤10 pg/mL; G2, 10–100 pg/mL; G3, ≥100 pg/mL. Results: Ctn was requested in an NTD context for 1,504 patients, 69 of whom had hypercalcitoninemia. Of these, 20 underwent surgery (G2, 11; G3, 9), and a histological diagnosis of MTC was established in 12 (G2, 3/27%; G3, 9/100%). Surgery was chosen based solely on Ctn levels in 7 cases, since only 5 had a positive cytology. Conclusions: Hypercalcitoninemia was found in 4.6% of NTD patients. Ctn levels ≥100 pg/mL were associated with a greater CMT risk than values between 10 and 100 pg/mL, reinforcing results from other groups. The need for an adequate interpretation of results as well as an appropriate selection of patients to surgery stresses the importance of endocrinologists requesting and interpreting results.

Uso della procalcitonina come marker del carcinoma midollare tiroideo

Here we reviewed the literature on the use of procalcitonin (PCT), a precursor of calcitonin (CT), as diagnostic marker of medullary thyroid carcinoma (MTC) in both preoperative and postsurgical setting. To date, about forty articles have been published on this topic. Some of these evaluated the reliability of PCT to detect MTC in thyroid nodule patients, and the other ones investigated the performance of PCT to identify recurrent MTC during postoperative follow-up. Based on published data, PCT measurement appears a promising and reliable serum marker for the diagnosis of MTC. The sample handling of PCT is less laborious and in specific conditions its assay could have significant impact and higher accuracy than CT. Some potential cut-offs have been reported but it would be worthwhile to establish a fixed threshold to use PCT during clinical practice.

Procalcitonin as a postoperative marker in the follow-up of patients affected by medullary thyroid carcinoma.

Due to the limits of calcitonin, other markers are warranted to better manage medullary thyroid carcinoma patients, and procalcitonin has been reported as promising. Here we aimed to evaluate procalcitonin as a marker of medullary thyroid carcinoma in the post-treatment follow-up. Medullary thyroid carcinoma patients previously treated by thyroidectomy were enrolled. After complete imaging work-up (i.e. ultrasonography, computed tomography, magnetic resonance and 18FDG-PET-CT) we identified patients with structural recurrent/persistent medullary thyroid carcinoma (active medullary thyroid carcinoma) and subjects with no evidence of disease. Then, both calcitonin and procalcitonin were measured and their performance analyzed. The final series included 55 medullary thyroid carcinoma patients treated and followed-up for about five years. Of these, 43 were assessed as no evidence of disease, and 12 as active medullary thyroid carcinoma. The median value of procalcitonin was significantly higher ( P < 0.0001) in active medullary thyroid carcinoma patients (3.10 ng/mL) than in those with no evidence of disease (0.10 ng/mL). Also, calcitonin levels of active medullary thyroid carcinoma (96.7 pg/mL) were significantly ( P < 0.0001) higher than that of no evidence of disease (2.0 pg/mL). At the receiver operating characteristic curve analysis, the optimal cut-off of procalcitonin was ≥0.32 ng/mL with 92% sensitivity and 98% specificity, while the most accurate threshold of calcitonin was ≥12.0 pg/mL with 100% sensitivity and 91% specificity. There was no active medullary thyroid carcinoma with simultaneously negative results of procalcitonin and calcitonin. Procalcitonin is reliable in discriminating medullary thyroid carcinoma patients with active disease from those with no evidence of disease. We suggest using procalcitonin as complementary to calcitonin to follow-up medullary thyroid carcinoma patients.

Patients with papillary thyroid carcinoma associated with high stimulated serum calcitonin levels.

Among various substances produced by C-cells, the most important one is calcitonin (CT) that is used for detection, post-operative follow-up and evaluation of individuals at risk of developing medullary thyroid carcinoma (MTC). However, the role of serum CT measurement in the evaluation of thyroid nodules has been widely discussed, and there is still no consensus about the role of CT in the initial evaluation of all thyroid nodules. Two patients with thyroid nodules whose fine-needle aspiration results were compatible with benign cytology besides having mildly elevated basal serum calcitonin levels were reported. Calcitonin responses (peak levels were 313 and 229 pg/mL, respectively) to calcium stimulation test were compatible with the possible diagnosis of MTC. However, the final diagnosis was papillary thyroid carcinoma of the thyroid gland. There are limited numbers of case reports showing such an increased serum calcitonin responses to calcium stimulation test associated with papillary or follicular thyroid carcinoma of the thyroid. We suggest to measure serum CT level once and in case of normal levels, no further CT measurement is necessary. Physicians should keep in mind that thyroid carcinomas other than MTCs may also be associated with high serum CT levels.Learning points:Although serum calcitonin is a valuable tumor marker for MTC, it is well known that mild elevations may be seen in some other diseases such as Hashimoto thyroiditis, neuroendocrine tumors or due to medications such as proton pump inhibitors, calcium salts, beta blockers and glucocorticoids.Those two cases indicate that high calcitonin responses to calcium stimulation test, mimicking MTC, may also be seen in patients with papillary thyroid carcinoma although the mechanism is not clear.