{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T10:56:36Z","timestamp":1794394596555,"version":"4.9.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Medullary thyroid carcinoma (MTC) is a rare cancer that accounts for 5% of thyroid cancers. Serum calcitonin is a good biomarker for MTC, which is used for diagnosis, prognosis, and monitoring of recurrence. Calcitonin-negative MTC (CNMTC) is rare but confounds diagnostic and prognostic directions. This study introduces 19 cases of CNMTC in a single center.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>From 2002 March to 2020 July, more than 76,500 patients had undergone thyroid surgery due to thyroid cancer at the Severance Hospital, and a total of 320 patients were diagnosed with MTC (0.4%). Serum calcitonin levels were obtained from every patient who was suspected with MTC. These patients had undergone either bilateral total thyroidectomy or unilateral thyroidectomy with central compartment lymph node dissection, and additional modified radical lymph node dissection if lateral lymph node metastasis was positive. Postoperative monitoring and out-patient clinic follow-up were performed with obtaining the serum calcitonin levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Result<\/jats:title><jats:p>Nineteen patients tested negative for calcitonin preoperatively (6%). The mean preoperative calcitonin level was 5.1pg\/mL if undetectable level is regarded as 0pg\/mL. Only two patients were males, and the female bias was significant (p = 0.017). No one except two patients with modified radical neck dissection showed central compartment lymph node metastasis. Every patient\u2019s postoperative calcitonin level remained low. The median follow-up period was 71 months. There was no recurrence and only one fatality, and the overall survival rate was 95%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Since incidence of CNMTC is not negligible, MTC should not be ruled out in the diagnostic phase even if serum calcitonin is negative in preoperative examination. We presented 19 cases of CNMTC whose prognosis in general were favorable. Markers of serum and immunohistochemical samples other than calcitonin should be actively examined.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2021.747704","type":"journal-article","created":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T12:59:01Z","timestamp":1636117141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":26,"title":["Serum Calcitonin-Negative Medullary Thyroid Carcinoma: A Case Series of 19 Patients in a Single Center"],"prefix":"10.3389","volume":"12","author":[{"given":"Sun Jung","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeok Jun","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Jin","family":"Shin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Sang","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang-Seok","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-010-9433-2","article-title":"Disparity Between Tissue and Serum Calcitonin and Carcinoembryonic Antigen in a Patient With Medullary Thyroid Carcinoma","volume":"39","author":"Alapat","year":"2011","journal-title":"Endocrine"},{"key":"B2","article-title":"Hypercalcitoninaemia in Patients With Chronic Inflammatory Disease","volume":"23","author":"Mulder","year":"1980","journal-title":"Neth J Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1186\/s12902-019-0435-7","article-title":"Medullary Thyroid Carcinoma With Double Negative Calcitonin and CEA: A Case Report and Update of Literature Review","volume":"19","author":"Gambardella","year":"2019","journal-title":"BMC Endocr Disord"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1308\/rcsann.2019.0153","article-title":"Calcitonin-Negative Medullary Thyroid Carcinoma: The \u2018Triple-Negative\u2019 Phenotype","volume":"102","author":"Murphy","year":"2020","journal-title":"Ann R Coll Surg Engl"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2010.0299","article-title":"Calcitonin-Negative Neuroendocrine Tumor of the Thyroid: A Distinct Clinical Entity","volume":"21","author":"Chernyavsky","year":"2011","journal-title":"Thyroid"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3978\/j.issn.2227-684X.2015.01.02","article-title":"Calcitonin-Negative Neuroendocrine Tumor of Thyroid Gland Mimicking Anaplastic Carcinoma: An Unusual Entity","volume":"4","author":"Ismi","year":"2015","journal-title":"Gland Surg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2007.0413","article-title":"Medullary Thyroid Carcinoma Without Marked Elevation of Calcitonin: A Diagnostic and Surveillance Dilemma","volume":"18","author":"Wang","year":"2008","journal-title":"Thyroid"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/nejm198902163200707","article-title":"Hormone-Negative, Chromogranin A-Positive Endocrine Tumors","volume":"320","author":"Sobol","year":"1989","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s004280050238","article-title":"\u201cAtypical\u201d Medullary Thyroid Carcinoma With Little or No Calcitonin Expression","volume":"433","author":"Schmid","year":"1998","journal-title":"Virchows Arch"},{"key":"B10","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1089\/thy.2012.0236","article-title":"Prevalence and Clinical Spectrum of Nonsecretory Medullary Thyroid Carcinoma in a Series of 839 Patients With Sporadic Medullary Thyroid Carcinoma","volume":"23","author":"Frank-Raue","year":"2013","journal-title":"Thyroid"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2017.05.003","article-title":"Clinical and Pathological Analysis of 19 Cases of Medullary Thyroid Carcinoma Without an Increase in Calcitonin","volume":"69","author":"Zhou","year":"2017","journal-title":"Exp Toxicol Pathol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-19-1-152","article-title":"Medullary (Solid) Carcinoma of the Thyroid; 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