{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:32:34Z","timestamp":1760059954702,"version":"build-2065373602"},"reference-count":54,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, University of Belgrade, School of Medicine","award":["451-03-137\/2025-03\/200110"],"award-info":[{"award-number":["451-03-137\/2025-03\/200110"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: Medullary thyroid carcinoma (MTC) is a rare malignancy derived from parafollicular C-cells, with calcitonin (Ct) as its key biomarker. While basal Ct (bCt) levels above 100 pg\/mL strongly suggest MTC, intermediate elevations (10\u2013100 pg\/mL) may reflect C-cell hyperplasia (CCH) or other benign conditions, making diagnostics challenging. Although calcium stimulation testing enhances sensitivity, the optimal cut-off values and comparative efficacy of calcium gluconate (CG) versus calcium chloride (CC) remain insufficiently researched. Methods: Data on 176 patients who underwent total thyroidectomy between 2009 and 2025 were retrospectively analyzed. BCt values ranged from 10 to 100 pg\/mL, and stimulated Ct (sCt) values were above 100 pg\/mL. CG was used from 2009 to 2019, and CC was used from 2020 to 2025. Definitive pathohistological findings divided patients into those with MTC, CCH, or no C-cell pathology. Receiver operating characteristic (ROC) analysis identified optimal Ct thresholds for predicting MTC for each stimulatory agent. Results: Of the 176 patients, 36 (20.5%) had confirmed MTC. A bCt threshold of 31.1 pg\/mL yielded 69.4% sensitivity and 87.1% specificity. For sCt, optimal cut-offs were 810.8 pg\/mL for CG and 1076 pg\/mL for CC. Lower thresholds (388.4 pg\/mL for CG and 431.5 pg\/mL for CC) improved sensitivity (\u226576.9%) and negative predictive value (&gt;91%). Conclusions: Calcium stimulation testing improves MTC detection in patients with moderate bCt elevation. Although CG showed marginally better diagnostic performance, CC remains a practical and reliable alternative, especially when higher cut-off values are considered. Early surgical intervention should be considered when sensitivity-driven thresholds are met.<\/jats:p>","DOI":"10.3390\/diagnostics15151850","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T10:49:17Z","timestamp":1753267757000},"page":"1850","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparing the Diagnostic Efficacy of Different Calcitonin Stimulation Tests for Sporadic Medullary Thyroid Carcinoma: Calcium Gluconate vs. Calcium Chloride"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0119-2056","authenticated-orcid":false,"given":"Jovan","family":"Ilic","sequence":"first","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarina","family":"Tausanovic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"School of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goran","family":"Zoric","sequence":"additional","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0118-8450","authenticated-orcid":false,"given":"Milan","family":"Jovanovic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"School of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5580-3247","authenticated-orcid":false,"given":"Matija","family":"Buzejic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Ivanis","sequence":"additional","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milan","family":"Parezanovic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milan","family":"Marinkovic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nemanja","family":"Karamarkovic","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic for Cardiosurgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8132-627X","authenticated-orcid":false,"given":"Ana","family":"Petakov","sequence":"additional","affiliation":[{"name":"Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladan","family":"Zivaljevic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrine Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"School of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.hoc.2007.04.002","article-title":"Medullary Thyroid Carcinoma","volume":"21","author":"Hoff","year":"2007","journal-title":"Hematol.\/Oncol. 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