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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Head and Neck Tumors</journal-id><journal-title-group><journal-title xml:lang="en">Head and Neck Tumors</journal-title><trans-title-group xml:lang="ru"><trans-title>Опухоли головы и шеи</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2222-1468</issn><issn publication-format="electronic">2411-4634</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">780</article-id><article-id pub-id-type="doi">10.17650/2222-1468-2022-12-2-79-88</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ORIGINAL REPORT</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНОЕ ИССЛЕДОВАНИЕ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Calcitonin testing in patients with thyroid nodules for screening medullary thyroid carcinoma: a “gray zone”</article-title><trans-title-group xml:lang="ru"><trans-title>Исследование кальцитонина у пациентов с узловыми образованиями щитовидной железы для скрининга медуллярного рака: «серая зона»</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9426-8459</contrib-id><name-alternatives><name xml:lang="en"><surname>Severskaya</surname><given-names>N. V.</given-names></name><name xml:lang="ru"><surname>Северская</surname><given-names>Н. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Natalia V. Severskaya.</p><p>4 Koroleva St., Obninsk 249036.</p></bio><bio xml:lang="ru"><p>Северская Наталья Викторовна.</p><p>249036 Обнинск, ул. Королева, 4.</p></bio><email>severskn@mrrc.obninsk.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6581-633X</contrib-id><name-alternatives><name xml:lang="en"><surname>Ilyin</surname><given-names>A. A.</given-names></name><name xml:lang="ru"><surname>Ильин</surname><given-names>А. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Koroleva St., Obninsk 249036.</p></bio><bio xml:lang="ru"><p>249036 Обнинск, ул. Королева, 4.</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2622-5641</contrib-id><name-alternatives><name xml:lang="en"><surname>Chebotareva</surname><given-names>I. V.</given-names></name><name xml:lang="ru"><surname>Чеботарева</surname><given-names>И. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Koroleva St., Obninsk 249036.</p></bio><bio xml:lang="ru"><p>249036 Обнинск, ул. Королева, 4.</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4514-4123</contrib-id><name-alternatives><name xml:lang="en"><surname>Zhelonkina</surname><given-names>N. V.</given-names></name><name xml:lang="ru"><surname>Желонкина</surname><given-names>Н. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Koroleva St., Obninsk 249036.</p></bio><bio xml:lang="ru"><p>249036 Обнинск, ул. Королева, 4.</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-9831-4814</contrib-id><name-alternatives><name xml:lang="en"><surname>Isaev</surname><given-names>P. A.</given-names></name><name xml:lang="ru"><surname>Исаев</surname><given-names>П. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Koroleva St., Obninsk 249036.</p></bio><bio xml:lang="ru"><p>249036 Обнинск, ул. Королева, 4.</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0857-321X</contrib-id><name-alternatives><name xml:lang="en"><surname>Polkin</surname><given-names>V. V.</given-names></name><name xml:lang="ru"><surname>Полькин</surname><given-names>В. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Koroleva St., Obninsk 249036.</p></bio><bio xml:lang="ru"><p>249036 Обнинск, ул. Королева, 4.</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7689-6032</contrib-id><name-alternatives><name xml:lang="en"><surname>Ivanov</surname><given-names>S. A.</given-names></name><name xml:lang="ru"><surname>Иванов</surname><given-names>С. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Koroleva St., Obninsk 249036.</p></bio><bio xml:lang="ru"><p>249036 Обнинск, ул. Королева, 4.</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8784-8415</contrib-id><name-alternatives><name xml:lang="en"><surname>Kaprin</surname><given-names>A. D.</given-names></name><name xml:lang="ru"><surname>Каприн</surname><given-names>А. Д.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Koroleva St., Obninsk 249036.</p></bio><bio xml:lang="ru"><p>249036 Обнинск, ул. Королева, 4.</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">A.F. Tsyb Medical Radiological Research Center — branch of the National Medical Research Radiological Center, Ministry of Health of Russia</institution></aff><aff><institution xml:lang="ru">Медицинский радиологический научный центр им. А.Ф. Цыба — филиал ФГБУ «Национальный медицинский исследовательский центр радиологии» Минздрава России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2022-08-01" publication-format="electronic"><day>01</day><month>08</month><year>2022</year></pub-date><volume>12</volume><issue>2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>79</fpage><lpage>88</lpage><history><date date-type="received" iso-8601-date="2022-08-01"><day>01</day><month>08</month><year>2022</year></date><date date-type="accepted" iso-8601-date="2022-08-01"><day>01</day><month>08</month><year>2022</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2022, Severskaya N.V., Ilyin A.A., Chebotareva I.V., Zhelonkina N.V., Isaev P.A., Polkin V.V., Ivanov S.A., Kaprin A.D.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2022, Северская Н.В., Ильин А.А., Чеботарева И.В., Желонкина Н.В., Исаев П.А., Полькин В.В., Иванов С.А., Каприн А.Д.</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="en">Severskaya N.V., Ilyin A.A., Chebotareva I.V., Zhelonkina N.V., Isaev P.A., Polkin V.V., Ivanov S.A., Kaprin A.D.</copyright-holder><copyright-holder xml:lang="ru">Северская Н.В., Ильин А.А., Чеботарева И.В., Желонкина Н.В., Исаев П.А., Полькин В.В., Иванов С.А., Каприн А.Д.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://ogsh.abvpress.ru/jour/article/view/780">https://ogsh.abvpress.ru/jour/article/view/780</self-uri><abstract xml:lang="en"><p><bold>Introduction</bold>. The results of the calcitonin (Ctn) study in patients with thyroid nodules are included in the clinical guidelines for the treatment of differentiated thyroid cancer. However, the management of patients with moderately elevated Ctn up to 100 pg/mL is not clearly defined.</p><p><bold>Materials and methods</bold>. The study included 103 patients with thyroid nodules and a Ctn level above the reference, but not more than 100 pg/ml. The Ctn concentration was determined using the Cobas e platform (Roche, Germany) or by the immunoradiometric method (Izotop, Hungary). 45 patients were operated on. The analysis of the incidence of medullary thyroid carcinoma (MTC), other thyroid and nonthyroid pathology in patients with elevated Ctn scan was carried out. The results of additional examination are presented: the serum cancer embryonic antigen, Ctn in wash-out, stimulated Ctn, gene <italic>RET</italic> mutation testing.</p><p><bold>The study objective</bold> is to evaluate the probability MTC with Ctn level &lt;100 pg/ml, propose management tactics for patients with elevated Ctn and negative cytological results.</p><p><bold>Results</bold>. The incidence of MTC was 22 % (23/103). The maximum probability of mTC was at Ctn above 50 pg/mL (81 %, 13/16), at Ctn 31-50 pg/mL mTC was detected in 38 % (3/8). With Ctn &lt;30 pg/mL and &lt;20 pg/mL, the incidence of MTC was 9 % (7/79) and 6 % (4/64), respectively. In the majority of MTC patients (65 %), the tumor size did not exceed 1 cm. However, 22 % (5/23) had metastases to the neck lymph nodes. postoperative Ctn normalization was achieved in 96 % (22/23). In 26 % (5/19), a <italic>RET</italic> germ-line mutation was detected, most often p.val804met.</p><p>Among patients without MTC, other thyroid tumors were found in 35 % (28/80), more often papillary thyroid cancer (25 %, 20/80). 13 % (10/80) had other malignant neoplasms. parathyroid adenoma was detected in 3 % (2/80). The maximum Ctn in this group was in patients with chronic kidney disease and metastatic liver disease with cholestasis and ascites.</p><p>Cancer embryonic antigen was increased in 53 % of patients with MTC and in 7 % of patients without MTC. Ctn in washout was &gt;2000 pg/mL in mTC and up to 938 pg/mL in patients with histologically confirmed absence of MTC.</p><p><bold>Conclusion</bold>. If the Ctn level is &lt;100 pg/mL and there is no cytological confirmation, the issue of surgery is decided individually, taking into account many factors. After excluding other causes of hypercalcitoninemia (hyperparathyroidism, kidney disease, other tumors), measurement of serum cancer embryonic antigen and Ctn in wash-out is recommended. In some cases, testing for a <italic>RET</italic> mutation can be helpful.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Введение</bold>. Исследование кальцитонина (КТ) у пациентов с узловыми образованиями щитовидной железы включено в клинические рекомендации по дифференцированному раку щитовидной железы. Однако тактика ведения больных с умеренно повышенным КТ (&lt;100 пг/мл) четко не определена. </p><p><bold>Цель исследования</bold> - оценить вероятность медуллярного рака щитовидной железы (МРЩЖ) при уровне КТ &lt;100 пг/мл, предложить тактику ведения больных с повышенным КТ и отрицательным цитологическим заключением. </p><p><bold>Материалы и методы</bold>. В исследование включены 103 пациента с узловыми образованиями щитовидной железы и уровнем КТ выше референса, но не более 100 пг/мл. Концентрацию КТ определяли на платформе Cobas e (Roche, германия) или иммунорадиометрическим методом (Izotop, Венгрия). были прооперированы 45 пациентов. проведен анализ частоты МРЩЖ, другой тиреоидной и нетиреоидной патологии у пациентов с повышенным КТ. представлены результаты дополнительного обследования: раково-эмбриональный антиген в сыворотке крови, КТ в смыве, стимулированный КТ, анализ на мутацию в гене <italic>RET</italic>. </p><p><bold>Результаты</bold>. частота встречаемости МРЩЖ составила 22 % (23/103). максимальная вероятность развития данной патологии была при КТ &gt;50 пг/мл (81 %; 13/16). при КТ 31-50 пг/мл МРЩЖ выявлен у 38 % (3/8) пациентов. при КТ &lt;30 пг/мл и &lt;20 пг/мл встречаемость МРЩЖ составила соответственно 9 % (7/79) и 6 % (4/64). у большинства больных МРЩЖ (65 %) размеры опухоли не превышали 1 см. Однако у 22 % (5/23) пациентов выявлены метастазы в лимфатические узлы шеи. Нормализация КТ после операции достигнута у 96 % (22/23) больных. у 26 % (5/19) пациентов выявлена герминальная мутация в гене <italic>RET</italic>, наиболее часто - p.val804met. </p><p>Среди пациентов без МРЩЖ другие опухоли ЩЖ выявлены в 35 % (28/80) случаев, чаще - папиллярный РЩЖ (25 %; 20/80). у 13 % (10/80) больных имелись другие злокачественные новообразования. Аденома паращитовидной железы выявлена у 3 % (2/80) пациентов. максимальное повышение Кт в данной группе наблюдалось у больных с хронической болезнью почек и метастатическим поражением печени с синдромом холестаза и асцитом. Раково-эмбриональный антиген был повышен у 53 % больных МРЩЖ и у 7 % больных без МРЩЖ. Кальцитонин в пунктате был &gt;2000 пг/мл при мРЩЖ и достигал 938 пг/мл у пациентов с гистологически подтвержденным отсутствием МРЩЖ. </p><p><bold>Заключение</bold>. при уровне КТ &lt;100 пг/мл и отсутствии цитологического подтверждения вопрос о хирургическом лечении решается индивидуально с учетом многих факторов. после исключения других причин гиперкальцитонинемии (гиперпаратиреоз, болезнь почек, другие опухоли) рекомендовано исследование раково-эмбрионального антигена в сыворотке и КТ в смыве. В некоторых случаях исследование на мутацию в гене <italic>RET</italic> может быть полезным. </p></trans-abstract><kwd-group xml:lang="en"><kwd>calcitonin</kwd><kwd>cancer embryonic antigen</kwd><kwd>medullary thyroid carcinoma</kwd><kwd>screening</kwd><kwd><italic>RET</italic></kwd></kwd-group><kwd-group xml:lang="ru"><kwd>кальцитонин</kwd><kwd>раково-эмбриональный антиген</kwd><kwd>медуллярный рак щитовидной железы</kwd><kwd>скрининг</kwd><kwd><italic>RET</italic></kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Wells S.A., Asa S.L., Dralle H. et al. American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015;25(6): 567-610. DOI: 10.1089/thy.2014.0335.</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Elisei R. 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