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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="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Terapevticheskii arkhiv</journal-id><journal-title-group><journal-title xml:lang="en">Terapevticheskii arkhiv</journal-title><trans-title-group xml:lang="ru"><trans-title>Терапевтический архив</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0040-3660</issn><issn publication-format="electronic">2309-5342</issn><publisher><publisher-name xml:lang="en">LLC Obyedinennaya Redaktsiya</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">34769</article-id><article-id pub-id-type="doi">10.26442/00403660.2021.04.200678</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные статьи</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Chromogranin A in diagnosis of pheochromocytoma (comparative analysis)</article-title><trans-title-group xml:lang="ru"><trans-title>Хромогранин А в диагностике феохромоцитомы (сравнительный анализ)</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8771-8300</contrib-id><name-alternatives><name xml:lang="en"><surname>Yukina</surname><given-names>Marina Yu.</given-names></name><name xml:lang="ru"><surname>Юкина</surname><given-names>Марина Юрьевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Leading Researcher of Department of therapeutic endocrinology</p></bio><bio xml:lang="ru"><p>к.м.н., ведущий научный сотрудник отдела терапевтической эндокринологии</p></bio><email>kuronova@yandex.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2704-1027</contrib-id><name-alternatives><name xml:lang="en"><surname>Karpova</surname><given-names>Polina L.</given-names></name><name xml:lang="ru"><surname>Карпова</surname><given-names>Полина Львовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>resident</p></bio><bio xml:lang="ru"><p>врач-ординатор</p></bio><email>polinakarpova95@mail.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8520-8702</contrib-id><name-alternatives><name xml:lang="en"><surname>Troshina</surname><given-names>Ekaterina A.</given-names></name><name xml:lang="ru"><surname>Трошина</surname><given-names>Екатерина Анатольевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Professor, Member-Correspondent of Russian Academy of Sciences, Deputy Director for coordination of endocrinology service, Head of Department of therapeutic endocrinology</p></bio><bio xml:lang="ru"><p>д.м.н., профессор, член-корреспондент РАН, заведующая отделом терапевтической эндокринологии, заместитель директора по координации эндокринологической службы</p></bio><email>troshina@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-6388-1544</contrib-id><name-alternatives><name xml:lang="en"><surname>Platonova</surname><given-names>Nadezhda M.</given-names></name><name xml:lang="ru"><surname>Платонова</surname><given-names>Надежда Михайловна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Сhief Researcher of Department of therapeutic endocrinology</p></bio><bio xml:lang="ru"><p>д.м.н., главный научный сотрудник отдела терапевтической эндокринологии</p></bio><email>doc-platonova@inbox.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7098-4584</contrib-id><name-alternatives><name xml:lang="en"><surname>Beltsevich</surname><given-names>Dmitry G.</given-names></name><name xml:lang="ru"><surname>Бельцевич</surname><given-names>Дмитрий Германович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Сhief Researcher of Department of Surgery</p></bio><bio xml:lang="ru"><p>д.м.н., главный научный сотрудник отдела хирургии</p></bio><email>beltsevich@rambler.ru</email><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Endocrinology Research Centre</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Endocrinology Research Center</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр эндокринологии» Минздрава России</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2021-04-15" publication-format="electronic"><day>15</day><month>04</month><year>2021</year></pub-date><volume>93</volume><issue>4</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>389</fpage><lpage>396</lpage><history><date date-type="received" iso-8601-date="2020-09-02"><day>02</day><month>09</month><year>2020</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2021, Consilium Medicum</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2021, ООО "Консилиум Медикум"</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="en">Consilium Medicum</copyright-holder><copyright-holder xml:lang="ru">ООО "Консилиум Медикум"</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-nc-sa/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://ter-arkhiv.ru/0040-3660/article/view/34769">https://ter-arkhiv.ru/0040-3660/article/view/34769</self-uri><abstract xml:lang="en"><p><bold>Aim.</bold> To study the prognostic value of determining Chromogranin A blood level in the diagnosis of PHEO.</p> <p><bold>Materials and methods.</bold> We conducted a comparative analytical study of 157 patients with suspected PHEO, statistical analysis of 24-hour urinary metanephrine and normetanephrine excretion test was performed, as well as a blood test for CrA, in groups that included patients without PHEO, with primary tumor or its recurrence, confirmed according to MSCT and/or scintigraphy with MIBG and/or the clonidine suppression test.</p> <p><bold>Results. </bold>The parameters of efficiency of these methods were calculated by groups and it was noted that the lowest sensitivity of the CrA determination method was observed in the group with recurrence of PHEO (43.8%), their exclusion from the entire sample didn’t change specificity of the method and it remained at a high level (85.45%), though sensitivity significantly increased up to 87.1%. Sensitivity of determining 24-hour urinary metanephrine excretion also increased significantly up to 96.8%, with 98.2% of specificity. The correlation between diameter of the tumor and its secretory activity was identified: small – with CrA level (rho 0.491) and strong – with total level of methylated catecholamines (rho 0.765). False positive results were more often observed in patients present with other neuroendocrine tumors (37.5%), as well as those taking proton-pump inhibitors (43.75%). The sensitivity and specificity of CrA determining method in the group of patients with methanephrins elevated within “gray zone” appeared to be 50 and 86.1%, respectively.</p> <p><bold>Conclusion. </bold>A blood test for CrA can be recommended as a confirmatory test for diagnosing PHEO in cases of questionable methylated catecholamines indicators or in cases of suspected relapse of PHEO. The use of the test as a first-line method is only possible if there is no possibility to study methylated catecholamines. When interpreting CrA level, it is necessary to take into account the conditions that may cause false-positive results.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Цель</bold>. Изучить прогностическую ценность определения хромогранина А (ХрА) в диагностике феохромоцитомы (ФХЦ).</p> <p><bold>Материалы и методы.</bold> Выполнено сравнительное аналитическое исследование с участием 157 пациентов с подозрением на ФХЦ, проводилась статистическая обработка результатов анализа суточной мочи на метанефрин (МН) и норметанефрин, а также анализа крови на ХрА по группам, которые включали пациентов без ФХЦ, с первичной опухолью или ее рецидивом, подтвержденными по данным мультиспиральной компьютерной томографии, и/или сцинтиграфии с метайодбензилгуанидином, и/или пробы с клонидином.</p> <p><bold>Результаты. </bold>Рассчитаны показатели эффективности методов по группам и отмечено, что наиболее низкие цифры чувствительности метода определения ХрА наблюдаются в группе с рецидивом ФХЦ (43,8%). При ее исключении из общей выборки специфичность метода сохранилась на высоком уровне (85,45%), а чувствительность значимо возросла – до 87,1%. Также значимо повысился и показатель чувствительности метода определения МН в суточной моче до 96,8% при специфичности в 98,2%. Получены данные о наличии корреляционной связи между диаметром опухоли и ее секреторной активностью: слабая – с уровнем ХрА [коэффициент корреляции Спирмена (rho) 0,491] и сильная с суммарным уровнем метилированных катехоламинов – МКА (rho 0,765). Ложноположительные результаты чаще отмечались у пациентов с другими нейроэндокринными опухолями (37,5%), а также у принимающих ингибиторы протонной помпы (43,75%). Чувствительность и специфичность метода определения ХрА в группе пациентов с результатами анализа на МН в пределах «серой зоны» оказались 50 и 86,1% соответственно.</p> <p><bold>Заключение. </bold>Анализ крови на ХрА можно рекомендовать в качестве подтверждающего теста для диагностики ФХЦ при сомнительных показателях МКА или при подозрении на рецидив ФХЦ. Применение теста в качестве метода 1-го ряда – только при отсутствии возможности исследования МКА. При интерпретации ХрА необходимо учитывать состояния, вызывающие ложноположительные результаты.</p></trans-abstract><kwd-group xml:lang="en"><kwd>pheochromocytoma</kwd><kwd>chromogranin A</kwd><kwd>methanephrine</kwd><kwd>normetanephrine</kwd><kwd>catecholamines</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>феохромоцитома</kwd><kwd>хромогранин А</kwd><kwd>метанефрин</kwd><kwd>норметанефрин</kwd><kwd>катехоламины</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Chen H, Sippel RS, O’Dorisio MS, et al. The north american neuroendocrine tumor society consensus guideline for the diagnosis and management of neuroendocrine tumors: Pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas. 2010;39(6):775-83. doi: 10.1097/MPA.0b013e3181ebb4f0</mixed-citation></ref><ref id="B2"><label>2.</label><mixed-citation>Omura M, Saito J, Yamaguchi K, et al. Prospective Study on the Prevalence of Secondary Hypertension among Hypertensive Patients Visiting a General Outpatient Clinic in Japan. Hypertens Res Vol. 2003;27(3):193-202. doi: 10.1291/hypres.27.193</mixed-citation></ref><ref id="B3"><label>3.</label><mixed-citation>Neumann HPH, Young WFJr, Eng C. Pheochromocytoma and Paraganglioma. N Engl J Med. 2019;381(6):552-65. doi: 10.1056/NEJMra1806651</mixed-citation></ref><ref id="B4"><label>4.</label><mixed-citation>Mannelli M, Lenders JWM, Pacak K, et al. Subclinical phaeochromocytoma. Best Pract Res Clin Endocrinol Metab. 2012;26(4):507-15. doi: 10.1016/j.beem.2011.10.008</mixed-citation></ref><ref id="B5"><label>5.</label><mixed-citation>Gimm O, Koch CA, Januszewicz A, et al. The genetic basis of pheochromocytoma. Front Horm Res. 2004;31:45-60. doi: 10.1159/000074657</mixed-citation></ref><ref id="B6"><label>6.</label><mixed-citation>Zuber S, Wesley R, Prodanov T, et al. Clinical utility of chromogranin A in SDHx- related paragangliomas. Eur J Clin Invest. 2014;44(4):365-71. doi: 10.1111/eci.12245</mixed-citation></ref><ref id="B7"><label>7.</label><mixed-citation>Lenders JWM, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915-42. doi: 10.1210/jc.2014-1498</mixed-citation></ref><ref id="B8"><label>8.</label><mixed-citation>Hsiao RJ, Parmer RJ, Takiyyuddin MA, O’Connor DT. Chromogranin A storage and secretion: sensitivity and specificity for the diagnosis of pheochromocytoma. Medicine (Baltimore). 1991;70(1):33-45. doi: 10.1097/00005792-199101000-00003</mixed-citation></ref><ref id="B9"><label>9.</label><mixed-citation>Bílek R, Ík LŠŘ, Ciprová V, et al. Chromogranin A, a member of neuroendocrine secretory proteins as a selective marker for laboratory diagnosis of pheochromocytoma. Physiol Res. 2008;57:171-9.</mixed-citation></ref><ref id="B10"><label>10.</label><mixed-citation>Bílek R, Zelinka T, Vlček P, et al. Radioimmunoassay of Chromogranin A and Free Metanephrines in Diagnosis of Pheochromocytoma. Physiol Res. 2017;66:397-408. doi: 10.33549/physiolres.933719</mixed-citation></ref><ref id="B11"><label>11.</label><mixed-citation>Bílek R, Zelinka T, Vlček P, et al. Deconjugated Urinary Metanephrine, Normetanephrine and 3-Methoxytyramine in Laboratory Diagnosis of Pheochromocytoma and Paraganglioma. Physiol Res. 2015;64:313-22. doi: 10.33549/physiolres.933109. PMID: 26680494</mixed-citation></ref><ref id="B12"><label>12.</label><mixed-citation>Unger N, Hinrichs J, Deutschbein T, et al. Plasma and Urinary Metanephrines Determined by an Enzyme Immunoassay, but not Serum Chromogranin A for the Diagnosis of Pheochromocytoma in Patients with Adrenal Mass. Exp Clin Endocrinol Diabetes. 2012;120(8):494-500. doi: 10.1055/s-0032-1309007</mixed-citation></ref><ref id="B13"><label>13.</label><mixed-citation>Al-risi ES, Al-essry FS. Chromogranin A as a Biochemical Marker for Neuroendocrine Tumors: A Single Center Experience at Royal Hospital, Oman. Oman Med J. 2017;32(5):365-70. doi: 10.5001/omj.2017.71</mixed-citation></ref><ref id="B14"><label>14.</label><mixed-citation>Yang X, Yang Y, Li Z, et al. Diagnostic value of circulating chromogranin a for neuroendocrine tumors: A systematic review and meta-analysis. PLoS One. 2015;10(4):1-14. doi: 10.1371/journal.pone.0124884</mixed-citation></ref><ref id="B15"><label>15.</label><mixed-citation>Kidd M, Bodei L, Modlin IM. Chromogranin A: any relevance in neuroendocrine tumors? Curr Opin Endocrinol Diabetes Obes. 2016. 2016;23(1):28-37. doi: 10.1097/MED.0000000000000215</mixed-citation></ref><ref id="B16"><label>16.</label><mixed-citation>Cimitan M, Buonadonna A, Cannizzaro R, et al. Somatostatin receptor scintigraphy versus chromogranin A assay in the management of patients with neuroendocrine tumors of different types: Clinical role. Ann Oncol. 2003;14(7):1135-41. doi: 10.1093/annonc/mdg279</mixed-citation></ref><ref id="B17"><label>17.</label><mixed-citation>Zawadzka-Leska SK, Radziszewski M, Malec K, Stadnik AUA. Predictive value of chromogranin a in a diagnosis towards Pheochromocytoma in adrenal incidentaloma. Endocr Care. 2016;12(4):437-42. doi: 10.4183/aeb.2016.437</mixed-citation></ref><ref id="B18"><label>18.</label><mixed-citation>Glinicki P, Jeske W, Bednarek-Papierska L, et al. Chromogranin A (CgA) in adrenal tumours. Endokrynol Pol. 2013;64(5):358-62. doi: 10.5603/ep.2013.0018</mixed-citation></ref><ref id="B19"><label>19.</label><mixed-citation>Giovanella L, Ceriani L, Balerna M, et al. Diagnostic value of serum chromogranin-A combined with MIBG scintigraphy in patients with adrenal incidentalomas. Q J Nucl Med Mol Imaging. 2008;52(1):84-8.</mixed-citation></ref><ref id="B20"><label>20.</label><mixed-citation>De Jong WHA, Eisenhofer G, Post WJ, et al. Dietary influences on plasma and urinary metanephrines: Implications for diagnosis of catecholamine-producing tumors. J Clin Endocrinol Metab. 2009;94(8):2841-9. doi: 10.1210/jc.2009-0303</mixed-citation></ref><ref id="B21"><label>21.</label><mixed-citation>Юкина М.Ю., Трошина Е.А,. Бельцевич Д.Г., и др. Феохромоцитома/параганглиома: клинико-генетические аспекты. Проблемы эндокринологии. 2013;3:19-26 [Yukina MY, Troshina EA, Beltsevich DG, et al. Pheochromocytoma/paraganglioma: clinical and genetic aspects. Problemy endokrinologii. 2013;3:19-2 (In Russ.)]. doi: 10.14341/probl201359319-26</mixed-citation></ref><ref id="B22"><label>22.</label><mixed-citation>Ardill JES, O’Dorisio TM. Circulating biomarkers in neuroendocrine tumors of the enteropancreatic tract: application to diagnosis, monitoring disease, and as prognostic indicators. Endocrinol Metab Clin North Am. 2010;39(4):777-90. doi: 10.1016/j.ecl.2010.09.001</mixed-citation></ref><ref id="B23"><label>23.</label><mixed-citation>Martucci VL, Pacak K. Pheochromocytoma and Paraganglioma: Diagnosis, Genetics, Management, and Treatment. Curr Probl Cancer. 2014;38(1):7-41. doi: 10.1038/jid.2014.371</mixed-citation></ref><ref id="B24"><label>24.</label><mixed-citation>Herman DS, Lam L, Taylor M, et al. Catecholamine metabolomic and secretory phenotypes in phaeochromocytoma. Endocr Relat Cancer. 2011;18(1):97-111. doi: 10.1038/jid.2014.371</mixed-citation></ref><ref id="B25"><label>25.</label><mixed-citation>Pregun I, Herszényi L, Juhász M, et al. Effect of proton-pump inhibitor therapy on serum chromogranin A level. Digestion. 2011;84(1):22-8. doi: 10.1159/000321535</mixed-citation></ref></ref-list></back></article>
