endosergЭндокринная хирургияEndocrine Surgery2306-35132310-3965Типография «Печатных дел Мастер»10.14341/serg9731endoserg-9731Research ArticleОбзоры литературыReview of literatureПерсонализированная диагностика хромаффинных опухолей (феохромоцитома, параганглиома) в онкоэндокринологииPersonalized diagnostics of chromaffin tumors (pheochromocytoma, paraganglioma) in oncoendocrinologyhttps://orcid.org/0000-0002-7721-634XРумянцевПавел ОлеговичRumyantsevPavel O.

доктор медицинских наук, заместитель директора, зав. отделом радионуклидной диагностики и терапии

MD, PhD, Deputy director

pavelrum@gmail.comhttps://orcid.org/0000-0001-5962-1360ЯзыковаДиана РинатовнаYazykovaDiana R.

зав.кабинетом, врач-эндокринолог

МD

diana.yazykova@gmail.comhttps://orcid.org/0000-0002-3220-2438СлащукКонстантин ЮрьевичSlashchukKonstantin Y.

Отдел радионуклидной диагностики и терапии, врач-эндокринолог

MD

slashuk911@gmail.comhttps://orcid.org/0000-0001-5652-2607ДегтяревМихаил ВладимировичDegtyarevMikhail V.

врач-радиолог, отдел радионуклидной диагностики и терапии

MD

germed@mail.ruhttps://orcid.org/0000-0002-7624-7953ЯсюченяВалентина СергеевнаYasyuchenyaValentina S.

врач-эндокринолог, отдел радионуклидной диагностики и терапии

MD

loveissiberia@gmail.comhttps://orcid.org/0000-0003-2326-1396СерженкоСергей СергеевичSerzhenkoSergey S.

врач-рентгенолог, отдел радионуклидной диагностики и терапии

vv1ld@yandex.comhttps://orcid.org/0000-0003-3785-0335ШереметаМарина СергеевнаSheremetaMarina S.

кандидат медицинских наук, заведующая отделением радионуклидной терапии

MD, PhD

marina888@yandex.ruhttps://orcid.org/0000-0002-8175-7886ДедовИван ИвановичDedovIvan I.

Академик РАН, директор

MD, PhD, Professor

dedov@endocrincentr.ru<p>ФГБУ &ldquo;Национальный медицинский исследовательский центр эндокринологии&rdquo; Минздрава России</p>Россия<p>Endocrinology Research Centre</p>Russian Federation<p>ФКУ &ldquo;Центральный военный клинический госпиталь им. П.В. Мандрыка&rdquo; Министерства обороны Российской Федерации</p>Россия<p>Central Military Clinical Hospital named after P.V. Mandryko</p>Russian Federation2018180720181211939Copyright &#x00A9; Румянцев П.О., Языкова Д.Р., Слащук К.Ю., Дегтярев М.В., Ясюченя В.С., Серженко С.С., Шеремета М.С., Дедов И.И., 20182018Румянцев П.О., Языкова Д.Р., Слащук К.Ю., Дегтярев М.В., Ясюченя В.С., Серженко С.С., Шеремета М.С., Дедов И.И.Rumyantsev P.O., Yazykova D.R., Slashchuk K.Y., Degtyarev M.V., Yasyuchenya V.S., Serzhenko S.S., Sheremeta M.S., Dedov I.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.surg-endojournals.ru/jour/article/view/9731

Феохромоцитомы и параганглиомы (ФХ/ПГ) – редкие катехоламин-секретирующие нейроэндокринные опухоли, почти в 40% случаев имеющие наследственную природу. Заболеваемость колеблется от 2 до 8 случаев на 1 млн человек в год, с пиком заболеваемости в 30–50 лет. Согласно последней классификации, хромаффинные опухоли отнесены к злокачественным новообразованиям. Частота метастазирования ФХ – 10%, ПГ – 25%. Клинические проявления ФХ и ПГ обусловлены избытком катехоламинов. Известно более 20 наследуемых генов, мутации в которых провоцируют развитие ФХ/ПГ. С точки зрения молекулярной клеточной патофизиологии известный на сегодня пул мутаций можно разделить на два кластера: первый (SDHх, SDHAF2 – фактор сборки SDH, FH, MDH2) нарушает функционирование цикла Кребса и энергетической транспортной цепи митохондрий, второй (RET, NF1, TMEM127, MAX) – мутации генов рецепторов трансмембранных белков-протеинкиназ (тирозинкиназ), активирующие внутриклеточные сигнальные пути (PI3K-AKT-mTOR и MYC), ответственные за клеточный рост, регуляцию роста и дифференцировку клеток. В итоге происходят стабилизация HIF-транскрипционных факторов (оксидативный стресс), изменение метилирования ДНК, приводящие в итоге к глубоким нарушениям экспрессии генов и опухолевой трансформации клетки. Выделяют три основных секреторно-биохимических фенотипа ФХ/ПГ: норадренергический, адренергический и допаминергический. В зависимости от типа секреции опухоли, возраста пациента и семейного анамнеза назначаются комплементарные генетические исследования и методы молекулярной визуализации. В клинической практике биохимический фенотип опухоли, стадия, семейный анамнез и особенно генетический “паспорт” опухоли позволяют подобрать оптимальный алгоритм молекулярной визуализации (ОФЭКТ/ПЭТ) в целях персонализации тактики лечения и клинического прогноза.

Pheochromocytomas and paragangliomas (PPGLs) are rare catecholamine-secreting neuroendocrine tumours, up to 40% of which occur in the setting of a hereditary syndrome. The incidence is 2 to 8 per million persons per year. The peak incidence occurs in the third to fifth decades of life. According to the most recent classification, chromaffin tumours refer to malignant neoplasms. The incidence of metastasis in pheochromocytomas is 10%; in paragangliomas it is 25%. Clinical manifestations of PPGLs are caused by the excess of catecholamines. More than 20 hereditary gene mutations are known to result in PPGLs development. According to the molecular and cellular pathophysiology, all currently known mutations can be divided into 2 groups: the first group – SDHх, SDHAF2 (the assembly factor of SDH, FH, MDH2) – disrupts the Krebs cycle and mitochondrial energy transport chain; the second group – RET, NF1, TMEM127, MAX – leads to mutations in receptor protein kinases (tyrosine kinase), activating intracellular signal pathways (PI3K-AKT-mTOR and MYC), which are responsible for cell growth, growth regulation and cell differentiation. As a result, HIF transcription factors are stabilized (oxidative stress), and DNA methylation is changed, which leads to severe disturbances in gene expression and to malignant transformations of cells. There are three main biochemical phenotypes of PPGLs: noradrenergic, adrenergic and dopaminergic. According to the tumor type, the patient’s age and family history, complementary genetic testing and molecular visualization are recommended. In clinical practice, the biochemical tumor phenotype, its stage, family history and especially the genetic tumor “passport” allow to choose the best molecular visualization method (SPECT-CT/PET-CT) to personalize treatment and prognosis.

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The authors declare that there are no conflicts of interest present.