Endocrine ophthalmopathy (EOP) is a multidisciplinary problem at the intersection of endocrinology and ophthalmology. The patients presenting with this condition experience deficit of adequate medical aid due to the poor cooperation between ophthalmologists and endocrinologists. There are practically no specialized centres in this country where the patients with EOP could receive the combined treatment of this pathology including the surgical intervention. Taken together, late diagnostics and delayed seeking the efficacious medical assistance, the absence of stable compensation of the functional disorders of the thyroid gland, erroneous identification of the phase of the disease, and incorrect choice of the methods for its treatment, the lack of coordination and consistency in the actions of ophthalmologists and endocrinologists are responsible for the low effectiveness of EOP treatment. On the other hand, the absence of the unified approach to diagnostics and treatment of endocrine ophthalmopathy, the necessity of introducing the international experience gained in this field into the routine clinical practice and pooling efforts of representatives of different medical disciplines (endocrinologists, ophthalmologists, radiologists, endocrine surgeons, and neurosurgeons) created the prerequisites for the solution of the EOP problems and gave impetus to the development of the recommendations being proposed.

BACKGROUND: Graves' Orbitopathy (GO) — also known as Thyroid Eye Disease (TED) — is an autoimmune condition in the modern sense. It is closely associated with autoimmune thyroid diseases. Cytokine-mediated mechanisms play a critical part in immunopathogenesis of autoimmune thyroid diseases including GO. Investigating cytokine profiles as well as antibodies to tissue-specific antigens is essential for explaining GO pathogenesis and developing future therapeutic strategies.AIMS: The study examines serum levels of cytokines, autoantibodies and immunoglobulins IgG and IgG4 as mediators of autoimmune inflammation in patients with GO and Graves' Disease (GD).MATERIALS AND METHODS: The study included 52 patients (104 orbits) aged 25-70 years (mean age 48,8±12,3) in the active phase of GO and GD verified with the international diagnostic standards. These patients did not get any treatment for GO before. The control group consisted of 14 individuals (28 orbits) aged 30-68 years without known autoimmune disease.Serum levels of IgG, IgG4,TNFα, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-13, sIL-6R, sTNFα- RI и TNFα- R2 IL-2R, TGFβ1, TGF β3, antibodies to TSH-receptor, free T4, free T3 and TSH were measured. A diagnostic ultrasound exam of thyroid gland, multislice computed tomography (MSCT) / magnetic resonance imaging (MRI) of orbits were performed.RESULTS: Mean duration of GO prior to being admitted to the centre was 8,8±1,5 months (range: 1 — 48 months). According to the degree of thyrotoxicosis compensation: 24 patients were clinically euthyroid, TSH 3,3±0,7 mU/L, free T4 11,9±0,59 pmol/L, free T3 3,97±0,1 pmol/L; 28 patients were considered to have subclinical thyrotoxicosis: TSH 0,03±0,01 mU/L, free T4 14,2±1,0 pmol/L, free T3 5,77±0,49 pmol/L. Serum levels of sTNFα-R2 (p=0,041, p≤0,05), sIL-2R (p=0,020, p≤0,05), TGFβ1 (p=0,000, p≤0,001) were significantly higher in patients with GO compared to the control group. Serum levels of sTNFRα2 (p=0,038, p<0,05) and TGFβ1 (P=0,011, p≤0,05) were positively correlated with the duration of GO. The positive correlations between the serum level of sIL-6R (p=0,034, p≤0,05) and the severity of GO as well as between the serum level of sTNFα- R 1 (P=0,012, p≤0,05) and activity of GO were observed. 54% of patients had elevated concentration level of IgG4 in IgG ( >5%).CONCLUSION: High levels of soluble cytokine receptors sTNFα-R2 and sIL-2R and cytokine TGFβ1 in patients with long-standing untreated GO and GD being euthyroid or having subclinical thyrotoxicosis indicate activation of regulatory T cells aimed at suppressing autoimmune processes. High concentration level of IgG4 in IgG and cytokine TGFβ1 can determine the development of fibrotic changes in the orbital tissues. A decrease in the concentration of cytokine TGFβ1 can indicate an unfavorable course of the disease GO.

Acute and chronic thyroid diseases are the most frequently detected disorders being second only to diabetes mellitus.The World Health Organization points out that thyroid diseases’ incidence tends to grow every year. The present paper consists of clinical practice guidelines that consider etiology, clinical course, diagnostics and treatment of acute and chronic inflammatory thyroid diseases (except those of autoimmune type).The clinical practice guidelines provide an important working tool for clinicians including specialty physicians and medical experts. Containing structured and concise information on the specific nosology, diagnostic methods and treatment tips these guidelines allow medical specialists to quickly resolve difficulties and choose the most efficient and personalized treatment (following strict principles of evidence-based medicine at the same time).The clinical practice guidelines were drawn up by highly-skilled professional team of specialty physicians approved by the Expert Council of Russian Federation’s Health Department. These guidelines contain the most complete and up-to-date information required to diagnose acute and chronic thyroiditis, provide patient care and treatment.The working group publishes the present paper in the professional journal dealing with endocrinology topics to improve healthcare quality and refine treatment of acute and chronic thyroiditis (autoimmune thyroiditis excluded). It is advisable to acquaint as many endocrinology and general (family) medicine specialists as possible with the full text of these clinical guidelines.

Диффузный токсический зоб (болезнь Грейвса) является наиболее частой причиной гипертиреоза у детей и подростков. Методами выбора в лечении являются терапия тиреостатиками, оперативное вмешательство, радиойодтерапия (РЙТ). Изучение эффективности и безопасности РЙТ тиреотоксикоза у детей и подростков является актуальной задачей. В настоящей статье мы суммировали результаты серии клинических наблюдений и проанализировали эффективность и безопасность РЙТ диффузного токсического зоба (ДТЗ) у детей и подростков. Мы наблюдали всего 25 пациентов в воз-расте от 11 до 17 лет (в среднем 14,8 года) с ДТЗ. Десяти пациентам в 2016 г. РЙТ (активности 550-920 мБк) была про-ведена в ФГБУ ЭНЦ. Период в этой подгруппе наблюдения -6-11 мес. Вторая подгруппа (15 пациентов) была пролече-на в радиологическом отделении города Нижнего Тагила (Свердловская область) в период с августа 2005 г. по сентябрь 2012 г. Период наблюдения составил от 3,5 до 11,5 лет (в среднем 8,54 ± 2,87 года). РЙТ была проведена без каких-либо осложнений, непосредственных или отдаленных. У двух пациентов, имевших признаки эндокринной офтальмопатии в неактивной фазе, не возникло ухудшения глазных симптомов после РЙТ. У 17 (68%) из 25 пациентов через 6 мес после РЙТ развился гипотиреоз. В одном случае -эутиреоз. В остальных 7 наблюдениях зарегистрирован рецидив тиреоток-сикоза. Подгруппы пациентов не различались по возрасту, соотношению по полу, объему щитовидной железы и титру антител к рецептору тиреотропного гормона, но отличались по величине лечебной активности 131 I (подгруппа ЭНЦ -550-920 МБк; подгруппа из Нижнего Тагила -168-400 МБк). При этом эффективность лечения значимо не отличалась (p = 0,99): 68 и 73% соответственно. Таким образом, РЙТ является эффективным, хорошо переносимым и безопасным методом лечения ДТЗ у детей и подростков. Необходимо продолжить исследование в более многочисленной выборке, при больших сроках наблюдения, а также совершенствовать эффективность РЙТ. Клю че вые сло ва: радиойодтерапия, диффузный токсический зоб, дети, подростки, эффективность, безопасность.There are three methods in treatment of Graves' disease in children and adolescents -antithyroid drugs, surgery and radioiodine therapy (RIT). However, treatment protocol of children and adolescents doesn't exist. In the present case series study we have evaluated the effectiveness and safety of RIT in children and adolescents. We have observed totally 25 patients in age 11-17 years old (mean 14.8 years) with Graves' disease. Ten patients were treated with RIT in Endocrinology Research Centre (Moscow) in 2016 year with activities 550-920 MBq. Follow-up period varied 6-11 months in this subgroup. The second subgroup (15 patients) was treated in radiology department in Nijniy Tagil rural hospital (Ural region) in the period 2005-2012 years. Follow-up period varied 3.5-11.5 years (mean 8.5 years). RIT was executed in all patients without any complications, direct or long-term. In two patients having endocrine ophtalmopathy in non-active phase it was no any signs of worsening in resul...

A total of 139 patients (278 eyes) presenting with Graves' disease (GD) and endocrine ophthalmopathy (EOP) were examined. The age of 35 men and 104 women ranged from 17 to 71 years. All of them were tested for the functional activity of the thyroid gland and underwent standard ophthalmologic examination; anti-TSH receptor antibodies were measured. Both the activity and severity of EOP were verified as recommended by the European Group on Graves' Orbitopathy (EUGOGO) It was shown that the frequency of detection of anti-TSH receptor antibodies and their titers in patients with GD and EOP depended on the activity of the intraorbital process and the severity of EOP manifestations. The functional state of the thyroid gland also influenced the level of anti-TSH receptor antibodies level during the active phase unlike that in the inactive phase. The in-depth analysis of the relationship between the level of anti-TSH receptor antibodies and clinical characteristics of either EOP (activity, severity, manifestation of selected clinical symptoms) or GD (thyrotoxicosis, euthyroidism, hypothyroidism) demonstrated the possibility to use these characteristics as the factors predicting the severity and outcome of EOP. Also, they may be helpful for the choice of a therapeutic strategy for the treatment of such patients.

RATIONALE: Insufficient world–wide clinical experience in radioiodine therapy (RIT) for Graves’ disease (GD) in children and adolescents, and limited knowledge of the predictors of RIT efficacy.AIMS: Analysis and identification of the most significant predictors of the efficacy of RIT in children and adolescents with Graves’ disease.MATERIALS AND METHODS: A total of 55 patients (48 females and 7 males) aged from 8 to 18 years receiving primary RIT for GD were enrolled. RIT planning was based on the dosimetric method. Analyzed parameters included gender, age, ultrasound thyroid volume before and 6 months after treatment, the presence of endocrine ophthalmopathy, duration of antithyroid drug (ATD) therapy, relapse of thyrotoxicosis after ATD dose reduction, blood fT3, fT4 and TSH levels initially and at 1, 3, 6 months after treatment, TSH receptor Ab initially and at 3 and 6 months after treatment, thyroid 99mTc–pertechnetate uptake at 10–20 minutes (%), maximum thyroid 131I uptake (%), specific 131I uptake (MBq/g) and therapeutic 131I activity (MBq). Fisher exact test, non–parametric Mann–Whitney test, Wilcoxon signed–rank test, logistic regression modelling, ROC–analysis, proportional hazard model (the Cox regression), the Kaplan–Meier method and log–rank test were used for statistical analysis as appropriate.RESULTS: Six months after RIT, hypothyroidism was achieved in 45 (81.8%), euthyroid state – in 2 (3.6%), and in 8 (14.6%) patients thyrotoxicosis persisted. On univariate statistical analysis, the smaller thyroid volume, higher fT4 and lower TSH receptor Ab levels, lower 99mTc–pertechnetate uptake and higher specific 131I uptake were associated with hypothyroidism. On multivariate logistic regression analysis, the older patient’s age (p=0.011), smaller thyroid volume (p=0.003) and higher fT4 (p=0.024) were independent predictors of RIT efficacy. Thyroid volume was also the only variable associated with achievement of hypothyroidism in time after RIT (p=0.011).CONCLUSION: The efficacy of dosimetry–based RIT in children and adolescents with GD 6 months after treatment was 81.2%. Older patients’ age, smaller thyroid volume and higher fT4 level were independent predictors of therapy success. Smaller thyroid volume was also a predictor of the favorable time–related outcome. Statistical models obtained in this work may be used to prospectively estimate the chance of efficient RIT for GD in pediatric patients.

Central Military Clinical Hospital named after P.V. Mandryko, Moscow, Russian FederationФеохромоцитомы 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.Ключевые слова : хромаффинные опухоли, феохромоцитома, параганглиома, радионуклидная диагностика, молекулярная визуализация, генетика, эндокринология, онкология, радиология, онкоэндокринология. 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 intoThe article can used under the CC BY-NC-ND 4.0 license. Статья может быть использована на условиях международной лицензии CC BY-NC-ND 4.0.

ВведениеЭндокринная офтальмопатия (ЭОП) определяется как аутоиммунное поражение мягких тканей орби ты: ретробульбарной клетчатки, глазодвигательных мышц с вторичным вовлечением зрительного нерва и вспомогательного аппарата глаза (век, роговицы, конъюнктивы, слезной железы) [1,2]. ЭОП наибо лее часто встречается при диффузном токсическом зобе (87%), реже -при аутоиммунном тиреоидите (3%) и может возникать при отсутствии тиреотокси коза -10% (эутиреоидная БГ) [1,3]. Терапия ЭОП включает в себя комплекс стандартов лечения: уст К КЛ