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Nuclear medicine (NM) is a medical specialty that uses radionuclides (radioactive tracers) and ionising radiation for diagnostic and therapeutic (theranostic) purposes. Nuclear medicine arose and developed at the intersection of physics, chemistry and clinical medicine. The radiation emitted by radioisotopes can consist of gamma-, beta- and alpha emission, or it’s combination. Radioisotope of choice for medical purposes should have futher requirements: low radiotoxicity, suitable type of radiation, energy and half-life (several minutes to several hours and days), and also convenient detection of gamma ray radiation. The radionuclide is part of radiopharmaceutical (RP) and acts as its indicator. RP accumulates in morphological structures, becomes a carrier of coordinated information from patient to gamma camera or other equipment and reflects the dynamics of processes occurring in the examined organ. In 2021 NM celebrates its 80th anniversary. The trajectory of NM combines modern methods of radiotheranostics and applied genomic and post-genomic technologies.

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, p5%).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.

Diagnosis of the causes of thyrotoxicosis (destruction or increased functional activity of the thyroid tissue in nodular and diffuse thyroid pathology) is a key point in determining the management of patients with this pathology. Scintigraphy is the method of choice in differential diagnosis of the causes of thyrotoxicosis assessing the functional state of the thyroid gland. According to variable medical interest, thyroid scintigraphy can be performed using 99mTc-pertechnetate or radioactive iodine isotopes (123I, 124I, 131I). For thyroid uptake evaluation used scintigraphy with 99mTc-pertechnetate radiopharmaceutical, which is not organificates and quickly excretes from thyroid tissue. In case of thyroid iodine pharmacokinetics investigation radiopharmaceuticals labeled by iodine isotopes (123I,131I, 124I) are used. The review includes original scintigrams, tables and diagrams. Article shows thyroid scintigraphy informativity analysis, evaluates the place and role of the thyroid scintigraphy examinations in modern diagnostic algorithms taking into account the history of the disease, laboratory tests, ultrasound (TIRADS) and result ofFNA (Bethesda). Additionally authors focused on existing clinical guidelines analysis. An optimized algorithm for the diagnosis and treatment of diffuse and/or nodular thyroid pathology associated with thyrotoxicosis is proposed.

The clinical manifetstations of endocrine orbitopathy (EOP) significantly because autoimmune process may involve various anatomical structures of the eye. Choosing an effective method for EOP treatment requires to determine the selectivity of orbital tissue damage, which is difficult when only clinical criteria are applied. 102 patients with EOP and Graves’ disease were examined. All patients underwent the standard ophthalmological examination and multispiral computed tomography of orbits. The analysis of clinical and tomographic parameters allowed us to distinguish 3 variants of EOP flow: classical, lipogenic, and myogenic. The prevailing symptoms of patients with the lipogenic variant were distinct exophthalmos without a disturbance of the function of extraocular muscles (EOM) and visual disturbances. Oculomotor disorders, diplopia, strabismus, and decreased vision were prevalent in patients with the myogenic variant. Patients with the classical variant suffered from exophthalmos, periorbital edema, and oculomotor disorders. The identification of independent clinical variants of EOP with specific clinical symptoms and different tomographic characteristics testifies different pathogenetic mechanisms of EOP development is to determine personalized approaches to treatment.

Purposes: Current research design is dedicated to 131-I SUV evaluation on post therapeutic scintigrams and setting up predictive model for radioiodine therapy repeated course prescription in differentiated thyroid cancer (DTC). Methods: Study includes 148 patients (f-105, m-43) with DTC treated with 131-iodine. Administered treatment activities of 131I calculated according to clinical features and tumor recurrence risk group. Patients were divided into three groups using ATA 2018 recommendations. Absolute risk groups: low risk (L), medium risk (M), high risk (H). Administered 131-I activity [MBq]: = 3223±729, = 3696±456, = 4589±1078; Tg [ng/ml]: = 7,4±1.7 ng/ml, = 14,8 ±5,9, = 68,3 ±18,5; TgAb [IU/ml]: = 124,3 ± 81.7, = 29,2 ±15,9, = 85,7 ±28,9. All null hypothesis were checked using paired Mann-Whitney U-test. Calibration of system SPECT/CT and evaluation SUVs completed according to protocols designed using Jaszczak phantom Deluxe. Model development based on logistic regression with ROC-analysis, regularization and cross-validation. Results: Reference intervals of SUVpeak and SUVmax calculated for all groups of risk. SUVpeak: low risk >155, medium risk 105-155, high risk 0-105 pL-M=0.069 pL-H=0.0037 pM-H=0.7514; SUVmax: low risk >38, medium risk 29-38, high risk 0-29 pL-M=0.052 pL-H=0.0033 pM-H=0.949. Logit model based on SUVpeak without regularization has: AUC = 0.67 (95%CI 0.33-1.00); Accuracy = 0.82; SE = 0.89; SP = 0.4; PPV = 0.41; NPV = 0.89, cross-validated AUC =0.67 (0.4-0.88), regression coefficients: B0=0.037, B1=0.001. Regularization (SUVpeakConclusion: Study shows that SUV has wide range of values and can be matched with existed model of risk assessment of DTC. Algorithm of image segmentation and evaluation of SUVpeak and SUVmax for SPECT/CT systems was developed. According to the ROC analysis, developed predictive model shows an acceptable performance for further clinical investigation and advancement focused on refining model parameters and introducing additional predictors

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.

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.

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.

In 1973 and 1976 R. Wasnich and R. Jackson described 2 cases of endocrine ophthalmopathy (EO) that occurred after external irradiation of the anterior surface of the neck due to a tumor (Hodgkin's lymphoma). Further observations showed that treatment of Graves' disease with radioactive iodine (131I) can worsen the course of EO. So, L. De Groot et al., Observing 264 patients after exposure to 131I for Graves' disease, found progression of EO in 4% of patients after the 1st course of therapy and in 12% after subsequent sessions. L. Bartalena et al. observed the appearance or significant progression of EO in 15% of 150 patients treated with 131I. At the same time, against the background of glucocorticoid therapy, only 10% of patients worsened the course of EO. Other studies have shown that the progression of EO after treatment with 131I without glucocorticoid administration was observed in 18-30% of cases. Along with this, it is believed that 131I does not affect the incidence of clinical symptoms in the orbit, and hypothyroidism that occurs after it does not lead to the progression of eye symptoms. The relationship between treatment and the onset or progression of EO is not clear. Nevertheless, there is evidence of an adverse effect of an elevated level of antibodies to the thyroid stimulating hormone receptor (TSH) in the blood serum after 1131I training for EO. This review is devoted to a review of the problem presented.Еще в 1973 и 1976 гг. R. Wasnich и R. Jackson описали 2 случая эндокринной офтальмопатии (ЭО), возникшей после наружного облучения передней поверхности шеи по поводу опухоли (лимфомы Ходжкина). Дальнейшие наблюдения показали, что лечение болезни Грейвса (БГ) радиоактивным йодом (131I) способно ухудшать течение ЭО. Так, L. De Groot и соавт., наблюдая за 264 пациентами после облучения 131I по поводу БГ, обнаружили прогрессирование ЭО у 4% больных после 1-го курса терапии и у 12% — после последующих сеансов. L. Bartalena и соавт. констатировали появление или значительное прогрессирование ЭО у 15% из 150 больных, леченных 131I. В то же время на фоне терапии глюкокортикоидами (ГК) ухудшение течения ЭО отмечалось только у 10% больных. В других исследованиях показано, что прогрессирование ЭО после лечения 131I без назначения ГК наблюдалось в 18—30% случаев. Наряду с этим существует мнение, что 131I не влияет на частоту появления клинических симптомов в орбите, и к прогрессированию глазных симптомов приводит не облучение, а гипотиреоз, возникший после него. Связь между лечением и появлением или прогрессированием ЭО не ясна. Тем не менее имеются данные о неблагоприятном воздействии повышенного уровня антител к рецептору тиреотропного гормона (ТТГ) в сыворотке крови после обучения 131I на течение ЭО. Настоящий обзор посвящен обзору представленной проблемы.

В июне 2016 г. состоялся международный симпозиум, посвященный новейшим исследованиям и достижениям в решении проблем тиреоид-ассоциированной офтальмопатии (TED). Симпозиум был организован по инициативе международного общества по тиреоид-ассоциированной офтальмопатии – International Thyroid Eye Disease (ITEDs). В его работе принимали участие члены EUGOGO (Европейской группы по эндокринной офтальмопатии), NANOS (Северо-Американского нейроофтальмологического общества) и Orbit Society (Ассоциации орбитологов).В симпозиуме приняли участие ведущие специалисты в области офтальмологии, орбитальной хирургии и эндокринологии: Rebecca S. Bahn, Maarten Mourits, Claudio Marcocci, George Kahaly, Mario Salvi, Antony Weetman, Anja Eckstein, Geoff Rose, Robert Goldberg, Michael Kazim, Richard Collin, Christoph Hintschich, Don Kikkawa, Jonathan Dutton, Susanne Pitz, а также врачи, специализирующиеся в области эндокринологии, офтальмологии, радиологии и др. Проблемы ТED обсуждали более 300 специалистов (65% – офтальмологи, 18% – офтальмохирурги, 17% – эндокринологи) в основном из Европы. Северная Америка была представлена 50 делегатами, менее многочисленным было представительство других континентов.Программа симпозиума была сосредоточена на обсуждении механизмов развития ТED, классификациях и новых терапевтических и хирургических подходах к ее лечению.

There was investigated the relationship between the clinical features of the diplopia in patients with the Graves’ orbitopathy and the specific signs of the orbit obtained by the multi-slice CT scanning in the study. The results of the study could improve the diagnosis of the Graves’ orbitopathy and evaluate the effectiveness of the treatment. Eighty five patients (170 eyes) of ages from 24 till 73 years were included in the study. The ophthalmological examination and multi-slice CT scanning of the orbit were performed in all cases. The activity and severity of the Graves’ orbitopathy were assessed according to EUGOGO clinical activity score. The severity of the diplopia was graduated subjectively using the clinical assessment technique described previously (Nagy E.V. et al., 2000). It was found that the severity of the diplopia was significanty higher during the active phase of the disease and correlated with the muscular index (p = 0,0320, r = 0,294589), the extraocular muscle enlargement (p = 0,0118) and the retrobulbar tissue density (p = 0,0335, r = 0,336906). The diplopia was associated with enhancement of the retrobulbar tissue density and the extraocular muscle density in the inactive phase of the disease. There wasn’t the correlation between the severity of the diplopia and the extraocular muscle enlargement in the inactive phase of the disease. There was established the relationship between the clinical features of the diplopia and the signs obtained by the multi-slice CT scanning of the orbit. These results are extremely important for the detection the causes of the diplopia, the treatment selection and the estimation the prognosis.

Existing European standard recommendations for dosimetry examination in case of thyrotoxicosis offers difficult to repeat examination protocols. The individual pharmacokinetics data of 343 patients diagnosed with Graves and Plummer disease and 133 cases with known thyroid volume are presented in the article. The data underwent parametrical statistical analysis. As a result, two clinically reproducible methods of calculating therapeutic activity have been proposed.