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BACKGROUND: Thyroid cancer is the most common endocrine malignancy, accounting for 3.4% of all cancers diagnosed annually. Differentiated thyroid cancer (DTC) is primarily treated with surgery, which can often involve complications such as postoperative pareses or reversible laryngeal nerve (RLN) paralysis. Currently, rehabilitation possibilities for patients with postoperative RLN pairs are relevant. In this study, we used neuromuscular electrostimulation with vocaSTIM in combination with drug therapy and evaluated the effectiveness of the rehabilitation. AIMS: To determine the possibility of using neuromuscular electrophonopathic laryngeal stimulation (NMELS) in restoring laryngeal function after surgical treatment of DTC complicated by pareses/paralysis of thr RLN. MATERIALS AND METHODS: Seventy-six patients with DTC who have undergone surgical treatment, complicated by paresis of RLN, were enrolled in this study. RESULTS: The study analyzed the treatment results of these 76 patients. The age of the patients ranged from 6 to 78 (average age, 47) years, the female-to-male ratio was 59 to 17 (women, 77.6%; men, 22.4%). Postoperative unilateral laryngeal paresis was present in 56 patients (73.68%) and bilateral lesions in 20 (26.32%). Phonation violation was found in all patients: dysphonia, 76 (100%); dysphagia, 28 (36.84%); and respiratory failure, 11 (14.47%), and 2 patients (2.63%) were tracheotomized postoperatively. All patients underwent neuro-phonic rehabilitation with mandatory assessment and video fixation of laryngeal function. As a result of neuromuscular electrophonopathic stimulation of the larynx, 69 out of 76 patients (90.79%) had improved larynx function. CONCLUSIONS: Based on our experience, NMELS with vocaSTIM can be used for restoring the functions of the larynx in patients with RLN paresis of varying severities, after surgical treatment for DTC.

Background: Primary hyperparathyroidism (PHPT) is the third most common endocrine disease, after diabetes mellitus and thyroid gland disorders. Surgical removal of the hyperfunctioning parathyroid glands is the only radical treatment. Various methods of preoperative imaging and intraoperative navigation are developed. Planar scintigraphy with 99mTc-MIBI is used for visualization and it is the most frequently performed radionuclide study in PHPT, while it has a relatively low sensitivity and specificity. SPECT/CT can reduce false-negative and false-positive results, and combines the advantages of radionuclide diagnostic methods and computed tomography. However, the factors that prevent the accumulation of 99mTc-MIBI in patients with PHPT are not clear enough. Aim: To identify the factors associated with the degree of accumulation (uptake rate) of 99mTc-MIBI in the parathyroid glands during planar scintigraphy and SPECT/CT. Materials and methods: The cross-sectional comparative study included 186 patients with PHPT who underwent planar scintigraphy and SPECT/CT for topical diagnosis of parathyroid glands and minimally invasive parathyroidectomy (MIP) followed by histological and immunohistochemical examination of parathyroid glands. The patients were divided into 3 groups depending on the accumulation of 99mTc-MIBI. The accumulation of 99mTc-MIBI was assessed by the expert as low-, moderate-, and high-intensity. Results: The association between the volume of the parathyroid glands on ultrasound and the intensity of the capture of the radiopharmaceutical was revealed, and 80% of low uptake is observed if volume is less than 0,215 cm3 (it corresponds to the linear size of the parathyroid gland 5 mm). Next factor that complicate the interpretation of the results of planar scintigraphy and SPECT/CT in patients with PHPT is thyroid diseases. The associations of the level of PTH, calcium in the blood, the localization and cellular composition of the parathyroid glands, the index of proliferative activity (Ki67), the expression of PTH, P-glycoprotein, cyclin D1 in the PTG tissue with the intensity of 99mTc-MIBI accumulation were not found. Conclusions: The main factor that positively associates with the degree of 99mTc-MIBI accumulation with planar scintigraphy and SPECT / CT is the volume of the parathyroid glands according to ultrasound data. Comorbidity of the thyroid gland has tendency to be associated with a negative result of radionuclide diagnostics, thus based on the ultrasound data of the thyroid and parathyroid glands it is possible to choose the second preferable method of imaging (SPECT/CT or contrast enhanced CT).

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.

Medullary thyroid cancer (MTC) is about 5% of all thyroid carcinomas and is hereditary in 2030% of cases. Multiple endocrine neoplasia syndrome type 2 (MEN2), in addition to medullary thyroid cancer, may include pheochromocytoma, hyperparathyroidism, and some other manifestations. The multidisciplinary data bank (MDB) developed by us is a specialized resource for storing, accumulating and subsequent analysis of data on patients with MTC and MEN2 syndromes. The MDB allows you to collect data from any sources (primary care, medical institutions at various levels, federal centers) and provides internal automated control of the quality and quantity of input data. It is necessary to keep a record of such data to improve the efficiency of diagnostics, treatment and rehabilitation of patients. MDB is an integrated digital platform containing reference materials for doctors, which allows combining evidence-based clinical experience in patients, and provides the opportunity for expert support of medical decisions. In the long run, it will help us organize digitally stored data for machine learning and lays the groundwork for the development of artificial neural networks.

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

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.

DNA repair can prevent mutations and cancer development, but it can also restore damaged tumor cells after chemo and radiation therapy. We performed RNA sequencing on 95 human pathological thyroid biosamples including 17 follicular adenomas, 23 follicular cancers, 3 medullar cancers, 51 papillary cancers and 1 poorly differentiated cancer. The gene expression profiles are annotated here with the clinical and histological diagnoses and, for papillary cancers, with BRAF gene V600E mutation status. DNA repair molecular pathway analysis showed strongly upregulated pathway activation levels for most of the differential pathways in the papillary cancer and moderately upregulated pattern in the follicular cancer, when compared to the follicular adenomas. This was observed for the BRCA1, ATM, p53, excision repair, and mismatch repair pathways. This finding was validated using independent thyroid tumor expression dataset PRJEB11591. We also analyzed gene expression patterns linked with the radioiodine resistant thyroid tumors (n = 13) and identified 871 differential genes that according to Gene Ontology analysis formed two functional groups: (i) response to topologically incorrect protein and (ii) aldo-keto reductase (NADP) activity. We also found RNA sequencing reads for two hybrid transcripts: one in-frame fusion for well-known NCOA4-RET translocation, and another frameshift fusion of ALK oncogene with a new partner ARHGAP12. The latter could probably support increased expression of truncated ALK downstream from 4th exon out of 28. Both fusions were found in papillary thyroid cancers of follicular histologic subtype with node metastases, one of them (NCOA4-RET) for the radioactive iodine resistant tumor. The differences in DNA repair activation patterns may help to improve therapy of different thyroid cancer types under investigation and the data communicated may serve for finding additional markers of radioiodine resistance., DNA repair, follicular thyroid adenoma, RNA sequencing, thyroid cancer, personalized medicine, molecular biomarkers, molecular pathway analysis, radiation iodine therapy resistance, papillary thyroid cancer, systems biology.