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Saul Hertz was a physician and scientist who invented and implemented the use of radioactive iodine (RAI) for medical purposes. The history of the development of this new non-invasive and effective method of treatment began in 1936, when Saul Hertz asked Karl Compton, president of the Massachusetts Institute of Technology: "Is it possible to artificially make iodine radioactive?" at the scientific session. The positive response was the beginning of Saul Hertz’s research in the field of nuclear medicine. Together with physicist Arthur Roberts, he studied the pharmacokinetics of radioactive isotopes of iodine and the possibility of using them for the diagnosis and treatment of thyroid disease (TD). In 1938, with the release of 131I, which emits gamma and beta rays and has a half-life of 8 days, RAI could be used not only in experiments, but also in clinical practice. On March 31, 1941, Dr. Saul Hertz performed the first RAI therapy for thyrotoxicosis. Nowadays, March 31 is called World Theranostics Day. Subsequently, Saul Hertz became the founder of the radionuclide treatment of TD, and based on the results of his work, the principles of RAI therapy for differentiated TD were developed. Currently, there are Dr. Saul Hertz Archives in Greenwich (Connecticut, USA) that store the works of this great physician and scientist.

BACKGROUND: Thyroid nodules are a prevalent issue, with an estimated incidence of 19% to 35% based on ultrasound examination and 8% to 65% based on autopsy findings [1]. In some cases, Plummer’s disease is observed, and nodular masses may be observed in 10% to 35% of Graves’ disease cases, with iodine accumulation of a different nature [2, 3]. One of the principal treatments for Graves’ and Plummer’s diseases is radioiodine therapy, which serves to exclude the possibility of malignancy in nodules. Furthermore, the pharmacokinetics of iodine is investigated, which represents the most time-consuming and labor-intensive stage of preparation for radioiodine therapy. In clinical practice, ultrasound is performed in accordance with the TI-RADS system, followed (if necessary) by fine-needle aspiration puncture biopsy, stratified according to the Bethesda system. However, the interpretation of ultrasound examinations is inherently subjective, whereas the use of decision support systems can reduce the number of fine-needle aspiration puncture biopsies by 27% and the number of missed malignant neoplasms by 1.9%. Furthermore, the quantitative characterization of nodal ultrasound may enhance the investigation of the pharmacokinetics of I-131 [4, 5]. AIM: The study aimed to develop a method for quantitatively characterizing ultrasound images of thyroid nodular masses for predicting malignancy and I-131 accumulation by nodular masses. MATERIALS AND METHODS: The study included 125 nodules with pathomorphologic findings (65 benign, 60 malignant) and 25 benign nodules (established by cytologic examination) of patients who underwent radioiodotherapy as part of the Russian Science Foundation grant project No. 22-15-00135. Longitudinal and transverse projections of thyroid nodules were obtained using GE Voluson E8 (36% of all benign nodules and 27% of malignant nodules) and GE Logiq E (64% of benign and 73% of malignant nodules). A pharmacokinetics study was conducted on 25 nodes obtained on a GE Logiq V2 device. The accumulation index of I-131 was determined after 24 hours. A spatial adjacency matrix, gray level line length matrix, gray level zone size matrix, and histogram were employed to investigate features based on ultrasound images. RESULTS: The malignancy prediction model, developed on the basis of the most significant features and after KNN correlation analysis, exhibited a diagnostic accuracy value of 72±3%, a sensitivity of 73±5%, and a specificity of 73±5%. An investigation of I-131 pharmacokinetics revealed that the maximum histogram intensity gradient (r=–0.48, p=0.08) and intensity entropy (r=–0.51, p=0.06) exhibited the highest Spearman correlation coefficient modulus with I-131 accumulation after 24 hours. CONCLUSIONS: The present study demonstrates the feasibility of using quantitative characterization of ultrasound images of nodal masses as a tool to monitor nodules before radioiodotherapy. This is with a view to subsequent adjunctive fine-needle aspiration puncture biopsy and prediction of I-131 accumulation after 24 hours.

BACKGROUND: Lacrimal glands and lacrimal pathways are one of the main undesirable targets during radionuclide therapy using I-131, namely, in 24% of cases, secondary lacrimal pathways obliteration occurs [1]. In the legislation of the Russian Federation in the field of atomic energy use, there are a number of administrative documents obliging to keep records and control of individual radiation doses with the provision of data to the unified system for monitoring individual radiation doses of citizens. At the same time, statistical analysis does not include systematic accounting and control of individual doses of internal radiation to patients, in particular, to the lacrimal apparatus, when using nuclear medicine methods for therapeutic purposes. AIM: To develop a software and hardware preventive complex — a system for accounting and monitoring dose loads on lacrimal pathways during radioiodotherapy. MATERIALS AND METHODS: GE Discovery NM/CT 670 imaging systems, GE Discovery NM 630, the Xeleris 4 DR Workstation nuclear Medicine Workstation and the I-131-based radioisotope were used. To exclude the ingress of radioisotope into lacrimal pathways, the use of vasoconstrictive drugs and the use of tear point obturators were considered. The client part of the web service was implemented based on the React JavaScript library. The development of the Backend component was carried out in the Python programming language. RESULTS: To assess the risk of complications, a method was developed that takes into account the following parameters: age, gender, total administered activity to the patient, the presence of current lacrimation at the time of hospitalization, the presence of menopause (for women) and the accumulation index I-131 in lacrimal pathways. The primary data (anamnesis and prescribed treatment) are entered by the patient's attending physician in the questionnaire during the initial examination. At 72 hours after the introduction of radioisotope, using a molecular imaging system, a medical physicist determines the index of accumulation of radioisotope in lacrimal pathways. Based on the data obtained, the overall risk level of secondary obliteration of the lacrimal tract is determined and, depending on the result obtained, appropriate recommendations are made to the patient. Since the described process is quite time-consuming in a clinical setting, an intelligent medical decision support system has been developed that allows automating the process and minimizing the likelihood of errors. CONCLUSION: The development of a software and hardware preventive complex will make it possible to prescribe preventive methods with greater efficiency at all stages of the course of treatment in order to minimize the occurrence of adverse events (such as secondary obliteration of the tear ducts), which in turn will improve the quality of life of patients.

Radioactive iodine 131I is a theranostic isotope used both for diagnosis and therapy of benign thyroid diseases and thyroid cancer for 85 years. The formation of nuclear medicine is closely linked with the use of 131I. The history of radioiodine therapy began in 1941, when endocrinologist Saul Hertz for the first time used 131I to treat patients with Graves' disease. Since 1946 radioactive iodine 131I became widely available, and its effectiveness became public knowledge after reports on thyrotoxicosis treatment published in the Journal of the American Medical Association by multidisciplinary groups of scientists physicists and endocrinologists. In 1951, isotope 131I became the first Food and Drug Administration approved RP for the treatment of thyroid disorders. Around the same time on the basis of the First Moscow Medical Institute studies on the use of radioiodine isotopes in patients with thyrotoxicosis began. The head of the Soviet group on the studying of radioactive iodine was the physician-scientist Vera Georgievna Spesivtseva. The research works of medical physicists Edith Quimby and Leonidas Marinelli in optimizing therapeutic strategies using radioactive substances in the late 1940s and the wording of the ALARA (As Low As Reasonably Achievable) principle of minimizing exposure of ionizing radiation by the International Commission on Radiological Protection in 1954 contributed to the greater introduction of radionuclides into the medicine.

Background. Traditional endogenous stimulation of thyroid-stimulating hormone (TSH) by means of long-term withdrawal of thyroid hormones for radioiodine diagnostics and radioiodine therapy causes severe hypothyroidism, which worsens patients general well-being and may lead to side effects and cause tumor growth and dissemination. Exogenous stimulation with recombinant human TSH (rh-TSH, thyrotropin-alfa) causes short-term increases in TSH levels and does not have the above-mentioned side effects. Purpose. To estimate the efficacy and safety of rh-TSH in preparation of patients with well-differentiated thyroid cancer for radioiodine diagnostics and radioiodine therapy. Methods. We conducted an interventional single-center prospective unblinded uncontrolled study of the efficacy and safety of thyrotropin-alfa to prepare patients with well-differentiated thyroid cancer to radioiodine diagnostics and post-surgery radioiodine ablation. The study included 88 patients with well-differentiated thyroid cancer: 54 patients were prepared for post-surgery radioiodine ablation; 34 patients for radioiodine diagnostics to evaluate combined treatment efficacy and exclusion of tumor recurrence. The level of TSH, thyroglobulin, antibodies to thyroglobulin, whole body scintigraphy, and side effects were measured during exogenous stimulation with thyrotropin-alfa. Results. The level of TSH reached or exceed the target level (30 mIU/ml) 24 hours after the first injection of recombinant thyrotropin-alfa in 86% of patients; after 48 hours in 100%, the level exceeding 100 IU/ml was observed in 66 (75.1%) patients. The maximum levels of thyroglobulin and antibodies to thyroglobulin were reached 72 and 48 hours after the first injection, respectively. The injections of thyrotropin-alfa were well-tolerated by the patients. In the group for radioiodine diagnostics 2 (5.8%) patients complained of fatigue, 1 (2.9%) patient had signs of dyspeptic disorder, while in the group for radioiodine ablation 4 (7.4%) patients complained of fatigue, 1 (1.8%) patient had marked memory problems that disappeared later (they must have been caused by the patients advanced age (82 years)). Conclusions. Exogenous recombinant human thyroid-stimulating hormone (thyrotropin-alpha) is highly effective in preparation of patients with well-differentiated thyroid cancer for radioiodine diagnostics and radioiodine ablation. It does not have side effects, which are typical of withdrawal of thyroid hormones. The levels of thyroglobulin and antibodies to thyroglobulin measured 72 hours after the first injection of thyrotropin-alfa have the biggest diagnostic informative value.

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 patients 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.

Osteogenesis imperfecta (OI) – is a group of genetically disorders, which are charaterized by a disturbed bone formation. In turn, the excess of thyroid hormones in Graves' disease (GD) also posses a negative effect on bone tissue, thereby aggravating OI. That requires from the endocrinologist the most careful management of patients with the combination of these pathologies. In this article, we present a unique clinical case of a combination of GD and OI.

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 doesnt 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 1117 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 550920 MBq. Follow-up period varied 611 months in this subgroup. The second subgroup (15 patients) was treated in radiology department in Nijniy Tagil rural hospital (Ural region) in the period 20052012 years. Follow-up period varied 3.511.5 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 result of RIT. In 17 (68%) of 25 patients the hypothyroidism occurred through 6 months. In one case euthyroidism. In remain 7 observations the hyperthyroidism recurred. Patient subgroups didnt differ in mean age, gender ratio, thyroid size and autoantibodies to TSH receptor levels, but were differed in treatment 131I activities (subset from ERC 550920 MBq; subset from Nijniy Tagil 168400 MBq). However the treatment efficacy did not differ significantly (p = 0.99): 68% and 73%, accordingly. In conclusion, RIT of Graves disease in a safe and effective method of treatment for hyperthyroidism in children and adolescents. Its necessary to prolong study in numerous patients cohort, longer-lasting follow-up period as well as to improve RIT efficiency.

In June 2016, an International Symposium dedicated to the cutting edge research and achievements in Thyroid Eye Disease (TED) diagnosis and treatment was held in London. The symposium was organized by the International Thyroid Eye Disease (ITEDs). It was attended EUGOGO, North American Neuro-Ophthalmological Society (NANOS) and Orbit Society members. The symposium was attended by leading experts in the field of ophthalmology, orbital surgery and endocrinology: Rebecca S. Bahn, Maarten Mourits, Claudio Marcocci, George Kahaly, Mario Salvi, Antony Weetman, Anja Eckstein, Daniel Rootman, Geoffrey Rose, Robert Goldberg and Susanne Pitz, as well as doctors, specializing in the field of endocrinology, ophthalmology, radiology and other specialties. The symposium program was focused on the discussion of TED pathogenesis, classification and new therapeutic and surgical approaches. TED problems discussed by more than 300 professionals (65% ophthalmologists, 18% ophthalmic surgeons and 17% endocrinologists). North America was represented by 50 delegates. Representation of other continents was not less impressive.

Background. Radioiodine therapy (RIT) is an alternative method to surgical treatment used in the treatment of hyperthyroidism (Graves’ disease or solitary/multinodular toxic goiter (STG/MTG) etiology). However, treatment protocol doesn’t exist. Aim. To evaluate the outcomes of the I131 treatment in hyperthyroidism using the standard dose (550 Mbq), and to explore the factors that influence the outcome of treatment. Methods. We studied 38 patients (35 women and 3 men) with hyperthyroidism. Each patient was carried I131 RIT in a dose of 550 Mbq. Patients were randomized 2 group – patients with Gravesapos; disease and patients with a solitary/multinodular toxic goiter. Antithyroid drugs withdraw was usually conducted for 7–14 days prior to RIT. Follow-up period ranged from 6 to 8 months, the average was 6.6 ± 0.4 months. Results. Six months after the RIT 23 patients (61%) reached hypothyroidism, 7 patients (18%) was observed euthyroidism, thyrotoxicosis stayed in 8 patients (21%). In patients with Gravesapos; disease onset hypothyroidism were more likely (75% vs 35.7%, p 0.001). Thus at STG/MTG achieve euthyrosis percentage was higher (28.6% vs 12.5%). Predictors of a positive outcome of the treatment are: less thyroid size (30 ml for women, 40 ml for men) and younger age (under 35 years old). Statistical significance in influencing the outcome of treatment by disease duration, level of stimulating antibodies against thyrotropin receptors have not been identified. Conclusions. Fixed activity of 550 MBq I131 has a different efficacy in the treatment of hyperthyroidism in patients with Graves’ disease and STG/MTG. In addition, on treatment results affect patient age and the size of the thyroid gland, which should be considered during planning RIT. In order to improve the effectiveness of radioiodine therapy of hyperthyroidism requires personalization tactics of treatment based on clinical factors, as well as the use of in vivo dosimetry planning when therapeutic activity calculating.

Purpose: Secondary acquired lacrimal duct obstruction (SALDO) is one of the complications of radioiodine therapy. SALDO is formed a few months after therapy if there is a sufficient uptake of radioactive iodine by the nasolacrimal duct. To date, risk factors leading to SALDO are unclear. The objective was to determine the correlation between the tear production level and radioactive iodine-131 uptake in the lacrimal ducts. Methods: Basal and reflex tear production was studied in 64 eyes prior to the therapy with radioactive iodine-131 after drug-induced hypothyroidism. The condition of the ocular surface was assessed using the Ocular Surface Disease Index (OSDI) questionnaire. Seventy-two hours after the radioactive iodine therapy, scintigraphy was performed, which determined the presence or absence of iodine-131 in the lacrimal ducts. T-statistics and the Mann–Whitney criterion were used to identify the differences between the groups. The differences were considered significant at P ≤ 0.05. The current tear production level in patients receiving radioiodine therapy was determined using a mathematical model. Results: A statistically significant difference between the basal (p = 0.044) and reflex (p = 0.015) tear production levels was found in cases with and without iodine-131 uptake by the lacrimal ducts. The probable current tear production level corresponds to the sum of basal and 10–20% of reflex tear production. The uptake of iodine-131 was found regardless of the OSDI results. Conclusion: The probability of iodine-131 uptake by the lacrimal ducts rises as the tear production level increases.