[Clinical and immunological predictors of Graves' orbitopathy after radioiodine therapy of Graves' disease].

BACKGROUND: Data on the effect of 131I on the course of Graves' orbitopathy (GO) are contradictory. A number of studies indicate a deterioration in the course of GO against the background of RAIT, in other studies such a connection has not been established. Cytokines that regulate inflammation could potentially be biomarkers for assessing GO activity and predicting the course of GO after RAIT. AIM: The purpose of this study was to evaluate the dynamics of eye symptoms and analyze immunological parameters: cytokine TGF-ß1 and cytokine receptors: sTNFα-R1, sTNFα-R2, sIL-2R, sIL-6R over time after RAIT, as possible predictors of GO activation. MATERIALS AND METHODS: The study included 59 patients (118 orbits) with GD in the state of euthyroidism and subclinical hyperthyroidism and low active and inactive GO, aimed at conducting RAIT. Concentrations of cytokine TGF-ß1, sTNFα-RI and sTNFα-R2, sIL-2R, sIL-6R, TSH receptor antibodies (rTSH-Ab), free thyroxine (FT4) and free triiodothyronine (FT3), -thyroid-stimulating hormone (TSH) in the blood serum were determined. Ultrasound examination of the thyroid gland, multispiral computed tomography (MSCT)/magnetic resonance imaging (MRI) of the orbits was performed. The examination was carried out 3, 6, 12 months after the RAIT. RESULTS: The deterioration of the course of the GO (1-2 points according to CAS) was noted after 3 months. (32.5%) and to a lesser degree after 6 and 12 months (13.2% and 8.45%, respectively). Dynamics were not noted, approximately, in the same number of patients (40.5%, 41.5%, 45.8%, respectively). An improvement in the course of the GO was noted after 6 and 12 months (45.3, 45.8, respectively). After 3 and 6 months, the achievement of hypothyroidism and a significant increase in the level of rTSH-Ab were noted. In the analysis of cytokines and their receptors a significant decrease in the level of TGF-ß1 was noted after 3, 6 and 12 months. There was also a significant decrease in sTNF-R1 and sIL-2R at 3 and 6 months. The level of sTNFα-R2 significantly decreased 3 months after RAIT. The level of sIL-6R has not changed significantly. After 3 months in patients with positive dynamics of image intensification, the level of TGF-ß1 did not significantly change compared with the level before RAIT, in patients with worsening of the course of GO or without dynamics, the level of TGF-ß1 significantly decreased. After 6 months, there was the same trend, not reaching statistical significance. The IgG4 level and the IgG4/IgG ratio increased to 6 and 12 months, which corresponded to an increase in diplopia index. CONCLUSION: The main limiting factor in the conduct of RAIT is the activity of the autoimmune process in the orbits. Since patients with inactive (CAS 0-2) or low activity (CAS 3-4) GO were referred for RAIT, there was no pronounced activation of GO after RAIT. There was a slight deterioration in the course of GO by only 1-2 points according to CAS after 3 months. (32.5%) and to a lesser degree after 6 months (13.2%). In the study, it was found that the main predictors of the deterioration of the course of GO after RAIT are uncompensated hypothyroidism, a high level of rTSH-Ab and a decrease in the level of cytokine TGF-ß1.

[Prevention of iodine deficiency diseases: focus on regional targeted programs].

The strategy for the elimination of diseases associated with iodine deficiency throughout the Russian Federation is based on the adoption of a federal law providing for the use of iodized salt as a means of mass (population) iodine prophylaxis. Chronic iodine deficiency that exists in Russia leads to dramatic consequences: the development of mental and physical retardation in children, cretinism, thyroid diseases, and infertility. Under conditions of iodine deficiency, the risk of radiation-induced thyroid cancer in children in the event of nuclear disasters increases hundreds of times. By definition, all iodine deficiency diseases (IDDs) can be prevented, while changes caused by iodine deficiency during fetal development and in early childhood are irreversible and practically defy treatment and rehabilitation. The actual average consumption of iodine by a resident of Russia is only 40-80 mcg per day, which is 3 times less than the established norm (150-250 mcg). Every year, more than 1.5 million adults and 650 thousand children with various thyroid diseases turn to medical institutions. The cause of 65% of cases of thyroid disease in adults and 95% in children is insufficient intake of iodine from the diet. At the stage of preparing the relevant legislative act, the development and implementation of regional programs for the prevention of IDD is of utmost importance. A typical draft of such a program is proposed in this article for its adaptation and use at the regional level.

[Radioiodine therapy for Graves' disease as a risk factor of endocrine ophthalmopathy].

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.

[Radioiodine therapy for Graves disease as a risk factor of endocrine ophthalmopathy].

In 1973 and 1976 2 cases of endocrine ophthalmopathy (EO) after external irradiation of the anterior surface of the neck due to a tumor (Hodgkin's lymphoma) was described. Further observations showed that treatment of Graves' disease (BG) with radioactive iodine (131I) can worsen the course of EO. So, L. De Groot et al., Observing 264 patients after exposure to 131I for BG, found progression of EO in 4% of patients after the 1st course of therapy and in 12% after subsequent sessions. Later the appearance or significant progression of EO in  patients treated with 131I has been observed. Some studies have shown that the progression of EO after treatment with 131I without glucocorticoids administration can be observed in 18-30% of cases. Along with this, there is an opinion that 131I does not affect the incidence of clinical symptoms in the orbit and that 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 in the blood serum after 131I training for EO.

[C-peptide and insulin ratio in patients with juvenile dyspituitarism in varying symptomatology]. / Sootnoshenie C-peptida i insulina u bol'nykh s iunosheskim dispituitarizmom pri razlichnoi klinicheskoi simptomatike.

Altogether 24 adolescents with pubertal juvenile dyspituitarism (PJD) were investigated in the course of an oral GTT for 3 hours. The patients were divided into 3 groups: (1) with liver dysfunction and normal BP; (2) with normal liver and arterial hypertension; (3) with normal BP and normal liver function. The levels of glycemia, immunoreactive insulin, C-peptide and a molar C-peptide/insulin ratio were measured. All the examinees were characterized by basal and stimulated hyperinsulinemia against a background of a normal C-peptide value, the absence of a tendency to IRI reduction by the end of the GTT. A decrease in the C-peptide/IRI ratio was marked in the 1st group. One of the reasons of hyperinsulinemia in PJD in parallel with high insulin secretory pancreatic function can be a decrease in the metabolic clearance of liver insulin, especially noticeable in patients with hepatocyte dysfunction.