Optimization of the treatment of patients with diffuse toxic goiter and autoimmune ophthalmopathy based on the analysis of clinical and immunological features of the course of the disease and long-term results of treatment

Abstract

The material of many years of research on some aspects of pathogenesis, clinical course, treatment, features of long-term observation of patients with autoimmune ophthalmopathy is summarizes and analyzes in the article. Autoimmune ophthalmopathy (AO) is an autoimmune disease characterized by complex damage of orbital tissues and is accompanied by changes in the functioning of the organ of vision. The pathogenesis of AO is closely related to autoimmune thyroid diseases (ATDs): in 90% of cases, autoimmune ophthalmopathy is combined with diffuse toxic goiter (DTG), and in only 10% with Hashimoto’s thyroiditis, but it can occur independently of the thyroid pathology. According to various sources, AO occurs with a frequency of 5 to 20 % of all cases of DTG. Women are ill 4 times more often than men, mostly between the ages of 40 and 60. Cytokines are actively involved in the development of autoimmune ophthalmopathy in DTG. For example, overexpression of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor (TNF), which increases several times in the active stage of AO, was detected. However, questions regarding the specificity of cytokines in AO remain debatable, the pathogenesis of AO, the effectiveness of various methods of treatment of this disease are still insufficiently studied. Selenium and vitamin D3 are involved in the development of autoimmune diseases, the question of the role of changes in the level of selenium and vitamin D3 in the blood of patients with AO and their participation in the pathogenesis of changes in the orbital tissues has not been fully elucidated. An urgent problem is the study of the results for AO treatment in DTG and the creation of the latest schemes for prevention and treatment. The aim – based on the analysis of clinical and immunological features of the course of the disease and evaluation of long-term results, to optimize the treatment of DTG with AO. The object of the study: long-term results of treatment of the patients with diffuse toxic goiter and AO, processes of AO treatment. Material and methods: questioning, clinical, MRI, ultrasound of the orbits, hormonal, enzyme immunoassay, biochemical. Results. Examination of patients with DTG and AO was carried out. Determination of the functional state of the thyroid gland (TG) showed that euthyroidism occurred in 65% of patients, hyperthyroidism — in 18%, and subclinical hyperthyroidism — in 17%, the rate of stimulating antibodies to the TSH receptor probably exceeded normal values. The level of pro-inflammatory cytokines — IL-1β significantly (p<0.05) increased in patients with DTG compared to the control group of healthy individuals. In patients with an active stage of AO, the IL-1β concentration significantly (p<0.05) exceeded this indicator in the group of patients without AO, which may indicate the specificity of this cytokine as a marker of the activity of the inflammatory autoimmune process in the orbital tissue. Most of patients with AO had stage III-IV AO according to NOSPECS and were active according to CAS — 5.2 points (active form of AO). Ultrasound of the orbits revealed that in all patients the structure of the eye muscles was hypoechoic and there was an increase in the level of tumor necrosis factor. When comparing the size of the orbital muscles according to ultrasound and MRI, significant differences were revealed, the thickness of the internal, external, superior and inferior rectus muscles, both of the right and left orbits, were probably greater according to MRI compared to ultrasound (p <0.05). After surgical treatment of DTG with AO, the level of antibodies to TSH receptor and TNF-α probably decreases already after 6 months, and they reached the minimum level after 24 months. In 14.3% of patients, the clinical manifestations of ophthalmopathy significantly decrease, which was manifested in the disappearance of spontaneous retrobulbar pain, periorbital edema, conjunctival hyperemia and chemosis. Patients with an active progressive course of autoimmune ophthalmopathy against the background of diffuse toxic goiter were treated with the mofetil mycophenylate. A clear positive effect was obtained regarding the reduction in manifestations of AO activity according to the CAS scale, the treatment led to a decrease in the level of antibodies to TSH receptor and the level of C-reactive protein. Conclusions. A modern algorithm for the diagnosis and treatment of diffuse toxic goiter with autoimmune ophthalmopathy has been developed, improved and tested, which will allow a personalized approach to planning programs for monitoring and treating patients.