Endocrine ophthalmopathy (EOP) is a multidisciplinary problem at the intersection of endocrinology and ophthalmology. The patients presenting with this condition experience deficit of adequate medical aid due to the poor cooperation between ophthalmologists and endocrinologists. There are practically no specialized centres in this country where the patients with EOP could receive the combined treatment of this pathology including the surgical intervention. Taken together, late diagnostics and delayed seeking the efficacious medical assistance, the absence of stable compensation of the functional disorders of the thyroid gland, erroneous identification of the phase of the disease, and incorrect choice of the methods for its treatment, the lack of coordination and consistency in the actions of ophthalmologists and endocrinologists are responsible for the low effectiveness of EOP treatment. On the other hand, the absence of the unified approach to diagnostics and treatment of endocrine ophthalmopathy, the necessity of introducing the international experience gained in this field into the routine clinical practice and pooling efforts of representatives of different medical disciplines (endocrinologists, ophthalmologists, radiologists, endocrine surgeons, and neurosurgeons) created the prerequisites for the solution of the EOP problems and gave impetus to the development of the recommendations being proposed.
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, p<0,05) and TGFβ1 (P=0,011, p≤0,05) were positively correlated with the duration of GO. The positive correlations between the serum level of sIL-6R (p=0,034, p≤0,05) and the severity of GO as well as between the serum level of sTNFα- R 1 (P=0,012, p≤0,05) and activity of GO were observed. 54% of patients had elevated concentration level of IgG4 in IgG ( >5%).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.
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.
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