Role of cytokines, IL1-β and IL-10, in the development of endocrine ophthalmopathy in Graves’ disease

Background: Endocrine ophthalmopathy (EO) is a disease which is characterized by progressive autoimmune inflammation of extraocular muscles and retrobulbar adipose tissue, and is accompanied by infiltration, edema and proliferation of retrobulbar adipose tissue, muscles and connective tissue, leading to worsened quality of life, limited capacity for work and even ocular atrophy. It has been demonstrated that cytokines are involved in the development of autoimmune ophthalmopathy in Graves’ disease (GD). Thus, the secretion of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and TNFα were increased several dozenfold in active ophthalmopathy, but the specificity of cytokines in EO is still a subject of discussion among researchers. Purpose: To assess the levels of proinflammtory cytokines (IL-1β) and anti-inflammatory cytokines (IL-10) in Graves’ disease complicated by endocrine ophthalmopathy. Material and Methods: Forty-three patients with Graves’ disease (33 women and 10 men; age, 18 to 71 years) underwent an examination. They were divided into two groups based on the presence or absence of EO: GD plus EO (24 patients) and GD only (19 patients). Disease duration was 2.2±0.4 years for patients with GD plus EO versus 3.98±0.74 years for patients with GD only (р<0.05). All patients were treated with antithyroid drugs (mercazolil and thyrozol) and were classified as having compensated thyroid disease at the time of the study. All patients with GD plus AO had a CAS score exceeding 3 (the active stage of EO). Patients underwent an examination including ultrasonic assessment of thyroid gland volume, hormonal examination (serum TSH, free T4 (fT4), and free T3 (fT3)), assessment of serum antithyroid antibodies (anti-thyroid peroxidase antibodies and TSHR-Ab) and serum IL-1β and IL-10 levels. Results: Serum IL-1β levels were significantly increased in patients with Graves’ disease compared to healthy controls. Serum IL-1β levels for patients with GD plus EO were significantly higher than for patients with GD only (45.48 ± 16.19 pg/ml versus 10.44±5.17 pg/ml; р 0.05)

Assessing the efficacy of various treatment regimens for patients with endocrine ophthalmopathy associated with Graves’ disease

Purpose: To assess the efficacy of various treatment regimens for patients with EO associated with Graves’ disease based on the retrospective analysis of clinical data, thyroid-stimulating hormone (TSH) receptor autoantibodies (TSHR-Ab) titers and orbital ultrasound imaging findings. Material and Methods: We retrospectively reviewed the medical records (including clinical and laboratory data and findings of ultrasound imaging of retrobulbar adipose tissue) of 155 patients with EO associated with Graves’ disease and either euthyroidism (in the presence of antithyroid therapy) or postoperative compensated hypothyroidism that underwent treatment at Komisarenko Institute for Endocrinology and Metabolism between 2009 and 2019. The duration of EO ranged from 8 months to 36 months. Patients with EO associated with Graves’ disease were medically treated in the presence of stable euthyroidism. Patients were divided into 4 groups based on the glucocorticoid treatment scheme. Group 1 of 15 patients received prednisolone tablets per os; group 2 of 68 patients, intravenous methylprednisolone (MP) pulse therapy only; group 3 of 32 patients, intravenous MP pulse therapy plus vitamin D3; and group 4 of 40 patients, intravenous MP pulse therapy 8 to 12 months after thyroidectomy. Results: As soon as 3 months after treatment initiation, there was an improvement in condition of patients in all groups as assessed by clinical examination, followed by further improvement by 6 months and 12 months. The best results were obtained in patients of group 4, with a statistically significant improvement in clinical condition (p < 0.05). Retrobulbar adipose tissue thickness as assessed by orbital ultrasound at baseline and at 6 months and 12 months was statistically significantly greater in patients of all the four groups than controls (p < 0.05). At 6 months, serum TSHR-Ab levels in groups 1, 2 and 3 significantly decreased compared to baseline, with no significant difference between these groups, whereas serum TSHR-Ab level in group 4 was significantly higher than in other groups both at baseline and at 6 months. At 12 months, serum TSHR-Ab level in group 4 was significantly lower (р < 0.05) than in other groups (2.41 ± 0.81 mU/L versus 5.97 ± 1.71 mU/L for group 1, 5.49 ± 1.27 mU/L for group 2, and 6.17 ± 1.18 mU/L for group 3). Conclusion: Patients with EO associated with Graves’ disease in group 4 (intravenous MP pulse therapy after thyroidectomy) showed a significantly better (р < 0.05) treatment outcome than patients in other groups. Ultrasound imaging of retrobulbar adipose tissue thickness is inadequately informative for assessing treatment efficacy