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Objective The prognosis of Graves' disease (GD) varies among patients. However, the immune pathogenesis of refractory GD is still unknown. The aim of this study was to explore the cytokine expression profile associated with refractory GD. Methods Preliminary cytokine protein microarray screening was performed to detect differentially expressed cytokines in the plasma of four patients with refractory GD and four patients with stable GD. Some differentially expressed cytokines were then validated in plasma by enzyme-linked immunosorbent assay (ELISA) and in peripheral blood mononuclear cells (PBMCs) by quantitative real-time polymerase chain reaction (qRT-PCR) on another independent set of samples. Results We found that 21 cytokines were differentially expressed between patients with intractable GD and those in remission, including 18 upregulated and 3 downregulated cytokines with a fold change >1·30 and <0·77, respectively. Intractability-related elevation of three cytokines (IL-4, IL-6 and IL-10) was validated by ELISA in plasma on another GD cohort with 30 patients in recurrence and 14 in remission ( t-test, P = 0·035, 0·033 and 0·041, respectively). Furthermore, mRNA expression of IL-4, IL-6 and IL-10 in PBMCs, detected by qRT-PCR, was significantly elevated in patients with refractory GD compared with those in remission ( P = 0·039, 0·047 and 0·042, respectively). Conclusion The severity of GD is associated with the aberrant expression and secretion of several cytokines that may serve as potential biomarkers and predictors for disease prognosis. Targeting these cytokines or their receptors may also lead to a novel therapeutic intervention for GD. [ABSTRACT FROM AUTHOR]

Objectives Radioactive iodine (131I) therapy is increasingly viewed as a safe and effective treatment for paediatric and adolescent hyperthyroidism. Our objective was to estimate treatment response and its predictors and describe current referral practices for 131I therapy. Design Retrospective study. Patients One hundred and thirty-one children 30 days–21 years old with laboratory evidence of hyperthyroidism, seen in an academic paediatric and adolescent endocrinology practice. Measurements Rate of referral, indications for 131I, predictors of poor treatment response. Results Thirty-eight of 102 patients with persistent hyperthyroidism (37%) received 131I (160 μCi/g thyroid tissue/131I uptake), as did an additional 10 patients initially evaluated by adult thyroidologists. Primary indications were intolerance to (29%) or poor control on (19%) antithyroid drugs, patient preference (50%) and unknown (2%). Of 48 patients treated with 131I, 89% and 11% became hypothyroid after one and two 131I doses, respectively. The goal of 131I therapy was attainment of hypothyroidism. ‘Poor treatment response’ (seen in 27%) was defined as requirement for a second 131I dose or failure to achieve hypothyroidism after 6 months. Predictors of poor treatment response included: previous use of antithyroid drugs (37% vs. 0%, P = 0·02), ophthalmopathy (58% vs. 8%, P = 0·002), and an interval of ≥12 months from diagnosis to 131I (50% vs. 10%, P = 0·003). A very elevated free T4 tended to be more prevalent in those with poor response. Conclusions In children and adolescents with hyperthyroidism, high rates of success after 131I are achievable. Use of antithyroid drugs, pre-existing eye disease and prolonged time to 131I may confer relative resistance to 131I. [ABSTRACT FROM AUTHOR]