Evaluation of disease-specific quality of life and its influencing factors in Bulgarian patients with Graves' orbitopathy.

PURPOSE: Graves' orbitopathy (GO) profoundly affects patients' quality of life (QoL). Our aim was to assess QoL in patients with different forms of GO and to search for predictors of QoL. METHODS: This was a cross-sectional study involving 221 consecutive unselected GO patients (77.4% females, mean age 52 ± 11.6) referred to our clinic in the period 2017-2021. Detailed medical history was obtained from all patients, followed by hormonal and immunological testing and comprehensive ocular status. QoL was assessed by a disease-specific questionnaire (GO-QoL), consisting of two scales-one related to visual functioning (QoL-VF) and the other-to physical appearance (QoL-AP). The results were calculated by formula and expressed as percentages. RESULTS: Mild GO patients had significantly higher scores on both scales of GO-QoL compared to moderate-to-severe and sight-threatening GO patients (82.0 vs. 54.6% and 27.3% for QoL-VF; 70.1 vs. 54.4% and 36.9% for QoL-AP). Patients with active GO had significantly poorer QoL-VF (56.6 vs. 76.6%) and QoL-AP (53.1 vs. 67.5%) in comparison to patients with inactive GO. The stepwise linear regression analysis showed that the variables with major predictive value for QoL-VF were: CAS, diplopia score, visual acuity and severity of the symptoms (R2 = 0.44), whereas gender, CAS, diplopia score and proptosis best predicted QoL-AP (R2 = 0.39). CONCLUSIONS: The impact of GO on patients' QoL depends on the severity and activity of the disease. The clinical predictors of the impairment of QoL should be taken into account when considering the optimal adjunctive treatment approaches aiming to improve patients' QoL.

Comparison of the efficacy of two different glucocorticoid regimens for treatment of active moderate-to-severe Graves' orbitopathy.

PURPOSE: Intravenous glucocorticoids (GCs) are the mainstay of treatment for severe forms of Graves' orbitopathy (GO). Our aim was to assess the effectiveness and safety of a modified monthly regimen (mMR) and to compare them with those of the established weekly regimen (WR). METHODS: This was a prospective non-randomized single-center study involving 62 patients, divided into two therapeutic groups depending on their referral time. Thirty-one subjects, admitted in the period 2017-2018, were treated with mMR, total dose-5.5 g, with intake of oral GCs after completion of intravenous infusions. Thirty subjects, who were referred in the period 2019-2020, were treated with WR, total dose-4.5 g One patient refused to be part of the WR group and was treated with mMR. Eye status and therapeutic response were evaluated on the 1st, 3rd and 6th months, quality of life-at 3rd and 6th month. RESULTS: At 1st month and 3rd month, there was no significant difference in the therapeutic response between the two groups. At 3rd month, the proportion of patients with improvement in soft tissue manifestations and subjective complaints was significantly higher in mMR group (65.6% vs. 40% and 81.3% vs. 46.7%, respectively) and the same manifestations were of significantly milder degree. At 3rd month, significant improvement in quality of life was found without significant difference between the two groups. At 6th month, worsening of GO occurred in 3 patients from WR group, while in 5 patients from mMR group further improvement was found. CONCLUSIONS: The two GC regimens have comparable efficacy with small differences in the time of onset of the effect and its duration, as well as in the effectiveness on some ocular manifestations. Trial registration number NCT05793359/29.03.2023, retrospectively registered..

Changes in therapeutic response, ocular manifestations of Graves' orbitopathy and quality of life during the first year after orbital radiotherapy.

PURPOSE: The aim of our study was to assess the changes in the therapeutic response, ocular manifestations of GO and quality of life during the first year after OR. METHODS: The study involved 26 consecutive patients with active moderate-to-severe GO indicated for OR, 18 females, mean age 57 ± 12.5. At baseline, all patients underwent comprehensive ocular examination and thyroid hormone and antibody testing. Then, OR was performed with a total dose of 20 Gy, divided into 10 sessions of 2 Gy each with concomitant oral intake of low-dose glucocorticoids. Therapeutic response and individual ocular manifestations were evaluated 1, 3, 6 and 12 months after OR, and QoL-at 3, 6 and 12 months by a disease-specific questionnaire. RESULTS: One month after OR, 61.6% of patients had a therapeutic response (full or partial). During the follow-up, the proportion of full-responders gradually increased up to 57.5% at 12 months, while that of non-responders gradually decreased, reaching 11.5% at 12 months. All individual ocular manifestations improved significantly 1-3 months after OR. QoL related to visual functioning increased significantly at 6 months, whereas QoL related to appearance improved significantly at 12 months. CONCLUSIONS: The vast majority of our patients with active moderate-to-severe GO exhibited full or partial therapeutic response after OR. The initial effect on the therapeutic response and individual ocular parameters was evident as soon as 1-3 months after the procedure. OR also has a beneficial effect on patients' QoL. TRIAL REGISTRATION NUMBER: NCT05775185/07.03.2023, retrospectively registered.

Selective Silencing of Disease-Associated B Lymphocytes from Hashimoto's Thyroiditis Patients by Chimeric Protein Molecules.

Hashimoto's thyroiditis is one of the most common endocrine disorders, affecting up to 20% of the adult population. No treatment or prevention exists except hormonal substitution for hypothyroidism. We hypothesize that it may be possible to selectively suppress anti-thyroglobulin (Tg) IgG antibody-producing B lymphocytes from HT patients by a chimeric protein molecule containing a monoclonal antibody specific for the human inhibitory receptor CR1, coupled to peptide epitopes derived from Tg protein. We expect that this treatment will down-regulate B-cell autoreactivity by delivering a strong inhibitory signal. Three peptides-two epitope-predicted ones derived from Tg and another irrelevant peptide-were synthesized and then coupled with monoclonal anti-human CR1 antibody to construct three chimeric molecules. The binding to CD35 on human B cells and the effects of the chimeric constructs on PBMC and TMC from patients with HT were tested using flow cytometry, ELISpot assay, and immunoenzyme methods. We found that after the chemical conjugation, all chimeras retained their receptor-binding capacity, and the Tg epitopes could be recognized by anti-Tg autoantibodies in the patients' sera. This treatment downregulated B-cell autoreactivity and cell proliferation, inhibited Tg-specific B-cell differentiation to plasmablasts and promoted apoptosis to the targeted cells. The treatment of PBMCs from HT patients with Tg-epitope-carrying chimeric molecules affects the activity of Tg-specific autoreactive B lymphocytes, delivering to them a strong suppressive signal.

Association between Clinical Activity Score and Serum Interleukin-6, Interleukin-8 and Interleukin-10 during Systemic Glucocorticoid Treatment for Active Moderate-to-Severe Graves' Orbitopathy.

Purpose: Some interleukins (ILs) play an important role in Graves' orbitopathy (GO) pathogenesis. We aimed to compare serum IL-6, IL-8 and IL-10 in GO patients, patients with Graves' disease (GD) without GO and healthy controls (HC); to follow IL changes during glucocorticoid (GC) treatment for GO; to examine associations between ILs and Clinical Activity Score (CAS).Materials and Methods: Thirty-one patients with active moderate-to-severe GO (GO(+) group), 30 patients with GD without GO (GO(-) group) and 30 HC were enrolled. At baseline, ILs were measured in all groups, CAS was evaluated in GO(+) patients, who were then treated with systemic GCs for 12 weeks. ILs and CAS were reassessed after the first week of treatment (W2) and at the end of the therapy (W12).Results: At baseline, IL-6 was significantly higher in GO(+) and GO(-) patients, IL-8 - higher in GO(-) patients and IL-10 - lower in GO(+) patients compared to HC. Baseline ILs did not correlate with CAS. At W2, all ILs and CAS decreased significantly. At W12, CAS decreased further, IL-6 remained low, IL-8 and IL-10 returned to baseline. CAS reduction correlated positively with IL-6 reduction at W12 (ρ = 0.38, p = .04).GO(+) patients with overall CAS reduction≥2 had higher baseline IL-6 (3.4 vs 2.6 pg/ml, p = .15), smaller IL-10 reduction at W2 (10.5 vs 18.2%, p = .09), lower IL-6 (1.4 vs 2.4 pg/ml, p < .01) and higher IL-6 reduction at W12 (48.6 vs 21.4%, p = .01) compared to patients with CAS reduction<2. Logistic regression analysis confirmed that overall CAS reduction≥2 was associated with higher baseline IL-6, lower IL-6 at W12 and smaller IL-10 reduction at W2 (R2 = 0.66).Conclusions: Higher baseline IL-6, lower IL-6 at W12 and smaller IL-10 reduction at W2 were associated with higher probability of significant overall CAS reduction. IL-6 might be a potential additional marker for assessing disease activity.