Role of selenium and myo-inositol supplementation on autoimmune thyroiditis progression.

Previous reports indicate that selenium supplementation may be useful to reduce cell oxidative stress. In particular, selenium may decrease the level of thyroid autoantibodies in patients with Hashimoto's thyroiditis (HT). Recent studies also indicate that myo-inositol may have beneficial effects on thyroid function in patients with HT. Hence, the aim of the present study is to evaluate whether myo-inositol may enhance the protective effect of selenium on HT progression to hypothyroidism. The study was designed as observational and retrospective. Thyroid hormones were evaluated in patients with HT who were either euthyroid or subclinically hypothyroid. These patients were subdivided into three groups: untreated, treated with selenomethionine alone (Se-meth: 83 µg/day) and treated with Se-meth plus myo-inositol (Se-meth + Myo-I: 83 µg/day + 600 mg/day). Outcome evaluation was performed at baseline and after 6 and 12 months of treatment. High-resolution ultrasound of the thyroid gland was performed to evaluate changes in thyroid echoic pattern during the study. Compared to baseline, levels of thyroid-stimulating hormone (TSH) increased significantly in untreated patients but decreased by 31% and 38%, respectively, in those treated with Se-meth and Se-meth + Myo-I. Moreover, in the latter group the TSH reduction was observed earlier than in the Se-meth-treated group. Densitometric analysis of thyroid ultrasonography showed an echoic pattern improvement in both treated groups compared to untreated patients, although this difference was not statistically significant. Thus, Se-meth treatment is effective in patients with HT and its effect may be improved in combination with Myo-I through earlier achievement of TSH levels closer to physiological concentrations.

Determinants of clinical outcome in patients with moderate/severe Graves' orbitopathy undergoing treatment with parenteral glucocorticoids: a retrospective study.

Background: Graves' orbitopathy (GO) occurs in approximately 25-40% of patients with Graves' disease (GD). High levels of anti-thyrotropin receptor antibodies (TRAbs), smoking habit, sex, older age, longer duration and amount of hyperthyroidism or hypothyroidism are well-recognized risk factors for the occurrence, severity and clinical course of GO. Oxidative stress (OX) has recently been shown to play a role in the pathogenesis of GO, and several clinical conditions related to OX have been investigated regarding the presentation and severity of GO. Aim: We aimed to evaluate the impact of clinical conditions related to oxidative stress on the outcome of intravenous glucocorticoid (ivGCs) therapy in a cohort of patients with active moderate to severe GO (AMS-GOs) treated at a single institution. Methods: We retrospectively studied a series of patients with AMS-GOs who were treated with ivGCs from January 2013 to May 2022. GO clinical evaluation was performed at baseline and at 6 (W6), 12 (W12) and 24 (W24) weeks after starting ivGCs by the seven-point clinical activity score (CAS) alone and by overall clinical criteria (CI) according to the European Group of Graves' Ophthalmopathy (EUGOGO). Total cholesterol and calculated LDL cholesterol (LDLc), triglyceride, body mass index (BMI), diabetes status, history of hypertension (HoH), smoking status, age and sex were used as covariates for the clinical outcome of GO to ivGCs. Results and conclusions: LDLc and HoH negatively and independently modulated the response of AMS-GOs to ivGCs. Notably, slightly elevated LDLc levels (> 130 mg/dl) reduced the response of orbital soft tissue to ivGCs, whereas more elevated LDLc levels (from 175 mg/dl to 190 mg/dl) and HoH were associated with poorer clinical response of eye motility and proptosis.

Levothyroxine therapy, calculated deiodinases activity and basal metabolic rate in obese or nonobese patients after total thyroidectomy for differentiated thyroid cancer, results of a retrospective observational study.

INTRODUCTION: Therapy for hypothyroid obese patients is still under definition since the thyrotropin-stimulating hormone (TSH) level is a less reliable marker of euthyroidism than nonobese patients. Indeed, TSH levels positively correlate with body mass index (BMI), and this increase may be a compensatory mechanism aimed at increasing energy expenditure in obese people. In contrast, the correlation of BMI with thyroid hormone levels is not completely clear, and conflicting results have been obtained by several studies. The L-T4 replacement dose is more variable in obese hypothyroid patients than in nonobese patients, and a recent study indicated that the L-T4 replacement dose is related to lean body mass in obese thyroidectomized patients. We aimed to study the correlations of L-T4-administered dose, thyroid hormone levels and TSH secretion with basal metabolic rate (BMR) and total calculated deiodinase activity (GD) in obese and nonobese athyreotic patients. We also looked for individualized L-T4 replacement dose set points to be used in clinical practice. METHODS: We studied retrospectively 160 athyreotic patients, 120 nonobese and 40 obese. GD was calculated by SPINA Thyr 4.2, the responsiveness of the hypothalamic/pituitary thyrotrope by Jostel's thyrotropin (TSH) index and BMR by the Mifflin-St. Jeor formula, the interplay of GD and BMR with L-T4, thyroid hormones and TSH index (TSHI) was also evaluated. RESULTS: In our study, the L-T4 dose was an independent predictor of GD, and approximately 30% of athyreotic patients under L-T4 therapy had a reduced GD; FT4 levels were higher and negatively modulated by BMR in obese athyreotic patients respect to nonobese, in these patients a T4 to T3 shunt, in terms of TSHI suppression is observed suggesting a defective hypothalamic pituitary T4 to T3 conversion and a resistance to L-T4 replacement therapy. CONCLUSIONS: L-t4 dose is the most important predictor of GD, BMR modulates T4 levels in obese athyreotic patients that are resistant to L-T4 replacement therapy.

Inflammasome activation as a link between obesity and thyroid disorders: Implications for an integrated clinical management.

Obesity is strongly associated with chronic low-grade inflammation. Obese patients have an increased risk to develop thyroid autoimmunity and to became hypothyroid, suggesting a pathogenetic link between obesity, inflammation and autoimmunity. Moreover, type 2 diabetes and dyslipidemia, also characterized by low-grade inflammation, were recently associated with more aggressive forms of Graves' ophthalmopathy. The association between obesity and autoimmune thyroid disorders may also go in the opposite direction, as treating autoimmune hyper and hypothyroidism can lead to weight gain. In addition, restoration of euthyroidism by L-T4 replacement therapy is more challenging in obese athyreotic patients, as it is difficult to maintain thyrotropin stimulation hormone (TSH) values within the normal range. Intriguingly, pro-inflammatory cytokines decrease in obese patients after bariatric surgery along with TSH levels. Moreover, the risk of thyroid cancer is increased in patients with thyroid autoimmune disorders, and is also related to the degree of obesity and inflammation. Molecular studies have shown a relationship between the low-grade inflammation of obesity and the activity of intracellular multiprotein complexes typical of immune cells (inflammasomes). We will now highlight some clinical implications of inflammasome activation in the relationship between obesity and thyroid disease.

Evidence That Baseline Levels of Low-Density Lipoproteins Cholesterol Affect the Clinical Response of Graves' Ophthalmopathy to Parenteral Corticosteroids.

Background: High dose intravenous glucocorticoid (ivGC) therapy is the first line treatment in moderate to severe Graves' ophthalmopathy (GO) and is associated with a clinical response rate ranging from 50% to 80%. Recently, a positive correlation between total cholesterol and low-density lipoproteins cholesterol (LDLc) with GO presentation and activity has been described. Objective: We aimed at evaluating whether, in patients with moderate to severe active GO treated with ivGC therapy, cholesterol, and LDLc could represent valuable predictive factors of medium-term GO outcome. Methods: This single center retrospective study was conducted in a consecutive series of 87 patients undergone ivGC therapy because affected by moderate to severe active GO. Clinical outcome of GO was evaluated at week 6 (W6) and 12 (W12) in respect to baseline conditions (week 0) by the seven points CAS according to EUGOGO recommendations. Univariate analysis and binary logistic regression were performed for the outcome variable W12CAS. Results: In patients with active GO, an early positive clinical response to ivGC therapy (as evaluated by CAS at 6W) was a strong determinant (OR=13) of the clinical outcome at week 12. Moreover, high levels of LDLc at baseline were positively associated with a reduction in the likelihood of being classified as improved at 12W. Patients with LDLc >193.6 mg/dl were very likely to respond negatively to ivGC therapy independently from the response at 6W. Based on these results, we propose a predictive decision-making model to be tested in future prospective studies. Discussion: We found that, in patients with active GO, both an early clinical response to ivGC therapy and baseline LDLc levels are significant determinants of GO outcome (W12CAS). These data support the need of a cholesterol-lowering treatment before addressing these patients to ivGC therapy.