Most patients with newly diagnosed Graves' disease have no ocular involvement. Moderate-to-severe and active GO or sight-threatening GO are rare at presentation and rarely develop during ATD treatment. Most patients (>80%) with no GO at baseline do not develop GO after an 18-month follow-up period. Remission of mild GO occurs in the majority of cases.
Background
Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.
Methods
A multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.
Results
In the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6–24.0, P = 0.52) and 22.4% (97.5% CI: 17.2–28.3, P < 0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.
Conclusions
Tocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.
Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092).
Similarities and differences exist between expert North American and European thyroidologists concerning the diagnosis and management of AIT. While differences reflect the frequent uncertainty of the underlying mechanism leading to AIT, similarities may represent the basis to refine the diagnostic criteria and to improve the therapeutic outcomes of this challenging clinical situation.
Autoimmune thyroid disorders (AITDs) are the result of a complex interplay between genetic and environmental factors, the former account for about 70-80% of liability to develop AITDs. However, at least 20-30% is contributed by environmental factors, which include certainly smoking (at least for Graves' disease and orbitopathy), probably stress, iodine and selenium intake, several drugs, irradiation, pollutants, viral and bacterial infections, allergy, pregnancy, and post-partum. Evidence for the intervention of these factors is often limited, and the mechanisms whereby environmental factors may concur to the onset of AITDs are in many instances unclear. Nevertheless, gene-environment interaction seems a fundamental process for the occurrence of AITDs.
The simultaneous finding of submandibular ectopic thyroid tissue and functional orthotopic thyroid gland is an extremely rare event. The present report describes the case of a woman presenting with a left submandibular mass, distant from a palpable multinodular goitre. Ultrasonography showed an ovoidal solid mass adjacent to the lower margin of the left submandibular gland. Cytological specimens showed colloid material and thyroid follicular cells with no malignant features. A preoperative CT scan demonstrated a very thin connection between the thyroid and the submandibular mass. The patient underwent total thyroidectomy and excision of the submandibular mass. The histopathological diagnosis of the thyroid tissue was multinodular goitre, and the submandibular mass was ectopic thyroid tissue showing a hyperplastic pattern. The main differential diagnosis of the submandibular mass was a metastasis from a well differentiated cancer. This case illustrates that an ectopic thyroid off the midline may not necessarily be a metastasis from a thyroid cancer.
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