Regulatory T cells in the pathogenesis of graves' disease

Maintaining a delicate balance between the prompt immune response to pathogens and tolerance towards self-antigens and commensals is crucial for health. T regulatory (Treg) cells are pivotal in preserving self-tolerance, serving as negative regulators of inflammation through the secretion of anti-inflammatory cytokines, interleukin-2 neutralization, and direct suppression of effector T cells. Graves' disease (GD) is a thyroid-specific autoimmune disorder primarily attributed to the breakdown of tolerance to the thyroid-stimulating hormone receptor. Given the limitations of currently available GD treatments, identifying potential pathogenetic factors for pharmacological targeting is of paramount importance. Both functional impairment and frequency reduction of Tregs seem likely in GD pathogenesis. Genome-wide association studies in GD have identified polymorphisms of genes involved in Tregs' functions, such as CD25 (interleukin 2 receptor), and Forkhead box protein P3 (FOXP3). Clinical studies have reported both functional impairment and a reduction in Treg frequency or suppressive actions in GD, although their precise involvement remains a subject of debate. This review begins with an overview of Treg phenotype and functions, subsequently delves into the pathophysiology of GD and into the existing literature concerning the role of Tregs and the balance between Tregs and T helper 17 cells in GD, and finally explores the ongoing studies on target therapies for GD

The old and the new in subacute thyroiditis: an integrative review

Subacute thyroiditis (SAT) is the most common cause of neck pain and thyrotoxicosis. Although this disease was recognized already by the end of the 18th century, new concepts regarding pathogenesis have emerged in recent years. Moreover, in the last two years, literature on SAT has increased significantly due to articles describing the possible connection with coronavirus disease 2019 (COVID-19). This integrative review depicts old and new concepts of this disease, proposing a detailed overview of pathogenesis, a practical approach to diagnosis and treatment, and a thorough description of the latest discoveries regarding the association of SAT with COVID-19

Immunomodulatory role of vitamin D and selenium supplementation in newly diagnosed Graves’ disease patients during methimazole treatment

IntroductionMethimazole (MMI) represents the conventional therapeutic agent for Graves’ disease (GD) hyperthyroidism, but MMI efficacy is limited since it marginally affects the underlying autoimmune process. In a previous study, we randomly assigned 42 newly diagnosed GD patients with insufficient vitamin D (VitD) and selenium (Se) levels to treatment with MMI alone (standard) or combined with selenomethionine and cholecalciferol (intervention) and observed a prompter resolution of hyperthyroidism in the intervention group.MethodsIn the present study, we aimed to explore changes in peripheral T regulatory (Treg) and circulating natural killer (NK) cell frequency, circulating NK cell subset distribution and function, during treatment.ResultsAt baseline, circulating total CD3-CD56+NK cells and CD56bright NK cells were significantly higher in GD patients than in healthy controls (HC) (15.7 ± 9.6% vs 9.9 ± 5.6%, p=0.001; 12.2 ± 10.3% vs 7.3 ± 4.1%, p=0.02, respectively); no differences emerged in Treg cell frequency. Frequencies of total NK cells and CD56bright NK cells expressing the activation marker CD69 were significantly higher in GD patients than in HC, while total NK cells and CD56dim NK cells expressing CD161 (inhibitory receptor) were significantly lower. When co-cultured with the K562 target cell, NK cells from GD patients had a significantly lower degranulation ability compared to HC (p<0.001). Following 6 months of treatment, NK cells decreased in both the intervention and MMI-alone groups, but significantly more in the intervention group (total NK: -10.3%, CI 95% -15.8; -4.8% vs -3.6%, CI 95% -9; 1.8%, p=0.09 and CD56bright NK cells: -6.5%, CI 95% -10.1; -3 vs -0.9%, CI 95% -4.4; 2%, p=0.03). Compared to baseline, CD69+ NK cells significantly decreased, while degranulation ability slightly improved, although no differences emerged between the two treatment groups. Compared to baseline, Treg cell frequency increased exclusively in the intervention group (+1.1%, CI 95% 0.4; 1.7%).DiscussionThis pilot study suggested that VitD and Se supplementation, in GD patients receiving MMI treatment, modulates Treg and NK cell frequency, favoring a more pronounced reduction of NK cells and the increase of Treg cells, compared to MMI alone. Even if further studies are needed, it is possible to speculate that this immunomodulatory action might have facilitated the prompter and better control of hyperthyroidism in the supplemented group observed in the previous study

Medullary thyroid carcinoma: surgical treatment advances

PURPOSE OF REVIEW: In recent years new technologies have been proposed and applied in thyroid surgery, among these molecular diagnosis and endoscopic procedures. The authors review relevant medical literature published on the influence of these new techniques in the treatment of medullary thyroid cancer. Searches were last updated in October 2007. RECENT FINDINGS: Mutations of the RET proto-oncogene have been demonstrated to be causative of the familial form of medullary thyroid cancer. The number and type of recognized RET genetic mutations have grown over the last years, especially after the introduction of genetic screening in the work-up of all patients with medullary thyroid cancer. Prophylactic surgery for patients carrying a positive RET proto-oncogene is highly effective. Cervical endoscopic procedures have been recently described and applied for positive RET carriers: a video-assisted thyroidectomy with central compartment dissection (level 6) has proved feasible, safe and effective for these patients. SUMMARY: There have been some important papers in the recent literature that apply to many aspects of new technologies for medullary thyroid cancer treatment. This article discusses some of these articles, emphasizing where this literature makes new contributions and supports established recommendations.PURPOSE OF REVIEW: In recent years new technologies have been proposed and applied in thyroid surgery, among these molecular diagnosis and endoscopic procedures. The authors review relevant medical literature published on the influence of these new techniques in the treatment of medullary thyroid cancer. Searches were last updated in October 2007. RECENT FINDINGS: Mutations of the RET proto-oncogene have been demonstrated to be causative of the familial form of medullary thyroid cancer. The number and type of recognized RET genetic mutations have grown over the last years, especially after the introduction of genetic screening in the work-up of all patients with medullary thyroid cancer. Prophylactic surgery for patients carrying a positive RET proto-oncogene is highly effective. Cervical endoscopic procedures have been recently described and applied for positive RET carriers: a video-assisted thyroidectomy with central compartment dissection (level 6) has proved feasible, safe and effective for these patients. SUMMARY: There have been some important papers in the recent literature that apply to many aspects of new technologies for medullary thyroid cancer treatment. This article discusses some of these articles, emphasizing where this literature makes new contributions and supports established recommendations. \ua9 2008 Lippincott Williams & Wilkins, Inc

The story of a vitamin for bone health that upgraded to hormone for systemic good health.

The discovery of Vitamin D is a multi-step history started in 1650 and culminated in 1963 with the determination of its chemical structure. The diffusion of rickets in North Europe and North America was the first reason for experimental studies. Nevertheless, in the last decades new potential actions have been revealed. Besides bone and intestine, the Vitamin D receptors have been demonstrated in different organs such as the brain, prostate, breast, colon, immune system cells, smooth muscle and heart. Not totally fulfilling the criteria of a vitamin, Vitamin D is actually considered a pleiotropic hormone with endocrine and paracrine actions. The current evidences support the role of Vitamin D in skeletal health and suggest that the treatment of Vitamin D deficiency should be desirable to reduce the risk of chronic health diseases