Current and future immunotherapies for thyroid cancer

Cancer immunotherapies were approved in recent years, including immune checkpoint inhibitors. Experience with ipilimumab (CTLA-4 antagonist), nivolumab and pembrolizumab (PD-1 antagonists), and atezolizumab (PD-L1 antagonist) has shown that the impact on overall survival in cancer patients is paramount. Immune checkpoint inhibitors target the immune system and they can be applied across multiple cancers; the response rate is ranging from 20 to 40%. Many studies have shown that thyroid cancer (TC) cells produce cytokines and chemokines, inducing several tumor-promoting effects. Targeting and/or lowering cytokines and chemokines concentrations within the tumor microenvironment would produce a therapeutic benefit. In TC, increased Treg and PD-1+ T cell frequencies are indicative of aggressive disease and PD-L1 expression correlates with a greater risk of recurrence. Area covered: After performing a literature search, a few pioneering studies have evaluated immunotherapy in thyroid cancer. More recently a case has been described involving anaplastic thyroid cancer treated with vemurafenib and nivolumab, with substantial regression and complete radiographic and clinical remission. Expert commentary: The use of immune checkpoint inhibitors in aggressive TC has not yet been extensively investigated and further studies in a large number of TC patients are urgently needed

Oral L-thyroxine liquid versus tablet in patients with hypothyroidism without malabsorption: a prospective study

No consistent data are present in literature about the effectiveness of levothyroxine (L-T4) liquid formulation in patients without malabsorption. The aim of this study is to compare the effectiveness of L-T4 liquid formulation, with L-T4 tablets, in hypothyroid patients without malabsorption or drug interference. One hundred and fifty two patients were recruited. Patients were switched from the L-T4 therapy in tablets, to liquid L-T4 at the same dosage, 30 min before breakfast. Serum thyrotropic hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were re-evaluated after 1-3 months (first control) and 5-7 months (second control) from the switch. TSH values significantly declined with respect to the basal value after the switch to liquid L-T4 both at the first control (P < 0.05) and at the second control (P < 0.01); FT4 and FT3 levels were not significantly changed. We show that liquid L-T4 is more effective than L-T4 tablet in controlling TSH levels in hypothyroid patients without malabsorption, gastric disorders, or drug interference

Hepatitis C virus infection and development of type 2 diabetes mellitus: Systematic review and meta-analysis of the literature

Type 2 diabetes mellitus (T2DM) is an endocrine disorder encompassing multifactorial mechanisms, and chronic hepatitis C virus infection (CHC) is a multifaceted disorder, associated with extrahepatic manifestations, including endocrinological disorders. CHC and T2DM are associated, but the subject remains controversial. We performed a systematic review and meta-analysis evaluating such association, searching on PubMed until February 29, 2016. Inclusion criteria were: 1) presence of at least one internal control group age- and gender-matched (non-hepatopathic controls; and/or hepatopathic, not HCV-positive, controls); 2) sufficient data to calculate odds ratio and relative risk. Exclusion criteria were: 1) literature reviews on the topic; 2) publications regarding special populations [human immunodeficiency virus and human T-lymphotropic virus-1 coinfections, hepatocellular carcinoma (HCC), post-transplantation DM, gender selection]; 3) no clear differentiation among HCV patients with CHC, cirrhosis or HCC. Data from each study were independently extracted by two reviewers and cross-checked by AA. Our systematic review returned 544 records, and 33 were included in our meta-analysis. HCV infection is associated with an increased risk of T2DM independently from the severity of the associated liver disease, in CHC and cirrhotic HCV patients. As expected T2DM risk is higher in cirrhotic HCV patients, than CHC, and the prevalence of HCV infection in T2DM patients is higher than in non-diabetic controls. Regarding HBV infection prevalence, no difference exists in diabetic and non-diabetic subjects. An unequivocal CHC and T2DM association was shown. A proactive, integrated approach to HCV and T2DM therapies should maximize benefits of both diseases treatment

Reversible normalisation of serum TSH levels in patients with autoimmune atrophic gastritis who received L-T4 in tablet form after switching to an oral liquid formulation: A case series

Background: L-thyroxine (L-T4) malabsorption is a potential concern in patients with autoimmune atrophic gastritis. Methods: We evaluated five patients with autoimmune gastritis, who showed high serum thyrotropin (TSH) levels (in the hypothyroid range) while in therapy with L-T4 in tablet. All patients were switched to receive an oral L-T4 liquid formulation maintaining the same dosage. Results: In all patients who received L-T4 in tablet form after switching to an oral liquid formulation with the same L-T4 dosage, TSH circulating levels were normalized. In four patients who were switched back again to receive L-T4 in tablets, maintaining the dosage, TSH levels worsened again reaching levels in the hypothyroid range. Conclusions: The fact that the change from tablets to liquid oral formulation normalised serum TSH levels, and that switching back to tablets caused thyrotropin levels to worsen, leads us to believe that absorption of L-T4 is greater with oral liquid formulations in these patients. These results suggest that the L-T4 oral liquid formulation could circumvent the pH alteration resulting from atrophic gastritis

Environmental Issues in Thyroid Diseases

Environmental factors are determinant for the appearance of autoimmune thyroid diseases (AITD) in susceptible subjects. Increased iodine intake, selenium, and vitamin D deficiency, exposure to radiation, from nuclear fallout or due to medical radiation, are environmental factors increasing AITD. Cigarette smoking is associated with Graves' disease and Graves' ophthalmopathy, while it decreases the risk of hypothyroidism and thyroid autoimmunity. Viral infections are important environmental factors in the pathogenesis of AITD, too, particularly human parvovirus B19 (EVB19) and hepatitis C virus. Among the many chemical contaminants, halogenated organochlorines and pesticides variably disrupt thyroid function. Polychlorinated biphenyls and their metabolites and polybrominated diethyl ethers bind to thyroid transport proteins, such as transthyretin, displace thyroxine, and disrupt thyroid function. Among drugs, interferon- and iodine-containing drugs have been associated with AITD. Moreover intestinal dysbiosis causes autoimmune thyroiditis. To reduce the risk to populations and also in each patient, it is necessary to comprehend the association between environmental agents and thyroid dysfunction

O uso da fauna silvestre para o fomento de actividades ecoturísticas: o caso do cóndor andino (vultur gryphus) na cuenca carbonífera de Río Turbio

[Resumo] O ecoturismo é unha modalidade turística ambientalmente responsable na cal os usuarios gozan en contacto coa natureza e con diversas manifestacións culturais, propiciando un involucramento activo e socio-economicamente benéfico das poboacións locais. Á súa vez, pode constituírse nunha ferramenta fundamental para mellorar a calidade de vida dos seus habitantes, contribuír á conservación da biodiversidade e ao rescate do patrimonio cultural dunha determinada rexión. Neste contexto, trabállase desde o ano 2002 ata a actualidade, na Cunca Carbonífera de Río Turbio (Patagonia Arxentina), utilizando como especie bandeira ao Cóndor Andino, que polo seu valor biolóxico e cultural e interese a nivel mundial considerouse clave para estimular estas actividades na zona, complementándose a outras ofertas turísticas existentes. Os estudos permitiron identificar dormideros e zonas de uso na área de influencia das localidades, cuantificar a súa abundancia e determinar áreas con potencial atractivo turístico. Estes estudos foron acompañados por diversas accións coa comunidade mediante procesos de participación pública, educación ambiental e capacitación de actores locais como Guías de Sitio, coa finalidade de que sexan os protagonistas na xestación desta nova alternativa de desenvolvemento e os beneficiarios directos.[Abstract] Ecotourism is an environmentally responsible modality in which the users enjoy being in contact with nature and with varied cultural expressions, encouraging an active involvement that is socio-economically beneficial for the local population. At the same time, it may become a fundamental tool to improve the inhabitants’ quality of life, contribute to the biodiversity conservation, and rescue the cultural patrimony of a determined region. In this context, work has been being carried out since 2002 in the Cuenca Carbonifera Río Turbio (Argentine Patagonia), using as an emblematic species the Andean Condor, which due to its biologic and cultural value and global-level interest was considered key in stimulating these activities in the area, being a complement to other existing touristic offers. The studies made possible to identify the resting sites and use zones in the area of influence of the towns, quantify its abundance and determine areas with potential tourist attraction. These studies were accompanied by several activities with the community by means of public participation processes, environmental education, and training of the local actors as Site Guides, in order for them to be the protagonists in the creation of this new development alternative and the direct beneficiaries

Application of Agents Against Interferon-Gamma-Dependent Chemokines in Immunotherapy

The CXC chemokine receptor (CXCR) 3 and its chemokines (CXCL9, CXCL10, CXCL11) are involved in the pathogenesis of autoimmune disesases. Under the influence of interferon (IFN) γ, the IFNγ-inducible chemokines are secreted by lymphocytes, and by target cells (fibroblasts, epithelial cells, etc). In target tissues, Th1 lymphocytes are recruited; hence IFNγ is enhanced, which stimulates IFNγ-inducible chemokines (CXCL9, CXCL10, CXCL11) secretion reiterating the autoimmune process. Many studies have evaluated if blockade of ..

Thyroid Involvement in Hepatitis C Virus-Infected Patients with/without Mixed Cryoglobulinemia

Thyroid involvement is a common condition that can be recorded during the natural course of different systemic rheumatic diseases, including the mixed cryoglobulinemia (MC) syndrome or cryoglobulinemic vasculitis. MC is triggered by hepatitis C virus (HCV) chronic infection in the majority of cases; it represents the prototype of autoimmune-lymphoproliferative disorders complicating a significant proportion of patients with chronic HCV infection. HCV is both hepato- and lymphotropic virus responsible for a great number of autoimmune/lymphoproliferative and/or neoplastic disorders. The complex of HCV-related hepatic and extrahepatic manifestations, including MC and thyroid involvement, may be termed "HCV syndrome." Here, we describe the prevalence and clinico-serological characteristics of thyroid involvement, mainly autoimmune thyroiditis and papillary thyroid cancer, in patients with HCV syndrome with or without cryoglobulinemic vasculitis

Systemic Lupus Erythematosus and Thyroid Autoimmunity

Most of the studies present in the literature show a high prevalence, and incidence, of new cases of hypothyroidism and autoimmune thyroiditis (AT) in systemic lupus erythematosus (SLE) patients, overall in female gender. A limited number of cases of Graves' disease have been also reported in SLE patients, in agreement with the higher prevalence of thyroid autoimmunity. It has been also demonstrated that a Th1 predominance is associated with AT in SLE patients. Furthermore, a higher prevalence of papillary thyroid cancer has been recently reported in SLE, in particular in the presence of thyroid autoimmunity. However, studies in larger number of SLE patients are needed to confirm findings about thyroid cancer. On the whole, data from literature strongly suggest that female SLE patients, with a high risk (a normal but at the higher limit thyroid-stimulating hormone value, positive antithyroid peroxidase antibodies, a hypoechoic pattern, and small thyroid), should undergo periodic thyroid function follow-up, and appropriate treatments when needed. A careful thyroid monitoring would be opportune during the follow-up of these patients

Cytokines and HCV-Related Disorders

Cytokines are intercellular mediators involved in viral control and liver damage being induced by infection with hepatitis C virus (HCV). The complex cytokine network operating during initial infection allows a coordinated, effective development of both innate and adaptive immune responses. However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th)2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN)-gamma-inducible CXC chemokine ligand (CXCL)-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process