Thyroid autoimmune disorders and cancer

In the last decades, many studies conducted in vitro, and in vivo, have shown that thyroid autoimmunity and thyroid cancer (TC) (mainly papillary TC) can be concomitant, even if the exact mechanisms at the basis of this association are still not clear. Growing incidence of TC coincides with increased registration of autoimmune thyroid disorders (AITD) suggesting an association between those pathologies. Elevated TSH levels and thyroid autoimmunity were defined as independent risk factors for TC. However a lot of evidence suggests that autoimmunity and inflammation, per se, are risk factors for TC. The link between inflammation and TC involves multiple components of the immune system, extracellular matrix, stroma, and adipose tissue, with pro-tumoral activity of inflammation being opposed to anti-inflammatory effects, favoring protection against cancer progression. Within the tumor microenvironment, inflammatory cells, belonging both to innate (macrophages) and adaptive (lymphocytes) immune responses, are interconnected with fibroblasts, endothelial cells, adipocytes, and extracellular matrix through cytokines, chemokines and adipocytokines. Under the influence of transcriptional regulators (such as Nuclear Factor-kappa B, mitogen-activated protein kinases, or Phosphoinositide-3 kinase/protein kinase-B), oncogenes connected to the different subtypes of TC promote their farthermost proliferative effect on the tumor microenvironment. Future studies will be necessary to understand the connections between thyroid autoimmunity and cancer, also in order to design a tailored therapy for TC patients with AITD

The Stability of TSH, and Thyroid Hormones, in Patients Treated With Tablet, or Liquid Levo-Thyroxine

Approximately, 5% of the population is affected by hypothyroidism, mainly women and persons aged more than 60 years. After the diagnosis of hypothyroidism the usual therapy is tablet levothyroxine (L-T4), with a monitoring of the thyroid-stimulating hormone (TSH) level in primary hypothyroidism every 6-8 weeks and L-T4 is adjusted as necessary to reach an euthyroid state. Once TSH is stabilized in the normal range, it is recommended to conduct annual testing in the treated subjects to warrant suitable replacement. More recently advances regarding L-T4 treatment are the introduction of new oral formulations: the liquid solution, and soft gel capsule. The soft gel capsule permits a quick dissolution in the acid gastric pH. The liquid preparation does not require an acid gastric environment. Many pharmacokinetic studies demonstrated a more rapid absorption for the liquid L-T4, or capsule, than with tablet. Many studies have shown that the liquid, or capsule, formulations can overcome the interaction with foods, drugs or malabsorptive conditions, that are able to impair the tablet L-T4 absorption. Lately studies have suggested that liquid L-T4 can permit to maintain more efficiently normal TSH levels in hypothyroid patients in the long-term follow-up, than tablet L-T4, both in patients with malabsorptive states, and in those without malabsorption. Further large, prospective, longitudinal studies are needed to evaluate the stability of TSH, in hypothyroid patients treated with different L-T4 formulations

On the variability of HD 170699 - a possible COROT target

We present the analysis of the variability of HD 170699, a COROT star showing the characteristics of a non evolutionary Delta Scuti star with high rotational velocity. There is a clear period of 10.45 c/d with 5.29 mmag amplitude in the y filter. From the data, it can be seen that the star shows multi-periodicity and it is necessary to add more frequencies to adjust the observationsComment: To appear in RevMexAA(SC) in Proceedings of XII Reunion Regional Latinoamericana de la UAI held in Isla Margarita, Venezuela, October 22-26, 200

Nutraceuticals in thyroidology: A review of in vitro, and in vivo animal studies

Nutraceuticals are defined as a food, or parts of a food, that provide medical or health benefits, including the prevention of different pathological conditions, and thyroid diseases, or the treatment of them. Nutraceuticals have a place in complementary medicines, being positioned in an area among food, food supplements, and pharmaceuticals. The market of certain nutraceuticals such as thyroid supplements has been growing in the last years. In addition, iodine is a fundamental micronutrient for thyroid function, but also other dietary components can have a key role in clinical thyroidology. Here, we have summarized the in vitro, and in vivo animal studies present in literature, focusing on the commonest nutraceuticals generally encountered in the clinical practice (such as carnitine, flavonoids, melatonin, omega-3, resveratrol, selenium, vitamins, zinc, and inositol), highlighting conflicting results. These experimental studies are expected to improve clinicians’ knowledge about the main supplements being used, in order to clarify the potential risks or side effects and support patients in their use

Chemokines in hyperthyroidism

The term “hyperthyroidism” indicates a condition due to an exaggerate production of thyroid hormone; the most frequent cause is Graves’ disease (GD). We review cytokines and chemokines in hyperthyroidism, with a special focus in GD. In GD, recruited Th1 lymphocytes are responsible for enhanced IFN-γ and TNF-α production, which in turn stimulates Th1 chemokines release from thyrocytes, initiating and perpetuating the autoimmune process. Circulating levels of these chemokines are associated with the active phase of GD. Additional studies are necessary to investigate whether Th1 chemokines could be a novel therapeutic target in this disease

Cytokines as Targets of Novel Therapies for Graves’ Ophthalmopathy

Graves' disease (GD) is an organ-specific autoimmune disorder of the thyroid, which is characterized by circulating TSH-receptor (TSH-R) stimulating antibodies (TSAb), leading to hyperthyroidism. Graves' ophthalmopathy (GO) is one of GD extra-thyroidal manifestations associated with the presence of TSAb, and insulin-like growth factor-1 receptor (IGF-1R) autoantibodies, that interact with orbital fibroblasts. Cytokines are elevated in autoimmune (i.e., IL-18, IL-6) and non-autoimmune hyperthyroidism (i.e., TNF-α, IL-8, IL-6), and this could be associated with the chronic effects of thyroid hormone increase. A prevalent Th1-immune response (not related to the hyperthyroidism per se, but to the autoimmune process) is reported in the immune-pathogenesis of GD and GO; Th1-chemokines (CXCL9, CXCL10, CXCL11) and the (C-X-C)R3 receptor are crucial in this process. In patients with active GO, corticosteroids, or intravenous immunoglobulins, decrease inflammation and orbital congestion, and are considered first-line therapies. The more deepened understanding of GO pathophysiology has led to different immune-modulant treatments. Cytokines, TSH-R, and IGF-1R (on the surface of B and T lymphocytes, and fibroblasts), and chemokines implicated in the autoimmune process, are possible targets of novel therapies. Drugs that target cytokines (etanercept, tocilizumab, infliximab, adalimumab) have been tested in GO, with encouraging results. The chimeric monoclonal antibody directed against CD20, RTX, reduces B lymphocytes, cytokines and the released autoantibodies. A multicenter, randomized, placebo-controlled, double-masked trial has investigated the human monoclonal blocking antibody directed against IGF-1R, teprotumumab, reporting its effectiveness in GO. In conclusion, large, controlled and randomized studies are needed to evaluate new possible targeted therapies for GO

Hashimotos’ thyroiditis: Epidemiology, pathogenesis, clinic and therapy

Hashimoto's thyroiditis (HT), the most frequent autoimmune thyroid disorders (AITDs), is the leading cause of hypothyroidism in the iodine-sufficient areas of the world. About 20-30% of patients suffers from HT, whose cause is thought to be a combination of genetic susceptibility and environmental factors that causes the loss of immunological tolerance, with a consequent autoimmune attack to the thyroid tissue and appearance of the disease. The pathologic features of lymphocytic infiltration, especially of T cells, and follicular destruction are the histological hallmark of autoimmune thyroiditis (AIT), that lead to gradual atrophy and fibrosis. An important role in the immune-pathogenesis of AITDs is due to chemokines and cytokines. In about 20% of patients, AITDs are associated with other organ specific/systemic autoimmune disorders. Many studies have demonstrated the relationship between papillary thyroid cancer and AITD. The treatment of hypothyroidism, as result of AIT, consists in daily assumption of synthetic levothyroxine