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L'ipotiroidismo subclinico nei pazienti diabetici

Flavia Magri, Giulia Bendotti, Luca Chiovato
2020 L Endocrinologo  
Conflitto di interesse Gli autori Flavia Magri, Giulia Bendotti e Luca Chiovato dichiarano di non avere conflitti di interesse.  ... 
doi:10.1007/s40619-020-00799-9 fatcat:jtk7e6a7ibesvoapg5xxbqcoqa

Cardiovascular Risk in Patients with Subclinical Hypothyroidism

Leonidas H Duntas, Luca Chiovato
2014 US Endocrinology  
Subclinical hypothyroidism (SCH) has been associated with increased cardiovascular mortality due to adverse effects mainly on lipids and blood pressure (BP). There is evidence that SCH, especially in patients with thyroid-stimulating hormone (TSH) >10mU/l, may increase cardiovascular risk. Some uncertainty exists regarding the association of SCH with BP; however, that the coexistence of SCH with BP and hypercholesterolaemia has a negative cardiovascular impact is beyond doubt. Insulin
more » ... , by modulating various risk factors including coagulation, may potentially increase cardiovascular risk. Periodic health examinations including screening has been advised in patients >35 years of age, while treatment with thyroxine should be tailored to each patient.
doi:10.17925/use.2014.10.02.157 fatcat:xgls74kklrc3zglx3q4izxt26y

Cardiovascular Risk in Patients with Subclinical Hypothyroidism

Leonidas H Duntas, Luca Chiovato
2014 European Endocrinology  
Subclinical hypothyroidism (SCH) has been associated with increased cardiovascular mortality due to adverse effects mainly on lipids and blood pressure (BP). There is evidence that SCH, especially in patients with thyroid-stimulating hormone (TSH) >10mU/l, may increase cardiovascular risk. Some uncertainty exists regarding the association of SCH with BP; however, that the coexistence of SCH with BP and hypercholesterolaemia has a negative cardiovascular impact is beyond doubt. Insulin
more » ... , by modulating various risk factors including coagulation, may potentially increase cardiovascular risk. Periodic health examinations including screening has been advised in patients >35 years of age, while treatment with thyroxine should be tailored to each patient.
doi:10.17925/ee.2014.10.02.157 pmid:29872482 pmcid:PMC5983087 fatcat:3lztyh6oinb75mkcivofut6kwm

An overview of the pathogenesis of thyroid autoimmunity

Giulia Cogni, Luca Chiovato
the organ-specific enzyme thyroid peroxidase (TPO), and the TSH-receptor (TSH-R). 3 In the first years of this century, the sodium-iodide symporter was also shown to behave as a thyroid-specific auto-antigen. 4 More recently, autoantibodies to pendrin, an iodide transporter located at the apical pole of thyroid follicular cells, were identified in the majority of patients with HT and GD. 5
doi:10.1007/bf03401283 fatcat:onpgaxdnjzfx7kiqjs6mocds5i

Role of Chemokines in Endocrine Autoimmune Diseases

Mario Rotondi, Luca Chiovato, Sergio Romagnani, Mario Serio, Paola Romagnani
2007 Endocrine reviews  
Chemokines are a group of peptides of low molecular weight that induce the chemotaxis of different leukocyte subtypes. The major function of chemokines is the recruitment of leukocytes to inflammation sites, but they also play a role in tumoral growth, angiogenesis, and organ sclerosis. In the last few years, experimental evidence accumulated supporting the concept that interferon-␥ (IFN-␥) inducible chemokines (CXCL9, CXCL10, and CXCL11) and their receptor, CXCR3, play an important role in the
more » ... initial stage of autoimmune disorders involving endocrine glands. The fact that, after IFN-␥ stimulation, endocrine epithelial cells secrete CXCL10, which in turn recruits type 1 T helper lymphocytes expressing CXCR3 and secreting IFN-␥, thus perpetuating autoimmune inflammation, strongly supports the concept that chemokines play an important role in endocrine autoimmunity. This ar-ticle reviews the recent literature including basic science, animal models, and clinical studies, regarding the role of these chemokines in autoimmune endocrine diseases. The potential clinical applications of assaying the serum levels of CXCL10 and the value of such measurements are reviewed. Clinical studies addressing the issue of a role for serum CXCL10 measurement in Graves' disease, Graves' ophthalmopathy, chronic autoimmune thyroiditis, type 1 diabetes mellitus, and Addison's disease have been considered. The principal aim was to propose that chemokines, and in particular CXCL10, should no longer be considered as belonging exclusively to basic science, but rather should be used for providing new insights in the clinical management of patients with endocrine autoimmune diseases. (Endocrine Reviews 28: 492-520, 2007)
doi:10.1210/er.2006-0044 pmid:17475924 fatcat:elump7qs2ravhdphsiefhsgxpq

Selenium in the Treatment of Thyroid Diseases

Michele Marinò, Claudio Marcocci, Paolo Vitti, Luca Chiovato, Luigi Bartalena
2017 European Thyroid Journal  
/Marcocci/Vitti/Chiovato/ Bartalena Eur Thyroid J 2017;6:113-114 DOI: 10.1159/000456660  ... 
doi:10.1159/000456660 pmid:28589094 pmcid:PMC5422754 fatcat:wc5lcqsmnvfkblwszacjz7cibu

A male patient with acromegaly and breast cancer: treating acromegaly to control tumor progression

Paola Leporati, Rodolfo Fonte, Luca de Martinis, Alberto Zambelli, Flavia Magri, Lorenzo Pavesi, Mario Rotondi, Luca Chiovato
2015 BMC Cancer  
Acromegaly is a rare disease associated with an increased risk of developing cancer. Case presentation: We report the case of a 72-year-old man who was diagnosed with acromegaly (IGF-1 770 ng/ml) and breast cancer. Four years before he suffered from a colon-rectal cancer. Pituitary surgery and octreotide-LAR treatment failed to control acromegaly. Normalization of IGF-1 (97 ng/ml) was obtained with pegvisomant therapy. Four years after breast cancer surgery, 2 pulmonary metastases were detected
more » ... at chest CT. The patient was started on anastrozole, but, contrary to medical advice, he stopped pegvisomant treatment (IGF-I 453 ng/ml). Four months later, chest CT revealed an increase in size of the metastatic lesion of the left lung. The patient was shifted from anastrozole to tamoxifen and was restarted on pegvisomant, with normalization of serum IGF-1 levels (90 ng/ml). Four months later, a reduction in size of the metastatic lesion of the left lung was detected by CT. Subsequent CT scans throughout a 24-month follow-up showed a further reduction in size and then a stabilization of the metastasis. Conclusions: This is the first report of a male patient with acromegaly and breast cancer. The clinical course of breast cancer was closely related to the metabolic control of acromegaly. The rapid progression of metastatic lesion was temporally related to stopping pegvisomant treatment and paralleled a rise in serum IGF-1 levels. Normalization of IGF-1 after re-starting pegvisomant impressively reduced the progression of metastatic breast lesions. Control of acromegaly is mandatory in acromegalic patients with cancer.
doi:10.1186/s12885-015-1400-0 pmid:25962899 pmcid:PMC4436112 fatcat:xy4qgafkpbanxfwuvgkxujoyoy

Thyroid and Obesity: Not a One-Way Interaction

Mario Rotondi, Flavia Magri, Luca Chiovato
2011 Journal of Clinical Endocrinology and Metabolism  
D uring the last few decades, obesity [defined as a body mass index (BMI) Ն 30 kg/m 2 ] has become a major health concern, mainly in developed countries. In the United States, epidemiological data documented a progressive increase in the prevalence of obesity among children, adolescents, and adults, with potentially serious repercussions for their future health and for national health care expenditures (1). Morbid obesity (BMI Ն 40 kg/m 2 ) appears as a "problem in the problem," accounting for
more » ... early 5.0% of all obese patients (1). Recently, several clinical studies evaluated the issue of hormonal changes associated with obesity. Based on the notion that T 3 promotes thermogenesis and energy expenditure and also plays a role in regulating food intake and glucose and lipid metabolism, thyroid function was extensively investigated in obese subjects. Studies focused mainly on investigating whether an increase of body weight might be related to an underlying thyroid disturbance (2-4). An elevated serum concentration of TSH, suggesting subclinical hypothyroidism, was frequently reported in human obesity. Several investigations, mostly represented by cross-sectional population studies, demonstrated a positive correlation between serum levels of TSH and BMI. These data suggested that thyroid function (even within the normal range) could be one of several factors contributing to determining body weight in the general population (5). From this evidence, the hypothesis was formulated that even slightly elevated serum levels of TSH, indicating mild thyroid failure, might be involved in the pathogenesis of excess body weight, being associated with an increased occurrence of obesity (5). A recently published study by Marzullo et al. (4) supported this concept by suggesting that obesity is a risk factor for thyroid autoimmunity, thus establishing a link between the main cause of acquired thyroid failure and obesity. This investigation (4), as well as other studies supporting a role for autoimmune subclinical hypothyroidism in the pathogenesis of obesity, enrolled patients with any degree of body weight excess, ranging from grade I to grade III (morbid) obesity. Although autoimmune subclinical hypothyroidism is an appealing explanation for some cases of human obesity, other studies go to the opposite direction, supporting the concept that obesity by itself is responsible for the observed changes in circulating thyroid function parameters. The first demonstration that serum thyroid function parameters in humans might change after weight gain was provided nearly 30 yr ago. Danforth et al. (6) reported that the production rate of T 3 increased significantly after weight gain, with no change in the serum levels of T 4 and TSH. At variance with more recent studies, a TSH-increasing effect of weight gain was not reported in this early investigation. The low sensitivity of the TSH assay used in those days might account for this discrepancy (6). More recently, in a large cohort study (3) , which included patients specifically selected for having morbid obesity (BMI Ͼ 40 kg/m 2 ), we also found a high rate of isolated hyperthyrotropinemia; however, this abnormality was not associated with the typical features of autoimmune subclinical hypothyroidism, which are: 1) positive tests for thyroid antibodies; 2) female gender prevalence; and 3) decreased free T 4 (FT4)/free T 3 (FT3) ratio. Similar to our findings, an unexpectedly low prevalence of thyroid antibodies was also reported by Michalaki et al. (2) in their cohort of morbid obese patients with raised serum TSH. These observations would fit with data from the NHANES III survey, indicating that the prevalence of positive tests for thyroid antibodies does not differ in patients with morbid obesity and normal serum TSH as compared with the general population (7). Support for the concept that autoimmune thyroid diseases are not a major cause C o m m e n t a r y 344 J Clin Endocrinol Metab, February 2011, 96(2):344 -346 Downloaded from by guest on 25 July 2018 for the elevated serum TSH levels observed in morbid obese patients derives from both clinical and experimental studies. Progressive fat accumulation is associated with a parallel increase in serum TSH, whereas the FT3 to FT4 ratio was reported to be positively associated with BMI in obese patients. As stated by Biondi (8) in a recent editorial published in JCEM, this finding suggests a high conversion of T 4 to T 3 in patients with central fat obesity due to increased deiodinase activity as a compensatory mechanism for fat accumulation to improve energy expenditure. The hyperthyrotropinemia of obese patients was found to revert after weight loss induced either by bariatric surgery or by hypocaloric diet (9). This phenomenon implies that autoimmune destruction of thyrocytes was not responsible for the raised serum TSH. Even in well-powered studies suggesting that obesity would be secondary to changes in thyroid function, no association between thyroid hormone levels and BMI was found (5). A recently published investigation in rats demonstrated that animals fed a high-fat diet for 8 wk display an increase in their serum levels of TSH, which was not accompanied by changes in serum FT4 and FT3 (10). Thus, by recollecting previous data in the literature, two contrasting hypotheses emerge regarding the relationship between thyroid function and obesity: 1) obese patients are more prone to develop autoimmune hypothyroidism, and even mild thyroid failure contributes to the progressive increase in body weight, which ultimately results in overt obesity; and 2) obese patients often present an elevated serum level of TSH, which is not indicative of hypothyroidism-this hyperthyrotropinemia being the consequence, rather than the cause, of weight excess. Clinical and genetic evidence supports the concept that obesity does not represent a continuous entity and that obese patients with BMI lower or higher than 40 kg/m 2 (morbid obesity) are likely to harbor a different disease. A reasonable explanation for the discrepant views regarding the relationship between thyroid function and obesity might be that studies reporting a high rate of autoimmune hypothyroidism in obesity included a considerable proportion of patients with lower degrees of adiposity (BMI Ͻ 40 kg/m 2 ). This peculiarity might introduce a bias when investigating the relationship between thyroid function and body weight excess. Because hypothyroidism is a well-known cause of mild to moderate weight gain, autoimmune thyroiditis might be more frequent in obese patients who do not achieve extreme degrees of adiposity. The fact that most studies regarding thyroid function and obesity thyroid antibodies did not evaluate thyroid antibodies and that only a minority of these studies exclusively included patients with morbid obesity may well account for the tendency of the current literature toward the "hypothyroid hypothesis." In our view, neither of the two hypotheses alone is sufficient to explain the complex relationship between thyroid function and obesity. Currently available evidence points toward an involvement of both mechanisms. Indeed, it is conceivable that autoimmune hypothyroidism is more prevalent in patients with lower degrees of weight excess, whereas a high serum level of TSH, not indicative of thyroid failure, would predominate in morbidly obese patients. From a clinical point of view, obesity and mild thyroid failure are common diseases. It is debatable whether an obese patient should be diagnosed as having subclinical hypothyroidism based only on an elevated serum TSH level. Previous data from our group suggest that elevated serum TSH might not be enough for diagnosing subclinical hypothyroidism in patients with morbid obesity. Thus, it would seem reasonable to propose that circulating thyroid antibodies should always be measured in these patients to further support a diagnosis of autoimmune thyroid failure.
doi:10.1210/jc.2010-2515 pmid:21296993 fatcat:kf3ex2wjiffxvbeudjbiuch3xa

DIAGNOSIS OF ENDOCRINE DISEASE: IgG4-related thyroid autoimmune disease

Mario Rotondi, Andrea Carbone, Francesca Coperchini, Rodolfo Fonte, Luca Chiovato
2019 European Journal of Endocrinology  
IgG4-related disease (IgG4-RD) is fibro-inflammatory, immune-mediated, systemic disease, recognized as a defined clinical condition only in 2001. The prevalence of IgG4-RD is 6/100,000 but it is likely to be underestimated due to insufficient awareness of the disease. The diagnostic approach is complex because of the heterogeneity of clinical presentation and because of rather variable diagnostic criteria. Indeed, high concentrations of IgG4 in tissue and serum are not a reliable diagnostic
more » ... er. The spectrum of IgG4-RD also includes well-known thyroid diseases including Riedel's thyroiditis, Hashimoto's thyroiditis and its fibrotic variant, Graves' disease and Graves' orbitopathy. Results from clinical studies indicate that a small subset of patients with the above-mentioned thyroid conditions present some features suggestive for IgG4-RD. However, according to more recent views, the use of the term thyroid disease with an elevation of IgG4 rather than IgG4-related-thyroid diseases would appear more appropriate. Nevertheless, the occurrence of high IgG4 levels in patients with thyroid disease is relevant due to peculiarities of their clinical course.
doi:10.1530/eje-18-1024 fatcat:zlbag7sfkngyrbailquib5njga

Role of chemokine receptors in thyroid cancer and immunotherapy

Francesca Coperchini, Laura Croce, M Marinò, Luca Chiovato, Mario Rotondi
2019 Endocrine-Related Cancer  
Another example is targeting the CC-chemokine receptor 5 (CCR5) in order to inhibit the entrance of HIV in T cells through CCR5 binding (Johnson et al. 2005 , Gulick et al. 2008 , Rotondi & Chiovato 2011  ...  inflammation without inducing generalized immunosuppression in several clinical settings, such as cancer, autoimmune disease and allograph transplant (Rot & von Andrian 2004 , Rotondi et al. 2007 , Rotondi & Chiovato  ... 
doi:10.1530/erc-19-0163 pmid:31146261 fatcat:kgwnv3zxf5dzzgycr6dk26yoje

Thyroid Disrupting Effects of Old and New Generation PFAS

Francesca Coperchini, Laura Croce, Gianluca Ricci, Flavia Magri, Mario Rotondi, Marcello Imbriani, Luca Chiovato
2021 Frontiers in Endocrinology  
Copyright © 2021 Coperchini, Croce, Ricci, Magri, Rotondi, Imbriani and Chiovato. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).  ... 
doi:10.3389/fendo.2020.612320 pmid:33542707 pmcid:PMC7851056 fatcat:2ocqwix5uvhyrlsat56bon7mly

In memoriam Professor Aldo Pinchera (1934–2012)

Luigi Bartalena, Luca Chiovato, Gianfranco Fenzi, Claudio Marocci, Stefano Mariotti, Enio Martino, Furio Pacini, Paolo Vitti
2012 European Thyroid Journal  
doi:10.1159/000345651 fatcat:4bh5wcsohvcj7aszwdnha6soay

Role of Chemokines in Thyroid Cancer Microenvironment: Is CXCL8 the Main Player?

Mario Rotondi, Francesca Coperchini, Francesco Latrofa, Luca Chiovato
2018 Frontiers in Endocrinology  
Tumor-related inflammation does influence the biological behavior of neoplastic cells and ultimately the patient's outcome. With specific regard to thyroid cancer, the issue of tumor-associated inflammation has been extensively studied and recently reviewed. However, the role of chemokines, which play a crucial role in determining the immunophenotype of tumor-related inflammation, was not addressed in previous reviews on the topic. Experimental evidence shows that thyroid cancer cells actively
more » ... ecrete a wide spectrum of chemokines and, at least for some of them, solid scientific data support a role for these immune-active molecules in the aggressive behavior of the tumor. Our proposal for a review article on chemokines and thyroid cancer stems from the notion that chemokines, besides having the ability to attract and maintain immune cells at the tumor site, also produce several pro-tumorigenic actions, which include proangiogenetic, cytoproliferative, and pro-metastatic effects. Studies taking into account the role of CCL15, C-X-C motif ligand 12, CXCL16, CXCL1, CCL20, and CCL2 in the context of thyroid cancer will be reviewed with particular emphasis on CXCL8. The reason for focusing on CXCL8 is that this chemokine is the most studied one in human malignancies, displaying multifaceted pro-tumorigenic effects. These include enhancement of tumor cells growth, metastatization, and angiogenesis overall contributing to the progression of several cancers including thyroid cancer. We aim at reviewing current knowledge on the (i) ability of both normal and tumor thyroid cells to secrete CXCL8; (ii) direct/ indirect pro-tumorigenic effects of CXCL8 demonstrated by in vitro and in vivo studies specifically performed on thyroid cancer cells; and (iii) pharmacologic strategies proven to be effective for lowering CXCL8 secretion and/or its effects on thyroid cancer cells.
doi:10.3389/fendo.2018.00314 pmid:29977225 pmcid:PMC6021500 fatcat:6fvy6fao5vfuxlyqg6yp2p6adi

Serum negative autoimmune thyroiditis displays a milder clinical picture compared with classic Hashimoto's thyroiditis

Mario Rotondi, Luca de Martinis, Francesca Coperchini, Patrizia Pignatti, Barbara Pirali, Stefania Ghilotti, Rodolfo Fonte, Flavia Magri, Luca Chiovato
2014 European Journal of Endocrinology  
BackgroundDespite high sensitivity of current assays for autoantibodies to thyroperoxidase (TPO) and to thyroglobulin (Tg), some hypothyroid patients still present with negative tests for circulating anti-thyroid Abs. These patients usually referred to as having seronegative autoimmune thyroiditis (seronegative CAT) have not been characterized, and definite proof that their clinical phenotype is similar to that of patients with classic chronic autoimmune thyroiditis (CAT) is lacking.ObjectiveTo
more » ... compare the clinical phenotype of seronegative CAT (SN-CAT) and CAT as diagnosed according to a raised serum level of TSH with negative and positive tests for anti-thyroid Abs respectively.MethodsA case–control retrospective study enrolling 55 patients with SN-CAT and 110 patients with CAT was performed. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, Tg Abs, and TPO Abs were measured in all patients.ResultsPatients with SN-CAT displayed significantly lower mean levels of TSH (6.6±3.4 vs 10.2±9.8 μU/ml; P=0.009), higher mean FT4 levels (1.1±0.2 vs 0.9±0.2 ng/dl; P=0.0002), and similar FT3 levels when compared with CAT patients. Mean thyroid volume was significantly greater in patients with CAT when compared with SN-CAT patients (11.2±6.5 vs 8.1±3.7 ml; P=0.001). Logistic regression demonstrated that FT4 (0.123 (0.019–0.775); (P=0.026)) and thyroid volume (1.243 (1.108–1.394); (P=0.0002)) were significantly and independently related to the diagnosis (CAT/SN-CAT). Patients with SN-CAT had a similar prevalence of thyroid nodules and female gender but a lower prevalence of overt hypothyroidism (5.4 vs 20.9%; P=0.012) as opposed to patients with CAT.ConclusionsThese results suggest an autoimmune etiology of SN-CAT, which, however, seems to have a milder clinical course when compared with CAT.
doi:10.1530/eje-14-0147 pmid:24743395 fatcat:jz2ni4hi3zh4vlbtplxi37v64m

Vitamin D deficiency in patients with Graves' disease: probably something more than a casual association

Mario Rotondi, Luca Chiovato
2012 Endocrine (Basingstoke)  
Chiovato (&) Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri I.R.C.C.S., Laboratory for Endocrine Disruptors and Chair of Endocrinology, University of Pavia, Via S.  ... 
doi:10.1007/s12020-012-9776-y pmid:22926719 fatcat:73ehwussafhurb36cq6ovdu3ki
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