Publications by authors named "Laura Croce"

26 Publications

  • Page 1 of 1

A unique presentation of Graves' disease in a pregnant woman with severe hypothyroidism.

Gynecol Endocrinol 2022 Jun 20:1-5. Epub 2022 Jun 20.

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy.

Background: Graves' disease occurrence during pregnancy is not a frequent event, showing an incidence of 0.2-0.4% in unselected pregnant women. Depending on their functional properties, TSH-receptor antibodies can induce hypothyroidism or hyperthyroidism. Recognizing the signs of altered thyroid function is essential to prevent possible complications on the fetus.

Materials And Methods: The case of a pregnant woman without previous history of thyroid disease presenting with severe overt hypothyroidism during the first trimester is reported. Levothyroxine therapy was started and 6 weeks later overt hyperthyroidism was observed. TRAb were detected at high titers. Levothyroxine was withdrawn and low dose methimazole was started. Serial obstetric ultrasound scans were negative for indirect signs of fetal thyroid dysfunctions and no fetal goiter was visualized throughout pregnancy. Spontaneous delivery occurred without complications at 39 weeks of gestation. In the post-partum, severe overt hypothyroidism recurred, thus methimazole was discontinued and levothyroxine was restarted. TRAb persisted at high levels. The infant experienced a transient thyrotoxicosis, which fully resolved in three months with normalization of thyroid function and negativization of TRAb levels.

Results: The present case report allows us to overview the challenges related to the management of hypo and hyperthyroidism in patients with high TRAb levels, requiring strict monitoring aimed at early detection of both maternal and fetal consequences.

Conclusions: This case underlines the importance of close follow-up and the need of collaboration in a multidisciplinary team when Graves's disease is diagnosed in a pregnant woman to prevent adverse neonatal outcomes.
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http://dx.doi.org/10.1080/09513590.2022.2087216DOI Listing
June 2022

Vitamin D Reduces Thyroid Cancer Cells Migration Independently From the Modulation of CCL2 and CXCL8 Chemokines Secretion.

Front Endocrinol (Lausanne) 2022 13;13:876397. Epub 2022 Apr 13.

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy.

Background: Vitamin D3 is largely involved in the regulation of calcium homeostasis. More recently, it was demonstrated that vitamin D exerts several beneficial effects against cancer progression through several mechanisms, including the reduction of cancer cells proliferation and migration. CXCL8 and CCL2 are two chemokines secreted by thyroid tumor cells. In the thyroid tumor microenvironment, these chemokines exert several pro-tumorigenic effects including the one to increase the metastatic potential. The aim of the present study was to investigate if vitamin D could modulate both thyroid cancer cell migration and their ability to secrete CCL2 and CXCL8.

Methods: TPC-1 (RET/PTC rearranged) and 8505C (BRAFV600e mutated) thyroid cancer cell lines were treated with increasing concentrations of 1,25-OH-vitamin D3 (0-1,000 nM). Cell viability was assessed by WST-1 assay, cell migration was evaluated by transwell-migration chamber system, and CCL2 and CXCL8 levels were measured in the cell culture supernatants by ELISA.

Results: Vitamin D did not affect cell viability but reduced, in a dose-dependent and significant manner, thyroid cancer cell migration (ANOVAs < 0.05 for both TPC-1 and 8505C). Vitamin D differently modulated the secretion of CCL2 and CXCL8, by significantly inhibiting the secretion of CCL2 in both thyroid cancer cell lines and inhibiting the secretion of CXCL8 only in TPC-1 (ANOVAs < 0.05).

Conclusions: Vitamin D treatment of thyroid cancer cell lines reduces cell migration independently from the inhibition of the secretion of pro-tumorigenic chemokines. Future studies specifically designed at clarifying the pathways involved in the different inhibitory effects of vitamin D on CCL2 and CXCL8 in thyroid cancer cells appear worthwhile.
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http://dx.doi.org/10.3389/fendo.2022.876397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044905PMC
May 2022

COVID-19-Associated Subacute Thyroiditis: Evidence-Based Data From a Systematic Review.

Front Endocrinol (Lausanne) 2021 29;12:707726. Epub 2021 Sep 29.

Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Istituti Clinici Scientifici Maugeri Istituto di Ricovero e Cura a Carattere Scientifico, (IRCCS), Pavia, Italy.

Subacute thyroiditis (SAT) is a thyroid disease of viral or post-viral origin. Whether SAT represents a complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still unclear. Our aim was to systematically review the literature to 1) explore the size of the literature about SAT in COVID-19 and 2) evaluate the clinical characteristics of SAT. PubMed/MEDLINE, Embase, and Scopus were searched until April 20, 2021. Original papers, case reports, and case series reporting SAT in COVID-19 patients were included. Authors and their country, journal, year of publication, COVID-19 and SAT clinical presentation, thyroid function, therapy, and follow-up data were extracted. Nineteen papers (17 case reports and 2 case series) were included, describing 27 patients, 74.1% females, aged 18 to 69 years. COVID-19 was diagnosed by nasopharyngeal swab in 66.7% cases and required hospitalization in 11.1%. In 83.3% cases, SAT occurred after COVID-19. Neck pain was present in 92.6% cases and fever in 74.1%. Median TSH, fT3, and fT4 were 0.01 mU/l, 10.79 pmol/l, and 27.2 pmol/l, respectively. C-reactive-protein and erythrocyte sedimentation rate were elevated in 96% of cases. Typical ultrasonographic characteristics of SAT were observed in 83.3% of cases. Steroids were the most frequent SAT therapy. Complete remission of SAT was recorded in most cases. In conclusion, the size and quality of published data of SAT in COVID-19 patients are poor, with only case reports and case series being available. SAT clinical presentation in COVID-19 patients seems to be similar to what is generally expected.
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http://dx.doi.org/10.3389/fendo.2021.707726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511511PMC
October 2021

Modulation of ACE-2 mRNA by inflammatory cytokines in human thyroid cells: a pilot study.

Endocrine 2021 12 5;74(3):638-645. Epub 2021 Jul 5.

Laboratory for Endocrine Disruptors, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, 27100, Pavia, PV, Italy.

Introduction: Angiotensin-converting-enzyme-2 (ACE-2) was demonstrated to be the receptor for cellular entry of SARS-CoV-2. ACE-2 mRNA was identified in several human tissues and recently also in thyroid cells in vitro.

Purpose: Aim of the present study was to investigate the effect of pro-inflammatory cytokines on the ACE-2 mRNA levels in human thyroid cells in primary cultures.

Methods: Primary thyroid cell cultures were treated with IFN-γ and TNF-α alone or in combination for 24 h. ACE-2 mRNA levels were measured by RT-PCR. As a control, the levels of IFN-γ inducible chemokine (CXCL10) were measured in the respective cell culture supernatants.

Results: The mean levels of ACE-2 mRNA increased after treatment with IFN-γ and TNF-α in all the thyroid cell preparations, while the combination treatment did not consistently synergically increase ACE-2-mRNA. At difference, CXCL10 was consistently increased by IFN-γ and synergically further increased by the combination treatment with IFN-γ + TNF-α, with respect to IFN-γ alone.

Conclusions: The results of the present study show that IFN-γ and, to a lesser extent TNF-α consistently increase ACE-2 mRNA levels in NHT primary cultures. More interestingly, the combined stimulation (proven to be effective according to the synergic effect registered for CXCL10) produces different responses in terms of ACE-2 mRNA modulation. These results would suggest that elevated levels of pro-inflammatory cytokines could facilitate the entering of the virus in cells by further increasing ACE-2 expression and/or account for the different degree of severity of SARS-COV-2 infection. This hypothesis deserves to be confirmed by further specific studies.
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http://dx.doi.org/10.1007/s12020-021-02807-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256224PMC
December 2021

The diagnostic accuracy of fine-needle aspiration cytology for thyroid nodules is not affected by coexistent chronic autoimmune thyroiditis: results from a cyto-histological series of patients with indeterminate cytology.

Eur J Endocrinol 2021 Jun 28;185(2):201-208. Epub 2021 Jun 28.

Laboratory for Endocrine Disruptors, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.

Objective: Indeterminate cytological result at fine-needle aspiration cytology (FNAC) remains a clinical challenge for endocrinologists. Aim of the present study was to evaluate whether a coexistent chronic autoimmune thyroiditis (CAT) might affect the diagnostic accuracy of fine-needle aspiration cytology for thyroid nodules.

Design And Methods: A retrospective cohort study was designed including all nodules receiving an indeterminate cytology result (TIR3A or TIR3B) undergoing thyroid surgery and subsequent histological confirmation. Patients were stratified into two groups according to the presence or absence of CAT. The hypothesis to be tested was whether follicular cell alterations induced by CAT might increase the rate of indeterminate cytological results in histologically benign thyroid nodules. Additional control groups were represented by nodules with determinate cytology, either benign (TIR 2) or malignant (TIR5).

Results: One hundred and eighty-nine indeterminate thyroid nodules were included (67 TIR3A and 122 TIR3B). At post-surgical histology, 46 nodules (24.3%) were malignant. No significant differences were observed in the rate of histologically proven malignancy between patients without CAT and patients with CAT in the TIR3B (29.4% vs 32.4%; P = 0.843) nor TIR3A (13.0% vs 11.4%; P = 1.000) nodules. The rate of coexistent CAT was similar between TIR3B and TIR5 nodules harboring PTC at histology (30.4% vs 39.4%, P = 0.491) and between indeterminate nodules and a control group of TIR2 nodules (39.2% vs 37.0%; P = 0.720).

Conclusions: The similar rates of histologically proven malignancy found in cytologically indeterminate nodules in the presence or absence of concomitant CAT would not support that CAT itself affects the diagnostic accuracy of fine-needle aspiration cytology.
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http://dx.doi.org/10.1530/EJE-21-0094DOI Listing
June 2021

The cytokine storm in COVID-19: Further advances in our understanding the role of specific chemokines involved.

Cytokine Growth Factor Rev 2021 04 8;58:82-91. Epub 2021 Jan 8.

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, 27100 Pavia PV, Italy; Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia PV, Italy. Electronic address:

SARS-COV-2 infection represents the greatest pandemic of the world, counting daily increasing number of subjects positive to the virus and, sadly, increasing number of deaths. Current studies reported that the cytokine/chemokine network is crucial in the onset and maintenance of the "cytokine storm", the event occurring in those patients in whom the progression of COVID-19 will progress, in most cases, to a very severe and potentially threatening disease. Detecting a possible "immune signature" in patients, as assessed by chemokines status in patients with COVID-19, could be helpful for individual risk stratification for developing a more or less severe clinical course of the disease. The present review is specifically aimed at overviewing current evidences provided by in vitro and in vivo studies addressing the issue of which chemokines seems to be involved, at least at present, in COVID-19. Currently available experimental and clinical studies regarding those chemokines more deeply studied in COVID-19, with a specific focus on their role in the cytokine storm and ultimately with their ability to predict the clinical course of the disease, will be taken into account. Moreover, similarities and differences between chemokines and cytokines, which both contribute to the onset of the pro-inflammatory loop characterizing SARS-COV-2 infection, will be briefly discussed. Future studies will rapidly accumulate in the next months and their results will hopefully provide more insights as to the complex physiopathology of COVID-19-related cytokine storm. This will likely make the present review somehow "dated" in a short time, but still the present review provides an overview of the scenario of the current knowledge on this topic.
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http://dx.doi.org/10.1016/j.cytogfr.2020.12.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837329PMC
April 2021

Thyroid Disrupting Effects of Old and New Generation PFAS.

Front Endocrinol (Lausanne) 2020 19;11:612320. Epub 2021 Jan 19.

Laboratory for Endocrine Disruptors, Unit of Internal Medicine and Endocrinology, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.

Per- and polyfluoroalkyl substances (PFAS) represent a group of synthetic compounds widely used in industry plants due to their low grade of degradation, surfactant properties, thermic and flame resistance. These characteristics are useful for the industrial production, however they are also potentially dangerous for human health and for the environment. PFAS are persistent pollutants accumulating in waters and soil and recoverable in foods due to their release by food packaging. Humans are daily exposed to PFAS because these compounds are ubiquitous and, when assimilated, they are difficult to be eliminated, persisting for years both in humans and animals. Due to their persistence and potential danger to health, some old generation PFAS have been replaced by newly synthesized PFAS with the aim to use alternative compounds presumably safer for humans and the environment. Yet, the environmental pollution with PFAS remains a matter of concern worldwide and led to large-scale epidemiological studies both on plants' workers and on exposed people in the general population. In this context, strong concern emerged concerning the potential adverse effects of PFAS on the thyroid gland. Thyroid hormones play a critical role in the regulation of metabolism, and thyroid function is related to cardiovascular disease, fertility, and fetal neurodevelopment. , data, and epidemiological studies suggested that PFASs may disrupt the thyroid hormone system in humans, with possible negative repercussions on the outcome of pregnancy and fetal-child development. However, data on the thyroid disrupting effect of PFAS remain controversial, as well as their impact on human health in different ages of life. Aim of the present paper is to review recent data on the effects of old and new generation PFAS on thyroid homeostasis. To this purpose we collected information from studies, animal models, and data on exposed workers, general population, and pregnant women.
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http://dx.doi.org/10.3389/fendo.2020.612320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851056PMC
May 2021

Basal and longitudinal changes in serum levels of TSH in morbid obese patients experiencing failure or success of dietary treatment.

Eat Weight Disord 2021 Aug 17;26(6):1949-1955. Epub 2020 Oct 17.

Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Department of Internal Medicine and Therapeutics, Istituti Clinici Scientifici Maugeri IRCCS, University of Pavia, Via S. Maugeri 4, 27100, Pavia, Italy.

Purpose: The relationship between thyroid function and obesity is a widely investigated one. The impact of thyroid hormones in determining the outcome of dietary/lifestyle interventions remains to be fully elucidated. The aim of this study was to compare basal and post dietary-intervention circulating thyroid-function parameters, lipid profile and fasting-glucose in euthyroid obese patients according to a success or failure of a dietary intervention program.

Methods: In a retrospective longitudinal case-control study we enrolled 50 euthyroid obese patients who experienced a success in dietary intervention, as defined by a BMI reduction of at least 5% from baseline (Success Group) and 50 sex and age-matched euthyroid obese patients who experienced failure in dietary intervention as defined by either stable or increased body weight throughout the follow-up (Failure Group). Serum thyroid function parameters and metabolic profile at baseline and at the end of follow-up were collected.

Results: At baseline, the two groups showed similar BMI, total-cholesterol, HDL-cholesterol and fasting-blood-glucose, but patients in Success Group had a significantly higher TSH as compared with Failure Group (2.20 ± 0.97 vs 1.66 ± 0.73, respectively, p < 0.001). Throughout a mean follow-up of 21.4 months TSH significantly decreased in Success Group (2.20 ± 0.97 vs 2.06 ± 0.98; p = 0.029) and increased in Failure Group (1.63 ± 0.72 vs 2.01 ± 0.99; p < 0.001). Multiple regression analysis showed that the outcome of the dietary intervention was significantly and independently related to baseline BMI (0.925; 0.861-0.993), age (0.957; 0.922-0.993), TSH (0.531; 0.290-0.973) and TSH-changes (1.011; 1.000-1.022) during follow-up.

Conclusions: Baseline serum TSH level is related to the final outcome of a dietary intervention program in obese patients.

Level Of Evidence Iii: Evidence obtained from a retrospective cohort or case-control analytic studies.
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http://dx.doi.org/10.1007/s40519-020-01043-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292288PMC
August 2021

Performance of the ACR TI-RADS and EU TI-RADS scoring systems in the diagnostic work-up of thyroid nodules in a real-life series using histology as reference standard.

Eur J Endocrinol 2020 Nov;183(5):521-528

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy.

Objective: The ultrasonographic scores EU TI-RADS and ACR TI-RADS were introduced to give the clinicians indications for fine needle aspiration cytology (FNAC). The predictive role of these scores was never evaluated and compared in a surgical series of patients. The aim of this study was to evaluate the ex post diagnostic accuracy of EU TI-RADS and ACR TI-RADS in a real-life series of thyroidectomized patients and to evaluate the 'missing' thyroid cancer following the operational indications of these scores.

Design: Retrospective monocentric cohort study.

Methods: In total, 255 patients (harboring 304 nodules) undergoing thyroidectomy for benign and malignant thyroid conditions were enrolled. The prevalence of thyroid malignancy for each class of ACR TI-RADS and EU TI-RADS, their diagnostic accuracy, the number of 'unnecessary' FNAC and the number of 'missed' cancers were evaluated.

Results: ACR TI-RADS and EU TI-RADS score had similar and satisfactory accuracy values for predicting thyroid malignancy (AUC: 0.835 for ACR TI-RADS vs 0.827 for EU TI-RADS). The ACR TI-RADS and EU TI-RADS categories (suspicious vs non-suspicious), age, sex and presence of a single nodule significantly and independently predicted the presence of malignancy in a logistic regression model. An ex post analysis according to the indications for FNAC for each score indicated that 31 and 16 cases of cancer would have been missed by ACR TI-RADS and EU TI-RADS scores, respectively.

Conclusions: ACR TI-RADS and EU TI-RADS display a good performance in predicting thyroid cancer when histology is taken as reference standard, but additional clinical judgement is required to decide the indication for FNAC.
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http://dx.doi.org/10.1530/EJE-20-0682DOI Listing
November 2020

Patients with chronic autoimmune thyroiditis are not at higher risk for developing clinically overt thyroid cancer: a 10-year follow-up study.

Eur J Endocrinol 2020 Sep;183(3):317-323

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy.

Objective: The association between chronic autoimmune thyroiditis (CAT) and differentiated thyroid cancer (DTC) remains controversial. The incidence of DTC increases when screening procedures are implemented, as typically occurs in CAT patients being routinely submitted to thyroid ultrasound (US). The aim of this study was to longitudinally evaluate the long-term development of DTC in patients with CAT.

Design And Methods: A retrospective longitudinal cohort study was designed. For the study, 510 patients with chronic autoimmune thyroiditis (CAT) with a 10-year follow-up were enrolled. Patients were divided in two groups according to the presence (CAT+ NOD+; n = 115) or absence (CAT+ NOD-; n = 395) of co-existent nodules at diagnosis. The main outcome measures were appearance of new thyroid-nodules and development of DTC during follow-up.

Results: During a 10-year median follow-up period, new thyroid-nodules were detected in 34/115 (29.5%) patients in the CAT+ NOD+ group and in 41/395 (10.3%) in the CAT+ NOD- group (P < 0.001). Logistic regression analysis showed that thyroid-volume at diagnosis and belonging to the CAT+ NOD+ group significantly predicted the appearance of a new thyroid nodule during follow-up, independently of baseline age and sex. Among the 75 patients experiencing the appearance of a new nodule, 27 (39%) met the criteria for fine-needle-aspiration-cytology (FNAC). A benign cytological diagnosis was rendered in all cases.

Conclusions: In our series of CAT patients, the appearance of new thyroid-nodules was frequent, but none of them were found to be malignant. The presence of CAT appears to be associated with a negligible risk of developing clinically overt DTC.
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http://dx.doi.org/10.1530/EJE-20-0350DOI Listing
September 2020

Nocturnal haemodialysis is associated with a reduced occurrence of low triiodothyronine serum levels in haemodialysed patients.

Clin Kidney J 2020 Jun 10;13(3):450-460. Epub 2020 Feb 10.

Nephrology Dialysis and Transplantation Unit, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Background: End-stage renal disease (ESRD) is associated with a broad spectrum of morphological and functional thyroid disorders. Recent studies have shown that low free triiodothyronine (fT3) levels are related to inflammatory status and endothelial activation in ESRD patients on haemodialysis (HD). Limited data exist about a possible relationship between dialysis regimen, namely long nocturnal haemodialysis (LNHD), and thyroid function parameters. The aim of this study was to evaluate the relationship between dialysis regimen and thyroid function, and consequently with the main patient outcomes.

Methods: To this purpose, we performed a retrospective, single-centre cohort study including 220 incident chronic HD patients treated during an 8-year period (from January 2010 to December 2017). The main clinical and haematochemical parameters, including thyroid function, were evaluated and related to the main patient outcomes.

Results: Patients with low fT3 levels (<3.05 ng/mL) showed significantly lower survival rates than patients with normal fT3 levels (>3.05 ng/mL) (P<0.001), although there were no substantial differences in the demographic and clinical characteristics between the two groups. After propensity score 1:3 matching of 25 patients treated with nocturnal HD to 75 patients treated with diurnal HD, LNHD patients showed significantly higher survival rates (88.0% versus 61.3%, P0.001) and lower incidence of cardiovascular events than patients on diurnal dialysis (8.0% versus 40.0%, P0.001). Moreover, an 8-year time-dependent analysis showed that at any time, except for baseline, the rate of patients with fT3 levels >3.05 ng/mL was significantly higher in LNHD patients than in patients treated with diurnal dialysis.

Conclusions: Our data suggest that the application of alternative dialysis regimens, also reducing the frequency of low T3, could ameliorate outcomes and therefore reduce the incidence of cardiovascular events in HD patients.
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http://dx.doi.org/10.1093/ckj/sfaa003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367136PMC
June 2020

The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system.

Cytokine Growth Factor Rev 2020 06 11;53:25-32. Epub 2020 May 11.

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, 27100 Pavia, PV, Italy; Department of Internal Medicine and Therapeutics, University of Pavia, 27100 Pavia, PV, Italy. Electronic address:

In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called "cytokine storm" an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.
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http://dx.doi.org/10.1016/j.cytogfr.2020.05.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211650PMC
June 2020

Adverse effects of in vitro GenX exposure on rat thyroid cell viability, DNA integrity and thyroid-related genes expression.

Environ Pollut 2020 Sep 10;264:114778. Epub 2020 May 10.

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, 27100, Pavia, Italy; Department of Internal Medicine and Therapeutics, University of Pavia, 27100, Pavia, Italy. Electronic address:

The hexafluoropropylene-oxide-dimer-acid (GenX) is a short-chain perfluoroalkyl substance that was recently introduced following the phase out of PFOA, as an alternative for the process of polymerization. GenX was detected at high concentrations in rivers, drinking water and in sera of exposed workers and recent findings suggested its potential dangerousness for human health. Aim of the study was to assess the consequences of GenX exposure on in vitro thyroid cells with particular attention to the effects on cell-viability, proliferation, DNA-damage and in the thyroid-related genes expression. FRTL-5 rat-thyroid cell line were incubated with increasing concentrations of GenX for 24 h, 48 h and 72 h to assess cell viability by WST-1. DNA-damage was assessed by comet assay and further confirmed by micronucleus assay. The proliferation of survived cells was measured by staining with crystal violet and evaluation of its optical density after incubation with SDS. Changes in TTF-1, Pax8, Tg, TSH-R, NIS and TPO genes expression were evaluated by RT-PCR. GenX exposure reduced FRTL-5 viability in a time and dose-dependent manner (24 h: ANOVA F = 22.286; p < 0.001; 48 h: F = 43.253, p < 0.001; 72 h: F = 49.708, p < 0.001). Moreover, GenX exerted a genotoxic effect, as assessed by comet assay (significant increase in tail-length, olive-tail-moment and percentage of tail-DNA) and micronucleus assay, both at cytotoxic and non-cytotoxic concentrations. Exposure to GenX at concentrations non-cytotoxic exerted a significant lowering of the expression of the regulatory gene TTF-1 (p < 0.05 versus untreated) and higher expression of Pax-8 (p < 0.05 versus untreated) and a down-regulation of NIS (p < 0.05 versus untreated). In addition, cells survived to GenX exposure showed a reduced re-proliferation ability (24 h: ANOVA F = 11,941; p < 0,001; 48 h: F = 93.11; p < 0.001; 72 h F = 21.65; p < 0.001). The exposure to GenX produces several toxic effects on thyroid cells in vitro. GenX is able to promote DNA-damage and to affect the expression of thyroid transcription-factor genes.
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http://dx.doi.org/10.1016/j.envpol.2020.114778DOI Listing
September 2020

Graves' Disease and the Post-partum Period: An Intriguing Relationship.

Front Endocrinol (Lausanne) 2019 10;10:853. Epub 2019 Dec 10.

Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, Italy.

The post-partum period is an immunologically peculiar period in a woman's life. Indeed, most of the pregnancy-related immune changes gradually revert in the 12 months following delivery. Although the post-partum period has long been identified as a period of aggravation of autoimmune thyroid diseases, most of the currently available studies took into account the relationship between post-partum and autoimmune thyroiditis. More recently, the potential repercussions of the post-partum period on Graves' disease were also taken into account. The present mini review will briefly overview the most recent advances in our knowledge of the immunology of the post-partum period in relation with the potential repercussions on the clinical course of Graves' disease. Moreover, some peculiar aspects of post-partum Graves' disease in terms of clinical and biochemical presentation, diagnostic challenges, and specific therapeutic considerations also taking into account the recommendation of the latest clinical guidelines on the management of thyroid diseases in pregnancy will be overviewed.
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http://dx.doi.org/10.3389/fendo.2019.00853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914725PMC
December 2019

Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy.

J Immunol Res 2019 5;2019:8483650. Epub 2019 Nov 5.

Clinical Pathology Unit and Center for Molecular Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy.

Primary membranous nephropathy (PMN) is a renal-specific autoimmune disease caused by circulating autoantibodies that target glomerular podocyte antigens (PLA2R/THSD7A). However, very little is known on the molecular mechanisms controlling B cell response in this nephropathy. The present study was aimed at correlating the serum levels of B cell activators BAFF/BLyS and APRIL with the presence of anti-PLA2R antibodies in PMN patients and with long-term clinical outcome. To this aim, 51 patients with anti-PLA2R-positive biopsy-proven PMN and nephrotic range proteinuria (>3.5 g/24 hours) were enrolled between January 2009 and December 2015 and treated with conventional 6-month immunosuppressive therapy. After 6 months, 29 patients (56.9%) cleared circulating anti-PLA2R, while in remaining 22 (43.1%), they persisted. Intriguingly, in the first group, baseline serum levels of BAFF/BLyS and APRIL were significantly lower than those in the second one. Moreover, after 6 months of immunosuppressive therapy, an overall reduction in both cytokine serum levels was observed. However, in PMN patients with anti-PLA2R clearance, this reduction was more prominent, as compared with those with anti-PLA2R persistence. When related to clinical outcome, lower baseline BAFF/BLyS (<6.05 ng/mL) and APRIL (<4.20 ng/mL) serum levels were associated with significantly higher probability to achieve complete or partial remission after 24-month follow-up. After dividing the entire study cohort into three groups depending on both cytokine baseline serum levels, patients with both BAFF/BLyS and APRIL below the cut-off showed a significantly higher rate of complete or partial remission as compared with patients with only one cytokine above the cut-off, while the composite endpoint was achieved in a very low rate of patients with both cytokines above the cut-off. Taken together, these results provide new insights into the role of BAFF/BLyS and APRIL in both the pathogenesis of anti-PLA2R-positive PMN and the response to immunosuppressive therapy.
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http://dx.doi.org/10.1155/2019/8483650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874868PMC
April 2020

The multifaceted anti-cancer effects of BRAF-inhibitors.

Oncotarget 2019 Nov 12;10(61):6623-6640. Epub 2019 Nov 12.

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, University of Pavia, Pavia, Italy.

The BRAF gene is commonly involved in normal processes of cell growth and differentiation. The BRAF (V600E) mutation is found in several human cancer, causing an increase of cell proliferation due to a modification of the ERK/MAPK-signal cascade. In particular, BRAFV600E mutation is found in those melanoma or thyroid cancer refractory to the common therapy and with a more aggressive phenotype. BRAF V600E was found to influence the composition of the so-called tumour microenvironment modulating both solid (immune-cell infiltration) and soluble (chemokines) mediators, which balance characterize the ultimate behaviour of the tumour, making it more or less aggressive. In particular, the presence of BRAFV600E mutation would be associated with a change of this balance to a more aggressive phenotype of the tumour and a worse prognosis. The investigation of the possible modulation of those components of tumour microenvironment is nowadays object of several studies as a new potential target therapy in those more complicated cases. At present several clinical trials both in melanoma and thyroid cancer are using BRAF-inhibitors with encouraging results, which are derived also from numerous pre-clinical studies aimed at evaluate the possible modulation of immune-cell density and of specific pro-tumorigenic chemokine secretion (CXCL8 and CCL2) by several BRAF-inhibitors in the context of melanoma and thyroid cancer. This review will encompass and studies which investigated the modulation of the tumour microenvironment by BRAF-inhibitors, highlighting also the most recent clinical trials with a specific focus on melanoma and thyroid cancer.
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http://dx.doi.org/10.18632/oncotarget.27304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859927PMC
November 2019

The anti-cancer effects of phenformin in thyroid cancer cell lines and in normal thyrocytes.

Oncotarget 2019 Nov 5;10(60):6432-6443. Epub 2019 Nov 5.

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy.

Phenformin is a biguanide drug which, besides the original anti-diabetic effect, also exerts anti-cancer effects. The aim of this study was to further characterize these latter in terms of both cell-viability and modulation of the secretion of the pro-tumorigenic chemokine CXCL8. Normal human thyrocytes in primary cultures (NHT) and thyroid cancer cell lines, TPC-1 and 8505C (RET/PTC and BRAFV600E mutated, respectively) were treated with increasing concentrations of phenformin at different times. Cell-viability was assessed by WST-1 and further characterized by AnnexinV/PI staining and cell proliferation colony-assay. CXCL8 levels were measured in cell supernatants. Phenformin reduced cell-viability in TPC-1 and 8505C and their ability to form colonies. In NHT cells, phenformin affected cell-viability only at the maximal dose but interestingly it inhibited CXCL8 secretion at all the concentrations not affecting cell-viability. Phenformin had no effect on CXCL8 secretion in thyroid cancer cell lines. Thus, phenformin exerts anti-cancer effects on both cancer cells (cell death induction) and surrounding normal cells (inhibition of CXCL8 secretion). These results highlight that the anti-cancer effects of phenformin are multifaceted and effective on both solid and soluble components of the tumor-microenvironment.
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http://dx.doi.org/10.18632/oncotarget.27266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849649PMC
November 2019

Risk factors, awareness of disease and use of medications in a deprived population: differences between indigent natives and undocumented migrants in Italy.

J Public Health (Oxf) 2021 06;43(2):302-307

Department of Clinical Sciences and Community Health (Pharmacology), University of Milan, 20129 Milan, Italy.

Background: Undocumented migrants experience many health problems; a comparison with a suitable control group of natives living in the same socio-economic conditions is still lacking.

Methods: Demographic data and data on risk factors, chronic conditions and dietary habits were obtained for 6933 adults (2950 Italians and 3983 undocumented migrants) receiving medical assistance from 40 non-governmental organizations all over the country.

Results: Attributed to the fact that these were unselected groups, differences were found in their demographic features, the main ones being their marital status (singles: 50.5% among Italians and 42.8% among migrants; P < 0.001). Smokers were more frequent among Italians (45.3% versus 42.7% P = 0.03); the same happened with hypertension (40.5% versus 34.5% P < 0.001). Migrants were more often overweight (44.1% versus 40.5% P < 0.001) and reporting a chronic condition (20.2% versus 14.4% P < 0.001). Among those on medications (n = 1354), Italians were fewer (n = 425) and on different medications. Differences emerged also in dietary habits.

Conclusions: Differences in health conditions exist between native-borns and undocumented migrants, not because of a bias related to socio-economic conditions. Further studies are needed to design sustainable health policies and tailored prevention plans.
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http://dx.doi.org/10.1093/pubmed/fdz123DOI Listing
June 2021

Thyroid hormone therapy for subclinical hypothyroidism.

Endocrine 2019 Oct 15;66(1):27-34. Epub 2019 Oct 15.

Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Department of Internal Medicine and Therapeutics, Istituti Clinici Scientifici Maugeri IRCCS, University of Pavia, Via S. Maugeri, 27100, Pavia, Italy.

Subclinical Hypothyroidism (SCH) is defined as a raised level of serum TSH level in the presence of normal circulating free thyroid hormones. SCH is a highly prevalent condition displaying some peculiarities, both in terms of the diagnostic and therapeutic approach, when specific population and/or concomitant diseases are taken into account. The debate upon whether LT4 therapy should be initiated or not in patients with SCH is a long lasting one and still it remains controversial. Current evidence supports the concept that the clinical consequences of SCH may be profoundly different in relation to several patient-specific characteristics. Aim of the present review is to provide updated indications for SCH treatment in specific clinical settings. These will include the management of SCH in obese and diabetic patients, in pregnant women, and in specific age groups. Treatment modalities, including LT4 doses and recommended follow-up strategy will also be discussed. In the era of "precision medicine" the decision to-treat-not-to-treat SCH should be individualized taking into account risks and beneficial outcomes of LT4 therapy. With this in mind, we reviewed the most relevant studies in the recent literature in order to provide evidence for or against LT4 replacement therapy for SCH in specific clinical settings.
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http://dx.doi.org/10.1007/s12020-019-02039-zDOI Listing
October 2019

Role of chemokine receptors in thyroid cancer and immunotherapy.

Endocr Relat Cancer 2019 08;26(8):R465-R478

Istituti Clinici Scientifici Maugeri IRCCS, Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Pavia, Italy.

Inflammation is currently regarded as an essential component of malignancies. It is now known that the tumor microenvironment may profoundly influence the biological behavior of cancer cells and ultimately the patient's outcome. Chemokine and their receptor play a major role in determining the immune phenotype of the cells infiltrating the thyroid tumor microenvironment. Experimental evidence shows that both normal and cancer thyroid cells express specific chemokine receptors. The expression of at least some of these receptors exerts several biological effects, which influence the course of the disease. The present review article will take into account the role of the most studied chemokine receptors (CXCR1, CXCR2, CXCR3, CXCR4, CXCR7, DARC, CCR3, CCR6 and CCR7) in the context of thyroid cancer. This review will focus on current knowledge provided by in vitro and in vivo studies specifically performed on thyroid cancer including (i) expression of chemokine receptors in normal and cancer thyroid cells; (ii) role of chemokine receptors in affecting the biological behavior of thyroid tumors including the metastatic process; (iii) current knowledge about immunotherapies through targeting of chemokine receptors in thyroid cancer.
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http://dx.doi.org/10.1530/ERC-19-0163DOI Listing
August 2019

The BRAF-inhibitor PLX4720 inhibits CXCL8 secretion in BRAFV600E mutated and normal thyroid cells: a further anti-cancer effect of BRAF-inhibitors.

Sci Rep 2019 03 13;9(1):4390. Epub 2019 Mar 13.

Unit of Internal Medicine and Endocrinology, ICS Maugeri I.R.C.C.S., Laboratory for Endocrine Disruptors and Chair of Endocrinology University of Pavia, 27100, Pavia, Italy.

CXCL8 is a chemokine secreted by normal and thyroid cancer cells with proven tumor-promoting effects. The presence of BRAFV600E mutation is associated with a more aggressive clinical behavior and increased ability to secrete CXCL8 by papillary-thyroid-cancer cells. Aim of this study was to test the effect of the BRAF-inhibitor (PLX4720) on the basal and TNF-α-induced CXCL8 secretions in BRAFV600E mutated (BCPAP, 8305C, 8505C), in RET/PTC rearranged (TPC-1) thyroid-cancer-cell-lines and in normal-human-thyrocytes (NHT). Cells were incubated with increasing concentrations of PLX4720 alone or in combination with TNF-α for 24-hours. CXCL8 concentrations were measured in the cell supernatants. PLX4720 dose-dependently inhibited the basal and the TNF-α-induced CXCL8 secretions in BCPAP (F: 14.3, p < 0.0001 for basal and F: 12.29 p < 0.0001 for TNF-α), 8305C (F: 407.9 p < 0.0001 for basal and F: 5.76 p < 0.0001 for TNF-α) and 8505C (F:55.24 p < 0.0001 for basal and F: 42.85 p < 0.0001 for TNF-α). No effect was found in TPC-1 (F: 1.8, p = 0.134 for basal; F: 1.6, p = 0.178 for TNF-α). In NHT an inhibitory effect was found only at the highest concentration of PLX4720 (F: 13.13 p < 0.001 for basal and F: 2.5 p < 0.01 for TNF-α). Cell migration assays showed that PLX4720 reduced both basal and CXCL8-induced cell migration in BCPAP, 8305C, 8505C and NHT but not in TPC-1 cells. These results constitutes the first demonstration that PLX4720 is able to inhibit the secretion of CXCL8 in BRAFV600E mutated thyroid cancer cells indicating that, at least some, of the anti-tumor activities of PLX4720 could be exerted through a lowering of CXCL8 in the thyroid-cancer-microenvironment.
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http://dx.doi.org/10.1038/s41598-019-40818-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416278PMC
March 2019

Nivolumab Induced Thyroid Dysfunction: Unusual Clinical Presentation and Challenging Diagnosis.

Front Endocrinol (Lausanne) 2018 17;9:813. Epub 2019 Jan 17.

Unit of Internal Medicine and Endocrinology, ICS Maugeri IRCCS, University of Pavia, Pavia, Italy.

In recent years, immune checkpoint inhibitors (ICIs) had a great impact in cancer therapy. ICIs display a peculiar toxicity profile, which is characterized by autoimmune-like manifestations against multiple organs, including endocrine glands. We hereby report the case history of two patients who experienced nivolumab-induced endocrine immuno-related adverse events (irAEs). Thyroid dysfunction in both patients presented with a low serum level of TSH. However, endocrine evaluation showed a completely different etiology and clinical evolution. The two patients' histories indicate that nivolumab can cause a large spectrum of thyroid and endocrine dysfunctions resulting in cumbersome diagnostic problems. In these peculiar patients the evaluation of endocrine experts is warranted.
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http://dx.doi.org/10.3389/fendo.2018.00813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345097PMC
January 2019

Post-partum and non-post-partum relapsing Graves' hyperthyroidism display different response to anti-thyroid drugs.

Eur J Endocrinol 2018 Jun 20;178(6):589-594. Epub 2018 Mar 20.

Unit of Internal Medicine and Endocrinology, ICS Maugeri I.R.C.C.S., University of Pavia, Pavia, Italy.

Design: Graves' disease (GD) patients in remission after a full course of methimazole (MMI) therapy are at risk for a relapse of hyperthyroidism during the post-partum (PP) period, but whether this relapse may display any peculiarity is still unknown. Aim of this study was to compare GD patients undergoing a relapse of hyperthyroidism either in the PP period or not.

Methods: We retrospectively evaluated forty-three GD female patients in their childbearing age who experienced a relapse of hyperthyroidism. Eighteen of them relapsed in the PP period (i.e. within 12 months after delivery, PP group); the remaining 25 relapsed elsewhere during life (NPP group).

Results: Age at relapse, thyroid volume, thyroid function tests, TRAb titers, smoking habit, presence and degree of orbitopathy and duration of methimazole (MMI) treatment did not differ in the two groups. However, the remission rate was much greater (79%) in the PP as compared with the NPP (32%) group ( = 0.002). A significant reduction in TRAb levels occurred at 12-month MMI treatment in the PP ( = 9.016;  = 0.001), but not in the NPP group ( = 2.433; NS). At 12 months, the PP group had significantly lower mean TRAb levels (0.6 ± 1.1 U/L and 4.5 ± 4.7 U/L in the PP and the NPP group, respectively;  = 0.029).

Conclusions: Relapsing Graves' hyperthyroidism in the PP period is more prone to undergo a remission after a second course of MMI treatment. In these patients, a conservative therapeutic approach is more appropriate.
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http://dx.doi.org/10.1530/EJE-17-1063DOI Listing
June 2018

Normal human thyroid cells, BCPAP, and TPC-1 thyroid tumor cell lines display different profile in both basal and TNF-α-induced CXCL8 secretion.

Endocrine 2016 Oct 8;54(1):123-128. Epub 2015 Oct 8.

Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors Fondazione Salvatore Maugeri I.R.C.C.S., University of Pavia, Via Maugeri 10, 27100, Pavia, Italy.

CXCL8 is secreted by both normal human thyrocytes (NHT) and thyroid cancer cell lines. CXCL8 displays several tumor-promoting effects and recent evidences indicate that its concentrations within the tumor microenvironment can impact the clinical course of the malignancy. Aim of this study was to compare the basal secretion of CXCL8 among NHT and thyroid cancer cell lines (TPC-1 and BCPAP), and to assess the specific cell response to TNF-α in terms of CXCL8 secretion. NHT primary cultures, TPC-1 and BCPAP cell lines were cultured with or without TNF-α (0, 0.1, 1, 10, and 100 ng/ml). CXCL8 levels were measured in the cell supernatants after 24 h. In basal condition, significant differences in the mean levels of CXCL8 were observed among the three cell types: NHT (110.5 ± 56.2 pg/ml), TPC1 (467.4 ± 43.2 pg/ml), and BCPAP (1731.8 ± 493.3 pg/ml), (F = 35.06; p < 0.0001). TNF-α significantly and in a dose-response manner induced CXCL8 secretion in NHT (F = 25.53; p < 0.00001), TPC-1 (F = 13.38; p < 0.0001), and BCPAP (F = 9.88; p < 0.001) cells. The magnitude of the TNF-α effect (fold-increase vs. basal level of CXCL8) differed significantly among the three cell types (F = 10.47; p < 0.0001). BCPAP were identified as the cells showing the highest basal secretion of CXCL8 and the less responsive to TNF-α. NHT, TPC-1, and BCPAP display significant differences in the secretion of both basal and TNF-α-induced CXCL8 secretion. These results indicate that the mechanisms regulating the secretion of CXCL8 differ in tumor cells harboring different genetic alterations suggesting that specific strategies aimed at inhibiting CXCL8 secretion will be required.
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http://dx.doi.org/10.1007/s12020-015-0764-xDOI Listing
October 2016

TNF-α increases the membrane expression of the chemokine receptor CCR6 in thyroid tumor cells, but not in normal thyrocytes: potential role in the metastatic spread of thyroid cancer.

Tumour Biol 2016 Apr 17;37(4):5569-75. Epub 2015 Nov 17.

Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Fondazione Salvatore Maugeri I.R.C.C.S., Via Maugeri 10, 27100, Pavia, Italy.

The chemokine receptor CCR6, selectively bound by CCL20, is involved in the metastatic spread of cancer cells. Tumor necrosis factor-α (TNF-α) displays a complex pro-tumorigenic actions, but it is unknown whether this cytokine could modulate the expression of chemokine receptors in thyroid tumors. The membrane expression of CCR6 was assessed by flow cytometry and immunofluorescence, in primary cultures of normal human thyroid (NHT) cells and in thyroid cancer cell lines (TPC-1 and BCPAP), both in basal conditions and after stimulation with TNF-α. In basal conditions, CCR6+ cells were virtually absent in NHT cells (0.4 ± 0.4 %), while they were detected in TPC-1 (23.6 ± 6.6 %) and in BCPAP (12.9 ± 9.4 %) tumor cells (ANOVA F: 10.534; p < 0.005). The incubation with TNF-α significantly increased the percentage of CCR6+ cells in TPC-1 (23.6 ± 6.6 % vs. 33.1 ± 8.7; p < 0.033) and in BCPAP (12.9 ± 9.4 % vs. 18.1 ± 11.5; p < 0.030), but not in NHT (0.4 ± 0.4 % vs. 0.2 ± 0.3; NS) cells. The magnitude of the TNF-α effect was similar for TPC-1 and BCPAP (∼40 % vs. baseline) cells. TPC-1 cells were characterized by a greater amount of CCR6 per cell as compared with BCPAP cells, both in basal conditions (148.3 ± 33.7 fluorescence intensity vs. 102.5 ± 22.1 p < 0.016) and after TNF-α stimulation (147.8 ± 46.3 fluorescence intensity vs. 95.3 ± 18.5; p < 0.025). Cell migration assays showed that TNF-α treatment significantly increased the rate of migrated cells in those cells in which it also increased the membrane expression of CCR6 (TPC-1 and BCPAP) as compared to basal condition (p < 0.05 for both TPC-1 and BCPAP cells). No effect was observed in NHT cells in which TNF-α stimulation had no effect in terms of CCR6 expression. We first report that TNF-α enhances the expression of CCR6 in thyroid tumor cells, thus providing evidence that TNF-α increases the metastatic potential of thyroid tumors.
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http://dx.doi.org/10.1007/s13277-015-4418-7DOI Listing
April 2016

Body weight changes in a large cohort of patients subjected to thyroidectomy for a wide spectrum of thyroid diseases.

Endocr Pract 2014 Nov;20(11):1151-8

Unit of Internal Medicine and Endocrinology, Fondazione Salvatore Maugeri I. R. C. C. S., Chair of Endocrinology, University of Pavia, Pavia, Italy.

Objective: Patients undergoing thyroidectomy often complain of weight gain. The aim of this study was to longitudinally evaluate body-weight changes in patients thyroidectomized for euthyroid and hyperthyroid conditions in order to identify predictive factors.

Methods: Anthropometric data and thyroid function parameters were retrospectively reviewed for 267 thyroidectomized patients before and 40 to 60 days and 9 months after surgery. Presurgery diagnoses included benign (Graves disease, nodular toxic goiter, nodular nontoxic goiter) and malignant (differentiated thyroid cancer) conditions.

Results: Mean preintervention weight of the entire study group significantly increased (P<.0001) 9-months after thyroidectomy, from 70.8 ± 16.0 to 72.5 ± 16.4 kg. Body weight increased in 156 (58.4%) patients, decreased in 59 (22.1%) patients, and remained stable in 52 (19.5%) patients. A multiple regression model was constructed by entering the percentage of body-weight change 9 months postsurgery as the dependent variable and age, sex, presurgery body mass index, percentage of weight change 40 to 60 days postsurgery, presurgery thyroid-stimulating hormone (TSH) level, TSH level 40 to 60 days postsurgery, TSH level 9 months postsurgery, thyroid disease driving thyroidectomy, and type of surgical intervention as the covariates. No significant relationship was found for any of the covariates tested, with the exception of percentage of body-weight change at 40 to 60 days postsurgery (correlation coefficient, 0.869; [95% confidence interval, 0.692 to 1.046; P<.0001]).

Conclusion: Thyroidectomy is associated with a significant increase in body weight, which is not limited to patients with Graves disease. Postsurgery TSH levels do not account for subsequent body-weight changes. Short-term changes (40 to 60 days postsurgery) in body weight are highly predictive of the outcome at 9 months, suggesting that early factors related to thyroidectomy per se might play a role.
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http://dx.doi.org/10.4158/EP14125.ORDOI Listing
November 2014
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