Search Results
Search for other papers by Giorgio Radetti in
Google Scholar
PubMed
Search for other papers by Franco Rigon in
Google Scholar
PubMed
Search for other papers by Alessandro Salvatoni in
Google Scholar
PubMed
Search for other papers by Irene Campi in
Google Scholar
PubMed
Search for other papers by Tiziana De Filippis in
Google Scholar
PubMed
Search for other papers by Valentina Cirello in
Google Scholar
PubMed
Search for other papers by Silvia Longhi in
Google Scholar
PubMed
Search for other papers by Fabiana Guizzardi in
Google Scholar
PubMed
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Search for other papers by Marco Bonomi in
Google Scholar
PubMed
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Search for other papers by Luca Persani in
Google Scholar
PubMed
Introduction
Patients with congenital hypothyroidism (CH) may transiently show a certain degree of pituitary resistance to levothyroxine (LT4) which, however, normalizes subsequently. However, in some individuals, thyroid-stimulating hormone (TSH) fails to normalize despite adequate LT4 treatment.
Methods
Nine patients with CH followed in three Academic Centre who developed over time resistance to thyroid hormones underwent extensive biochemical and genetic analyses. These latter were performed by Sanger sequence or targeted next-generation sequencing technique including a panel of candidate genes involved in thyroid hormone actions and congenital hypothyroidism (CH): THRA, THRB, DIO1, DIO2, SLC16A2, SECISBP2, DUOX2, DUOXA2, FOXE1, GLIS3, IYD, JAG1, NKX2-1, NKX2- 5, PAX8, SLC26A4, SLC5A5, TG, TPO, TSHR.
Results
All patients displayed a normal sensitivity to thyroid hormone (TH) in the first years of life but developed variable degrees of resistance to LT4 treatment at later stages. In all cases, TSH normalized only in the presence of high free thyroxine levels. Tri-iodothyronine suppression test followed by thyrotrophin-releasing hormone stimulation was performed in two cases and was compatible with central resistance to THs. This biochemical feature was present independently on the cause of CH, being observed either in patients with an ectopic (n = 2) or eutopic gland (n = 3) or in case of athyreosis (n = 1). None of the patients had genetic variants in genes involved in the regulation of TH actions, while in two cases, we found two double heterozygous missense variants in TSHR and GLIS3 or in DUOX2 and SLC26A4 genes, respectively.
Conclusions
We report CH patients who showed an acquired and unexplainable pituitary refractoriness to TH action.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Valentina Cirello in
Google Scholar
PubMed
Search for other papers by Marina Lugaresi in
Google Scholar
PubMed
Search for other papers by Claudia Moneta in
Google Scholar
PubMed
Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium
Search for other papers by Patrice Dufour in
Google Scholar
PubMed
Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy
Search for other papers by Alessandro Manzo in
Google Scholar
PubMed
Search for other papers by Erika Carbone in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Carla Colombo in
Google Scholar
PubMed
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
Search for other papers by Laura Fugazzola in
Google Scholar
PubMed
Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium
Search for other papers by Corinne Charlier in
Google Scholar
PubMed
Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium
Search for other papers by Catherine Pirard in
Google Scholar
PubMed
Objective
The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case–control cohort.
Methods
We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4′-DDT and 4,4′-DDE) were measured in the serum by liquid or gas chromatography–mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants’ levels, considered individually or as mixture. BRAF V600E mutation was assessed by standard methods.
Results
The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10–3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41–0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants’ mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180.
Conclusion
Our study suggests, for the first time in a case–control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants’ mixture, likely due to a potential reverse causality.
