{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T15:50:05Z","timestamp":1782316205828,"version":"3.54.5"},"reference-count":58,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T00:00:00Z","timestamp":1664582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIAAA at NIH)","award":["K23AA029198-01 (VV)"],"award-info":[{"award-number":["K23AA029198-01 (VV)"]}]},{"name":"National Institutes of Health (NIAAA at NIH)","award":["R15CA170091-01A1 (MK)"],"award-info":[{"award-number":["R15CA170091-01A1 (MK)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>(1) Background: Heavy and chronic alcohol drinking leads to altered gut dysfunction, coupled with a pro-inflammatory state. Thyroid-associated hormones and proteins may be dysregulated by heavy and chronic alcohol intake; however, the mechanism for altered gut-derived changes in thyroid function has not been studied thus far. This study investigates the role of alcohol-induced gut dysfunction and pro-inflammatory cytokine profile in the thyroid function of patients with alcohol use disorder (AUD). (2) Methods: Male and female AUD patients (n = 44) were divided into Gr.1, patients with normal thyroid-stimulating hormone (TSH) levels (n = 28, 0.8 \u2264 TSH \u2264 3 mIU\/L); and Gr.2, patients with clinically elevated TSH levels (n = 16, TSH &gt; 3 mIU\/L). Demographics, drinking measures, comprehensive metabolic panels, and candidate thyroid markers (TSH, circulating triiodothyronine (T3), and free thyroxine (fT4)) were analyzed. Gut-dysfunction-associated markers (lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble LPS-induced pathogen-associated protein (sCD14)), and candidate pro-inflammatory cytokines (IL-1\u03b2, TNF-\u03b1, IL-6, IL-8, MCP-1, PAI-1) were also evaluated. (3) Results: Patients in both groups presented with a borderline overweight BMI category. Gr.2 reported numerically higher indices of chronic and heavy drinking patterns than Gr.1. The fT4 levels were elevated, while T3 was within normal limits in both groups. The gut dysfunction markers LBP and sCD14 were numerically elevated in Gr.2 vs. Gr.1, suggesting subtle ongoing changes. Candidate pro-inflammatory cytokines were significantly elevated in Gr.2, including IL-1 \u03b2, MCP-1, and PAI-1. Gr.2 showed a strong and statistically significant effect on the gut\u2013immune\u2013thyroid response (r = 0.896, 36 p = 0.002) on TSH levels in a multivariate regression model with LBP, sCD14, and PAI-1 levels as upstream variables in the gut\u2013thyroid pathway. In addition, AUROC analysis demonstrated that many of the cytokines strongly predicted TSH in Gr.2, including IL-6 (area = 0.774, 39 p &lt; 0.001) and TNF-\u03b1 (area = 0.708, p = 0.017), among others. This was not observed in Gr.1. Gr.2 demonstrated elevated fT4, as well as TSH, which suggests that there was subclinical thyroiditis with underlying CNS dysfunction and a lack of a negative feedback loop. (4) Conclusions: These findings reveal the toxic effects of heavy and chronic drinking that play a pathological role in thyroid gland dysregulation by employing the gut\u2013brain axis. These results also emphasize potential directions to carefully evaluate thyroid dysregulation in the overall medical management of AUD.<\/jats:p>","DOI":"10.3390\/cells11193100","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T01:52:21Z","timestamp":1665193941000},"page":"3100","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Illustration of Gut\u2013Thyroid Axis in Alcohol Use Disorder: Interplay of Gut Dysfunction, Pro-Inflammatory Responses, and Thyroid Function"],"prefix":"10.3390","volume":"11","author":[{"given":"Manasa","family":"Sagaram","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amor J.","family":"Royer","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huirong","family":"Hu","sequence":"additional","affiliation":[{"name":"Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA"},{"name":"Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-9681","authenticated-orcid":false,"given":"Abhas","family":"Rajhans","sequence":"additional","affiliation":[{"name":"Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA"},{"name":"Department of Neuroscience, University of California Los Angeles, Los Angeles, CA 90095, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranganathan","family":"Parthasarathy","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathya Sridevi","family":"Krishnasamy","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism & Diabetes, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sri Prakash","family":"Mokshagundam","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism & Diabetes, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maiying","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY 40202, USA"},{"name":"University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie L.","family":"Schwandt","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipendra","family":"Parajuli","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Robley Rex VA Medical Center, Louisville, KY 40206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-6696","authenticated-orcid":false,"given":"Matthew C.","family":"Cave","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA"},{"name":"Robley Rex VA Medical Center, Louisville, KY 40206, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6764-6891","authenticated-orcid":false,"given":"Vatsalya","family":"Vatsalya","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Clinical Laboratory for the Intervention Development of AUD and Organ Severity, University of Louisville, Louisville, KY 40202, USA"},{"name":"University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY 40202, USA"},{"name":"National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.35946\/arcr.v40.3.02","article-title":"Epidemiology of recovery from alcohol use disorder","volume":"40","author":"Tucker","year":"2020","journal-title":"Alcohol Res. Curr. Rev."},{"key":"ref_2","unstructured":"(2022, July 01). Alcohol Use in the United States National Institute on Alcohol Abuse and Alcoholism, Available online: https:\/\/www.niaaa.nih.gov\/publications\/brochures-and-fact-sheets\/alcohol-facts-and-statistics#:~:text=Prevalence%20of%20Drinking%3A%20According%20to,in%20this%20age%20group%20and."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2","DOI":"10.35946\/arcr.v42.1.02","article-title":"Age, period, and cohort effects in alcohol use in the United States in the 20th and 21st centuries: Implications for the coming decades","volume":"42","author":"Keyes","year":"2022","journal-title":"Alcohol Res. Curr. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/S0140-6736(62)90572-X","article-title":"Thyroid function in chronic alcoholism","volume":"2","author":"Goldberg","year":"1962","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1111\/j.1530-0277.1996.tb05277.x","article-title":"Chronic ethanol treatment reduces the responsiveness of the hypothalamic-pituitary-thyroid axis to central stimulation","volume":"20","author":"Zoeller","year":"1996","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1176\/ajp.140.9.1145","article-title":"Thyrotropin-releasing hormone (TRH) in abstinent alcoholic men","volume":"140","author":"Loosen","year":"1983","journal-title":"Am. J. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/0165-1781(85)90113-1","article-title":"Thyrotropin-releasing hormone test in recently abstinent alcoholics","volume":"16","author":"Casacchia","year":"1985","journal-title":"Psychiatry Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1093\/alcalc\/agl056","article-title":"Thyroid function in early and late alcohol withdrawal: Relationship with aggression, family history, and onset age of alcoholism","volume":"41","author":"Ozsoy","year":"2006","journal-title":"Alcohol Alcohol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1046\/j.1360-0443.2002.00200.x","article-title":"Dysregulation of the hypothalamic-pituitary-thyroid axis in alcoholism","volume":"97","author":"Hermann","year":"2002","journal-title":"Addiction"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Canesso, M.C.C., Lacerda, N.L., Ferreira, C.M., Goncalves, J.L., Almeida, D., Gamba, C., Cassali, G., Pedroso, S.H., Moreira, C., and Martins, F.S. (2014). Comparing the effects of acute alcohol consumption in germ-free and conventional mice: The role of the gut microbiota. BMC Microbiol., 14.","DOI":"10.1186\/s12866-014-0240-4"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.biopsych.2014.02.003","article-title":"Role of inflammatory pathways, blood mononuclear cells, and gut-derived bacterial products in alcohol dependence","volume":"76","author":"Leclercq","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Bull-Otterson, L., Feng, W., Kirpich, I., Wang, Y., Qin, X., Liu, Y., Gobejishvili, L., Joshi-Barve, S., Ayvaz, T., and Petrosino, J. (2013). Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0053028"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1111\/liv.12271","article-title":"Intestinal epithelial barrier function in liver cirrhosis: An extensive review of the literature","volume":"33","author":"Pijls","year":"2013","journal-title":"Liver Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"16639","DOI":"10.3748\/wjg.v20.i44.16639","article-title":"Gut microbiota in alcoholic liver disease: Pathogenetic role and therapeutic perspectives","volume":"20","author":"Malaguarnera","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.redox.2014.10.002","article-title":"Intestinal CYP2E1: A mediator of alcohol-induced gut leakiness","volume":"3","author":"Forsyth","year":"2014","journal-title":"Redox Biol."},{"key":"ref_16","first-page":"579","article-title":"Pro- and anti-inflammatory gene expression in the murine small intestine and liver after chronic exposure to alcohol","volume":"25","author":"Fleming","year":"2001","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1053\/jhep.2001.25350","article-title":"Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice","volume":"34","author":"Uesugi","year":"2001","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S116","DOI":"10.1080\/10408398.2018.1544542","article-title":"n-3 Polyunsaturated fatty acids for the management of alcoholic liver disease: A critical review","volume":"59","author":"Wang","year":"2019","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1111\/acer.13197","article-title":"Effects of sex, drinking history, and omega-3 and omega-6 fatty acids dysregulation on the onset of liver injury in very heavy drinking alcohol-dependent patients","volume":"40","author":"Vatsalya","year":"2016","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1210\/jc.2005-0455","article-title":"The evidence for a narrower thyrotropin reference range is compelling","volume":"90","author":"Wartofsky","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4236","DOI":"10.1210\/jc.2007-0287","article-title":"National health and nutrition examination survey III thyroid-stimulating hormone (TSH)-thyroperoxidase antibody relationships demonstrate that TSH upper reference limits may be skewed by occult thyroid dysfunction","volume":"92","author":"Spencer","year":"2007","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sobell, L.C., and Sobell, M.B. (1992). Timeline follow-back. Measuring Alcohol Consumption, Springer.","DOI":"10.1037\/t06202-000"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.15288\/jsa.1982.43.1157","article-title":"Reliability of alcohol use indices. The lifetime drinking history and the MAST","volume":"43","author":"Skinner","year":"1982","journal-title":"J. Stud. Alcohol"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1055\/s-2007-1007110","article-title":"Cytokines in alcoholic liver disease","volume":"Volume 19","author":"McClain","year":"1999","journal-title":"Seminars in Liver Disease"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"6748","DOI":"10.4049\/jimmunol.163.12.6748","article-title":"The CD14 ligands lipoarabinomannan and lipopolysaccharide differ in their requirement for Toll-like receptors","volume":"163","author":"Means","year":"1999","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"33419","DOI":"10.1074\/jbc.274.47.33419","article-title":"Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products","volume":"274","author":"Lien","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"G881","DOI":"10.1152\/ajpgi.00006.2004","article-title":"Recent advances in alcoholic liver disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease","volume":"286","author":"Rao","year":"2004","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1093\/alcalc\/36.4.314","article-title":"The effect of long-term ethanol feeding on Brucella melitensis infection of rats","volume":"36","author":"Yumuk","year":"2001","journal-title":"Alcohol Alcohol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1016\/j.burns.2004.09.021","article-title":"Effect of acute alcohol ingestion prior to burn injury on intestinal bacterial growth and barrier function","volume":"31","author":"Kavanaugh","year":"2005","journal-title":"Burns"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.smim.2003.10.003","article-title":"TLR signaling pathways","volume":"16","author":"Takeda","year":"2004","journal-title":"Semin. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/B978-0-12-801284-0.00011-7","article-title":"Converging actions of alcohol on liver and brain immune signaling","volume":"118","author":"Szabo","year":"2014","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/jgh.12030","article-title":"Alcoholic liver disease: Pathogenesis, management, and novel targets for therapy","volume":"28","author":"Orman","year":"2013","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8285","DOI":"10.1523\/JNEUROSCI.0976-10.2010","article-title":"Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage","volume":"30","author":"Blanco","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1615\/CritRevImmunol.2013008686","article-title":"The inflammasome and its regulation","volume":"34","author":"Tsuchiya","year":"2014","journal-title":"Crit. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF03344951","article-title":"Increased serum interleukin-6 concentration in patients with subacute thyroiditis: Relationship with concomitant changes in serum T4-binding globulin concentration","volume":"16","author":"Bartalena","year":"1993","journal-title":"J. Endocrinol. Investig."},{"key":"ref_36","first-page":"435","article-title":"Serum cytokines in thyrotoxicosis","volume":"84","author":"Siddiqi","year":"1999","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"270149","DOI":"10.4061\/2011\/270149","article-title":"Clinical utility of serum interleukin-8 and interferon-alpha in thyroid diseases","volume":"2011","author":"Kobawala","year":"2011","journal-title":"J. Thyroid. Res."},{"key":"ref_38","first-page":"227","article-title":"Hormones and the immunological capacity. IV. Restorative effects of developmental hormones or of lymphocytes on the immunodeficiency syndrome of the dwarf mouse","volume":"9","author":"Fabris","year":"1971","journal-title":"Clin. Exp. Immunol."},{"key":"ref_39","first-page":"81","article-title":"Hormonal influences on the secretion of the thymus","volume":"1","author":"Comsa","year":"1979","journal-title":"Thymus"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3181\/00379727-182-42328","article-title":"Effect of mammalian growth hormone and prolactin on the growth of hypophysectomized chickens","volume":"182","author":"King","year":"1986","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1089\/thy.2010.0429","article-title":"Thyroid hormones as modulators of immune activities at the cellular level","volume":"21","author":"Incerpi","year":"2011","journal-title":"Thyroid"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/S0006-291X(84)80329-0","article-title":"Enhancement of the in vitro antibody response by thyrotropin","volume":"125","author":"Blalock","year":"1984","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_43","first-page":"661","article-title":"The thyrotropin releasing hormone stimulation test in alcoholism","volume":"30","author":"Pienaar","year":"1995","journal-title":"Alcohol Alcohol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"577","DOI":"10.3109\/00048679209072092","article-title":"The clinical significance of the thyrotropin-releasing hormone test in alcoholic men","volume":"26","author":"Sellman","year":"1992","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"ref_45","first-page":"235","article-title":"Hormonal changes in noncirrhotic male alcoholics during ethanol withdrawal","volume":"19","author":"Valimaki","year":"1984","journal-title":"Alcohol Alcohol."},{"key":"ref_46","first-page":"695","article-title":"Administration of thyrotropin-releasing hormone at weekly intervals results in a diminished thyrotropin response","volume":"19","author":"Winokur","year":"1984","journal-title":"Biol. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1677\/joe.0.1010101","article-title":"Desensitization of rat anterior pituitary gland to thyrotrophin releasing hormone","volume":"101","author":"Sheppard","year":"1984","journal-title":"J. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1210\/jcem-58-5-930","article-title":"Decreased thyroid gland volume in alcoholic cirrhosis of the liver","volume":"58","author":"Hegedus","year":"1984","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/0026-0495(88)90100-X","article-title":"Independent effects of liver disease and chronic alcoholism on thyroid function and size: The possibility of a toxic effect of alcohol on the thyroid gland","volume":"37","author":"Hegedus","year":"1988","journal-title":"Metabolism"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1046\/j.1365-2265.2001.01325.x","article-title":"Alcohol consumption is associated with reduced prevalence of goitre and solitary thyroid nodules","volume":"55","author":"Knudsen","year":"2001","journal-title":"Clin. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1148\/radiology.190.2.8284411","article-title":"Treatment of autonomous thyroid nodules with percutaneous ethanol injection: 4-year experience","volume":"190","author":"Livraghi","year":"1994","journal-title":"Radiology"},{"key":"ref_52","first-page":"514659","article-title":"Salivary C-reactive protein in Hashimoto\u2019s thyroiditis and subacute thyroiditis","volume":"2010","author":"Rao","year":"2010","journal-title":"Int. J. Inflam."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"976","DOI":"10.4103\/2230-8210.103002","article-title":"Significant role of serum CRP in differentiating inflammatory from non-inflammatory causes of thyrotoxicosis","volume":"16","author":"Baruah","year":"2012","journal-title":"Indian J. Endocrinol. Metab."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1089\/105072503322239989","article-title":"The prevalence of elevated serum C-reactive protein levels in inflammatory and noninflammatory thyroid disease","volume":"13","author":"Pearce","year":"2003","journal-title":"Thyroid"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"5250","DOI":"10.1210\/endo.137.12.8940342","article-title":"Induced illness in interleukin-6 (IL-6) knock-out mice: A causal role of IL-6 in the development of the low 3,5,3\u2032-triiodothyronine syndrome","volume":"137","author":"Boelen","year":"1996","journal-title":"Endocrinology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1046\/j.1365-2265.1996.668489.x","article-title":"Relation between serum interleukin-6 and thyroid hormone concentrations in 270 hospital in-patients with non-thyroidal illness","volume":"44","author":"Davies","year":"1996","journal-title":"Clin. Endocrinol."},{"key":"ref_57","first-page":"2157583","article-title":"Abnormalities of thyroid hormone metabolism during systemic illness: The low T3 syndrome in different clinical settings","volume":"2016","year":"2016","journal-title":"Int. J. Endocrinol."},{"key":"ref_58","first-page":"1387","article-title":"Hypothalamus-pituitary-thyroid axis","volume":"6","author":"Chiamolera","year":"2016","journal-title":"Compr. Physiol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/19\/3100\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:45:15Z","timestamp":1760143515000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/19\/3100"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,1]]},"references-count":58,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cells11193100"],"URL":"https:\/\/doi.org\/10.3390\/cells11193100","relation":{"has-preprint":[{"id-type":"doi","id":"10.20944\/preprints202209.0254.v1","asserted-by":"object"}]},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,1]]}}}