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Guarino S, Calcaterra V, Di Sessa A, Labati L, Marrapodi MM, Grandone A, Zanfardino A, Zuccotti G, Iafusco D, Miraglia Del Giudice E, Marzuillo P. Sensitivity to thyroid hormones in children developing acute kidney injury at the onset of type 1 diabetes mellitus. BMC Med 2025; 23:123. [PMID: 40011875 DOI: 10.1186/s12916-025-03936-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Accepted: 02/07/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Thyroid hormone (TH) sensitivity at type 1 diabetes mellitus (T1DM) onset and its connection with acute kidney injury (AKI) has not been investigated. We aimed to evaluate changes in TH sensitivity in children with and without AKI at T1DM onset and to assess the role of euthyroid sick syndrome (ESS) in this relationship. METHODS We included 161 children with new-onset T1DM and followed them until renal function normalized. The free triiodothyronine (FT3)/free thyroxine (FT4) ratio was used to assess peripheral TH sensitivity, while the TSH index (TSHI), thyrotroph T4 resistance index (TT4RI), thyrotroph T3 resistance index (TT3RI), Thyroid Feedback Quantile-based Index (TFQI), and parametric TFQI (PTFQI) were used for central sensitivity. RESULTS Patients with AKI exhibited greater weight loss, higher serum ketones, creatinine, corrected sodium, and glycated hemoglobin, but lower bicarbonate and estimated glomerular filtration rate compared to those without AKI. Logistic regression showed that the odds of AKI increased by 11.5-fold for each unit decrease in TFQI, 4.0-fold per unit decrease in PTFQI, and 1.7-fold per unit decrease in TSHI, adjusting for age and gender. After adjusting for age, gender, and ESS, the odds for AKI significantly increased (4.8-fold for each 1-unit decrease) only for TFQI. CONCLUSIONS AKI at the onset of T1DM has a dual effect on TH. It reduces peripheral sensitivity while increasing central sensitivity. This effect appears to be largely driven by ESS, with the exception of the association between AKI and TFQI, which remains independent of ESS.
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Affiliation(s)
- Stefano Guarino
- Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Valeria Calcaterra
- Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100, Pavia, Italy
- Pediatric Department, Buzzi Children's Hospital, 20154, Milan, Italy
| | - Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Lucia Labati
- Pediatric Department, Buzzi Children's Hospital, 20154, Milan, Italy
- Department of Biomedical and Clinical Science, University of Milan, 20157, Milan, Italy
| | - Maria Maddalena Marrapodi
- Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Anna Grandone
- Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Angela Zanfardino
- Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Gianvincenzo Zuccotti
- Pediatric Department, Buzzi Children's Hospital, 20154, Milan, Italy
- Department of Biomedical and Clinical Science, University of Milan, 20157, Milan, Italy
| | - Dario Iafusco
- Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Naples, Italy.
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Elsayed AA, Barghash SM, El-Kattan AM, Wassif IM, Osman WA, Ateya AI. Analysis of potential genes, immunological and antioxidant profiles associated with trypanosomiasis susceptibility in dromedary camels. Vet Parasitol 2024; 331:110264. [PMID: 39059159 DOI: 10.1016/j.vetpar.2024.110264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 07/06/2024] [Accepted: 07/12/2024] [Indexed: 07/28/2024]
Abstract
Trypanosomiasis is associated with tissue damage and may trigger an immunological response. These tissue lesions are linked to metabolic issues and oxidative stress. The current study aimed to investigate the immunological, antioxidant, and metabolic changes that may be connected to camel trypanosomiasis. Blood samples were collected from 54 camels and allocated into two groups: The control group (35 camels) and the infected group (19 camels). The genes TLR2, TLR5, IL-17, MARCHF3, RASGRP1, EPS15L1, PPIE, ASB16, CMPK2, LPCAT1, FPGT, GPHN, TNNI3K, DIO3, keap1, and OXSR1 were significantly up-regulated in trypanosomiasis camels. However, down-regulation was observed for the genes Nrf2, PRDX6, and NDUFS5. PCR-DNA sequencing was used to identify nucleotide sequence polymorphisms in the immune (TLR2, TLR5, IL-17, MARCHF3, RASGRP1, and EPS15L1), metabolic (PPIE, ASB16, CMPK2, LPCAT1, FPGT, GPHN, TNNI3K, and DIO3), and antioxidant (Nrf2, Keap1, PRDX6, NDUFS5, and OXSR1) genes between healthy and trypanosomiasis-affected camels. Exploring the serum profile also showed a significant (P ˂ 0.05) increase in Hp, SAA, Cp, IL-1β, IL-6, IL 10, TNF-α, and MDA, with significant (P ˂ 0.05) reduction in the serum levels of CAT, SOD, GSH, T3, and T4 in diseased camels compared with healthy ones. Our findings confirm the significance of nucleotide variations, gene expression patterns, and the biochemical profile of the investigated markers as indicators for the susceptibility of trypanosomiasis in dromedary camels and may be utilized to create management strategies.
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Affiliation(s)
- Ahmed A Elsayed
- Department of Animal Health and Poultry, Animal and Poultry Production Division, Desert Research Center (DRC), Cairo, Egypt
| | - Safaa M Barghash
- Department of Animal Health and Poultry, Animal and Poultry Production Division, Desert Research Center (DRC), Cairo, Egypt
| | - Adel M El-Kattan
- Department of Animal Health and Poultry, Animal and Poultry Production Division, Desert Research Center (DRC), Cairo, Egypt
| | - Islam M Wassif
- Department of Animal Health and Poultry, Animal and Poultry Production Division, Desert Research Center (DRC), Cairo, Egypt
| | - Wafaa A Osman
- Department of Animal Health and Poultry, Animal and Poultry Production Division, Desert Research Center (DRC), Cairo, Egypt
| | - Ahmed I Ateya
- Department of Animal Wealth Development, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt.
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Fastiggi M, Meneghel A, Gutierrez de Rubalcava Doblas J, Vittadello F, Tirelli F, Zulian F, Martini G. Prognostic role of euthyroid sick syndrome in MIS-C: results from a single-center observational study. Front Pediatr 2023; 11:1217151. [PMID: 37635797 PMCID: PMC10448823 DOI: 10.3389/fped.2023.1217151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Accepted: 07/17/2023] [Indexed: 08/29/2023] Open
Abstract
Background Euthyroid sick syndrome (ESS) is characterized by low serum levels of free triiodothyronine (fT3) with normal or low levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) and is reported in different acute clinical situations, such as sepsis, diabetic ketoacidosis and after cardiac surgery. Our aim was to evaluate the predicting role of ESS for disease severity in patients with Multisystem Inflammatory Syndrome in children (MIS-C). Methods A single-centre observational study on consecutive patients with MIS-C. Before treatment clinical, and laboratory data were collected and, in a subset of patients, thyroid function tests were repeated 4 weeks later. Variables distribution was analyzed by Mann-Whitney U-test and correlations between different parameters were calculated by Spearman's Rho coefficient. Results Forty-two patients were included and 36 (85.7%) presented ESS. fT3 values were significantly lower in patients requiring intensive care, a strong direct correlation was shown between fT3 and Hb, platelet count and ejection fraction values. A significant inverse correlation was retrieved between fT3 levels and C-reactive protein, brain natriuretic peptide, IL-2 soluble receptor and S-100 protein. Subjects with severe myocardial depression (EF < 45%) had lower fT3 values than subjects with higher EF. The thyroid function tests spontaneously normalized in all subjects who repeated measurement 4 weeks after admission. Conclusion ESS is a frequent and transient condition in acute phase of MIS-C. A severe reduction of fT3 must be considered as important prognostic factor for severe disease course, with subsequent relevant clinical impact in the management of these patients.
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Affiliation(s)
- Michele Fastiggi
- Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
| | - Alessandra Meneghel
- Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
| | | | - Fabio Vittadello
- Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
| | - Francesca Tirelli
- Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
| | - Francesco Zulian
- Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
| | - Giorgia Martini
- Pediatric Rheumatology Unit, Department of Woman and Child Health, University of Padova, Padova, Italy
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Lasa M, Contreras-Jurado C. Thyroid hormones act as modulators of inflammation through their nuclear receptors. Front Endocrinol (Lausanne) 2022; 13:937099. [PMID: 36004343 PMCID: PMC9393327 DOI: 10.3389/fendo.2022.937099] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Accepted: 07/14/2022] [Indexed: 11/13/2022] Open
Abstract
Reciprocal crosstalk between endocrine and immune systems has been well-documented both in physiological and pathological conditions, although the connection between the immune system and thyroid hormones (THs) remains largely unclear. Inflammation and infection are two important processes modulated by the immune system, which have profound effects on both central and peripheral THs metabolism. Conversely, optimal levels of THs are necessary for the maintenance of immune function and response. Although some effects of THs are mediated by their binding to cell membrane integrin receptors, triggering a non-genomic response, most of the actions of these hormones involve their binding to specific nuclear thyroid receptors (TRs), which generate a genomic response by modulating the activity of a great variety of transcription factors. In this special review on THs role in health and disease, we highlight the relevance of these hormones in the molecular mechanisms linked to inflammation upon their binding to specific nuclear receptors. In particular, we focus on THs effects on different signaling pathways involved in the inflammation associated with various infectious and/or pathological processes, emphasizing those mediated by NF-kB, p38MAPK and JAK/STAT. The findings showed in this review suggest new opportunities to improve current therapeutic strategies for the treatment of inflammation associated with several infections and/or diseases, such as cancer, sepsis or Covid-19 infection.
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Affiliation(s)
- Marina Lasa
- Departamento de Bioquímica-Instituto de Investigaciones Biomédicas “Alberto Sols”, Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas, Madrid, Spain
| | - Constanza Contreras-Jurado
- Departamento de Bioquímica, Facultad de Medicina, Universidad Alfonso X El Sabio, Madrid, Spain
- Departamento de Fisiopatología Endocrina y del Sistema Nervioso, Instituto de Investigaciones Biomédicas “Alberto Sols”, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain
- Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
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Xiong Y, Xia Z, Yang L, Huang J. Low T3 syndrome is associated with poor prognosis in patients with hepatitis B virus-related acute-on-chronic liver failure. Expert Rev Gastroenterol Hepatol 2022; 16:681-687. [PMID: 35723536 DOI: 10.1080/17474124.2022.2090336] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
BACKGROUND Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a critical disease with high mortality risk. Low triiodothyronine syndrome (LT3S) is associated with various severe acute and chronic diseases. We investigated the relationship between LT3S and poor prognosis in patients with HBV-ACLF. RESEARCH DESIGN AND METHODS A total of 198 patients with HBV-ACLF were enrolled between January 2018 and March 2019. We screened for independent risk factors for 28-day mortality using univariate and multivariate logistic regression analyses. Spearman's correlation analysis was used to evaluate the correlation between LT3S and the poor prognostic parameters of HBV-ACLF. RESULTS LT3S was an independent risk factor for 28-day mortality in HBV-ACLF patients (odds ratio: 4.035, 95% confidence interval 1.117-14.579; p = 0.033). The death group had a lower serum FT3 level (Z-value = 2639.000, p < 0.001). Serum FT3 levels were negatively correlated with age, C-reactive protein, international normalized ratio, and neutrophil count but positively correlated with lymphocyte count. A negative correlation between FT3 and various prognostic scores was observed, indicating that a low FT3 level was closely related to a poor prognosis. CONCLUSIONS LT3S was an independent risk factor for 28-day mortality and was correlated with poor prognosis in patients with HBV-ACLF.
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Affiliation(s)
- Ye Xiong
- The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Zuoxun Xia
- Guizhou Medical University, Guiyang, Guizhou, China
| | - Lu Yang
- The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jianrong Huang
- The Department of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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Stanculescu D, Bergquist J. Perspective: Drawing on Findings From Critical Illness to Explain Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne) 2022; 9:818728. [PMID: 35345768 PMCID: PMC8957276 DOI: 10.3389/fmed.2022.818728] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 02/11/2022] [Indexed: 12/15/2022] Open
Abstract
We propose an initial explanation for how myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) could originate and perpetuate by drawing on findings from critical illness research. Specifically, we combine emerging findings regarding (a) hypoperfusion and endotheliopathy, and (b) intestinal injury in these illnesses with our previously published hypothesis about the role of (c) pituitary suppression, and (d) low thyroid hormone function associated with redox imbalance in ME/CFS. Moreover, we describe interlinkages between these pathophysiological mechanisms as well as “vicious cycles” involving cytokines and inflammation that may contribute to explain the chronic nature of these illnesses. This paper summarizes and expands on our previous publications about the relevance of findings from critical illness for ME/CFS. New knowledge on diagnostics, prognostics and treatment strategies could be gained through active collaboration between critical illness and ME/CFS researchers, which could lead to improved outcomes for both conditions.
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Affiliation(s)
| | - Jonas Bergquist
- Division of Analytical Chemistry and Neurochemistry, Department of Chemistry - Biomedical Center, Uppsala University, Uppsala, Sweden.,The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Collaborative Research Centre at Uppsala University, Uppsala, Sweden
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7
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Lisco G, Giagulli VA, Iovino M, Zupo R, Guastamacchia E, De Pergola G, Iacoviello M, Triggiani V. Endocrine system dysfunction and chronic heart failure: a clinical perspective. Endocrine 2022; 75:360-376. [PMID: 34713389 PMCID: PMC8553109 DOI: 10.1007/s12020-021-02912-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 10/13/2021] [Indexed: 11/01/2022]
Abstract
Chronic heart failure (CHF) leads to an excess of urgent ambulatory visits, recurrent hospital admissions, morbidity, and mortality regardless of medical and non-medical management of the disease. This excess of risk may be attributable, at least in part, to comorbid conditions influencing the development and progression of CHF. In this perspective, the authors examined and described the most common endocrine disorders observed in patients with CHF, particularly in individuals with reduced ejection fraction, aiming to qualify the risks, quantify the epidemiological burden and discuss about the potential role of endocrine treatment. Thyroid dysfunction is commonly observed in patients with CHF, and sometimes it could be the consequence of certain medications (e.g., amiodarone). Male and female hypogonadism may also coexist in this clinical context, contributing to deteriorating the prognosis of these patients. Furthermore, growth hormone deficiency may affect the development of adult myocardium and predispose to CHF. Limited recommendation suggests to screen endocrine disorders in CHF patients, but it could be interesting to evaluate possible endocrine dysfunction in this setting, especially when a high suspicion coexists. Data referring to long-term safety and effectiveness of endocrine treatments in patients with CHF are limited, and their impact on several "hard" endpoints (such as hospital admission, all-cause, and cardiovascular mortality) are still poorly understood.
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Affiliation(s)
- Giuseppe Lisco
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari "Aldo Moro", School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Vito Angelo Giagulli
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari "Aldo Moro", School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Michele Iovino
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari "Aldo Moro", School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Roberta Zupo
- National Institute of Gastroenterology, Saverio de Bellis, Research Hospital, Castellana Grotte, Bari, Italy
| | - Edoardo Guastamacchia
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari "Aldo Moro", School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Giovanni De Pergola
- National Institute of Gastroenterology, Saverio de Bellis, Research Hospital, Castellana Grotte, Bari, Italy
- Clinical Nutrition Unit, Medical Oncology, Department of Internal Medicine and Clinical Oncology, University of Bari, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy
| | - Massimo Iacoviello
- Department of Medical and Surgical Sciences, Cardiology Department, University of Foggia, Foggia, Italy
| | - Vincenzo Triggiani
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, University of Bari "Aldo Moro", School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124, Bari, Italy.
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8
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Shi Q, Wu M, Chen P, Wei B, Tan H, Huang P, Chang S. Criminal of Adverse Pregnant Outcomes: A Perspective From Thyroid Hormone Disturbance Caused by SARS-CoV-2. Front Cell Infect Microbiol 2022; 11:791654. [PMID: 35047419 PMCID: PMC8761741 DOI: 10.3389/fcimb.2021.791654] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/06/2021] [Indexed: 01/11/2023] Open
Abstract
Nowadays, emerging evidence has shown adverse pregnancy outcomes, including preterm birth, preeclampsia, cesarean, and perinatal death, occurring in pregnant women after getting infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the underlying mechanisms remain elusive. Thyroid hormone disturbance has been unveiled consistently in various studies. As commonly known, thyroid hormone is vital for promoting pregnancy and optimal fetal growth and development. Even mild thyroid dysfunction can cause adverse pregnancy outcomes. We explored and summarized possible mechanisms of thyroid hormone abnormality in pregnant women after coronavirus disease 2019 (COVID-19) infection and made a scientific thypothesis that adverse pregnancy outcomes can be the result of thyroid hormone disorder during COVID-19. In which case, we accentuate the importance of thyroid hormone surveillance for COVID-19-infected pregnant women.
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Affiliation(s)
- Qiman Shi
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Min Wu
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Pei Chen
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Bo Wei
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Hailong Tan
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Peng Huang
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China
| | - Shi Chang
- Department of General Surgery, Xiangya Hospital Central South University, Changsha, China.,Clinical Research Center for Thyroid Disease in Hunan Province, Changsha, China.,Hunan Provincial Engineering Research Center for Thyroid and Related Diseases Treatment Technology, Changsha, China.,National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China
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9
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Murugan AK, Alzahrani AS. SARS-CoV-2: Emerging Role in the Pathogenesis of Various Thyroid Diseases. J Inflamm Res 2021; 14:6191-6221. [PMID: 34853527 PMCID: PMC8628126 DOI: 10.2147/jir.s332705] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 10/11/2021] [Indexed: 12/12/2022] Open
Abstract
Coronavirus disease-2019 (COVID-19) is asymptomatic in most cases, but it is impartible and fatal in fragile and elderly people. Heretofore, more than four million people succumbed to COVID-19, while it spreads to every part of the globe. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) induces various dysfunctions in many vital organs including the thyroid by utilizing ACE2 as a receptor for cellular entry. Emerging reports clearly show the involvement of SARS-CoV-2 in diverse thyroid disorders. Thus, this review article aims to review comprehensively all the recent developments in SARS-CoV-2-induced pathogenesis of thyroid diseases. The review briefly summarizes the recent key findings on the mechanism of SARS-CoV-2 infection, the role of ACE2 receptor in viral entry, SARS-CoV-2-activated molecular signaling in host cells, ACE2 expression in the thyroid, cytokine storm, and its vital role in thyroid dysfunction and long-COVID in relation to thyroid and autoimmunity. Further, it extensively discusses rapidly evolving knowledge on the potential part of SARS-CoV-2 in emerging various thyroid dysfunctions during and post-COVID-19 conditions which include subacute thyroiditis, Graves' diseases, Hashimoto’s thyroiditis, thyrotoxicosis, and other recent advances in further discerning the implications of this virus within thyroid dysfunction. Unraveling the pathophysiology of SARS-CoV-2-triggered thyroid dysfunctions may aid pertinent therapeutic options and management of these patients in both during and post-COVID-19 scenarios.
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Affiliation(s)
- Avaniyapuram Kannan Murugan
- Division of Molecular Endocrinology, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia
| | - Ali S Alzahrani
- Division of Molecular Endocrinology, Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia.,Department of Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, 11211, Saudi Arabia
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10
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Lisco G, De Tullio A, Jirillo E, Giagulli VA, De Pergola G, Guastamacchia E, Triggiani V. Thyroid and COVID-19: a review on pathophysiological, clinical and organizational aspects. J Endocrinol Invest 2021; 44:1801-1814. [PMID: 33765288 PMCID: PMC7992516 DOI: 10.1007/s40618-021-01554-z] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Accepted: 03/10/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Thyroid dysfunction has been observed in patients with COVID-19, and endocrinologists are requested to understand this clinical issue. Pandemic-related restrictions and reorganization of healthcare services may affect thyroid disease management. OBJECTIVE AND METHODS To analyze and discuss the relationship between COVID-19 and thyroid diseases from several perspectives. PubMed/MEDLINE, Google Scholar, Scopus, ClinicalTrial.gov were searched for this purpose by using free text words and medical subject headings as follows: "sars cov 2", "covid 19", "subacute thyroiditis", "atypical thyroiditis", "chronic thyroiditis", "hashimoto's thyroiditis", "graves' disease", "thyroid nodule", "differentiated thyroid cancer", "medullary thyroid cancer", "methimazole", "levothyroxine", "multikinase inhibitor", "remdesivir", "tocilizumab". Data were collected, analyzed, and discussed to answer the following clinical questions: "What evidence suggests that COVID-19 may induce detrimental consequences on thyroid function?"; "Could previous or concomitant thyroid diseases deteriorate the prognosis of COVID-19 once the infection has occurred?"; "Could medical management of thyroid diseases influence the clinical course of COVID-19?"; "Does medical management of COVID-19 interfere with thyroid function?"; "Are there defined strategies to better manage endocrine diseases despite restrictive measures and in-hospital and ambulatory activities reorganizations?". RESULTS SARS-CoV-2 may induce thyroid dysfunction that is usually reversible, including subclinical and atypical thyroiditis. Patients with baseline thyroid diseases are not at higher risk of contracting or transmitting SARS-CoV-2, and baseline thyroid dysfunction does not foster a worse progression of COVID-19. However, it is unclear whether low levels of free triiodothyronine, observed in seriously ill patients with COVID-19, may worsen the disease's clinical progression and, consequently, if triiodothyronine supplementation could be a tool for reducing this burden. Glucocorticoids and heparin may affect thyroid hormone secretion and measurement, respectively, leading to possible misdiagnosis of thyroid dysfunction in severe cases of COVID-19. High-risk thyroid nodules require a fine-needle aspiration without relevant delay, whereas other non-urgent diagnostic procedures and therapeutic interventions should be postponed. DISCUSSION Currently, we know that SARS-CoV-2 could lead to short-term and reversible thyroid dysfunction, but thyroid diseases seem not to affect the progression of COVID-19. Adequate management of patients with thyroid diseases remains essential during the pandemic, but it could be compromised because of healthcare service restrictions. Endocrine care centers should continuously recognize and classify priority cases for in-person visits and therapeutic procedures. Telemedicine may be a useful tool for managing patients not requiring in-person visits.
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Affiliation(s)
- G Lisco
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari "Aldo Moro", Bari, Apulia, Italy.
| | - A De Tullio
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari "Aldo Moro", Bari, Apulia, Italy
| | - E Jirillo
- Department of Basic Medical Science, Neuroscience and Sensory Organs, University of Bari Aldo Moro, Bari, Apulia, Italy
| | - V A Giagulli
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari "Aldo Moro", Bari, Apulia, Italy
| | - G De Pergola
- Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Aldo Moro, Bari, Apulia, Italy
| | - E Guastamacchia
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari "Aldo Moro", Bari, Apulia, Italy
| | - V Triggiani
- Interdisciplinary Department of Medicine, Section of Internal Medicine, Geriatrics, Endocrinology and Rare Diseases, School of Medicine, University of Bari "Aldo Moro", Bari, Apulia, Italy.
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11
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Ruggeri RM, Campennì A, Deandreis D, Siracusa M, Tozzoli R, Petranović Ovčariček P, Giovanella L. SARS-COV-2-related immune-inflammatory thyroid disorders: facts and perspectives. Expert Rev Clin Immunol 2021; 17:737-759. [PMID: 34015983 PMCID: PMC8182818 DOI: 10.1080/1744666x.2021.1932467] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Accepted: 05/18/2021] [Indexed: 02/06/2023]
Abstract
Introduction: During the COVID-19 pandemic thyroid gland alteration/dysfunction has been emerged as a possible endocrine complication. The present review is focused on inflammatory and autoimmune thyroid complications triggered by SARS-CoV-2 infection by searching through databases like MEDLINE and Scopus up to April 2021.Areas covered: Beside the occurrence of 'non-thyroidal illness' in severe clinical conditions, alterations of thyroid function and structure may occur during COVID-19 as a consequence of either direct or indirect effects of SARS-CoV-2 infection on the gland. On the one hand, SARS-CoV-2 uses ACE2 as a receptor to infect the host cells and ACE2 is highly expressed by follicular thyroid cells. On the other hand, COVID-19 is associated with a systemic inflammatory and immune response, involving Th1/Th17/Th2 lymphocytes and proinflammatory cytokines, which resembles the immune activation that occurs in immune-mediated thyroid diseases. COVID-19-related thyroid disorders include destructive thyroiditis and onset or relapse of autoimmune thyroid disorders, leading to a broad spectrum of thyroid dysfunction ranging from thyrotoxicosis to hypothyroidism, that may worsen COVID-19 clinical course and affect prognosis.Expert opinion: Physicians should be aware of the possible occurrence of thyroid dysfunction during and after SARS-CoV-2 infection. Further longitudinal studies are warranted to evaluate potential long-term sequelae.
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Affiliation(s)
- Rosaria Maddalena Ruggeri
- Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Alfredo Campennì
- Unit of Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy
| | - Desiree Deandreis
- Department of Nuclear Medicine, Nuclear Medicine Division, AOU Città Della Salute E Della Scienza, University of Turin, Turin, Italy
| | - Massimiliano Siracusa
- Unit of Nuclear Medicine, Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, University of Messina, Messina, Italy
| | - Renato Tozzoli
- Endocrinology Unit, S. Giorgio Hospital, Pordenone, Italy
| | - Petra Petranović Ovčariček
- Department of Oncology and Nuclear Medicine, University Hospital Center “Sestre Milosrdnice”, Zagreb, Croatia
| | - Luca Giovanella
- Clinic for Nuclear Medicine and Competence Centre for Thyroid Diseases, Imaging Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
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12
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Stanculescu D, Larsson L, Bergquist J. Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Med (Lausanne) 2021; 8:672370. [PMID: 34026797 PMCID: PMC8137963 DOI: 10.3389/fmed.2021.672370] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 04/01/2021] [Indexed: 12/20/2022] Open
Abstract
We here provide an overview of treatment trials for prolonged intensive care unit (ICU) patients and theorize about their relevance for potential treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these treatment trials generally target: (a) the correction of suppressed endocrine axes, notably through a "reactivation" of the pituitary gland's pulsatile secretion of tropic hormones, or (b) the interruption of the "vicious circle" between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. There are significant parallels in the treatment trials for prolonged critical illness and ME/CFS; this is consistent with the hypothesis of an overlap in the mechanisms that prevent recovery in both conditions. Early successes in the simultaneous reactivation of pulsatile pituitary secretions in ICU patients-and the resulting positive metabolic effects-could indicate an avenue for treating ME/CFS. The therapeutic effects of thyroid hormones-including in mitigating O&NS and inflammation and in stimulating the adreno-cortical axis-also merit further studies. Collaborative research projects should further investigate the lessons from treatment trials for prolonged critical illness for solving ME/CFS.
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Affiliation(s)
| | - Lars Larsson
- Basic and Clinical Muscle Biology, Department of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden
| | - Jonas Bergquist
- Analytical Chemistry and Neurochemistry, Department of Chemistry–Biomedical Center, Uppsala University, Uppsala, Sweden
- The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Collaborative Research Centre at Uppsala University, Uppsala, Sweden
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13
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Croce L, Gangemi D, Ancona G, Liboà F, Bendotti G, Minelli L, Chiovato L. The cytokine storm and thyroid hormone changes in COVID-19. J Endocrinol Invest 2021; 44:891-904. [PMID: 33559848 PMCID: PMC7871522 DOI: 10.1007/s40618-021-01506-7] [Citation(s) in RCA: 52] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Accepted: 01/09/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND COVID-19 is now a worldwide pandemic. Among the many extra-pulmonary manifestations of COVID-19, recent evidence suggested a possible occurrence of thyroid dysfunction. PURPOSE The Aim of the present review is to summarize available studies regarding thyroid function alterations in patients with COVID-19 and to overview the possible physio-pathological explanations. CONCLUSIONS The repercussions of the thyroid of COVID-19 seem to be related, in part, with the occurrence of a "cytokine storm" that would, in turn, induce a "non-thyroidal illness". Some specific cytokines and chemokines appear to have a direct role on the hypothalamus-pituitary-thyroid axis. On the other hand, some authors have observed an increased incidence of a destructive thyroiditis, either subacute or painless, in patients with COVID-19. The hypothesis of a direct infection of the thyroid by SARS-Cov-2 stems from the observation that its receptor, ACE2, is strongly expressed in thyroid tissue. Lastly, it is highly probable that some pharmaceutical agents largely used for the treatment of COVID-19 can act as confounding factors in the laboratory evaluation of thyroid function parameters.
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Affiliation(s)
- L Croce
- Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Istituti Clinici Scientifici Maugeri IRCCS, 27100, Pavia, Italy
- PHD Course in Experimental Medicine, University of Pavia, 27100, Pavia, Italy
- Department of Internal Medicine and Therapeutics, University of Pavia, Via S. Maugeri 4, 27100, Pavia, Italy
| | - D Gangemi
- Postgraduate School in Endocrinology and Metabolism, University of Pavia, 27100, Pavia, Italy
| | - G Ancona
- Postgraduate School in Endocrinology and Metabolism, University of Pavia, 27100, Pavia, Italy
| | - F Liboà
- Postgraduate School in Endocrinology and Metabolism, University of Pavia, 27100, Pavia, Italy
| | - G Bendotti
- Postgraduate School in Endocrinology and Metabolism, University of Pavia, 27100, Pavia, Italy
| | - L Minelli
- Postgraduate School in Endocrinology and Metabolism, University of Pavia, 27100, Pavia, Italy
| | - L Chiovato
- Unit of Internal Medicine and Endocrinology, Laboratory for Endocrine Disruptors, Istituti Clinici Scientifici Maugeri IRCCS, 27100, Pavia, Italy.
- Department of Internal Medicine and Therapeutics, University of Pavia, Via S. Maugeri 4, 27100, Pavia, Italy.
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14
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Stanculescu D, Larsson L, Bergquist J. Hypothesis: Mechanisms That Prevent Recovery in Prolonged ICU Patients Also Underlie Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front Med (Lausanne) 2021; 8:628029. [PMID: 33585528 PMCID: PMC7876311 DOI: 10.3389/fmed.2021.628029] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 01/08/2021] [Indexed: 12/13/2022] Open
Abstract
Here the hypothesis is advanced that maladaptive mechanisms that prevent recovery in some intensive care unit (ICU) patients may also underlie Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these mechanisms are: (a) suppression of the pituitary gland's pulsatile secretion of tropic hormones, and (b) a "vicious circle" between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. This hypothesis should be investigated through collaborative research projects.
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Affiliation(s)
| | - Lars Larsson
- Basic and Clinical Muscle Biology, Department of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden
| | - Jonas Bergquist
- Analytical Chemistry and Neurochemistry, Department of Chemistry – Biomedical Center, Uppsala University, Uppsala, Sweden
- The Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Collaborative Research Centre at Uppsala University, Uppsala, Sweden
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15
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Arambam P, Kaul U, Ranjan P, Janardhanan R. Prognostic implications of thyroid hormone alterations in acute coronary syndrome-A systematic review. Indian Heart J 2020; 73:143-148. [PMID: 33865509 PMCID: PMC8065368 DOI: 10.1016/j.ihj.2020.11.147] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Accepted: 11/20/2020] [Indexed: 12/28/2022] Open
Abstract
There is considerable association of thyroid function and the cardiovascular system during various acute systemic illnesses. It is well established that the normal thyroid homeostasis is known to alter in disease states including the acute coronary syndromes (ACS). Abnormal thyroid hormonal status has been shown to be related to worse outcomes and prognosis. This review focuses on the relationship of alterations in thyroid function and its influence on the pathophysiological mechanisms and cardiovascular hemodynamics in ACS and based upon the literature, summarises all the existing evidence to this date on this subject. The data largely points out that low levels of triiodothyronine (T3) levels seen in ACS might be useful in prognosticating the outcomes of ACS.
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Affiliation(s)
- Priyadarshini Arambam
- Academics & Research Department, Batra Heart Center, Batra Hospital and Medical Research Center, New Delhi, India; Labratory of Disease Dynamics and Molecular Epidemiology, Amity Institute of Public Health, Amity University Campus, Noida, Uttar Pradesh, India.
| | - Upendra Kaul
- Academics & Research Department, Batra Heart Center, Batra Hospital and Medical Research Center, New Delhi, India
| | - Priya Ranjan
- Amity School of Engineering and Technology, Amity University Campus, Noida, Uttar Pradesh, India
| | - Rajiv Janardhanan
- Labratory of Disease Dynamics and Molecular Epidemiology, Amity Institute of Public Health, Amity University Campus, Noida, Uttar Pradesh, India
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16
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Zhang T, Shi J, Peng Y, Wang S, Mu Q, Fang Q, Gu W, Hong J, Zhang Y, Wang W. Sex-influenced association between free triiodothyronine levels and poor glycemic control in euthyroid patients with type 2 diabetes mellitus. J Diabetes Complications 2020; 34:107701. [PMID: 32888789 DOI: 10.1016/j.jdiacomp.2020.107701] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Revised: 07/07/2020] [Accepted: 07/26/2020] [Indexed: 01/12/2023]
Abstract
OBJECTIVE The study investigated the association between free triiodothyronine (FT3) and poor glycemic control with different definitions in euthyroid patients with type 2 diabetes mellitus (T2DM). METHODS This was a cross-sectional study which included 2172 patients from National Metabolic Management Center in Ruijin Hospital. The association between thyroid function and glycated hemoglobin A1c (HbA1c) was determined by multiple liner regression models. The association between FT3 and poor glycemic control was further determined by binary logistic regression models. Two definitions of poor glycemic control (HbA1c ≥ 7% and HbA1c ≥ 8%) were applied when we analyzed the association. RESULTS Prevalence of HbA1c ≥ 7% and HbA1c ≥ 8% were 63.8% and 39.3%, respectively. After adjusting for confounding factors, FT3, rather than free tetraiodothyronine (FT4) or thyroid stimulating hormone (TSH), was independently associated with HbA1c (β = -0.104, P = 0.002). Further analysis after gender stratification showed that the association was only found in males (β = -0.164, P < 0.001). We further analyzed the association between FT3 quartiles and poor glycemic control. FT3 quartiles were not significantly associated with the risk of HbA1c ≥ 7% before and after adjusting for confounding factors in both genders. FT3 quartiles were negatively associated with the risk of HbA1c ≥ 8% only in males, independent of traditional risk factors for poor glycemic control (P for trend = 0.030). CONCLUSIONS FT3 in the reference range was significantly associated with reduced risk of HbA1c ≥ 8% in males, independent of traditional risk factors for poor glycemic control.
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Affiliation(s)
- Tianyue Zhang
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Juan Shi
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ying Peng
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Shujie Wang
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qian Mu
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qianhua Fang
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiqiong Gu
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jie Hong
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yifei Zhang
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Weiqing Wang
- Shanghai National Clinical Research Center for Metabolic Diseases, Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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17
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Borisov DV, Gubaeva DN, Praskurnichiy EA. [Use of thyroid hormones in the treatment of cardiovascular diseases: literature review]. ACTA ACUST UNITED AC 2020; 66:6-14. [PMID: 33351333 DOI: 10.14341/probl12471] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 06/29/2020] [Accepted: 06/30/2020] [Indexed: 12/18/2022]
Abstract
Cardiovascular diseases remain the leading cause of death all over the world. Thyroid hormones play a significant role in the regulation of cardiac function. According to a number of researches, patients with cardiovascular diseases usually have a decrease in the concentration of thyroid hormones in the blood serum, which may be associated with a poor prognosis. Today it still remains unclear whether the change in the bioavailability of thyroid hormones in the myocardium is a favorable physiological mechanism or a replication of an adaptation disorder. Experimental researches suggest that thyroid hormone therapy may be applied in clinical cardiology. This review describes the results of researches examining the use of thyroid hormones in patients with cardiovascular diseases, as well as experiment data on animal models. The available data on the use of thyroid hormones in patients with acute myocardial infarction and heart failure allow us to suggest that normalization of thyroid hormone levels is a safe and potentially effective treatment method in the group of patients with cardiovascular disease. At the same time, the data on the use of thyroid hormones in patients who have undergone an open-heart surgery or heart transplantation are limited. However, at present, it is difficult to draw unambiguous conclusions about the benefits, as well as about the possible risk of using thyroid hormones in the described conditions. Large-scale clinical researches are required to confirm the safety and evaluate the effectiveness of such therapy. Moreover, it is necessary to set parameters for evaluating the safety and effectiveness and understand which hormone (thyroxine or triiodothyronine), what dosage and at what stage of the disease should be applied. Until we do not have answers for these questions, thyroid hormone therapy in patients with cardiovascular diseases should remain within the research field.
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18
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Abdel-Moneim A, Gaber AM, Gouda S, Osama A, Othman SI, Allam G. Relationship of thyroid dysfunction with cardiovascular diseases: updated review on heart failure progression. Hormones (Athens) 2020; 19:301-309. [PMID: 32488814 DOI: 10.1007/s42000-020-00208-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Accepted: 05/05/2020] [Indexed: 12/21/2022]
Abstract
Heart disease remains the leading cause of death globally. Heart failure (HF) is a clinical syndrome that results from impairment of the ability of the ventricle to fill with or eject blood. Over the past two decades, accumulated evidence has revealed the contribution of thyroid hormones to cardiovascular (CV) events, exerting their action through genomic and non-genomic pathways within the cardiomyocytes. The pivotal role of thyroid hormones in maintaining cardiac homeostasis has been observed in previous investigations which suggest that the CV system is adversely impacted by fluctuations in thyroid hormone levels, such as those that occur in hypothyroidism, hyperthyroidism, and low triiodothyronine syndrome (LT3S). Thyroid dysfunction has direct effects on myocardial contractility, systolic and diastolic blood pressure, heart mass, heart rate, ejection fraction, and heart output, which may ultimately lead to HF. Recent clinical data have shown that thyroid hormone replacement therapy for hypothyroid patients appears to provide the potential for reducing CV events. Therefore, this review aims to address the impact of thyroid hormone dysfunction on pathophysiological mechanisms contributing to the development and progression of HF.
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Affiliation(s)
- Adel Abdel-Moneim
- Molecular Physiology Division, Faculty of Science, Beni-Suef University, Salah Salem St., Beni Suef, 62511,, Egypt.
| | - Asmaa M Gaber
- Molecular Physiology Division, Faculty of Science, Beni-Suef University, Salah Salem St., Beni Suef, 62511,, Egypt
| | - Sherouk Gouda
- Zoology/Chemistry Program, Faculty of Science, Beni-Suef University, Beni Suef, Egypt
| | - Aya Osama
- Zoology/Chemistry Program, Faculty of Science, Beni-Suef University, Beni Suef, Egypt
| | - Sarah I Othman
- Biology Department, Faculty of Science, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia
| | - Gamal Allam
- Immunology Section, Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt
- Egyptian-Korean Faculty for Technological Industry and Energy, Beni-Suef Technological University, Beni-Suef, Egypt
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19
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Lisco G, De Tullio A, Iacoviello M, Triggiani V. Congestive Heart Failure and Thyroid Dysfunction: The Role of the Low T3 Syndrome and Therapeutic Aspects. Endocr Metab Immune Disord Drug Targets 2020; 20:646-653. [PMID: 31742499 DOI: 10.2174/1871530319666191119112950] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2019] [Revised: 10/23/2019] [Accepted: 11/25/2019] [Indexed: 01/13/2023]
Abstract
Background:
Both the morbidity and mortality rates from congestive heart failure (CHF)
remain elevated despite the medical and non-medical management of the disease, thus suggesting the
existence of residual risk factors such as thyroid dysfunction. Particularly, the 15-30% of patients with
CHF, especially those with severe ventricular dysfunction, display the so-called low T3 syndrome
(LT3S), which seems to negatively affect the cardiovascular prognosis.
Objective:
Only a few clinical trials have been carried out to verify both the safety and the efficacy of
thyroid replacement in the LT3S, aiming to ameliorate the prognosis of CHF, and most of the results
were controversial.
Methods:
Since the aim of the present review was to briefly overview both the indication and contraindication
of triiodothyronine replacement in CHF and LT3S, the authors searched PubMed using the
medical subject headings (MeSH) related to the following terms: “congestive heart failure” and “low
T3 syndrome” or “euthyroid sick syndrome” or “non-thyroidal sick syndrome”. The research study
only focused on the narrative and systematic reviews, randomized clinical trials and meta-analysis
studies which were conducted before June 2019.
Results:
Studies conducted in both animal models and humans provided controversial information
about the effectiveness and safety of the T3 replacement for improving ventricular dysfunction, particularly
in the long-term.
Conclusion:
Further clinical trials are needed to better explore the role of LT3S in patients with CHF
and its consequent therapeutic strategy in this clinical setting.
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Affiliation(s)
- Giuseppe Lisco
- Hospital Unit of Internal Medicine, Miulli Hospital, Acquaviva delle Fonti, Bari, Italy
| | - Anna De Tullio
- Local Health District of Bari, Section of Endocrinology, Bari, Italy
| | - Massimo Iacoviello
- University Cardiology Unit, Cardiothoracic Department, Policlinic University Hospital, Bari, Italy
| | - Vincenzo Triggiani
- Interdisciplinary Department of Medicine, University of Bari, Bari, Italy
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Abstract
Thyroid hormone levels are reduced in cardiovascular diseases and this phenomenon is associated with worse outcomes. It is unclear whether the changes in thyroid hormone bioavailability to the affected myocardium are beneficial or if this is a maladaptive response. Experimental studies from animal models of acute myocardial infarction (AMI) suggest that thyroid hormone treatment may be beneficial. There is limited data available on the use of thyroid hormones in patients with AMI and heart failure and this suggests that treatment to normalise thyroid hormone levels may be safe and potentially efficacious. Similarly, evidence of thyroid hormone therapy in patients undergoing cardiac surgery or during cardiac transplantation is limited. It is therefore difficult to draw any firm conclusions about benefits or risks of thyroid hormone treatment in these conditions. Large scale clinical trials of thyroid hormones in patients with cardiac conditions are required to confirm safety and evaluate efficacy. Furthermore, it needs to be elucidated which hormone to administer (thyroxine or triiodothyronine), when in the disease pathway to treat, dose of thyroid hormone to administer, and which parameters to utilise to assess safety and efficacy. Until these important questions are answered thyroid hormone therapy in cardiovascular diseases must remain within the research domain.
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Affiliation(s)
- Salman Razvi
- Institute of Genetic Medicine and Queen Elizabeth Hospital, Newcastle University, Centre for Life, Central Park, Newcastle upon Tyne, NE1 3BZ, UK.
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21
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Gałecka E, Kumor-Kisielewska A, Górski P. Assessment of serum levels of DIO1 and DIO3 in patients diagnosed with COPD. Adv Med Sci 2019; 64:344-348. [PMID: 31022560 DOI: 10.1016/j.advms.2019.04.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 03/18/2019] [Accepted: 04/03/2019] [Indexed: 10/27/2022]
Abstract
PURPOSE Chronic obstructive pulmonary disease is the most common chronic lung disease, which may be caused by different pathological processes, including inflammation. Furthermore, signs of changes in thyroid hormone levels are found in some patients. Deiodinases (DIOs) are selenoproteins (enzymes) involved in the synthesis of thyroid hormones. It has been found that these molecules are involved in inflammatory processes. We carried out this preliminary study to investigate the levels of two deiodinases, i.e. type 1 deiodinase (DIO1) and type 3 deiodinase (DIO3), and their possible association with COPD and specific clinical parameters. PATIENTS AND METHODS Serum levels of DIO1 and DIO3 as well as lung function parameters were measured in 50 patients suffering from COPD and 30 healthy control subjects. The Mann-Whitney U test and Pearson's correlation coefficient were used to compare and correlate data. RESULTS Serum levels of DIO1 and DIO3 were significantly elevated in COPD patients (97.9 ± 55.6 versus 28.2 ± 28.3 U/L for DIO1 and 19.6 ± 10.7 versus 6.4 ± 6.3 U/L for DIO3; p < 0.001). No correlation between serum levels of the examined DIOs and other sociodemographic and clinical parameters was identified in this study. CONCLUSION For the first time we observed that peripheral DIO1 and DIO3 concentrations were elevated in COPD; hence, we may cautiously begin considering these molecules as potential circulating biomarkers of COPD. It may also be beneficial to conduct further studies to confirm and clarify their potential role.
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22
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Falkowski B, Rogowicz-Frontczak A, Grzelka A, Uruska A, Schlaffke J, Araszkiewicz A, Zozulinska-Ziolkiewicz D. Higher free triiodothyronine concentration is associated with lower prevalence of microangiopathic complications and better metabolic control in adult euthyroid people with type 1 diabetes. Endocrine 2018; 60:458-465. [PMID: 29603069 PMCID: PMC5937901 DOI: 10.1007/s12020-018-1582-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 03/09/2018] [Indexed: 12/24/2022]
Abstract
PURPOSE Type 1 diabetes mellitus (T1DM) is a disorder of insulin deficiency but with a wide range of hormones simultaneously disturbed. The study was performed to explore relation of free triiodothyronine (FT3) with metabolic control and occurrence of microangiopathic complications. METHODS A total of 266 adult T1DM participants [56% men; 32 (interquartile range, IQR: 25-39) years and disease duration 13 (IQR: 8-19) years] in euthyroid state with negative history for hypothyroidism were included to the study. Participants were screened for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and FT3. Moreover, microangiopathic complications (retinopathy, diabetic kidney disease, peripheral and autonomic neuropathy), markers of metabolic control such as glycated hemoglobin (HbA1c) were evaluated. RESULTS A total of 114 (42.9%) people had diagnosed at least one microangiopathic complication. In multivariable linear regression higher HbA1c was statistically significant independent predictor of lower FT3 (β = -0.25; p < 0.0001) after adjustment for sex, T1DM duration, HbA1c, waist-to-hip ratio (WHR) (R2 = 0.15, p < 0.0001). Higher FT3 was simultaneously a predictor of lower prevalence of microangiopathy in multivariate logistic regression analysis (odds ratio, 0.51; 95% confidence interval, 0.27-0.98; p = 0.04) after an adjustment for: age, hypertension, HbA1c, WHR and total cholesterol (TC). CONCLUSIONS FT3 as tissue active hormone plays a clinically important role in T1DM people. The higher FT3 concentration is related to the lower prevalence of microangiopathy and better metabolic control of the disease in adult euthyroid people with T1DM.
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Affiliation(s)
- Bogusz Falkowski
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Mickiewicza 2, Poznan, 60-834, Poland.
| | - Anita Rogowicz-Frontczak
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Mickiewicza 2, Poznan, 60-834, Poland
| | - Agata Grzelka
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Mickiewicza 2, Poznan, 60-834, Poland
| | - Aleksandra Uruska
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Mickiewicza 2, Poznan, 60-834, Poland
| | - Judyta Schlaffke
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Mickiewicza 2, Poznan, 60-834, Poland
| | - Aleksandra Araszkiewicz
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Mickiewicza 2, Poznan, 60-834, Poland
| | - Dorota Zozulinska-Ziolkiewicz
- Department of Internal Medicine and Diabetology, Poznan University of Medical Sciences, Mickiewicza 2, Poznan, 60-834, Poland
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Testosterone and Cardiovascular Diseases: Causes or Consequences: The Lesson from the Last 5 Years. CURRENT SEXUAL HEALTH REPORTS 2017. [DOI: 10.1007/s11930-017-0132-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
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Corona G, Dicuio M, Rastrelli G, Maseroli E, Lotti F, Sforza A, Maggi M. Testosterone treatment and cardiovascular and venous thromboembolism risk: what is 'new'? J Investig Med 2017; 65:964-973. [PMID: 28495861 DOI: 10.1136/jim-2017-000411] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/19/2017] [Indexed: 12/21/2022]
Abstract
In men, testosterone (T) production declines as a function of ageing. Late-onset hypogonadism (LOH) is the most commonly used term to indicate this age-related condition. In LOH, the relative clinical significance and the potential benefit of testosterone treatment (TTh) are still the subject of strong criticisms in the scientific community. The debate is further complicated by the recent position statement of the US Food and Drug Administration (FDA) emphasizing that, in LOH, the benefits and safety of TTh have not been fully established. Hence, the FDA required a labeling change to inform patients about a possible increased cardiovascular (CV) risk of TTh. Similar considerations were previously released by the FDA and by Health Canada concerning a TTh-related venous thromboembolism (VTE) risk. In this review, we will summarize the available evidence concerning a possible link among TTh and CV and VTE risks. For this purpose, data derived from epidemiological studies analyzing relationships between the aforementioned risks and endogenous T levels will be analyzed. In addition, evidence deriving from interventional studies including pharmacoepidemiological and placebo-controlled randomized controlled trials (RCTs) will be examined. Our analysis shows that available data do not support an increased CV risk related to TTh. Similar considerations can be drawn for the relationship between TTh and VTE. The previously reported cases of TTh-related VTE were frequently related to a previously undiagnosed thrombophilia-hypofibrinolysis status. Hence, an anamnestic screening for thrombophilia before starting TTh is recommended, just as it is for the use of oral contraceptives.
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Affiliation(s)
- G Corona
- Endocrinology Unit, Medical Department, Maggiore-Bellaria Hospital, Azienda-Usl Bologna, Bologna, Italy
| | - M Dicuio
- Urology Unit, Maggiore Hospital, Bologna, Italy.,Department of Urology, Sahlgrenska University Hospital, Göteborg, Sweden
| | - G Rastrelli
- Sexual Medicine and Andrology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy
| | - E Maseroli
- Sexual Medicine and Andrology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy
| | - F Lotti
- Sexual Medicine and Andrology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy
| | - A Sforza
- Endocrinology Unit, Medical Department, Maggiore-Bellaria Hospital, Azienda-Usl Bologna, Bologna, Italy
| | - M Maggi
- Sexual Medicine and Andrology Unit, Department of Experimental, Clinical and Biomedical Sciences, University of Florence, Florence, Italy
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25
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Gałecka E, Kumor-Kisielewska A, Orzechowska A, Maes M, Górski P, Szemraj J. Assessment of type 1 and type 3 deiodinase expression levels in depressive disorders. Acta Neurobiol Exp (Wars) 2017. [DOI: 10.21307/ane-2017-056] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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26
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Khan MA, Garg K, Bhurani D, Agarwal NB. Early manifestation of mild cognitive impairment in B-cell non-Hodgkin’s lymphoma patients receiving CHOP and rituximab-CHOP chemotherapy. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:1253-1265. [DOI: 10.1007/s00210-016-1290-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 08/18/2016] [Indexed: 02/04/2023]
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27
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Contreras-Jurado C, Alonso-Merino E, Saiz-Ladera C, Valiño AJ, Regadera J, Alemany S, Aranda A. The Thyroid Hormone Receptors Inhibit Hepatic Interleukin-6 Signaling During Endotoxemia. Sci Rep 2016; 6:30990. [PMID: 27484112 PMCID: PMC4971531 DOI: 10.1038/srep30990] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2016] [Accepted: 07/11/2016] [Indexed: 02/07/2023] Open
Abstract
Decreased thyroidal hormone production is found during lipopolysaccharide (LPS)-induced endotoxic shock in animals as well as in critically ill patients. Here we studied the role of the thyroid hormone receptors (TRs) in activation of STAT3, NF-κB and ERK, which play a key role in the response to inflammatory cytokines during sepsis. TR knockout mice showed down-regulation of hepatic inflammatory mediators, including interleukin 6 (IL-6) in response to LPS. Paradoxically, STAT3 and ERK activity were higher, suggesting that TRs could act as endogenous repressors of these pathways. Furthermore, hyperthyroidism increased cytokine production and mortality in response to LPS, despite decreasing hepatic STAT3 and ERK activity. This suggested that TRs could directly repress the response of the cells to inflammatory mediators. Indeed, we found that the thyroid hormone T3 suppresses IL-6 signalling in macrophages and hepatocarcinoma cells, inhibiting STAT3 activation. Consequently, the hormone strongly antagonizes IL-6-stimulated gene transcription, reducing STAT3 recruitment and histone acetylation at IL-6 target promoters. In conclusion, TRs are potent regulators of inflammatory responses and immune homeostasis during sepsis. Reduced responses to IL-6 should serve as a negative feedback mechanism for preventing deleterious effects of excessive hormone signaling during infections.
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Affiliation(s)
- Constanza Contreras-Jurado
- Departamento de Fisiopatología Endocrina y del Sistema Nervioso, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain
| | - Elvira Alonso-Merino
- Departamento de Fisiopatología Endocrina y del Sistema Nervioso, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain
| | - Cristina Saiz-Ladera
- Departamento de Fisiopatología Endocrina y del Sistema Nervioso, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain
| | - Arturo José Valiño
- Departamento de Fisiopatología Endocrina y del Sistema Nervioso, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain
| | - Javier Regadera
- Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
| | - Susana Alemany
- Departamento de Fisiopatología Endocrina y del Sistema Nervioso, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain
| | - Ana Aranda
- Departamento de Fisiopatología Endocrina y del Sistema Nervioso, Instituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain
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Lee WK, Hwang S, Kim D, Lee SG, Jeong S, Seol MY, Kim H, Ku CR, Shin DY, Chung WY, Lee EJ, Lee J, Jo YS. Distinct Features of Nonthyroidal Illness in Critically Ill Patients With Infectious Diseases. Medicine (Baltimore) 2016; 95:e3346. [PMID: 27057916 PMCID: PMC4998832 DOI: 10.1097/md.0000000000003346] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Nonthyroidal illness (NTI), often observed in critically ill patients, arises through diverse alterations in the hypothalamus-pituitary-thyroid (HPT) axis. However, the causal relationship between underlying disease and NTI diversity in critically ill patients is poorly understood.The aim of this study was to examine NTI severity and adverse outcomes in critically ill patients with respect to their underlying disease(s).The medical records of 616 patients admitted to the intensive care unit (ICU) between January 2009 and October 2014 were retrospectively reviewed. Patients with known diseases or taking medications that affect thyroid function were excluded. All-cause mortality (ACM) and length of stay (LOS) in the ICU were assessed as adverse outcomes.The enrolled patients (n = 213) were divided into the following 4 groups according to the severity of NTI at the nadir of their thyroid function test (TFT): normal (n = 11, 5.2%), mild NTI (n = 113, 53.1%), moderate NTI (n = 78, 36.6%), and severe NTI (n = 11, 5.2%). There was no significant difference between the groups in terms of age and gender. NTI severity showed a significantly strong association with ACM (P < 0.0001) and a significant positive association with LOS in the ICU (P = 0.031). After adjusting for age, gender, and current medications affecting TFT, increasing NTI severity led to increased ACM (odds ratio = 3.101; 95% confidence interval = 1.711-5.618; P < 0.0001). Notably, the prevalence of moderate-to-severe NTI was markedly higher in patients with infectious disease than in those with noninfectious disease (P = 0.012). Consistent with this, serum C-reactive protein levels were higher in patients with moderate-to-severe NTI (P = 0.016).NTI severity is associated with increased ACM, LOS, and underlying infectious disease. Future studies will focus on the biological and clinical implications of infectious disease on the HPT axis.
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Affiliation(s)
- Woo Kyung Lee
- From the Department of Internal Medicine (WKL, SH, DK, SJ, CRK, DYS, EJL, YSJ); Department of Surgery (SGL, M-YS, HK, WYC, JL); Open NBI Convergence Technology Research Laboratory, Severance Hospital, Yonsei Cancer Center, Yonsei University College of Medicine; and Brain Korea 21 PLUS Project for Medical Science (WKL, EJL), Yonsei University, Seoul, Korea
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Quispe E Á, Li XM, Yi H. Comparison and relationship of thyroid hormones, IL-6, IL-10 and albumin as mortality predictors in case-mix critically ill patients. Cytokine 2016; 81:94-100. [PMID: 26974766 DOI: 10.1016/j.cyto.2016.03.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Revised: 02/26/2016] [Accepted: 03/07/2016] [Indexed: 10/22/2022]
Abstract
OBJECTIVE To compare the ability of thyroid hormones, IL-6, IL-10, and albumin to predict mortality, and to assess their relationship in case-mix acute critically ill patients. METHODS APACHE II scores and serum thyroid hormones (FT3, FT4, and TSH), IL-6, IL-10, and albumin were obtained at EICU admission for 79 cases of mix acute critically ill patients without previous history of thyroid disease. Patients were followed for 28 days with patient's death as the primary outcome. All mean values were compared, correlations assessed with Pearson' test, and mortality prediction assessed by multivariate logistic regression and ROC. RESULTS Non survivors were older, with higher APACHE II score (p=0.000), IL-6 (p<0.05), IL-10 (p=0.000) levels, and lower albumin (p=0.000) levels compared to survivors at 28 days. IL-6 and IL-10 had significant negative correlation with albumin (p=0.001) and FT3 (p ⩽ 0.05) respectively, while low albumin had a direct correlation with FT3 (p<0.05). In the mortality prediction assessment, IL-10, albumin and APACHE II were independent morality predictors and showed to have a good (0.70-0.79) AUC-ROC (p<0.05). Despite that the entire cohort showed low FT3 serum levels (p=0.000), there was not statistical difference between survivors and non-survivors; neither showed any significance as mortality predictor. CONCLUSIONS IL-6 and IL-10 are correlated with Low FT3 and hypoalbuminemia. Thyroid hormones assessed at EICU admission did not have any predictive value in our study. And finally, high levels of IL-6 and IL-10 in conjunction with albumin could improve our ability to evaluate disease's severity and predict mortality in the critically ill patients. When use in combination with APACHE II scores, our model showed improved mortality prediction.
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Affiliation(s)
- Álvaro Quispe E
- Emergency Intensive Care Unit, Emergency Department of Xiangya Hospital - Central South University, 87 Xiangya Road, Changsha 410008, China
| | - Xiang-Min Li
- Emergency Intensive Care Unit, Emergency Department of Xiangya Hospital - Central South University, 87 Xiangya Road, Changsha 410008, China.
| | - Hong Yi
- Department of Molecular Biology, Xiangya Hospital - Central South University, 87 Xiangya Road, Changsha 410008, China
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30
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Brozaitiene J, Mickuviene N, Podlipskyte A, Burkauskas J, Bunevicius R. Relationship and prognostic importance of thyroid hormone and N-terminal pro-B-Type natriuretic peptide for patients after acute coronary syndromes: a longitudinal observational study. BMC Cardiovasc Disord 2016; 16:45. [PMID: 26892923 PMCID: PMC4757967 DOI: 10.1186/s12872-016-0226-2] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Accepted: 02/12/2016] [Indexed: 12/26/2022] Open
Abstract
Background Altered thyroid function and increased rates of N-terminal pro-B-Type natriuretic peptide (NT-pro-BNP) are highly prevalent in coronary artery disease (CAD) patients with heart failure, and are associated with unfavorable prognosis. This study was undertaken to examine the relationship and prognostic impact of thyroid hormones, inflammatory biomarkers, and NT-pro-BNP on long-term outcomes in patients after acute coronary syndrome (ACS). Methods The study comprised of 642 patients (age 58 ± 10 years, 77 % male) attending an in-patient cardiac rehabilitation program after experiencing ACS. Patients were evaluated for demographic, clinical and CAD risk factors as well as thyroid hormones (e.g., fT3, fT4 level, fT3/fT4 ratio), inflammatory biomarkers (hs-CRP, IL-6) and NT-pro-BNP levels. Data on fT3/fT4 ratio and NT-pro-BNP levels were not normally distributed and were natural-log transformed (ln). Both all-cause (cumulative) and cardiac-related mortality were considered the primary outcomes of interest. Results According to the Cox model, age, NYHA class, (ln)NT-pro-BNP levels (HR 1.53, 95 % CI 1.13–2.07), fT4 level (HR 1.15, 95 % CI 1.04–1.27), and (ln)fT3/fT4 ratio (HR 0.08, 95 % CI 0.02–0.32) were the most important predictors of all-cause mortality among CAD patients after ACS. Similarly, age, NYHA class, (ln)NT-pro-BNP levels (HR 1.62, 95 % CI 1.11–2.36), fT4 (HR 1.15, 95 % CI 1.02–1.29) and (ln)fT3/fT4 ratio (HR 0.10, 95 % CI 0.02–0.55) independently predicted cardiac-related mortality. Kaplan-Meier analyses provided significant prognostic information with the highest risk for all-cause mortality in the low cut off measures of fT3/fT4 ratio <0.206 and NT-pro-BNP ≥290.4 ng/L (HR 2.03, 95 % CI 1.39–2.96) and fT4 level >12.54 pg/ml (HR = 2.34, 95 % CI 1.05–5.18). There was no association between hs-CRP, IL-6 and mortality in CAD patients after ACS. Conclusions Thyroid hormones (i.e., fT4 level and fT3/fT4 ratio) together with NT-pro-BNP level may be valuable and simple predictors of long-term outcomes of CAD patients after experiencing ACS.
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Affiliation(s)
- Julija Brozaitiene
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga, Lithuania.
| | - Narseta Mickuviene
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga, Lithuania.
| | - Aurelija Podlipskyte
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga, Lithuania.
| | - Julius Burkauskas
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga, Lithuania.
| | - Robertas Bunevicius
- Behavioral Medicine Institute, Lithuanian University of Health Sciences, Palanga, Lithuania.
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31
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Pingitore A, Iervasi G, Forini F. Role of the Thyroid System in the Dynamic Complex Network of Cardioprotection. Eur Cardiol 2016; 11:36-42. [PMID: 30310446 DOI: 10.15420/ecr.2016:9:2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Cardioprotection is a common goal of new therapeutic strategies in patients with coronary artery disease and/or left ventricular dysfunction. Myocardial damage following ischaemia/reperfusion injury lead to left ventricular adverse remodelling through many mechanisms arising from different cell types in different myocardial districts, namely the border and remote zone. Cardioprotection must face this complex, dynamic network of cooperating units. In this scenario, thyroid hormones can represent an effective therapeutic strategy due to the numerous actions and regulating mechanisms carried out at the level of the myocytes, interstitium and the vasculature, as well as to the activation of different pro-survival intracellular pathways involved in cardioprotection.
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Affiliation(s)
| | - Giorgio Iervasi
- Clinical Physiology Institute, National Research Council (CNR), Pisa, Italy
| | - Francesca Forini
- Clinical Physiology Institute, National Research Council (CNR), Pisa, Italy
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Kahl S, Elsasser TH, Rhoads RP, Collier RJ, Baumgard LH. Environmental heat stress modulates thyroid status and its response to repeated endotoxin challenge in steers. Domest Anim Endocrinol 2015; 52:43-50. [PMID: 25804834 DOI: 10.1016/j.domaniend.2015.02.001] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2014] [Revised: 02/19/2015] [Accepted: 02/21/2015] [Indexed: 11/27/2022]
Abstract
The objective of this study was to evaluate in cattle, the effects of acute exposure to a heat stress (HS) environment on the status of the pituitary (thyrotropin, TSH)-thyroid (thyroxine, T4)-peripheral tissue T4 deiodination (type 1 5'-deiodinase [D1]; triiodothyronine [T3]; reverse-triiodothyronine [rT3]) axis, and the further response of this pituitary-thyroid-peripheral tissue axis (PTTA) to perturbation caused by the induction of the proinflammatory innate immune state provoked by the administration of gram-negative bacteria endotoxin (lipopolysaccharide [LPS]). Ten steers (318 ± 49 kg body weight) housed in controlled environment chambers were subjected to either a thermoneutral (TN: constant 19°C) or HS temperature conditions (cyclical daily temperatures: 32.2°C-40.0°C) for a total period of 9 d. To minimize the effects of altered plane of nutrition due to HS, steers in TN were pair-fed to animals in HS conditions. Steers received 2 LPS challenges 3 d apart (LPS1 and LPS2; 0.2 μg/kg body weight, intravenously, Escherichia coli 055:B5) with the first challenge administered on day 4 relative to the start of the environmental conditioning. Jugular blood samples were collected at 0, 1, 2, 4, 7, and 24 h relative to the start of each LPS challenge. Plasma TSH, T4, T3, and rT3 were measured by radioimmunoassay. Liver D1 activity was measured in biopsy samples collected before the LPS1 (0 h) and 24 h after LPS2. Before the start of LPS1, HS decreased (P < 0.01 vs TN) plasma TSH (40%), T4 (45.4%), and T3 (25.9%), but did not affect rT3 concentrations. In TN steers, the LPS1 challenge decreased (P < 0.01 vs 0 h) plasma concentrations of TSH between 1 and 7 h and T4 and T3 at 7 and 24 h. In HS steers, plasma TSH concentrations were decreased at 2 h only (P < 0.05), whereas plasma T3 was decreased at 7 and 24 h (P < 0.01). Whereas plasma T4 concentrations were already depressed in HS steers at 0 h, LPS1 did not further affect the levels. Plasma rT3 concentrations were increased in all steers at 4, 7, and 24 h after LPS1 (P < 0.01). The patterns of concentration change of T4, T3, and rT3 during LPS2 mirrored those observed in LPS1; the responses in plasma TSH were of smaller magnitude than those incurred after LPS1. The LPS challenges reduced (P < 0.01) hepatic activity of D1 in all animals but no differences were observed between steers subjected to TN or HS environment. The data are consistent with the concept that acute exposure of cattle to a HS environment results in the depression of the pituitary and thyroid components of the PTTA, whereas a normal capacity to generate T3 from T4 in the liver is preserved. The data also suggest that LPS challenge further suppresses all components of the PTTA including liver T3 generation, and these PTTA perturbations are more pronounced in steers that encounter a HS exposure.
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Affiliation(s)
- S Kahl
- U.S. Department of Agriculture, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Beltsville, MD 20705, USA.
| | - T H Elsasser
- U.S. Department of Agriculture, Animal Biosciences and Biotechnology Laboratory, Beltsville Agricultural Research Center, Beltsville, MD 20705, USA
| | - R P Rhoads
- Animal Sciences Department, William J. Parker Agricultural Research Center, University of Arizona, Tucson, AZ 85721, USA
| | - R J Collier
- Animal Sciences Department, William J. Parker Agricultural Research Center, University of Arizona, Tucson, AZ 85721, USA
| | - L H Baumgard
- Animal Sciences Department, William J. Parker Agricultural Research Center, University of Arizona, Tucson, AZ 85721, USA
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Twisk FNM. Accurate diagnosis of myalgic encephalomyelitis and chronic fatigue syndrome based upon objective test methods for characteristic symptoms. World J Methodol 2015; 5:68-87. [PMID: 26140274 PMCID: PMC4482824 DOI: 10.5662/wjm.v5.i2.68] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Revised: 02/10/2015] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
Although myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) are considered to be synonymous, the definitional criteria for ME and CFS define two distinct, partially overlapping, clinical entities. ME, whether defined by the original criteria or by the recently proposed criteria, is not equivalent to CFS, let alone a severe variant of incapacitating chronic fatigue. Distinctive features of ME are: muscle weakness and easy muscle fatigability, cognitive impairment, circulatory deficits, a marked variability of the symptoms in presence and severity, but above all, post-exertional “malaise”: a (delayed) prolonged aggravation of symptoms after a minor exertion. In contrast, CFS is primarily defined by (unexplained) chronic fatigue, which should be accompanied by four out of a list of 8 symptoms, e.g., headaches. Due to the subjective nature of several symptoms of ME and CFS, researchers and clinicians have questioned the physiological origin of these symptoms and qualified ME and CFS as functional somatic syndromes. However, various characteristic symptoms, e.g., post-exertional “malaise” and muscle weakness, can be assessed objectively using well-accepted methods, e.g., cardiopulmonary exercise tests and cognitive tests. The objective measures acquired by these methods should be used to accurately diagnose patients, to evaluate the severity and impact of the illness objectively and to assess the positive and negative effects of proposed therapies impartially.
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Abstract
The 'sick euthyroid syndrome' or 'non-thyroidal illness syndrome' (NTIS) occurs in a large proportion of hospitalized patients and comprises a variety of alterations in the hypothalamus-pituitary-thyroid (HPT) axis that are observed during illness. One of the hallmarks of NTIS is decreased thyroid hormone (TH) serum concentrations, often viewed as an adaptive mechanism to save energy. Downregulation of hypophysiotropic TRH neurons in the paraventricular nucleus of the hypothalamus and of TSH production in the pituitary gland points to disturbed negative feedback regulation during illness. In addition to these alterations in the central component of the HPT axis, changes in TH metabolism occur in a variety of TH target tissues during NTIS, dependent on the timing, nature and severity of the illness. Cytokines, released during illness, are known to affect a variety of genes involved in TH metabolism and are therefore considered a major determinant of NTIS. The availability of in vivo and in vitro models for NTIS has elucidated part of the mechanisms involved in the sometimes paradoxical changes in the HPT axis and TH responsive tissues. However, the pathogenesis of NTIS is still incompletely understood. This review focusses on the molecular mechanisms involved in the tissue changes in TH metabolism and discusses the gaps that still require further research.
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Affiliation(s)
- Emmely M de Vries
- Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Eric Fliers
- Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
| | - Anita Boelen
- Department of Endocrinology and Metabolism Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands
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Haemato-biochemical and thyroxin status in Trypanosoma evansi infected dogs. J Parasit Dis 2014; 40:491-5. [PMID: 27413326 DOI: 10.1007/s12639-014-0531-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 08/12/2014] [Indexed: 10/24/2022] Open
Abstract
In one year period of study, dogs with inappetence, fever, ocular discharges, dullness, enlarged lymph nodes were screened for the presence of haemoprotozoans at College Hospital of College of Veterinary Science, Tirupati. Wet blood film examination and stained blood smear examination was done to confirm the condition. Peripheral blood smears of dogs revealed the presence of Trypansomes. Trypanosoma evansi was confirmed based on the morphology and measurements of the organisms in the stained blood smears. Haematology revealed decreased total erythrocyte count, packed cell volume, haemoglobin and total leucocyte count values. Total serum proteins, albumin and glucose levels were decreased significantly (P < 0.01), but a significant increase (P < 0.01) in cholesterol, blood urea nitrogen, serum alkaline phosphatase, serum aspartate aminotransferase and serum alanine aminotransferase levels were observed. Decreased total T4 and free T4 were also observed in the T. evansi infected dogs.
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Corona G, Rastrelli G, Maseroli E, Fralassi N, Sforza A, Forti G, Mannucci E, Maggi M. Low testosterone syndrome protects subjects with high cardiovascular risk burden from major adverse cardiovascular events. Andrology 2014; 2:741-7. [DOI: 10.1111/j.2047-2927.2014.00241.x] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2014] [Revised: 04/07/2014] [Accepted: 05/21/2014] [Indexed: 11/29/2022]
Affiliation(s)
- G. Corona
- Endocrinology Unit; Medical Department; Azienda Usl, Maggiore-Bellaria Hospital; Bologna Italy
| | - G. Rastrelli
- Sexual Medicine and Andrology Unit; Department of Experimental, Clinical and Biomedical Sciences; University of Florence; Florence Italy
| | - E. Maseroli
- Sexual Medicine and Andrology Unit; Department of Experimental, Clinical and Biomedical Sciences; University of Florence; Florence Italy
| | - N. Fralassi
- Sexual Medicine and Andrology Unit; Department of Experimental, Clinical and Biomedical Sciences; University of Florence; Florence Italy
| | - A. Sforza
- Endocrinology Unit; Medical Department; Azienda Usl, Maggiore-Bellaria Hospital; Bologna Italy
| | - G. Forti
- Endocrinology Unit; Department of Experimental, Clinical and Biomedical Sciences; University of Florence; Florence Italy
| | - E. Mannucci
- Diabetes Agency; Careggi Hospital; Florence Italy
| | - M. Maggi
- Endocrinology Unit; Medical Department; Azienda Usl, Maggiore-Bellaria Hospital; Bologna Italy
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Kajimoto M, Ledee DR, Xu C, Kajimoto H, Isern NG, Portman MA. Triiodothyronine Activates Lactate Oxidation Without Impairing Fatty Acid Oxidation and Improves Weaning From Extracorporeal Membrane Oxygenation. Circ J 2014. [DOI: 10.1253/circj.cj-14-0821] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Masaki Kajimoto
- Center for Developmental Therapeutics, Seattle Children’s Research Institute
| | - Dolena R. Ledee
- Center for Developmental Therapeutics, Seattle Children’s Research Institute
| | - Chun Xu
- Center for Developmental Therapeutics, Seattle Children’s Research Institute
| | - Hidemi Kajimoto
- Center for Developmental Therapeutics, Seattle Children’s Research Institute
| | - Nancy G. Isern
- Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory
| | - Michael A. Portman
- Center for Developmental Therapeutics, Seattle Children’s Research Institute
- Division of Cardiology, Department of Pediatrics, University of Washington
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Corona G, Rastrelli G, Balercia G, Sforza A, Forti G, Maggi M. Testosterone and cardiovascular risk in patients with erectile dysfunction. J Endocrinol Invest 2012; 35:809-16. [PMID: 22082753 DOI: 10.3275/8063] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND The relationship between cardiovascular (CV) diseases (CVD) and testosterone (T) levels in men has not been completely clarified. AIM To evaluate the association between T levels and CV risk in subjects with erectile dysfunction (ED) and to verify whether their body mass index might (BMI) represents a possible confounder in T-related CV stratification. MATERIAL AND METHODS A consecutive series of 2269 male patients attending the Outpatient Clinic for ED was studied. The assessment of CV risk was evaluated using the engine derived from the Progetto Cuore study. RESULTS After adjustment and for BMI and associated morbidities, SHBG-bound and -unbound T levels decreased as a function of CV risk assessed thorough Progetto Cuore risk engine. In addition, a higher prevalence of hypogonadism related symptoms and signs was associated with a higher CV risk. Among factors included in the Progetto Cuore risk engine age, total and HDL cholesterol and diabetes were all significantly associated with CV risk-dependent modification of total and calculated free-T levels. When the relationship between SHBG bound and unbound T and CV risk was evaluated as a function of obesity (BMI>30 kg/m(2)), all the aforementioned associations were confirmed only in non obese patients. CONCLUSIONS Hypogonadism could be associated either with an increased or reduced CV risk, depending on the characteristics of subjects. Low T observed in obese patients might represent the result of higher CV risk rather than a direct pathogenetic mechanism.
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Affiliation(s)
- G Corona
- Sexual Medicine and Andrology and Unit, Department of Clinical Physiopathology, University of Florence, Italy
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Corona G, Rastrelli G, Monami M, Melani C, Balzi D, Sforza A, Forti G, Mannucci E, Maggi M. Body mass index regulates hypogonadism-associated CV risk: results from a cohort of subjects with erectile dysfunction. J Sex Med 2011; 8:2098-105. [PMID: 21561538 DOI: 10.1111/j.1743-6109.2011.02292.x] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
INTRODUCTION Obesity is an independent cardiovascular (CV) risk factor. Testosterone (T) is inversely related to body mass index (BMI) in males. There is substantial evidence suggesting that low T could play a role as a moderator of CV mortality in men. AIM This study is designed to assess the possible interaction between T and obesity in predicting major CV events (MACE) in a sample of subjects with erectile dysfunction. METHODS A consecutive series of 1,687 patients were studied. Different clinical, biochemical, and instrumental parameters were evaluated. According to BMI, subjects were divided into normal weight (BMI = 18.5-24.9 kg/m(2) ), overweight (BMI = 25.0-29.9 kg/m(2) ), and obese (BMI ≥ 30.0 kg/m(2) ). Hypogonadism was defined as total T below 10.4 nmol/L. Information on MACE was obtained through the City of Florence Registry Office. MAIN OUTCOME MEASURES Information on MACE was obtained through the City of Florence Registry Office. RESULTS Among the patients studied, 39.8% had normal weight, whereas 44.1% and 16.1% were overweight and obese, respectively. Unadjusted analysis in the whole sample showed that while hypogonadism and obesity were significantly associated with an increased risk of MACE, their interaction term was associated with a protective effect. In a Cox regression model, adjusting for confounders, hypogonadism showed a significant increased risk of MACE in normal weight subjects, whereas it was associated with a reduced risk in obese patients. CONCLUSIONS Hypogonadism-associated CV risk depends on the characteristics of subjects, being more evident in normal weight than in obese patients. Further studies are advisable to clarify if low T in obese patients is a (positive) consequence of a comorbid condition (i.e., to save energy) or if it represents a pathogenetic issue of the same illness. Hence, possible misuse/abuse of T treatment in obese subjects must be avoided.
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Affiliation(s)
- Giovanni Corona
- Sexual Medicine and Andrology Unit, University of Florence, Florence, Italy
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Corona G, Rastrelli G, Forti G, Maggi M. Update in Testosterone Therapy for Men (CME). J Sex Med 2011; 8:639-54; quiz 655. [DOI: 10.1111/j.1743-6109.2010.02200.x] [Citation(s) in RCA: 92] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Lado-Abeal J, Romero A, Castro-Piedras I, Rodriguez-Perez A, Alvarez-Escudero J. Thyroid hormone receptors are down-regulated in skeletal muscle of patients with non-thyroidal illness syndrome secondary to non-septic shock. Eur J Endocrinol 2010; 163:765-73. [PMID: 20736347 DOI: 10.1530/eje-10-0376] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AIM Non-thyroidal illness syndrome (NTIS) is related to changes in thyroid hormone (TH) physiology. Skeletal muscle (SM) plays a major role in metabolism, and TH regulates SM phenotype and metabolism. We aimed to characterize the SM of non-septic shock NTIS patients in terms of: i) expression of genes and proteins involved in TH metabolism and actions; and ii) NFKB's pathway activation, a responsible factor for some of the phenotypic changes in NTIS. We also investigated whether the patient's serum can induce in vitro the effects observed in vivo. METHODS Serum samples and SM biopsies from 14 patients with non-septic shock NTIS and 11 controls. Gene and protein expression and NFKB1 activation were analyzed by quantitative PCR and immunoblotting. Human SM cell (HSkMC) cultures to investigate the effects of patient's serum on TH action mediators. RESULTS Patients with non-septic shock NTIS showed higher levels of pro-inflammatory cytokines than controls. Expression of TRβ (THRB), TRα1 (THRA), and retinoid X receptor γ (RXRG) was decreased in NTIS patients. RXRA gene expression was higher, but its protein was lower in NTIS than controls, suggesting the existence of a post-transcriptional mechanism that down-regulates protein levels. NFKB1 pathway activation was not different between NTIS and control patients. HSkMC incubated with patient's serum increased TH receptor and RXRG gene expression after 48 h. CONCLUSIONS Patients with non-septic shock NTIS showed decreased expression of TH receptors and RXRs, which were not related to increased activation of the NFKB1 pathway. These findings could not be replicated in cultures of HSkMCs incubated in the patient's serum.
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Affiliation(s)
- J Lado-Abeal
- Division of Endocrinology, Department of Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 3601 4th Street, STOP 9410, Lubbock, Texas 79430-9410, USA.
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Lubrano V, Pingitore A, Carpi A, Iervasi G. Relationship between triiodothyronine and proinflammatory cytokines in chronic heart failure. Biomed Pharmacother 2009; 64:165-9. [PMID: 19926244 DOI: 10.1016/j.biopha.2009.09.001] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2009] [Accepted: 09/07/2009] [Indexed: 10/20/2022] Open
Abstract
UNLABELLED Cytokines and thyroid hormones are involved in the biochemical changes associated to heart failure (HF). AIM Aims of the study were to investigate: plasma circulating levels of the cytokines Interleukine-6 (IL-6) TNF alpha and C reactive protein (CRP) in patients with stable HF in relation to the severity of left ventricular dysfunction; the relationship between these inflammatory markers and thyroid hormones. METHODS One-hundred and sixty-six patients (121 males, age 64+/-12), with non-ischemic cardiomyopathy, were admitted to the Institute of Clinical Physiology for progressive deterioration of symptoms. Forty-eight healthy subjects (30 males, age range 26-75 years) were also enrolled as control group (Group N). High sensitivity (hs)-IL-6 and hs-TNFalpha were quantified using solid phase sandwich ELISA kits. Hs-CRP was measured by Immulite System. RESULTS In the whole population (HF and N), the association between inflammatory markers and age resulted statistically significant only for IL-6 serum concentration (p<0.001) but not for TNFalpha and CRP. IL-6 and TNFalpha were strongly higher in the HF in comparison with N (p<0.001) while CRP showed a less significant difference (p<0.05). Whole population showed a negative association between IL-6 and EF% and between CRP and EF% (respectively p<0.01, r=-0.23; p<0.05, r=0.19). Comparing normal subjects with two classes of patients, respectively with EF>35% and EF<35%, we clearly observed the progressive enhancement of the inflammatory markers. Considering normal subjects, patients without and with low T3 syndrome, IL-6 and TNFalpha increased progressively from normal to patients with fT3<2 pg/ml (p<0.01 and p<0.01) while CRP only respect to the group with low T3 syndrome (p<0.01). The inflammatory markers were all inversely correlated with FT3 levels. CONCLUSION Because low FT3 serum concentration represents a negative prognostic index, it is likely that impairment of T3 production and enhanced inflammation represent pathogenic mechanisms linked to HF progression.
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Affiliation(s)
- V Lubrano
- G. Monasterio Foundation, Pisa, Italy
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The role of thyroid hormone in the pathophysiology of heart failure: clinical evidence. Heart Fail Rev 2008; 15:155-69. [DOI: 10.1007/s10741-008-9126-6] [Citation(s) in RCA: 85] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2008] [Accepted: 11/06/2008] [Indexed: 11/26/2022]
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Rodriguez-Perez A, Palos-Paz F, Kaptein E, Visser TJ, Dominguez-Gerpe L, Alvarez-Escudero J, Lado-Abeal J. Identification of molecular mechanisms related to nonthyroidal illness syndrome in skeletal muscle and adipose tissue from patients with septic shock. Clin Endocrinol (Oxf) 2008; 68:821-7. [PMID: 17986277 DOI: 10.1111/j.1365-2265.2007.03102.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE Septic shock is one of various causes of nonthyroidal illness syndrome (NTIS). In humans, the molecular mechanisms involved in NTIS are mostly unknown. The aim of this study was to investigate, in patients with NTIS secondary to septic shock, changes in the expression of genes involved in the actions of thyroid hormones and in the activity of deiodinase enzymes, in two tissues important for protein and energy metabolism, skeletal muscle (SM) and subcutaneous adipose tissue (SAT). DESIGN Hospitalized patients were divided into a control and a septic shock NTIS group. MEASUREMENT Serum collection for biochemical measurements, and SM and SAT biopsies for mRNA expression analysis of thyroid hormone receptors (THRB1, THRA1), retinoid X receptors (RXRA, RXRB, RXRG), nuclear receptor corepressor (NCOR1), silencing mediator of retinoid and thyroid hormone receptor (SMRT), steroid receptor coactivator (SRC1), type 1 and 2 deiodinases (D1, D2), monocarboxylate transporter 8 (MCT8), SECIS binding protein 2 (SBP2) and uncoupling protein 3 (UCP3) as well as D1, D2 and D3 enzyme activity measurements. RESULTS The NTIS group had lower serum TSH, and free T3 and higher rT3 than controls. D1 and D3 were detected in SAT, with no differences found between the two groups; SM had very low D2 activity and again no differences were found between groups; D3 activity in SM was higher in NTIS than controls. SM expression of THRB1, RXRG and D2 was lower and RXRA higher in NTIS than controls. SAT from NTIS patients had lower MCT8, THRB1, THRA1, RXRG and SMRT, and higher UCP3 expression than controls. CONCLUSIONS In patients with septic shock NTIS tissue responses are orientated to decrease production and increase degradation (muscle) or decrease uptake (adipose tissue) of T3, as well as to decrease thyroid hormone actions.
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Affiliation(s)
- Alfonso Rodriguez-Perez
- Anaesthesia and Reanimation Section, Complejo Hospitalario Universitario de Santiago, University of Santiago de Compostela, Santiago de Compostela, Spain
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Post-thyroidectomy thyroxine replacement dose in patients with or without compensated heart failure: The role of cytokines. Cytokine 2008; 41:121-6. [DOI: 10.1016/j.cyto.2007.10.014] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2007] [Revised: 10/26/2007] [Accepted: 10/31/2007] [Indexed: 11/23/2022]
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Sabugo F, Liberman C, Niedmann JP, Soto L, Cuchacovich M. Infliximab can induce a prolonged clinical remission and a decrease in thyroid hormonal requirements in a patient with SAPHO syndrome and hypothyroidism. Clin Rheumatol 2007; 27:533-5. [DOI: 10.1007/s10067-007-0767-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2007] [Revised: 09/20/2007] [Accepted: 09/23/2007] [Indexed: 11/28/2022]
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Melis D, Pivonello R, Parenti G, Della Casa R, Salerno M, Lombardi G, Sebastio G, Colao A, Andria G. Increased prevalence of thyroid autoimmunity and hypothyroidism in patients with glycogen storage disease type I. J Pediatr 2007; 150:300-5, 305.e1. [PMID: 17307551 DOI: 10.1016/j.jpeds.2006.11.056] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2005] [Revised: 07/27/2006] [Accepted: 11/22/2006] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To investigate the hypothalamus-pituitary-thyroid axis in patients with glycogen storage disease type 1(GSD1). STUDY DESIGN Ten patients with GSD1a, 7 patients with GSD1b, and 34 sex- and age-matched healthy control subjects were enrolled in the study. RESULTS The levels of serum-free thyroxine (FT4) were significantly lower in patients with GSD1a and GSD1b (P < .05), whereas thyrotropin was significantly higher compared with control subjects only in patients with GSD1b (P < .005). Thyroglobulin and thyroperoxidase auto-antibodies were significantly higher in patients with GSD1b than in patients with GSD1a and control subjects (P < .005). After thyrotropin-releasing hormone stimulation, an enhanced thyrotropin response was found in patients with GSD1a and patients with GSD1b (P < .005) compared with control subjects. The presence of a subclinical or overt hypothyroidism was found in 4 of 7 patients with GSD1b and in no patient with GSD1a (chi2 = 7.47, P < .005) or control subject (chi2 = 27.2, P < .0001). CONCLUSIONS Patients with GSD1b have an increased prevalence of thyroid autoimmunity and hypothyroidism, although patients with GSD1a have little evidence of thyroid abnormalities. Concomitant damage at the level of the hypothalamus or pituitary gland might be hypothesized on the basis of the slightly elevated thyrotropin levels, even in patients with overt hypothyroidism.
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Affiliation(s)
- Daniela Melis
- Department of Pediatrics, Federico II University, Naples, Italy
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Chow EKH, Razani B, Cheng G. Innate immune system regulation of nuclear hormone receptors in metabolic diseases. J Leukoc Biol 2007; 82:187-95. [PMID: 17314330 DOI: 10.1189/jlb.1206741] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
The immune system modulates a number of biological processes to properly defend against pathogens. Here, we review how crosstalk between nuclear hormone receptors and the innate immune system may influence multiple biological functions during an immune response. Although nuclear hormone receptor repression of innate immune responses and inflammation has been well studied, a number of new studies have identified repression of nuclear hormone receptor signaling by various innate immune responses. IFN regulatory factor 3, a key transcription factor involved in the induction of antiviral genes, may play a role in mediating such crosstalk between the innate immune response and nuclear receptor-regulated metabolism. This crosstalk mechanism is now implicated in the pathogenesis of atherosclerosis and Reye's syndrome and could provide an explanation for other pathogen-associated metabolic and developmental disorders.
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Affiliation(s)
- Edward Kai-Hua Chow
- Molecular Biology Institute, University of California Los Angeles, Los Angeles, California 90095, USA
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Abstract
In euthyroid sick syndrome [non-thyroidal illness (NTI)], a number of investigators have described TSH and serum thyroid hormone abnormalities, low T3, low T3 and T4, increased T4, low TSH, etc. Those cases of NTI where there is only T3 decrease [and normal serum T4, free T4 (FT4), and TSH levels] are specifically referred to as low T3 syndrome. However, the information in regard to low T3 syndrome in psychiatric subjects who are clinically euthyroid and do not have any other systemic illness is scanty. In our facility, since thyroid function is routinely assessed in psychiatric patients at admission, this provided the opportunity to study low T3 syndrome in a large group of psychiatric patients. Out of 250 subjects with major psychiatric depression, 6.4% exhibited low T3 syndrome (mean serum T3 concentration 0.94 nmol/l vs normal mean serum concentration of 1.77 nmol/l). The low T3 levels could not be ascribed to malnutrition or any other illness and the metabolic parameters were all normal. Possible mechanisms contributing to low T3 are discussed. The depression might constitute an illness having the same relation to low T3 as found in the low T3 syndrome previously described in euthyroid sick subjects. The present findings, besides describing low T3 syndrome in psychiatric patients without systemic illnesses, suggest the possibility of subgrouping in clinical psychiatric depression which may have a broader clinical significance.
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