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Sun Q, Wang W, Mao X, Liu H. The impact of thyroid function on surgical prognosis in patients undergoing cardiac and major vascular surgeries. J Cardiothorac Surg 2025; 20:152. [PMID: 40083000 PMCID: PMC11907883 DOI: 10.1186/s13019-025-03365-2] [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: 10/12/2024] [Accepted: 02/08/2025] [Indexed: 03/16/2025] Open
Abstract
OBJECTIVE This study aims to elucidate the relationship between thyroid function and surgical prognosis in patients undergoing cardiac and major vascular surgeries. METHODS A retrospective cohort study was conducted on patients undergoing cardiac or major vascular surgeries. Preoperative thyroid function tests, including TSH, free T3, and free T4 levels, as well as postoperative thyroid function tests, were assessed. Key postoperative outcomes, such as total hospital stay, postoperative hospital stay, ICU stay, and duration of mechanical ventilation, were recorded and analyzed. The analytical approach included Pearson correlation, multivariable logistic regression models, and restricted cubic splines. RESULTS This study analyzed a cohort of 472 patients who underwent various cardiovascular surgeries, including coronary artery bypass grafting (173 patients), aortic surgery (131 patients), valve surgery (125 patients), and primary cardiac neoplasms resection (43 patients). Significant changes in thyroid hormone levels were observed preoperatively and postoperatively, with TSH, FT3, and FT4 levels showing a significant decrease from preoperative values (p < 0.001). Multivariate logistic regression analysis further revealed that ΔTSH is significantly associated with total hospital stay, postoperative hospital stay, and duration of mechanical ventilation; postoperative FT3 levels were significantly inversely related to total hospital stay, ICU stay, and ventilator requirements. Additionally, although no significant nonlinear relationships were found (all p > 0.05). CONCLUSIONS Thyroid dysfunction may impact postoperative outcomes in cardiac and major vascular surgery patients.
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Affiliation(s)
- Qi Sun
- Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong University, Nantong, China
| | - Wei Wang
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Xiaoming Mao
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
| | - Hao Liu
- Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
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Kovacevic M, Nesek-Adam V, Klokic S, Mujaric E. Low T3 vs low T3T4 euthyroid sick syndrome in septic shock patients: A prospective observational cohort study. World J Crit Care Med 2024; 13:96132. [PMID: 39253312 PMCID: PMC11372517 DOI: 10.5492/wjccm.v13.i3.96132] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2024] [Revised: 06/08/2024] [Accepted: 06/24/2024] [Indexed: 08/30/2024] Open
Abstract
BACKGROUND Both phases of euthyroid sick syndrome (ESS) are associated with worse prognosis in septic shock patients. Although there are still no indications for supplementation therapy, there is no evidence that both phases (initial and prolonged) are adaptive or that only prolonged is maladaptive and requires supplementation. AIM To analyze clinical, hemodynamic and laboratory differences in two groups of septic shock patients with ESS. METHODS A total of 47 septic shock patients with ESS were divided according to values of their thyroid hormones into low T3 and low T3T4 groups. The analysis included demographic data, mortality scores, intensive care unit stay, mechanical ventilation length and 28-day survival and laboratory with hemodynamics. RESULTS The Simplified Acute Physiology Score II score (P = 0.029), dobutamine (P = 0.003) and epinephrine requirement (P = 0.000) and the incidence of renal failure and multiple organ failure (MOF) (P = 0.000) were significantly higher for the low T3T4. Hypoalbuminemia (P = 0.047), neutrophilia (P = 0.038), lymphopenia (P = 0.013) and lactatemia (P = 0.013) were more pronounced on T2 for the low T3T4 group compared to the low T3 group. Diastolic blood pressure at T0 (P = 0.017) and T1 (P = 0.007), as well as mean arterial pressure at T0 (P = 0.037) and T2 (P = 0.033) was higher for the low T3 group. CONCLUSION The low T3T4 population is associated with higher frequency of renal insufficiency and MOF, with worse laboratory and hemodynamic parameters. These findings suggest potentially maladaptive changes in the chronic phase of septic shock.
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Affiliation(s)
- Mirza Kovacevic
- Department of Anesthesiology, Resuscitation and Intensive Care, Cantonal Hospital, Zenica 72000, Bosnia and Herzegovina
| | - Visnja Nesek-Adam
- Department of Anesthesiology, Resuscitation and Intensive Care, Clinical Hospital Sveti Duh, Zagreb 10000, Croatia
| | - Semir Klokic
- Gruppenpraxis, General Practitioner's Office, Laufen 4242, Switzerland
| | - Ekrema Mujaric
- Department of Internal Diseases, Cantonal Hospital, Zenica 72000, Bosnia and Herzegovina
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Feldkamp JD, Feldkamp J. Indications for Intravenous T3 and T4. Horm Metab Res 2024. [PMID: 38698631 DOI: 10.1055/a-2318-5156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/05/2024]
Abstract
Therapy with thyroid hormones normally is restricted to substitution therapy of patients with primary or secondary hypothyroidism. Typically, thyroid hormones are given orally. There are few indications for intravenous use of thyroid hormones. Indications for parenteral application are insufficient resorption of oral medications due to alterations of the gastrointestinal tract, partial or total loss of consciousness, sedation in the intensive care unit or shock. In almost all cases, levothyroxine is the therapy of choice including congenital hypothyroidism. In preterm infants with an altered thyroid hormone status, studies with thyroid hormones including intravenous liothyronine showed a normalisation of T3 levels and in some cases an amelioration of parameters of ventilation. A benefit for mortality or later morbidity could not be seen. Effects on neurological improvements later in life are under discussion. Decreased thyroid hormone levels are often found after cardiac surgery in infants and adults. Intravenous therapy with thyroid hormones improves the cardiac index, but in all other parameters investigated, no substantial effect on morbidity and mortality could be demonstrated. Oral liothyronine therapy in these situations was equivalent to an intravenous route of application. In myxoedema coma, intravenous levothyroxine is given for 3 to 10 days until the patient can take oral medication and normal resorption in the gastrointestinal tract is achieved by restoring at least peripheral euthyroidism. Intravenous levothyroxine is the standard in treating patients with myxoedema coma. A protective effect on the heart of i.v. levothyroxine in brain-dead organ donors may be possible.
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Affiliation(s)
- Jasper David Feldkamp
- Division of Hematology, Oncology, and Cancer Immunology, Charite Medical Faculty Berlin, Berlin, Germany
| | - Joachim Feldkamp
- Klinikum Bielefeld, Academic Department of General Internal Medicine, Endocrinology and Diabetes, Infectiology, Bielefeld University, Medical School and University Medical Center East Westphalia-Lippe, Bielefeld, Germany
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Ning N, Li J, Sun W, Ma C, Li J, Sheng H, Chen Y, Zhao B, Zhang J, Zhu J, Gao C, Mao E. Different subtypes of nonthyroidal illness syndrome on the prognosis of septic patients: a two-centered retrospective cohort study. Front Endocrinol (Lausanne) 2023; 14:1227530. [PMID: 37745722 PMCID: PMC10517721 DOI: 10.3389/fendo.2023.1227530] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Accepted: 08/23/2023] [Indexed: 09/26/2023] Open
Abstract
Background Nonthyroidal illness syndrome (NTIS) is a common endocrine dysfunction predicting unfavorable outcomes in critical illness. The objective of the study is to evaluate the association between different NTIS subtypes with outcomes in septic patients. Methods Septic patients in two Chinese academic centers from October 2012 and October 2022 are enrolled in analysis. Multivariable regressions are used to assess associations between NTIS and outcomes. Outcomes include in-hospital mortality, length of stay in hospital (LOS), non-invasive ventilation failure and weaning failure. Patients with NTIS are categorized into 4 types according to the different levels of FT4 and TSH. The association between different NTIS subtypes and mortality are further analyzed. Survival curve is plotted using the Kaplan-Meier method. Results After screening, a total of 1226 septic patients with complete thyroid hormones result are eventually enrolled. Among them, 520 (42.4%) patients are diagnosed as NTIS. In multivariable regression analysis, NTIS is independently associated with increased 30-days mortality (OR=1.759, CI 1.009-3.104, p=0.047), but has no association with 60-days mortality (OR=1.524, CI 0.893-2.618, p=0.123), 90-days mortality (OR=1.411, CI 0.831-2.408, p=0.203), LOS, non-invasive ventilation failure or weaning failure. In NTIS subtypes, NTIS patients with low FT3 and TSH levels, regardless of the FT4 values, have significantly higher mortality than euthyroid patients (30-days mortality, OR= 6.488, CI 1.546-27.808, p=0.01; 60-days mortality, OR=3.973, CI 1.006-15.579, p=0.046; 90-days mortality, OR=3.849, CI 0.977-15.088, p=0.051). This result is consistent in patients with low FT3 and FT4 levels, regardless of the TSH values (30-days mortality, OR=3.349, CI 1.402-7.957, p=0.006; 60-days mortality, OR= 2.594, CI 1.122-5.930, p=0.024; 90-days mortality, OR=2.55, CI 1.110-5.804, p=0.025). There is no survival difference between NTIS patients with low FT3 only and euthyroid patients. Survival plot shows the worst prognosis is in NTIS patients with low FT3, FT4 and TSH level. Conclusions NTIS is frequent in sepsis. A reduction of FT3 together with FT4 or TSH, but not FT3 only, is associated with an increased risk of mortality.
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Affiliation(s)
- Ning Ning
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Juan Li
- Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenwu Sun
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Chaoping Ma
- Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiaoyan Li
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Huiqiu Sheng
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Ying Chen
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Bing Zhao
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jiyuan Zhang
- Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiyue Zhu
- Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Chengjin Gao
- Department of Emergency, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Enqiang Mao
- Departments of Emergency, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Esmaeilzadeh A, Elahi R, Siahmansouri A, Maleki AJ, Moradi A. Endocrine and metabolic complications of COVID-19: lessons learned and future prospects. J Mol Endocrinol 2022; 69:R125-R150. [PMID: 35900847 DOI: 10.1530/jme-22-0036] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 07/18/2022] [Indexed: 01/08/2023]
Abstract
Coronavirus disease 2019 (COVID-19) is well known for its respiratory complications; however, it can also cause extrapulmonary manifestations, including cardiovascular, thrombotic, renal, gastrointestinal, neurologic, and endocrinological symptoms. Endocrinological complications of COVID-19 are rare but can considerably impact the outcome of the patients. Moreover, preexisting endocrinologic disorders can affect the severity of COVID-19. Thyroid, pancreas, adrenal, neuroendocrine, gonadal, and parathyroid glands are the main endocrinologic organs that can be targeted by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Endocrinological complications of COVID-19 are rare but can significantly deteriorate the patients' prognosis. Understanding the interaction between COVID-19 and the endocrine system can provide a potential treatment option to improve the outcome of COVID-19. In this article, we aim to review the short-term and long-term organ-based endocrinological complications of COVID-19, the pathophysiology, the influence of each complication on COVID-19 prognosis, and potential therapeutic interventions based on current published data. Moreover, current clinical trials of potential endocrinological interventions to develop therapeutic strategies for COVID-19 have been discussed.
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Affiliation(s)
- Abdolreza Esmaeilzadeh
- Department of Immunology, Zanjan University of Medical Sciences, Zanjan, Iran
- Cancer Gene Therapy Research Center (CGRC), Zanjan University of Medical Sciences, Zanjan, Iran
| | - Reza Elahi
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Amir Siahmansouri
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | | | - Amirhosein Moradi
- School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
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Tharmapoopathy M, Thavarajah A, Kenny RPW, Pingitore A, Iervasi G, Dark J, Bano A, Razvi S. Efficacy and Safety of Triiodothyronine Treatment in Cardiac Surgery or Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Thyroid 2022; 32:879-896. [PMID: 35403448 DOI: 10.1089/thy.2021.0609] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background: Low levels of the active thyroid hormone triiodothyronine (T3) in cardiac patients are associated with worse outcomes. The aim of this analysis was to assess if T3 treatment is beneficial and safe in patients undergoing cardiac surgery or those with cardiovascular diseases in whom there is observed or expected reduction in serum T3 levels. Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) was performed as per the PRISMA guidelines. Pubmed, EMBASE, and Web of Science databases were searched for RCTs published between January 1, 1960 and March 30, 2022 that evaluated the effects of T3 therapy in patients undergoing cardiac surgery or with cardiovascular diseases. The primary outcomes were measures of cardiac function. Weighted mean difference (MD) or relative risk was calculated using a random effects model. PROSPERO registration number CRD42020211966. Results: Of the 3181 full-text articles screened, 34 studies with 2547 participants (number ranging between 13 and 223, mean ages between 0.5 and 73 years, mean percentage of women between 7% and 64%) were included. In 12 RCTs with 1093 adults undergoing cardiac surgery T3 therapy was associated with improvement in cardiac index (MD [95% confidence interval], 0.24 [0.08 to 0.40] L/min/m2, I2 = 74%). The quality of evidence was high to moderate. In 3 RCTs with 188 children undergoing cardiac surgery, 3 RCTs with 131 adult cardiac donors, 3 RCTs with 83 adult patients with heart failure, and 2 RCTs with 89 adults with acute myocardial infarction, T3 therapy did not improve cardiac index or left ventricular function; the quality of evidence ranged from high (pediatric cardiac surgery) to low (other groups). No detrimental effect of T3 therapy was observed on heart rate, risk of in-hospital atrial fibrillation, or mortality. Conclusions: Short-term T3 therapy is safe and trials in adults undergoing cardiac surgical procedures to evaluate longer term clinical endpoints are required. Current data do not support the routine use of T3 therapy in children undergoing cardiac surgery or in cardiac donors. Adequately designed trials are required to determine if T3 therapy improves cardiac function and clinical outcomes in patients with heart failure or acute myocardial infarction.
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Affiliation(s)
- Mathuri Tharmapoopathy
- Department of Endocrinology, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Abishan Thavarajah
- Department of Endocrinology, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Ryan P W Kenny
- Department of Biostatistics, Institute of Population Health Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom
| | | | | | - John Dark
- Department of Endocrinology, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Arjola Bano
- Department of Cardiology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of Cardiology, Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland
| | - Salman Razvi
- Department of Endocrinology, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
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Kobayashi Y, Okumura G, Morizumi T, Nagamatsu K, Shimizu Y, Sasaki T, Sato A, Sekijima Y, Hongo K. Thyroid hormone decreasing after mechanical thrombectomy for cerebral infarction. Clin Neurol Neurosurg 2022; 219:107335. [PMID: 35724614 DOI: 10.1016/j.clineuro.2022.107335] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2022] [Revised: 05/05/2022] [Accepted: 06/07/2022] [Indexed: 11/03/2022]
Abstract
OBJECTIVE Mechanical thrombectomy (MT) is an established treatment for large vessel occlusion in patients with cerebral infarction. The use of iodine contrast agent decreases thyroid hormone levels via the Wolff-Chaikoff effect. Low triiodothyronine (T3) syndrome caused due to severe illness status can contribute to decreased levels of thyroid hormones. Reportedly, a low T3 level is associated with poor prognosis in patients with cerebral infarction. This study aimed to clarify the changes in thyroid hormone levels in the acute phase after MT and the effects of the iodine contrast agent on these hormones. METHODS This was a single-center, prospective, and single-arm trial. Thyroid stimulating hormone (TSH), free T3 (FT3), and free T4 (FT4) levels were tested on admission and 24 h postoperatively in patients who were approved for MT. RESULTS A total of 37 patients were screened during the study period and 31 patients were enrolled in this study. Significant decreases were observed in TSH (P < 0.001) and FT3 (P < 0.001) levels 24 h after MT. Moreover, there was a correlation between the decrease in ratio of change in FT3 levels and the amount of iodine contrast agent used per body surface area (r = 0.43, P = 0.019), while no such correlations were detected for TSH and FT4. CONCLUSION We demonstrated that TSH and FT3 levels decreased in the acute phase after MT and that FT3 levels were associated with the amount of iodine contrast agent used.
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Affiliation(s)
- Yuya Kobayashi
- Department of Neurology, Ina Central Hospital, 1313-1, Ina, Nagano, 396-8555, Japan.
| | - Gaku Okumura
- Department of Neurology, Ina Central Hospital, 1313-1, Ina, Nagano, 396-8555, Japan
| | - Teruya Morizumi
- Department of Neurology, Ina Central Hospital, 1313-1, Ina, Nagano, 396-8555, Japan
| | - Kiyoshiro Nagamatsu
- Department of Neurology, Ina Central Hospital, 1313-1, Ina, Nagano, 396-8555, Japan
| | - Yusaku Shimizu
- Department of Neurology, Ina Central Hospital, 1313-1, Ina, Nagano, 396-8555, Japan
| | - Tetsuo Sasaki
- Department of Neurosurgery, Ina Central Hospital, 1313-1, Ina, Nagano, 396-8555, Japan
| | - Atsushi Sato
- Department of Neurosurgery, Ina Central Hospital, 1313-1, Ina, Nagano, 396-8555, Japan
| | - Yoshiki Sekijima
- Department of Medicine (Neurology & Rheumatology), Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390-8621, Japan
| | - Kazuhiro Hongo
- Department of Neurosurgery, Ina Central Hospital, 1313-1, Ina, Nagano, 396-8555, Japan
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Vidart J, Jaskulski P, Kunzler AL, Marschner RA, Ferreira de Azeredo da Silva A, Wajner SM. Non-thyroidal illness syndrome predicts outcome in adult critically ill patients: a systematic review and meta-analysis. Endocr Connect 2022; 11:e210504. [PMID: 35015701 PMCID: PMC8859965 DOI: 10.1530/ec-21-0504] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/11/2022] [Indexed: 11/24/2022]
Abstract
We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of non-thyroidal illness syndrome (NTIS) in critically ill patients. We included studies that assessed thyroid function by measuring the serum thyroid hormone (TH) level and in-hospital mortality in adult septic patients. Reviews, case reports, editorials, letters, animal studies, duplicate studies, and studies with irrelevant populations and inappropriate controls were excluded. A total of 6869 patients from 25 studies were included. The median prevalence rate of NTIS was 58% (IQR 33.2-63.7). In univariate analysis, triiodothyronine (T3) and free T3 (FT3) levels in non-survivors were relatively lower than that of survivors (8 studies for T3; standardized mean difference (SMD) 1.16; 95% CI, 0.41-1.92; I2 = 97%; P < 0.01). Free thyroxine (FT4) levels in non-survivors were also lower than that of survivors (12 studies; SMD 0.54; 95% CI, 0.31-0.78; I2 = 83%; P < 0.01). There were no statistically significant differences in thyrotropin levels between non-survivors and survivors. NTIS was independently associated with increased risk of mortality in critically ill patients (odds ratio (OR) = 2.21, 95% CI, 1.64-2.97, I2 = 65% P < 0.01). The results favor the concept that decreased thyroid function might be associated with a worse outcome in critically ill patients. Hence, the measurement of TH could provide prognostic information on mortality in adult patients admitted to ICU.
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Affiliation(s)
- Josi Vidart
- Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Intensive Care Unit, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Paula Jaskulski
- Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Ana Laura Kunzler
- Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Rafael Aguiar Marschner
- Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - André Ferreira de Azeredo da Silva
- Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Simone Magagnin Wajner
- Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Internal Medicine Division, Hospital de Clínicas de Porto Alegre, Internal Medicine Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Correspondence should be addressed to S M Wajner:
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Sciacchitano S, Capalbo C, Napoli C, Anibaldi P, Salvati V, De Vitis C, Mancini R, Coluzzi F, Rocco M. Nonthyroidal Illness Syndrome: To Treat or Not to Treat? Have We Answered the Question? A Review of Metanalyses. Front Endocrinol (Lausanne) 2022; 13:850328. [PMID: 35620389 PMCID: PMC9128382 DOI: 10.3389/fendo.2022.850328] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 03/16/2022] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND AND OBJECTIVE Nonthyroidal Illness Syndrome (NTIS) occurs in approximately 70% of patients admitted to Intensive Care Units (ICU)s and has been associated with increased risk of death. Whether patients with NTIS should receive treatment with thyroid hormones (TH)s is still debated. Since many interventional randomized clinical trials (IRCT)s were not conclusive, current guidelines do not recommend treatment for these patients. In this review, we analyze the reasons why TH treatment did not furnish convincing results regarding possible beneficial effects in reported IRCTs. METHODS We performed a review of the metanalyses focused on NTIS in critically ill patients. After a careful selection, we extracted data from four metanalyses, performed in different clinical conditions and diseases. In particular, we analyzed the type of TH supplementation, the route of administration, the dosages and duration of treatment and the outcomes chosen to evaluate the results. RESULTS We observed a marked heterogeneity among the IRCTs, in terms of type of TH supplementation, route of administration, dosages and duration of treatment. We also found great variability in the primary outcomes, such as prevention of neurological alterations, reduction of oxygen requirements, restoration of endocrinological and clinical parameters and reduction of mortality. CONCLUSIONS NTIS is a frequent finding in critical ill patients. Despite several available IRCTs, it is still unclear whether NTIS should be treated or not. New primary endpoints should be identified to adequately validate the efficacy of TH treatment and to obtain a clear answer to the question raised some years ago.
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Affiliation(s)
- Salvatore Sciacchitano
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
- Laboratory of Biomedical Research, Niccolò Cusano University Foundation, Rome, Italy
| | - Carlo Capalbo
- Unit of Medical Oncology, Sant’Andrea University Hospital, Rome, Italy
- Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Christian Napoli
- Department of Surgical and Medical Science and Translational Medicine, Sapienza University of Rome, Rome, Italy
| | - Paolo Anibaldi
- Health Management Director, Sant’Andrea University Hospital, Rome, Italy
| | - Valentina Salvati
- Scientific Direction, IRCCS Regina Elena National Cancer Institute, Rome, Italy
| | - Claudia De Vitis
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Rita Mancini
- Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Flaminia Coluzzi
- Unit of Anesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, Rome, Italy
- Department Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Latina, Italy
- *Correspondence: Flaminia Coluzzi,
| | - Monica Rocco
- Department of Surgical and Medical Science and Translational Medicine, Sapienza University of Rome, Rome, Italy
- Unit of Anesthesia, Intensive Care and Pain Medicine, Sant’Andrea University Hospital, Rome, Italy
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10
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Effects of Thyroid Hormone on Tissue Hypoxia: Relevance to Sepsis Therapy. J Clin Med 2021; 10:jcm10245855. [PMID: 34945151 PMCID: PMC8703810 DOI: 10.3390/jcm10245855] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Revised: 11/29/2021] [Accepted: 12/10/2021] [Indexed: 01/14/2023] Open
Abstract
Tissue hypoxia occurs in various conditions such as myocardial or brain ischemia and infarction, sepsis, and trauma, and induces cellular damage and tissue remodeling with recapitulation of fetal-like reprogramming, which eventually results in organ failure. Analogies seem to exist between the damaged hypoxic and developing organs, indicating that a regulatory network which drives embryonic organ development may control aspects of heart (or tissue) repair. In this context, thyroid hormone (TH), which is a critical regulator of organ maturation, physiologic angiogenesis, and mitochondrial biogenesis during fetal development, may be of important physiological relevance upon stress (hypoxia)-induced fetal reprogramming. TH signaling has been implicated in hypoxic tissue remodeling after myocardial infarction and T3 prevents remodeling of the postinfarcted heart. Similarly, preliminary experimental evidence suggests that T3 can prevent early tissue hypoxia during sepsis with important physiological consequences. Thus, based on common pathways between different paradigms, we propose a possible role of TH in tissue hypoxia after sepsis with the potential to reduce secondary organ failure.
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Gao S, Ma W, Huang S, Lin X, Yu M. Impact of low triiodothyronine syndrome on long-term outcomes in patients with myocardial infarction with nonobstructive coronary arteries. Ann Med 2021; 53:741-749. [PMID: 34037508 PMCID: PMC8158241 DOI: 10.1080/07853890.2021.1931428] [Citation(s) in RCA: 5] [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: 04/08/2021] [Accepted: 05/12/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Low triiodothyronine syndrome (LT3S), frequently seen in patients with acute myocardial infarction (AMI), has been regarded as a predictor of poor outcomes after AMI. However, little is known about the prognostic value of LT3S in euthyroid patients with myocardial infarction with nonobstructive coronary arteries (MINOCA). METHODS A total of 1162 MINOCA patients were enrolled and divided into LT3S and no-LT3S groups. LT3S was defined as decreased free T3 (fT3 < 2.36 pg/mL) with normal values of thyroid-stimulating hormone. The primary endpoint was a composite of major adverse cardiovascular events (MACE), including all-cause death, nonfatal MI, stroke, revascularization, and hospitalization for unstable angina or heart failure. Kaplan-Meier, Cox regression, propensity score matching (PSM), and receiver-operating characteristic analyses were performed. RESULTS Patients with LT3S (prevalence of 17.5%) had a significantly higher incidence of MACE (19.6% vs. 12.9%; p = .013) than patients without during the median follow-up of 41.7 months. LT3S was closely associated with an increased risk of MACE even after multivariable adjustment (HR 1.50, 95% CI: 1.03-2.18, p = .037). After PSM, 197 pairs of patients with or without LT3S were identified, and LT3S remained a robust risk factor of worse outcomes (HR 1.53, 95% CI: 1.02-2.65, p = .042). Moreover, LT3S had an area under the curve (AUC) of 0.60 for predicting MACE. When adding LT3S to the thrombolysis in myocardial infarction (TIMI) risk score, the combined model yielded a significant improvement in discrimination for MACE. CONCLUSIONS LT3S was independently associated with poor outcomes after MINOCA. Routine assessment of LT3S may provide valuable prognostic information in this specific population.
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Affiliation(s)
- Side Gao
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenjian Ma
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Sizhuang Huang
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuze Lin
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mengyue Yu
- Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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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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Karmaniolou I, Lamprou K, Staikou C, Giamarellos-Bourboulis E, Theodoraki K, Papalois A, Mylonas A, Orfanos N, Smyrniotis V, Arkadopoulos N. Effect of Triiodothyronine Administration on the Kidney During Haemorrhagic Shock and Resuscitation. Turk J Anaesthesiol Reanim 2020; 48:406-413. [PMID: 33103146 PMCID: PMC7556640 DOI: 10.5152/tjar.2019.81542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Accepted: 09/02/2019] [Indexed: 11/22/2022] Open
Abstract
Objective Apoptosis, measured via caspase activity, can be used to assess renal tissue damage in haemorrhagic shock. We investigated whether Triiodothyronine could attenuate apoptosis and protect against haemorrhagic shock-induced renal injury. Methods Haemorrhagic shock was induced in swine until the mean arterial pressure (MAP) was 35–40 mmHg for 40 minutes. Animals were randomly assigned to a control group (n=5), Group-F (Fluid resuscitation, n=6), and Group-T3 (Fluid plus Triiodothyronine, n=6). The swine were resuscitated for 1 hour aiming to MAP restoration (±10% from baseline) and were followed up for another 360 minutes. Haemodynamic parameters, fluids, acid-base status, plasma urea nitrogen, creatinine levels and caspase activity in the kidney were measured. Results Haemodynamic parameters did not differ significantly amongst the three groups. Group-T3 required less normal saline (Group-T3: 1083±204 mL versus F: 2500±547 mL, p=0.001) and hydroxyethyl starch (Group-T3: 558±102 mL versus F: 916±204 mL, p=0.004) during resuscitation. Additionally, Group-T3 swine experienced less acidosis following haemorrhage/resuscitation with a pH of 7.39 versus a pH of 7.26 in Group-F (p=0.004) at 360 minutes. Urea remained within normal limits in all groups, but creatinine levels were elevated at 6 hours in Group-F as compared to Group-T3 (p=0.019). Apoptosis, assessed by renal caspase-3 activity, was increased in Group-T3 (132±174 pmol minute−1 g−1) and reduced in Group-F (32±18 pmol minute−1 g−1) as compared to the control group, but without statistical significance (p=0.245 between Group-T3 and Group-F). Conclusion Administration of Triiodothyronine in a swine model of haemorrhagic shock seems to interfere with renal cell apoptosis. The exact mechanism needs to be further investigated in future research.
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Affiliation(s)
- Iosifina Karmaniolou
- Department of Anaesthesia, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - Konstantinos Lamprou
- Department of Obstetrics and Gynaecology, Bradford Royal Infirmary, Bradford, UK
| | - Chryssoula Staikou
- 1 Department of Anaesthesia, Aretaieion Hospital, University of Athens Medical School, Athens, Greece
| | | | - Kassiani Theodoraki
- 1 Department of Anaesthesia, Aretaieion Hospital, University of Athens Medical School, Athens, Greece
| | | | - Anastasios Mylonas
- 4 Department of Surgery, Attikon Hospital, Medical School, University of Athens, Chaidari, Greece
| | - Nikolaos Orfanos
- 4 Department of Surgery, Attikon Hospital, Medical School, University of Athens, Chaidari, Greece
| | - Vassilios Smyrniotis
- 4 Department of Surgery, Attikon Hospital, Medical School, University of Athens, Chaidari, Greece
| | - Nikolaos Arkadopoulos
- 4 Department of Surgery, Attikon Hospital, Medical School, University of Athens, Chaidari, Greece
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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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15
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Nistal-Nuño B. Euthyroid sick syndrome in paediatric and adult patients requiring extracorporeal circulatory support and the role of thyroid hormone supplementation: a review. Perfusion 2020; 36:21-33. [PMID: 32423366 DOI: 10.1177/0267659120914136] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Non-thyroid disorders may modify thyroid hormone metabolism, resulting in an 'euthyroid sick syndrome'. Studies determining the association of cardiopulmonary bypass to thyroid function showed changes in line with this euthyroid sick syndrome. In some cases, cardiovascular dysfunction after cardiac surgery with cardiopulmonary bypass is comparable to that noticed in hypothyroidism associated with low cardiac output and elevated systemic vascular resistance. Numerous lines of research have proposed that triiodothyronine can behave acutely as a positive inotropic and vasodilator agent. The aim of this review is to present an update on the current literature about in what clinical situations the use of thyroid supplementation during the perioperative period of extracorporeal circulation in the adult and paediatric populations may impact outcome to any appreciable degree. The contribution of thyroid function in patients undergoing a ventricular assist device implantation is additionally reviewed and future study directions are proposed. This is a narrative review, where the search strategy consisted on retrieving the articles through an extensive literature search performed using electronic databases from January 1978 up to September 2019. All controlled trials randomly allocating to perioperative thyroid hormone administration in children and adults undergoing extracorporeal circulation for cardiac surgery were considered. Thyroid hormone supplementation may be recommended particularly in selected paediatric sub-populations. There is currently no firm evidence regarding the benefits of routine use of thyroid hormone administration in cardiac adult patients. Further studies are required to assess the beneficial effect of thyroid hormone on patients with end-stage heart failure supported by ventricular assist devices.
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Affiliation(s)
- Beatriz Nistal-Nuño
- Department of Anesthesiology, Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
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16
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Zhang X, Liu L, Ma X, Hu W, Xu X, Huang S, Hua B, Wang H, Chen Z, Sun L. Clinical significance of non-thyroidal illness syndrome on disease activity and dyslipidemia in patients with SLE. PLoS One 2020; 15:e0231622. [PMID: 32298352 PMCID: PMC7162454 DOI: 10.1371/journal.pone.0231622] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Accepted: 03/29/2020] [Indexed: 12/19/2022] Open
Abstract
Objectives Nonthyroidal illness syndrome (NTIS), also known as low triiodothyronine (T3) syndrome, frequently affects patients with systemic lupus erythematosus (SLE) and may affect lipid metabolism. Dyslipidemia is highly prevalent and associated with the long-term prognosis of SLE. The aim of the present study was to explore the clinical significance of NTIS on disease activity and dyslipidemia in patients with SLE. Methods Clinical and laboratory data were collected retrospectively from 223 patients with SLE. The correlation between free triiodothyronine (FT3), SLE disease activity, and lipid profiles were estimated. The correlation coefficient (r) was calculated using a Pearson’s regression model. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for dyslipidemia in SLE. Results Serum FT3 levels were negatively correlated with the levels of 24 h urine protein (UP), blood urea nitrogen (BUN), creatinine (Cr) and SLE disease activity index (SLEDAI) (all p < 0.001) in NTIS patients but not in euthyroid patients. ApoB/ApoA1 was significantly correlated with SLEDAI (p < 0.01) in NTIS patients and CRP (p < 0.001) and ESR (p < 0.01) in euthyroid patients. A multivariate analysis revealed that only FT3 exhibited an independent negative association with dyslipidemia (P = 0.01; OR = 0.48; 95% CI 0.27–0.85). Conclusion NTIS frequently occurs in patients with SLE. Low FT3 is associated with disease activity in SLE patients complicated with NTIS. Low FT3 is an independent risk factor for dyslipidemia in patients with SLE.
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Affiliation(s)
- Xin Zhang
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Lirong Liu
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
- Department of Rheumatology and Immunology, The first Hospital of Changshu, Changshu, China
| | - Xiaolei Ma
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Wei Hu
- Department of Clinical Laboratory, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Xue Xu
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Saisai Huang
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Bingzhu Hua
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Hong Wang
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Zhiyong Chen
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
- * E-mail: (LS); (ZC)
| | - Lingyun Sun
- Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
- * E-mail: (LS); (ZC)
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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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18
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von Hafe M, Neves JS, Vale C, Borges-Canha M, Leite-Moreira A. The impact of thyroid hormone dysfunction on ischemic heart disease. Endocr Connect 2019; 8:R76-R90. [PMID: 30959486 PMCID: PMC6499922 DOI: 10.1530/ec-19-0096] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2019] [Accepted: 04/02/2019] [Indexed: 12/16/2022]
Abstract
Thyroid hormones have a central role in cardiovascular homeostasis. In myocardium, these hormones stimulate both diastolic myocardial relaxation and systolic myocardial contraction, have a pro-angiogenic effect and an important role in extracellular matrix maintenance. Thyroid hormones modulate cardiac mitochondrial function. Dysfunction of thyroid axis impairs myocardial bioenergetic status. Both overt and subclinical hypothyroidism are associated with a higher incidence of coronary events and an increased risk of heart failure progression. Endothelial function is also impaired in hypothyroid state, with decreased nitric oxide-mediated vascular relaxation. In heart disease, particularly in ischemic heart disease, abnormalities in thyroid hormone levels are common and are an important factor to be considered. In fact, low thyroid hormone levels should be interpreted as a cardiovascular risk factor. Regarding ischemic heart disease, during the late post-myocardial infarction period, thyroid hormones modulate left ventricular structure, function and geometry. Dysfunction of thyroid axis might even be more prevalent in the referred condition since there is an upregulation of type 3 deiodinase in myocardium, producing a state of local cardiac hypothyroidism. In this focused review, we summarize the central pathophysiological and clinical links between altered thyroid function and ischemic heart disease. Finally, we highlight the potential benefits of thyroid hormone supplementation as a therapeutic target in ischemic heart disease.
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Affiliation(s)
- Madalena von Hafe
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
| | - João Sergio Neves
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal
- Correspondence should be addressed to J S Neves:
| | - Catarina Vale
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
| | - Marta Borges-Canha
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar São João, Porto, Portugal
| | - Adelino Leite-Moreira
- Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
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20
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Abstract
Thyroid hormone is integral for normal function, yet during illness, circulating levels of the most active form (triiodothyronine [T3]) decline. Whether this is an adaptive response in critical illness or contributes to progressive disease has remained controversial. This review outlines the basis of thyroid hormone changes during critical illness and considers the evidence regarding T3 replacement.
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Affiliation(s)
- Matthew J Maiden
- Intensive Care Unit, Royal Adelaide Hospital, Port Road, Adelaide, South Australia 5000, Australia; Intensive Care Unit, Barwon Health, Ryrie St, Geelong, Victoria 3220, Australia; Discipline of Acute Care Medicine, University of Adelaide, Adelaide, South Australia 5005, Australia.
| | - David J Torpy
- Endocrine and Metabolic Unit, Royal Adelaide Hospital, Port Road, Adelaide, South Australia 5000, Australia
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21
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Pantos C, Mourouzis I. Thyroid hormone receptor α1 as a novel therapeutic target for tissue repair. ANNALS OF TRANSLATIONAL MEDICINE 2018; 6:254. [PMID: 30069456 DOI: 10.21037/atm.2018.06.12] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
Abstract
Analogies between the damaged tissue and developing organ indicate that a regulatory network that drives embryonic organ development may control aspects of tissue repair. In this regard, there is a growing body of experimental and clinical evidence showing that TH may be critical for recovery after injury. Especially TRα1 has been reported to play an essential role in cell proliferation and differentiation and thus in the process of repair/regeneration in the heart and other tissues. Patients after myocardial infarction, stroke or therapeutic interventions [such as PCI for coronary artery disease (CAD)] with lower TH levels appear to have increased morbidity and mortality. Accordingly, TH treatment in clinical settings of ischemia/reperfusion such as by-pass surgery seems to be cardioprotective against ischemic injury. Furthermore, TH therapy of donors is shown to result in organ preservation and increased numbers of donors and improved post-transplantation graft survival. TH and thyroid analogs may prove novel therapeutic agents for tissue repair.
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Triiodothyronine Administration in a Model of Septic Shock: A Randomized Blinded Placebo-Controlled Trial. Crit Care Med 2017; 44:1153-60. [PMID: 26963323 DOI: 10.1097/ccm.0000000000001644] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVES Triiodothyronine concentration in plasma decreases during septic shock and may contribute to multiple organ dysfunction. We sought to determine the safety and efficacy of administering triiodothyronine, with and without hydrocortisone, in a model of septic shock. DESIGN Randomized blinded placebo-controlled trial. SETTING Preclinical research laboratory. SUBJECTS Thirty-two sheep rendered septic with IV Escherichia coli and receiving protocol-guided sedation, ventilation, IV fluids, and norepinephrine infusion. INTERVENTIONS Two hours following induction of sepsis, 32 sheep received a 24-hour IV infusion of 1) placebo + placebo, 2) triiodothyronine + placebo, 3) hydrocortisone + placebo, or 4) triiodothyronine + hydrocortisone. MEASUREMENTS AND MAIN RESULTS Primary outcome was the total amount of norepinephrine required to maintain a target mean arterial pressure; secondary outcomes included hemodynamic and metabolic indices. Plasma triiodothyronine levels increased to supraphysiological concentrations with hormonal therapy. Following 24 hours of study drug infusion, the amount of norepinephrine required was no different between the study groups (mean ± SD μg/kg; placebo + placebo group 208 ± 392; triiodothyronine + placebo group 501 ± 370; hydrocortisone + placebo group 167 ± 286; triiodothyronine + hydrocortisone group 466 ± 495; p = 0.20). There was no significant treatment effect on any hemodynamic variable, metabolic parameter, or measure of organ function. CONCLUSIONS A 24-hour infusion of triiodothyronine, with or without hydrocortisone, in an ovine model of septic shock did not markedly alter norepinephrine requirement or any other physiological parameter.
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Gao R, Liang JH, Wang L, Zhu HY, Wu W, Wu JZ, Xia Y, Cao L, Fan L, Yang T, Li JY, Xu W. Low T3 syndrome is a strong prognostic predictor in diffuse large B cell lymphoma. Br J Haematol 2017; 177:95-105. [PMID: 28146267 DOI: 10.1111/bjh.14528] [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] [Received: 10/09/2016] [Accepted: 11/23/2016] [Indexed: 12/22/2022]
Abstract
The aim of this study was to evaluate the prognostic effect of low triiodothyronine (T3) syndrome on patients with diffuse large B cell lymphoma (DLBCL). A hundred and eighty-eight patients with detailed thyroid hormone levels at diagnosis of DLBCL were enrolled. Low T3 syndrome was defined as a low serum free T3 (FT3) level with low or normal serum free tetraiodothyronine (FT4) and thyroid stimulating hormone levels. Multivariate Cox regression analysis was used to screen prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver-operator characteristic curves and the corresponding areas under the curve were calculated to assess the predictive accuracy of International Prognostic Index (IPI) and low T3 syndrome. Twenty-four patients were diagnosed with low T3 syndrome, which was associated with worse PFS and OS in the rituximab era. It was an independent prognostic factor for PFS and OS, especially for those with IPI 0-2, extranodal sites ≤1 and stage III-IV. Synchronously low FT3 and FT4 had poorer survival outcome compared to only low FT3 and adding criterion of low T3 syndrome improved the prognostic capacity of IPI for predicting PFS and OS in DLBCL. Low T3 syndrome was found to be a strong prognostic predictor in DLBCL.
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Affiliation(s)
- Rui Gao
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China.,Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Jin-Hua Liang
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Li Wang
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Hua-Yuan Zhu
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Wei Wu
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Jia-Zhu Wu
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Yi Xia
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Lei Cao
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Lei Fan
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Tao Yang
- Department of Endocrinology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
| | - Jian-Yong Li
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
| | - Wei Xu
- Department of Haematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Collaborative Innovation Centre for Cancer Personalized Medicine, Nanjing, China
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Langouche L, Lehmphul I, Perre SV, Köhrle J, Van den Berghe G. Circulating 3-T1AM and 3,5-T2 in Critically Ill Patients: A Cross-Sectional Observational Study. Thyroid 2016; 26:1674-1680. [PMID: 27676423 DOI: 10.1089/thy.2016.0214] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Critical illness is hallmarked by low circulating thyroxine (T4) and triiodothyronine (T3) concentrations, in the presence of elevated reverse T3 (rT3) and low-normal thyrotropin (TSH), referred to as nonthyroidal illness (NTI). Thyroid hormone (TH) metabolism is substantially increased during NTI, in part explained by enhanced deiodinase 3 (D3) activity. T4- and T3-sulfate concentrations are elevated, due to suppressed D1 activity in the presence of unaltered sulfotransferase activity, and 3,3'-diiodothyronine (3,3'-T2) concentrations are normal. To elucidate further the driving forces behind increased TH metabolism during NTI, two other potential T4 metabolites-3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM)-were measured and related to their potential TH precursors. METHODS Morning blood samples were collected cross-sectionally from 83 critically ill patients on a University Hospital intensive care unit and from 38 demographically matched healthy volunteers. Serum TH and binding proteins were quantified with commercial assays, and 3,5-T2 and 3-T1AM with in-house developed immunoassays. RESULTS Critically ill patients revealed, besides the NTI, a median 44% lower serum 3-T1AM concentration (p < 0.0001) and a 30% higher serum 3,5-T2 concentration (p = 0.01) than healthy volunteers did. Non-survivors and patients diagnosed with sepsis upon admission to the intensive-care unit had significantly higher 3,5-T2 (p ≤ 0.01) but comparable 3-T1AM (p > 0.2) concentrations than other patients did. Multivariable linear regression analysis adjusted for potential precursors revealed that the reduced serum 3-T1AM was positively correlated with the low serum T3 (p < 0.001) but unrelated to serum T4 or rT3. The elevated 3,5-T2 concentration did not independently correlate with TH. CONCLUSIONS Increased TH metabolism during NTI could not be explained by increased conversion to 3-T1AM, as circulating 3-T1AM was suppressed in proportion to the concomitantly low T3 concentrations. Increased conversion of T4 and/or T3 to 3,5-T2 could be possible, as serum 3,5-T2 concentrations were elevated. Whether 3-T1AM or 3,5-T2 plays a functional role during critical illness needs further investigation.
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Affiliation(s)
- Lies Langouche
- 1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven , Leuven, Belgium
| | - Ina Lehmphul
- 2 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany
| | - Sarah Vander Perre
- 1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven , Leuven, Belgium
| | - Josef Köhrle
- 2 Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin , Berlin, Germany
| | - Greet Van den Berghe
- 1 Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven , Leuven, Belgium
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Non-thyroidal illness syndrome in patients with cardiovascular diseases: A systematic review and meta-analysis. Int J Cardiol 2016; 226:1-10. [PMID: 27776249 DOI: 10.1016/j.ijcard.2016.10.039] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2016] [Revised: 10/09/2016] [Accepted: 10/14/2016] [Indexed: 12/21/2022]
Abstract
BACKGROUND Non-thyroidal illness syndrome (NTIS) is characterized by decreased serum triiodothyronine level without increased thyroid-stimulating hormone level during critical illness. The summary data on the prevalence of NTIS in cardiovascular patients are lacking, and its prognostic role in cardiovascular patients is also unclear. METHODS We performed a systematic review and meta-analysis to comprehensively determine the prevalence and the prognostic role of NTIS in cardiovascular patients. The prevalence of NTIS was pooled using random-effect meta-analysis and the hazard ratios (HRs) for all-cause mortality, cardiac mortality and major adverse cardiovascular events (MACE) were also pooled. RESULTS Forty-one studies were finally included. The pooled prevalence of NTIS in cardiovascular patients was 21.7% (95% CI 18.4%-25.3%). Subgroup by the types of cardiovascular diseases showed the prevalence of NTIS was highest in patients with heart failure (24.5%), followed by acute myocardial infarction (18.9%) and acute coronary syndrome (17.1%). Meta-analysis of studies using strict diagnostic criteria of NITS showed that the pooled prevalence of NTIS in cardiovascular patients was 17.6% (95% CI 14.5%-21.2%). NTIS was independently associated with increased risks of all-cause mortality (HR=2.52, 95% CI 1.87-3.40, P<0.001) and cardiac mortality (HR=2.06, 95% CI 1.58-2.69, P<0.001) in cardiovascular patients. NTIS was also an independent predictor of MACE in cardiovascular patients (HR=1.73, 95% CI 1.32-2.26, P<0.001). CONCLUSION NTIS is very common in patients with cardiovascular diseases. NTIS is an independent prognostic factor in cardiovascular patients and is associated with increased risks of all-cause mortality, cardiac mortality and MACE.
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Abstract
In this review, we discuss the characteristics, pathophysiology, and therapeutic implications of the euthyroid sick syndrome. Multiple mechanisms have been identified to contribute to the development of euthyroid sick syndrome, including alterations in the iodothyronine deiodinases, thyroid-stimulating hormone secretion, thyroid hormone binding to plasma protein, transport of thyroid hormone in peripheral tissues, and thyroid hormone receptor activity. The euthyroid sick syndrome appears to be a complex mix of physiologic adaptation and pathologic response to acute illness. The underlying cause for these alterations has not yet been elucidated. Treatment of the euthyroid sick syndrome with thyroid hormone to restore normal serum thyroid hormone levels in an effort to improve disease prognosis and outcomes continues to be a focus of many clinical studies, although currently available data do not provide evidence of a clear benefit of treatment.
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Affiliation(s)
- Sun Lee
- Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts, USA
| | - Alan P Farwell
- Section of Endocrinology, Diabetes and Nutrition, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts, USA
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Qari FA. Thyroid function status and its impact on clinical outcome in patients admitted to critical care. Pak J Med Sci 2015; 31:915-9. [PMID: 26430429 PMCID: PMC4590373 DOI: 10.12669/pjms.314.7497] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE To analyze alterations in thyroid function and the correlation between results of thyroid function test and mortality in medical and surgical intensive care unit (ICU) patients. It also aimed to evaluate the effect of thyroid dysfunction in ICU patients and their need for mechanical ventilation (MV). METHODS A single-center, prospective, observational study was conducted on patients admitted to medical and surgical ICU between 2013-2014.. Clinical and paraclinical findings (free triiodothyronine, free thyroxine and thyroid stimulating hormone) were documented for all patients. Regression analysis and chi-square were used for death and MV outcome variables. RESULTS We included 502 patients. Of these, 340 (67.7%) were admitted to the medical ICU. Results of thyroid function tests were normal in 320 (64%) and 162 (32.3%) medical and surgical ICU patients, respectively. Euthyroid sick syndrome (ESS) was documented in 86 patients (17%). Mortality was twice higher among surgical ICU patients with ESS compared to those with normal thyroid function (p=0.085), which is not statistically significant. Based on thyroid function status, no differences in the risk to be mechanically ventilated was found between medical or surgical ICU patients. CONCLUSION There is a significant association between ESS and mortality in ICU patients. Future studies should determine whether abnormal thyroid function increases the risk for MV in ICU patients.
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Affiliation(s)
- Faiza A Qari
- Faiza A. Qari, FRCP, ABIM. Department of Internal Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia
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Dietrich JW, Müller P, Schiedat F, Schlömicher M, Strauch J, Chatzitomaris A, Klein HH, Mügge A, Köhrle J, Rijntjes E, Lehmphul I. Nonthyroidal Illness Syndrome in Cardiac Illness Involves Elevated Concentrations of 3,5-Diiodothyronine and Correlates with Atrial Remodeling. Eur Thyroid J 2015; 4:129-37. [PMID: 26279999 PMCID: PMC4521060 DOI: 10.1159/000381543] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Revised: 03/10/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Although hyperthyroidism predisposes to atrial fibrillation, previous trials have suggested decreased triiodothyronine (T3) concentrations to be associated with postoperative atrial fibrillation (POAF). Therapy with thyroid hormones (TH), however, did not reduce the risk of POAF. This study reevaluates the relation between thyroid hormone status, atrial electromechanical function and POAF. METHODS Thirty-nine patients with sinus rhythm and no history of atrial fibrillation or thyroid disease undergoing cardiac surgery were prospectively enrolled. Serum concentrations of thyrotropin, free (F) and total (T) thyroxine (T4) and T3, reverse (r)T3, 3-iodothyronamine (3-T1AM) and 3,5-diiodothyronine (3,5-T2) were measured preoperatively, complemented by evaluation of echocardiographic and electrophysiological parameters of cardiac function. Holter-ECG and telemetry were used to screen for POAF for 10 days following cardiac surgery. RESULTS Seven of 17 patients who developed POAF demonstrated nonthyroidal illness syndrome (NTIS; defined as low T3 and/or low T4 syndrome), compared to 2 of 22 (p < 0.05) patients who maintained sinus rhythm. In patients with POAF, serum FT3 concentrations were significantly decreased, but still within their reference ranges. 3,5-T2 concentrations directly correlated with rT3 concentrations and inversely correlated with FT3 concentrations. Furthermore, 3,5-T2 concentrations were significantly elevated in patients with NTIS and in subjects who eventually developed POAF. In multivariable logistic regression FT3, 3,5-T2, total atrial conduction time, left atrial volume index and Fas ligand were independent predictors of POAF. CONCLUSION This study confirms reduced FT3 concentrations in patients with POAF and is the first to report on elevated 3,5-T2 concentrations in cardiac NTIS. The pathogenesis of NTIS therefore seems to involve more differentiated allostatic mechanisms.
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Affiliation(s)
- Johannes W. Dietrich
- Department of Endocrinology and Diabetes, Medical Hospital I, Berlin, Germany
- *Dr. Johannes W. Dietrich, Department of Endocrinology and Diabetes, Medical Hospital I, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bürkle-de-la-Camp-Platz 1, DE-44789 Bochum (Germany), E-Mail
| | - Patrick Müller
- Department of Cardiology and Angiology, Medical Hospital II, Berlin, Germany
- Heart Center Bad Neustadt, Clinic for Interventional Electrophysiology, Bad Neustadt an der Saale, Berlin, Germany
| | - Fabian Schiedat
- Department of Cardiology and Angiology, Medical Hospital II, Berlin, Germany
| | - Markus Schlömicher
- Department of Cardiac Surgery, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Berlin, Germany
| | - Justus Strauch
- Department of Cardiac Surgery, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Berlin, Germany
| | | | - Harald H. Klein
- Department of Endocrinology and Diabetes, Medical Hospital I, Berlin, Germany
| | - Andreas Mügge
- Department of Cardiology and Angiology, Medical Hospital II, Berlin, Germany
| | - Josef Köhrle
- Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Eddy Rijntjes
- Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Ina Lehmphul
- Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany
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Pantos C, Mourouzis I. Translating thyroid hormone effects into clinical practice: the relevance of thyroid hormone receptor α1 in cardiac repair. Heart Fail Rev 2014; 20:273-82. [DOI: 10.1007/s10741-014-9465-4] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Jonklaas J, Bianco AC, Bauer AJ, Burman KD, Cappola AR, Celi FS, Cooper DS, Kim BW, Peeters RP, Rosenthal MS, Sawka AM. Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement. Thyroid 2014; 24:1670-751. [PMID: 25266247 PMCID: PMC4267409 DOI: 10.1089/thy.2014.0028] [Citation(s) in RCA: 1014] [Impact Index Per Article: 92.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
BACKGROUND A number of recent advances in our understanding of thyroid physiology may shed light on why some patients feel unwell while taking levothyroxine monotherapy. The purpose of this task force was to review the goals of levothyroxine therapy, the optimal prescription of conventional levothyroxine therapy, the sources of dissatisfaction with levothyroxine therapy, the evidence on treatment alternatives, and the relevant knowledge gaps. We wished to determine whether there are sufficient new data generated by well-designed studies to provide reason to pursue such therapies and change the current standard of care. This document is intended to inform clinical decision-making on thyroid hormone replacement therapy; it is not a replacement for individualized clinical judgment. METHODS Task force members identified 24 questions relevant to the treatment of hypothyroidism. The clinical literature relating to each question was then reviewed. Clinical reviews were supplemented, when relevant, with related mechanistic and bench research literature reviews, performed by our team of translational scientists. Ethics reviews were provided, when relevant, by a bioethicist. The responses to questions were formatted, when possible, in the form of a formal clinical recommendation statement. When responses were not suitable for a formal clinical recommendation, a summary response statement without a formal clinical recommendation was developed. For clinical recommendations, the supporting evidence was appraised, and the strength of each clinical recommendation was assessed, using the American College of Physicians system. The final document was organized so that each topic is introduced with a question, followed by a formal clinical recommendation. Stakeholder input was received at a national meeting, with some subsequent refinement of the clinical questions addressed in the document. Consensus was achieved for all recommendations by the task force. RESULTS We reviewed the following therapeutic categories: (i) levothyroxine therapy, (ii) non-levothyroxine-based thyroid hormone therapies, and (iii) use of thyroid hormone analogs. The second category included thyroid extracts, synthetic combination therapy, triiodothyronine therapy, and compounded thyroid hormones. CONCLUSIONS We concluded that levothyroxine should remain the standard of care for treating hypothyroidism. We found no consistently strong evidence for the superiority of alternative preparations (e.g., levothyroxine-liothyronine combination therapy, or thyroid extract therapy, or others) over monotherapy with levothyroxine, in improving health outcomes. Some examples of future research needs include the development of superior biomarkers of euthyroidism to supplement thyrotropin measurements, mechanistic research on serum triiodothyronine levels (including effects of age and disease status, relationship with tissue concentrations, as well as potential therapeutic targeting), and long-term outcome clinical trials testing combination therapy or thyroid extracts (including subgroup effects). Additional research is also needed to develop thyroid hormone analogs with a favorable benefit to risk profile.
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Affiliation(s)
| | - Antonio C. Bianco
- Division of Endocrinology, Rush University Medical Center, Chicago, Illinois
| | - Andrew J. Bauer
- Division of Endocrinology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
| | - Kenneth D. Burman
- Endocrine Section, Medstar Washington Hospital Center, Washington, DC
| | - Anne R. Cappola
- Division of Endocrinology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
| | - Francesco S. Celi
- Division of Endocrinology, Virginia Commonwealth University School of Medicine, Richmond, Virginia
| | - David S. Cooper
- Division of Endocrinology, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brian W. Kim
- Division of Endocrinology, Rush University Medical Center, Chicago, Illinois
| | - Robin P. Peeters
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
| | - M. Sara Rosenthal
- Program for Bioethics, Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, Kentucky
| | - Anna M. Sawka
- Division of Endocrinology, University Health Network and University of Toronto, Toronto, Ontario, Canada
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Abstract
Thyroid hormone deficiency can have important repercussions. Treatment with thyroid hormone in replacement doses is essential in patients with hypothyroidism. In this review, we critically discuss the thyroid hormone formulations that are available and approaches to correct replacement therapy with thyroid hormone in primary and central hypothyroidism in different periods of life such as pregnancy, birth, infancy, childhood, and adolescence as well as in adult patients, the elderly, and in patients with comorbidities. Despite the frequent and long term use of l-T4, several studies have documented frequent under- and overtreatment during replacement therapy in hypothyroid patients. We assess the factors determining l-T4 requirements (sex, age, gender, menstrual status, body weight, and lean body mass), the major causes of failure to achieve optimal serum TSH levels in undertreated patients (poor patient compliance, timing of l-T4 administration, interferences with absorption, gastrointestinal diseases, and drugs), and the adverse consequences of unintentional TSH suppression in overtreated patients. Opinions differ regarding the treatment of mild thyroid hormone deficiency, and we examine the recent evidence favoring treatment of this condition. New data suggesting that combined therapy with T3 and T4 could be indicated in some patients with hypothyroidism are assessed, and the indications for TSH suppression with l-T4 in patients with euthyroid multinodular goiter and in those with differentiated thyroid cancer are reviewed. Lastly, we address the potential use of thyroid hormones or their analogs in obese patients and in severe cardiac diseases, dyslipidemia, and nonthyroidal illnesses.
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Affiliation(s)
- Bernadette Biondi
- Department of Clinical Medicine and Surgery (B.B.), University of Naples Federico II, 80131 Naples, Italy; and Washington Hospital Center (L.W.), Washington, D.C. 20010
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Fekete C, Lechan RM. Central regulation of hypothalamic-pituitary-thyroid axis under physiological and pathophysiological conditions. Endocr Rev 2014; 35:159-94. [PMID: 24423980 PMCID: PMC3963261 DOI: 10.1210/er.2013-1087] [Citation(s) in RCA: 202] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2013] [Accepted: 11/05/2013] [Indexed: 12/18/2022]
Abstract
TRH is a tripeptide amide that functions as a neurotransmitter but also serves as a neurohormone that has a critical role in the central regulation of the hypothalamic-pituitary-thyroid axis. Hypophysiotropic TRH neurons involved in this neuroendocrine process are located in the hypothalamic paraventricular nucleus and secrete TRH into the pericapillary space of the external zone of the median eminence for conveyance to anterior pituitary thyrotrophs. Under basal conditions, the activity of hypophysiotropic TRH neurons is regulated by the negative feedback effects of thyroid hormone to ensure stable, circulating, thyroid hormone concentrations, a mechanism that involves complex interactions between hypophysiotropic TRH neurons and the vascular system, cerebrospinal fluid, and specialized glial cells called tanycytes. Hypophysiotropic TRH neurons also integrate other humoral and neuronal inputs that can alter the setpoint for negative feedback regulation by thyroid hormone. This mechanism facilitates adaptation of the organism to changing environmental conditions, including the shortage of food and a cold environment. The thyroid axis is also affected by other adverse conditions such as infection, but the central mechanisms mediating suppression of hypophysiotropic TRH may be pathophysiological. In this review, we discuss current knowledge about the mechanisms that contribute to the regulation of hypophysiotropic TRH neurons under physiological and pathophysiological conditions.
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Affiliation(s)
- Csaba Fekete
- Department of Endocrine Neurobiology (C.F.), Institute of Experimental Medicine, Hungarian Academy of Sciences, 1083 Budapest, Hungary; Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (C.F., R.M.L.), Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111; and Department of Neuroscience (R.M.L.), Tufts University School of Medicine, Boston, Massachusetts 02111
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Cerillo AG, Storti S, Kallushi E, Haxhiademi D, Miceli A, Murzi M, Berti S, Glauber M, Clerico A, Iervasi G. The low triiodothyronine syndrome: a strong predictor of low cardiac output and death in patients undergoing coronary artery bypass grafting. Ann Thorac Surg 2014; 97:2089-95. [PMID: 24636708 DOI: 10.1016/j.athoracsur.2014.01.049] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 01/04/2014] [Accepted: 01/14/2014] [Indexed: 11/17/2022]
Abstract
BACKGROUND There is strong clinical and experimental evidence that altered thyroid homeostasis negatively affects survival in cardiac patients, but a negative effect of the low triiodothyronine (T3) syndrome on the outcome of coronary artery bypass grafting (CABG) has not been demonstrated. This study was designed to evaluate the prognostic significance of low T3 syndrome in patients undergoing CABG. METHODS The thyroid profile was evaluated at hospital admission in 806 consecutive CABG patients. Known thyroid disease, severe systemic illness, and use of drugs interfering with thyroid metabolism were considered exclusion criteria. The effect of the baseline free T3 (fT3) concentration and of preoperative low T3 syndrome (fT3 <2.23 pmol/L) on the risk of low cardiac output (CO) and death was analyzed in a logistic regression model. RESULTS There were 19 (2.3%) deaths, and 64 (7.8%) patients experienced major complications. After univariate analysis, fT3, low T3, New York Heart Association class greater than II, low left ventricular ejection fraction (LVEF), and emergency were associated with low CO and hospital death. History of atrial fibrillation, cardiopulmonary bypass time, and peripheral vascular disease were associated only with low CO. At multivariate analysis, only fT3, low T3, emergency, and LVEF were associated with low CO, and fT3 (odds ratio, 0.172, 95% confidence interval, 0.078 to 0.379; p < 0.0001) and LVEF (odds ratio, 0.934, 95% confidence interval, 0.894 to 0.987; p = 0.03) were the only independent predictors of death. CONCLUSIONS Our study demonstrates that low T3 is a strong predictor of death and low CO in CABG patients. For this reason, the thyroid profile should be evaluated before CABG, and patients with low T3 should be considered at higher risk and treated accordingly.
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Affiliation(s)
- Alfredo Giuseppe Cerillo
- Operative Unit of Cardiac Surgery, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy.
| | - Simona Storti
- Clinical Chemistry Laboratory, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy
| | - Enkel Kallushi
- Operative Unit of Cardiac Surgery, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy
| | - Dorela Haxhiademi
- Anesthesia and Intensive Care, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy
| | - Antonio Miceli
- Operative Unit of Cardiac Surgery, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy
| | - Michele Murzi
- Operative Unit of Cardiac Surgery, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy
| | - Sergio Berti
- Cardiology, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy
| | - Mattia Glauber
- Operative Unit of Cardiac Surgery, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy
| | - Aldo Clerico
- Clinical Chemistry Laboratory, "G. Pasquinucci" Hospital, "G. Monasterio" Foundation, Massa, Italy
| | - Giorgio Iervasi
- Operative Unit of Cardiovascular Endocrinology and Metabolism, "G. Monasterio" Foundation, Istituto di Fisiologia Clinica del Consiglio Nazionale delle Ricerche, Pisa, Italy
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Abstract
PURPOSE OF REVIEW The current state of the pathophysiology, diagnosis, and therapeutic implications of the nonthyroidal illness syndrome is reviewed. RECENT FINDINGS Previous studies attributed the development of the nonthyroidal illness syndrome to alterations in three main areas of thyroid hormone metabolism: deiodinase activity, thyroid-stimulating hormone secretion, and hormone binding to serum proteins. New studies suggest that alterations in thyroid hormone transport into tissues and alterations of the nuclear thyroid hormone receptors may also play a role. Therapy of the nonthyroidal illness syndrome remains a controversial topic. SUMMARY Multiple factors lead to the development of the nonthyroidal illness syndrome, including alterations in type 1 and 3 deiodinase activity, thyrotropin-releasing hormone and thyroid-stimulating hormone secretion, hormone binding to plasma proteins, thyroid hormone transporter expression and activity, and the thyroid hormone nuclear receptor complex. These data show that acute and chronic illness affect all aspects of thyroid hormone metabolism and action. Some of these changes are physiologic and some are pharmacologic. The mediators of these alterations are still largely unclear. There continues to be no indication for thyroid hormone therapy in the vast majority of patients with the nonthyroidal illness syndrome, although interesting data suggest a possible role for treating a small subset of patients.
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Affiliation(s)
- Alan P Farwell
- Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts 01583, USA.
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Meuwese CL, Dekkers OM, Stenvinkel P, Dekker FW, Carrero JJ. Nonthyroidal illness and the cardiorenal syndrome. Nat Rev Nephrol 2013; 9:599-609. [PMID: 23999398 DOI: 10.1038/nrneph.2013.170] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The cardiorenal syndrome represents a final common pathway for renal and congestive heart failure and heralds a poor prognosis. Factors that link the failing heart and the failing kidneys--the so-called cardiorenal connectors--are, therefore, of clinical and therapeutic interest. Alterations in the levels and function of thyroid hormones that fit the spectrum of nonthyroidal illnesses could be considered to be cardiorenal connectors as both renal failure and heart failure progress with the development of nonthyroidal illness. In addition, circumstantial evidence suggests that nonthyroidal illness can induce deterioration in the function of the heart and the kidneys via multiple pathways. As a consequence, these reciprocal associations could result in a vicious cycle of deterioration that likely contributes to increased mortality. In this Review, we describe the evidence for a pathophysiological role of nonthyroidal illness in the cardiorenal syndrome. We also discuss the available data from studies that have investigated the efficacy of thyroid hormone replacement therapy in patients with renal failure and the rationale for interventional trials to examine the effects of normalization of the thyroid hormone profile in patients with renal failure and congestive heart failure.
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Affiliation(s)
- Christiaan L Meuwese
- Department of Clinical Epidemiology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
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Abstract
BACKGROUND Studies have documented a correlation between hypothyroxinemia and mortality in critically ill patients; however, there are limited data in sepsis. The objective of this study was to assess baseline thyroid function studies and their association with mortality in surgical sepsis. We hypothesized that the relatively decreased levels of free thyroxine (T4), decreased levels of triiodothyronine (T3), and increased thyrotropin-stimulating hormone levels would be associated with mortality. METHODS This was a retrospective review of prospectively collected data in a surgical intensive care unit. Data evaluated included patient demographics, baseline thyroid function studies, and mortality. Patients were categorized as having sepsis, severe sepsis, or septic shock. A value of p < 0.05 was considered significant. RESULTS Within 24 months, 231 septic patients were accrued. The mean age was 59 ± 3 years, and 43% were male. Thirty-nine patients were diagnosed as having sepsis, 131 as having severe sepsis, and 61 as having septic shock. There were no statistically significant differences between the T3, free T4, or thyrotropin-stimulating hormone levels at baseline and the different categorizations of sepsis.T4 levels were increased in all patients but to a significantly lesser extent in those who died. Similarly, T3 levels were significantly decreased in patients who died. CONCLUSION In surgical sepsis, decreased T3 levels at baseline are associated with mortality. These data do not support the administration of levothyroxine (T4) because it is already elevated and would preferentially be converted to reverse T3 (inactive) in critical illness; however, replacement with liothyronine (T3) might be rational. LEVEL OF EVIDENCE Epidemiologic study, level III.
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Choi YS, Shim JK, Song JW, Song Y, Yang SY, Kwak YL. Efficacy of perioperative oral triiodothyronine replacement therapy in patients undergoing off-pump coronary artery bypass grafting. J Cardiothorac Vasc Anesth 2013; 27:1218-23. [PMID: 23958074 DOI: 10.1053/j.jvca.2013.01.027] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2012] [Indexed: 11/11/2022]
Abstract
OBJECTIVE The aim of this study was to assess the effects of oral triiodothyronine (T3) therapy on postoperative thyroid hormone concentrations, hemodynamic variables, and outcomes. DESIGN A prospective, randomized, controlled, double-blind study. SETTING Cardiac operating room at a single institution. PARTICIPANTS One hundred patients undergoing elective off-pump coronary artery bypass graft surgery. INTERVENTIONS Patients received either 20 μg of oral T3 or placebo every 12 hours starting 20 minutes before anesthetic induction, for a total of 4 doses. MEASUREMENTS AND MAIN RESULTS Plasma concentrations of thyroid hormones were measured serially before surgery, upon arrival in the intensive care unit, and 12, 24, and 36 hours after surgery. Hemodynamic variables also were recorded serially. Postoperative inotrope requirement and major morbidity endpoints were assessed. Serum T3 concentrations were significantly higher with fewer patients having T3 concentrations below the normal range in the T3 group than the placebo group throughout the postoperative period. Hemodynamic variables, postoperative inotrope requirement, and outcome variables showed no differences between the groups. CONCLUSIONS Oral T3 therapy significantly attenuated the postoperative decline in T3 concentrations in patients undergoing off-pump coronary artery bypass graft surgery. The lack of apparent clinical benefit merits further investigations in patients with reduced cardiac performance.
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Affiliation(s)
- Yong Seon Choi
- Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine
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von Saint Andre-von Arnim A, Farris R, Roberts JS, Yanay O, Brogan TV, Zimmerman JJ. Common endocrine issues in the pediatric intensive care unit. Crit Care Clin 2013; 29:335-58. [PMID: 23537679 DOI: 10.1016/j.ccc.2012.11.006] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
Thyroid hormone is central to normal development and metabolism. Abnormalities in thyroid function in North America often arise from autoimmune diseases, but they rarely present as critical illness. Severe deficiency or excess of thyroid hormone both represent life-threatening disease, which must be treated expeditiously and thoroughly. Such deficiencies must be considered, because presentation may be nonspecific.
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Gielen M, Mesotten D, Wouters PJ, Desmet L, Vlasselaers D, Vanhorebeek I, Langouche L, Van den Berghe G. Effect of tight glucose control with insulin on the thyroid axis of critically ill children and its relation with outcome. J Clin Endocrinol Metab 2012; 97:3569-76. [PMID: 22872689 PMCID: PMC3462949 DOI: 10.1210/jc.2012-2240] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
CONTEXT Tight glucose control (TGC) to normal-for-age fasting blood glucose levels reduced morbidity and mortality in surgical adult and pediatric intensive care unit (ICU) patients. In adults, TGC did not affect the illness-induced alterations in thyroid hormones. With better feeding in children than in adult patients, we hypothesized that TGC in pediatric ICU patients reactivates the thyroid axis. OBJECTIVE The aim of this study was to assess the impact of TGC on the thyroid axis in pediatric ICU patients and to investigate how these changes affect the TGC outcome benefit. DESIGN AND PATIENTS We conducted a preplanned analysis of all patients not treated with thyroid hormone, dopamine, or corticosteroids who were included in a randomized controlled trial on TGC (n=700). MAIN OUTCOME MEASURES Serum TSH, T4, T3, and rT3 were measured upon admission and on ICU day 3 or the last ICU day for patients discharged earlier. Changes from baseline were compared for the TGC and usual care groups. The impact on the outcome benefit of TGC was assessed with multivariable Cox proportional hazard analysis, correcting for baseline risk factors. RESULTS TGC further lowered the T)/rT3 ratio (P=0.03), whereas TSH (P=0.09) and T4 (P=0.3) were unaltered. With TGC, the likelihood of earlier live discharge from the ICU was 19% higher at any time (hazard ratio, 1.190; 95% confidence interval, 1.010-1.407; P=0.03). This benefit was statistically explained by the further reduction of T3/rT3 with TGC because an increase in T3/rT3 was strongly associated with a lower likelihood for earlier live discharge (hazard ratio per unit increase, 0.863; 95% confidence interval, 0.806-0.927; P<0.0001). CONCLUSIONS TGC further accentuated the peripheral inactivation of thyroid hormone. This effect, mimicking a fasting response, statistically explained part of the clinical outcome benefit of TGC.
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Affiliation(s)
- Marijke Gielen
- Clinical Department and Laboratory of Intensive Care Medicine, Catholic University of Leuven, B-3000 Leuven, Belgium
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Grill E, Strong M, Sonnad SS, Sarani B, Pascual J, Collins H, Sims CA. Altered thyroid function in severely injured patients. J Surg Res 2012; 179:132-7. [PMID: 23043865 DOI: 10.1016/j.jss.2012.09.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2012] [Revised: 08/20/2012] [Accepted: 09/05/2012] [Indexed: 11/19/2022]
Abstract
BACKGROUND Hemorrhagic shock profoundly affects the neuroendocrine profile of trauma patients, and we hypothesized that massive resuscitation would negatively impact thyroid function. METHODS A prospective, observational study investigating thyroid function in hypotensive trauma patients (systolic blood pressure <90 mm Hg × 2) who survived >48 h was conducted at a Level I center over a 6-mo period. Blood samples for thyroid function were collected at time of presentation to the trauma bay and serially for 48 h. Collected data included demographics, injury data, vital signs, transfusion needs, crystalloid use, and vasopressor requirements. Patients receiving >5 units packed red blood cells (PRBC) within 12 h were compared with those receiving ≤5 units. RESULTS Patients who required >5 units of PRBC/12 h had significantly lower total and free T4 levels on initial presentation, and levels remained significantly depressed over the next 48 h when compared with patients who required a less aggressive resuscitative effort. T3 values were markedly suppressed during the initial 48 h post trauma in all patients, but were significantly lower in patients requiring >5 units PRBC. TSH levels remained within the normal range for all time points. Lower trauma admission T4 levels were associated with the need for greater crystalloid resuscitation within the first 24 h. CONCLUSION Measurements of thyroid function are significantly altered in severely injured patients on initial presentation, and low T4 levels predict the need for large resuscitation. Further research investigating the profile and impact of thyroid function in trauma patients during resuscitation and recovery is warranted.
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Affiliation(s)
- Elena Grill
- Division of Traumatology, Surgical Critical Care, and Emergency Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA
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Pantos C, Mourouzis I, Cokkinos DV. Thyroid hormone and cardiac repair/regeneration: from Prometheus myth to reality? Can J Physiol Pharmacol 2012; 90:977-87. [PMID: 22762197 DOI: 10.1139/y2012-031] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Nature's models of repair and (or) regeneration provide substantial evidence that a natural healing process may exist in the heart. The potential for repair and (or) regeneration has been evolutionarily conserved in mammals, and seems to be restricted to the early developmental stages. This window of regeneration is reactivated during the disease state in which fetal gene reprogramming occurs in response to stress. Analogies exist between the damaged and developing heart, indicating that a regulatory network that drives embryonic heart development may control aspects of heart repair and (or) regeneration. In this context, thyroid hormone (TH), which is a critical regulator of the maturation of the myocardium, appears to have a reparative role later in adult life. Changes in TH - thyroid hormone receptor (TR) homeostasis govern the return of the injured myocardium to the fetal phenotype. Accordingly, TH can induce cardiac repair and (or) regeneration by reactivating developmental gene programming. As a proof of concept in humans, TH is found to be an independent determinant of functional recovery and mortality after myocardial infarction. The potential of TH to regenerate and (or) repair the ischemic myocardium is now awaited to be tested in clinical trials.
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Priest JR, Slee A, Olson AK, Ledee D, Morrish F, Portman MA. Triiodothyronine supplementation and cytokines during cardiopulmonary bypass in infants and children. J Thorac Cardiovasc Surg 2012; 144:938-943.e2. [PMID: 22743177 DOI: 10.1016/j.jtcvs.2012.05.063] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2011] [Revised: 04/16/2012] [Accepted: 05/17/2012] [Indexed: 11/28/2022]
Abstract
OBJECTIVE The Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC) study demonstrated a shortened time to extubation in children younger than 5 months old undergoing cardiopulmonary bypass for congenital heart surgery with triiodothyronine supplementation. Cardiopulmonary bypass precipitates a systemic inflammatory response that affects recovery, and triiodothyronine is related to cytokine mediators of inflammation. We sought to investigate the preoperative cytokine levels by age and relationship to the triiodothyronine levels and to examine the effect of the cytokine levels on the time to extubation. METHODS We measured 6 cytokines at preoperative time 0 and 6 and 24 hours after crossclamp removal in 76 subjects. RESULTS The preoperative cytokine levels were related to both the triiodothyronine levels and the patient age. The postoperative cytokine levels were predictive of the triiodothyronine levels at 6, 12, 24, and 72 hours. Preoperative CCL4 was associated with an increased chance of early extubation. Inclusion of the cytokines did not change the relationship of triiodothyronine to the time to extubation, and the postoperative course of interleukin-6 was independently associated with a decreased chance of early extubation. CONCLUSIONS The preoperative and postoperative cytokine levels, in particular, interleukin-1β, showed complex time-dependent relationships with triiodothyronine. The data suggest that cytokine-mediated suppression of triiodothyronine plays an important role in determining the clinical outcome after cardiopulmonary bypass.
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Affiliation(s)
- James R Priest
- Seattle Children's Hospital and University of Washington, Seattle, WA, USA
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Wajner SM, Maia AL. New Insights toward the Acute Non-Thyroidal Illness Syndrome. Front Endocrinol (Lausanne) 2012; 3:8. [PMID: 22654851 PMCID: PMC3356062 DOI: 10.3389/fendo.2012.00008] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2011] [Accepted: 01/10/2012] [Indexed: 11/13/2022] Open
Abstract
The non-thyroidal illness syndrome (NTIS) refers to changes in serum thyroid hormone levels observed in critically ill patients in the absence of hypothalamic-pituitary-thyroid primary dysfunction. Affected individuals have low T3, elevated rT3, and inappropriately normal TSH levels. The pathophysiological mechanisms are poorly understood but the acute and chronic changes in pituitary-thyroid function are probably the consequence of the action of multiple factors. The early phase seems to reflect changes occurring primarily in the peripheral thyroid hormone metabolism, best seen in humans since 80-90% of the circulating T3 are derived from the pro-hormone T4. The conversion of T4 to T3 is catalyzed by type 1 (D1) and type 2 (D2) deiodinases via outer-ring deiodination. In contrast, type 3 deiodinase (D3) catalyzes the inactivation of both T4 and T3. Over the last decades, several studies have attempted to elucidate the mechanisms underlying the changes on circulating thyroid hormones in NTIS. Increased inflammatory cytokines, which occurs in response to virtually any illness, has long been speculated to play a role in derangements of deiodinase expression. On the other hand, oxidative stress due to augmented reactive oxygen species (ROS) generation is characteristic of many diseases that are associated with NTIS. Changes in the intracellular redox state may disrupt deiodinase function by independent mechanisms, which might include depletion of the as yet unidentified endogenous thiol cofactor. Here we aim to present an updated picture of the advances in understanding the mechanisms that result in the fall of thyroid hormone levels in the acute phase of NTIS.
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Affiliation(s)
- Simone Magagnin Wajner
- Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do SulPorto Alegre, Brasil
| | - Ana Luiza Maia
- Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do SulPorto Alegre, Brasil
- *Correspondence: Ana Luiza Maia, Serviço de Endocrinologia, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, CEP 90035-003 Porto Alegre, Brasil. e-mail:
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Boelen A, Kwakkel J, Fliers E. Beyond low plasma T3: local thyroid hormone metabolism during inflammation and infection. Endocr Rev 2011; 32:670-93. [PMID: 21791567 DOI: 10.1210/er.2011-0007] [Citation(s) in RCA: 159] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Decreased serum thyroid hormone concentrations in severely ill patients were first reported in the 1970s, but the functional meaning of the observed changes in thyroid hormone levels, together known as nonthyroidal illness syndrome (NTIS), remains enigmatic. Although the common view was that NTIS results in overall down-regulation of metabolism in order to save energy, recent work has shown a more complex picture. NTIS comprises marked variation in transcriptional and translational activity of genes involved in thyroid hormone metabolism, ranging from inhibition to activation, dependent on the organ or tissue studied. Illness-induced changes in each of these organs appear to be very different during acute or chronic inflammation, adding an additional level of complexity. Organ- and timing-specific changes in the activity of thyroid hormone deiodinating enzymes (deiodinase types 1, 2, and 3) highlight deiodinases as proactive players in the response to illness, whereas the granulocyte is a novel and potentially important cell type involved in NTIS during bacterial infection. Although acute NTIS can be seen as an adaptive response to support the immune response, NTIS may turn disadvantageous when critical illness enters a chronic phase necessitating prolonged life support. For instance, changes in thyroid hormone metabolism in muscle during critical illness may be relevant for the pathogenesis of myopathy associated with prolonged ventilator dependence. This review focuses on NTIS as a timing-related and organ-specific response to illness, occurring independently from the decrease in serum thyroid hormone levels and potentially relevant for disease progression.
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Affiliation(s)
- Anita Boelen
- Department of Endocrinology and Metabolism, F5-165, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, The Netherlands.
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Mazza A, Beltramello G, Armigliato M, Montemurro D, Zorzan S, Zuin M, Rampin L, Marzola M, Grassetto G, Al-Nahhas A, Rubello D. Arterial hypertension and thyroid disorders: What is important to know in clinical practice? ANNALES D'ENDOCRINOLOGIE 2011; 72:296-303. [DOI: 10.1016/j.ando.2011.05.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/27/2010] [Revised: 04/30/2011] [Accepted: 05/05/2011] [Indexed: 11/27/2022]
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Acute T3 treatment protects the heart against ischemia-reperfusion injury via TRα1 receptor. Mol Cell Biochem 2011; 353:235-41. [DOI: 10.1007/s11010-011-0791-8] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2011] [Accepted: 03/17/2011] [Indexed: 10/18/2022]
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