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Wilson JB, Hoang TD, Lee ML, Epstein M, Friedman TC. Reverse T3 in patients with hypothyroidism on different thyroid hormone replacement. PLoS One 2025; 20:e0325046. [PMID: 40489725 DOI: 10.1371/journal.pone.0325046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2025] [Accepted: 05/06/2025] [Indexed: 06/11/2025] Open
Abstract
BACKGROUND Reverse T3 (rT3) is a biologically inactive form of T3 (triiodothyronine), a thyroid hormone, that is created by peripheral 5 deiodination of T4 (thyroxine) by type 1 and type 3 deiodinase enzymes (D1 and D3 respectively) and may block T3 binding to the thyroid hormone receptor. Approximately 15% of patients on L-T4 replacement therapy with a normalized thyroid-stimulating hormone (TSH) report experience continued fatigue and other hypothyroid symptoms; therefore, efforts are needed to understand why this occurs and how it can be corrected. Decades ago, endocrinologists realized that in patients with severe illnesses, rT3 is typically high and T3 is typically low; this was termed "euthyroid sick syndrome". More recently, functional medicine and other doctors, have argued that high rT3 is detrimental and can block T3 from binding to the thyroid hormone receptor. Due to the lack of peer-reviewed publications on this topic, functional medicine doctors continue to rely heavily on rT3 levels to treat patients that may have no other laboratory findings of hypothyroidism and often prescribe L-T3-only preparations to patients in an effort to lower rT3. METHODS The initial rT3 measurements done by liquid chromatography/tandem mass spectrometry (LC/MS-MS) were retrospectively analyzed from the initial blood tests in 976 consecutive patients, with symptoms of fatigue and treated for hypothyroidism, in a private Endocrinology practice. TSH, free T3 and free T4 were measured by electrochemiluminescence immunoassay (ECLIA). The upper limit of normal rT3 (24.1 ng/dL) was used as a cut-off for results above the normal range. RESULTS The number of patients with rT3 levels above normal range varied significantly with the type of thyroid hormone replacement prescribed. The highest rate of an elevated rT3 was 20.9% (29/139) in patients taking T4 alone. Nine% (31/345) of patients not taking thyroid hormone replacement had elevated rT3. Patients on all types of L-T4 treatment had higher rT3 levels than those not on L-T4 treatment (p < 0.00001) and they also had a higher percentage of rT3 levels above the cutoff of 24.1 ng/dL (p < 0.00001). Linear regression analysis showed rT3 levels correlated with free T4 and free T3 levels and inversely with log TSH levels. CONCLUSIONS This study found elevated rT3 levels in patients with symptoms of fatigue on various thyroid hormone replacements with the highest levels of rT3 in those taking L-T4 replacement alone and the lowest levels of rT3 in those on preparations that contained L-T3 alone.
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Affiliation(s)
- Julian B Wilson
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, United States of America
| | - Thanh D Hoang
- Endocrinology Division, Walter Reed National Military Medical Center, Bethesda, Maryland, United States of America
| | - Martin L Lee
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, United States of America
- UCLA Fielding School of Public Health, Los Angeles, California, United States of America
| | - Ma'ayan Epstein
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, United States of America
- UCLA Fielding School of Public Health, Los Angeles, California, United States of America
| | - Theodore C Friedman
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, United States of America
- David Geffen School of Medicine at University of California, Los Angeles, California, United States of America
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Wu H, Mu Y, Liu Y, Zhang R, Xu Y, Zhang Y, Zhao C, Zhang W, Lin L, Chen Z. The Impact of Non-Thyroidal Illness Syndromes on The Prognosis and Immune Profile in Severe Fever with Thrombocytopenia Syndrome Patients. Infect Drug Resist 2025; 18:1439-1449. [PMID: 40104280 PMCID: PMC11914451 DOI: 10.2147/idr.s506378] [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: 11/14/2024] [Accepted: 03/06/2025] [Indexed: 03/20/2025] Open
Abstract
Background Non-thyroidal illness syndrome (NTIS) is the most common endocrine dysfunction in critically ill patients and is often associated with poor prognosis. Thyroid dysfunction and immune cell disturbances are frequently observed in patients with severe fever with thrombocytopenia syndrome (SFTS). This study aims to evaluate the impact of NTIS on the prognosis of SFTS patients and to explore the relationship between thyroid hormones (THs) and immune cell profiles. Methods Adult patients admitted to Yantai Qishan Hospital for SFTS from January 2023 to December 2023 with no prior history of thyroid disease were retrospectively recruited. Multivariable regressions were used to assess the associations between NTIS and clinical outcomes. Spearman correlation analysis was conducted to evaluate the relationships between immune cells and THs. SFTS patients with NTIS were categorized into four subtypes based on different levels of FT4 and TSH, and the association between NTIS subtypes and mortality was further analyzed. Results Of the 84 SFTS patients included in the study, 62 (73.8%) were diagnosed with NTIS. Independent risk predictors which may affect prognosis of SFTS patients include NTIS subtype (P =0.002), viral load (P = 0.029), FT3 (P = 0.032), and FT4 (P = 0.041). SFTS patients with NTIS exhibited a higher mortality rate compared to euthyroid patients (P = 0.033). Spearman correlation analysis revealed that LYM, LYM%, MONO, MONO%, BAS, CD3+T, CD3+T%, Th, and Th% were positively correlated with FT3, FT4, or TSH levels. NTIS patients were more likely to present with coagulation abnormalities (APTT, P = 0.005; D-Dimer, P < 0.001), liver enzyme abnormalities (AST, P = 0.001), electrolyte imbalances (Sodium, P = 0.003), elevated LDH (P = 0.001), and increased ɑ-HBDH (P = 0.003). Conclusion NTIS is common in SFTS patients, and SFTS patients with NTIS have a lower survival rate compared to euthyroid patients. The mortality risk in NTIS type 3 patients is higher than in those with NTIS type 1.
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Affiliation(s)
- Hongxiao Wu
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
| | - Yameng Mu
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
| | - Yuanni Liu
- Department of Infectious Diseases, Yantai Qishan Hospital, Yantai, People's Republic of China
| | - Ruihua Zhang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
| | - Yanli Xu
- Department of Infectious Diseases, Yantai Qishan Hospital, Yantai, People's Republic of China
| | - Yuanyuan Zhang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
- Beijing Institute of Infectious Diseases, Beijing, 100015, People's Republic of China
| | - Chenxi Zhao
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
| | - Wei Zhang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
| | - Ling Lin
- Department of Infectious Diseases, Yantai Qishan Hospital, Yantai, People's Republic of China
| | - Zhihai Chen
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People's Republic of China
- Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
- National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People's Republic of China
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Zhong Z, Xiao X. Relationship between serum thyroid hormone and interleukin-1b levels and postmortem tissue deiodinase activity in critically ill patients. J Med Biochem 2024; 43:681-689. [PMID: 39712509 PMCID: PMC11662955 DOI: 10.5937/jomb0-46999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 03/05/2024] [Indexed: 12/24/2024] Open
Abstract
Background This study investigated the relationship between serum thyroid hormones and interleukin-1b (IL-1β) levels and postmortem tissue deiodinase activity in critically ill patients. Methods Serum thyroid hormones and IL-1β were measured on the 5th, 15th, and last day of 80 critically ill patients. Forty of these patients were non-survived, and liver and skeletal muscle were harvested to analyze type 1, 2, and 3 iodothyronine deiodinases (D1, D2, and D3) activity.
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Affiliation(s)
- Zhenzhou Zhong
- Ganzhou People's Hospital, Department of Emergency, Ganzhou City, JiangXi Province, China
| | - Xiaoliu Xiao
- Ganzhou People's Hospital, Department of Emergency, Ganzhou City, JiangXi Province, China
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Corsini A, Del Baldo F, Lunetta F, Ribichini S, Giunti M, Fidanzio F, Fracassi F. Total thyroxine, triiodothyronine, and thyrotropin concentrations during acute nonthyroidal illness and recovery in dogs. J Vet Intern Med 2024; 38:1345-1352. [PMID: 38654457 PMCID: PMC11099717 DOI: 10.1111/jvim.17059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Accepted: 03/20/2024] [Indexed: 04/26/2024] Open
Abstract
BACKGROUND Acute illness can result in changes in serum total thyroxine (tT4), total triiodothyronine (tT3), and thyrotropin (TSH) concentrations in euthyroid dogs defined as nonthyroidal illness syndrome, but longitudinal evaluation of these hormones during the recovery phase is lacking. OBJECTIVES To longitudinally evaluate serum tT4, tT3, and TSH concentrations during the acute phase and recovery from acute illness in dogs. ANIMALS Nineteen euthyroid client-owned dogs hospitalized for acute illness at a veterinary teaching hospital. METHODS Prospective longitudinal study. Serum tT4, tT3, and TSH concentrations were measured at the admission (T0), at last day of hospitalization (T1), and during the recovery phase at 3, 7, 14, and 21 days after the discharge (T2, T3, T4, and T5), respectively. RESULTS tT4 and tT3 were below the reference interval (RI) at T0 in 3 (16%) and 18 (95%) dogs, respectively; tT4 normalized in all dogs early in the recovery phase, while low tT3 persisted at the end of the study in 16 (83%) dogs. Median TSH concentrations were increased at T5 compared with T1 (0.19 ng/mL [range 0.03-0.65] vs 0.11 ng/mL [range (0.05-0.26)], mean difference = 0.09 ng/mL; P = .03). Five (26%) dogs had TSH above the RI at least at 1 time point during the recovery phase. None of the dogs had concurrent low tT4 and high TSH during the study. CONCLUSIONS AND CLINICAL RELEVANCE In euthyroid dogs acute illness can interfere with evaluation of thyroid function up to 21 days during the recovery phase. Thyroid testing should be avoided or postponed in these dogs.
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Affiliation(s)
- Andrea Corsini
- Department of Veterinary Medical SciencesAlma Mater Studiorum‐University of BolognaOzzano EmiliaItaly
- Department of Veterinary Medical SciencesUniversity of ParmaParmaItaly
| | - Francesca Del Baldo
- Department of Veterinary Medical SciencesAlma Mater Studiorum‐University of BolognaOzzano EmiliaItaly
| | - Francesco Lunetta
- Department of Veterinary Medical SciencesAlma Mater Studiorum‐University of BolognaOzzano EmiliaItaly
| | - Serena Ribichini
- Department of Veterinary Medical SciencesAlma Mater Studiorum‐University of BolognaOzzano EmiliaItaly
| | - Massimo Giunti
- Department of Veterinary Medical SciencesAlma Mater Studiorum‐University of BolognaOzzano EmiliaItaly
| | | | - Federico Fracassi
- Department of Veterinary Medical SciencesAlma Mater Studiorum‐University of BolognaOzzano EmiliaItaly
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Dai JJ, Du DF, Ma G, Jiang MJ. Association between serum-free thyroxine level and all-cause mortality in critically ill patients: a retrospective study from MIMIC-IV. Front Endocrinol (Lausanne) 2023; 14:1164369. [PMID: 37305055 PMCID: PMC10248474 DOI: 10.3389/fendo.2023.1164369] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2023] [Accepted: 05/09/2023] [Indexed: 06/13/2023] Open
Abstract
Background Low thyroxine (T4) levels have been observed in critically ill patients; however, controversial results regarding T4 supplemental therapy are reported. The association between serum free T4 (FT4) levels and mortality in critically ill patients has not been fully established and needs to be clarified. Methods Data from the Medical Information Mart for Intensive Care (MIMIC)-IV were collected and analyzed. The association between FT4 level and 30-day mortality after ICU admission was analyzed using Kaplan-Meier curves, spline smoothing fitting, martingale residuals of the null Cox model, and restricted cubic spline (RCS). Logistic regression, Cox regression, and receiver operating characteristic curve (ROC) were used to uncover the relationship and predictive value of serum FT4 and 30-day mortality in critically ill patients. Results In the final analysis, 888 patients were enrolled, and the serum FT4 levels were divided into four groups. A significant difference in 30-day mortality was observed between the four groups. Kaplan-Meier curves also presented significantly higher 30-day mortality in groups 1 and 2 (p < 0.0001). Further multivariance logistic regression showed that group 1 with FT4 levels lower than 0.7 μg/dl can predict 30-day mortality (odds ratio (OR) = 3.30, 95% confidence interval (CI) = 1.04-11.31). Spline smoothing fitting analysis showed a "V"-shaped line between 30-day mortality and FT4 level within 0-3 μg/dl. Further RCS analysis showed that the risk of death decreased rapidly as FT4 levels increased when serum FT4 levels were lower than 1.2 μg/dl and started to become flat afterward. The area under the ROC of the lower FT4 level to predict 30-day mortality was 0.833 (95% CI = 0.788-0.878). Both multivariant Cox regression and logistic regression showed that FT4 levels lower than 1.2 μg/dl can independently predict 30-day mortality when adjusted for other potential confounders (HR = 0.34, 95% CI = 0.14-0.82; OR = 0.21, 95% CI = 0.06-0.79, respectively), but its predictive power disappeared when adjusted for T3 or total T4. Conclusion Serum FT4 levels were significantly negatively associated with 30-day mortality when they were lower than 1.2 μg/dl and could predict the risk of 30-day mortality. A higher FT4 level is potentially related to increased 30-day mortality.
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Affiliation(s)
- Juan-Juan Dai
- Department of Intensive Care Unit, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ding-Fu Du
- Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Gang Ma
- Department of Intensive Care Unit, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
| | - Ming-Jie Jiang
- Department of Head and Neck Surgery, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
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Li S, Zeng X, Wang S, Xie X, Lan J. Association between MMP2 gene polymorphisms and dilated cardiomyopathy in a Chinese Han population. ESC Heart Fail 2023; 10:1793-1802. [PMID: 36866790 DOI: 10.1002/ehf2.14333] [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: 10/15/2022] [Revised: 01/31/2023] [Accepted: 02/12/2023] [Indexed: 03/04/2023] Open
Abstract
AIMS Dilated cardiomyopathy (DCM) belongs to the common types of cardiomyopathies. The pathogenesis remains unclear despite the fact that various genes have been found associated with DCM. MMP2 is a zinc-dependent and calcium-containing secreted endoproteinases, which could cleave a broad spectrum of substrates including extracellular matrix components and cytokines. It has proved to play an important role in the cardiovascular diseases. This study aimed to investigate the potential role of MMP2 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population. METHODS AND RESULTS A total of 600 idiopathic DCM patients and 700 healthy controls were enrolled. Patients with contact information were followed up for a median period of 28 months. Three tagged single nucleotide polymorphisms (rs243865, rs2285052, and rs2285053) in the promoter of MMP2 gene were genotyped. A series of function analysis were conducted to illuminate the underlying mechanism. The frequency of rs243865-C allele was increased in DCM patients when compared with healthy controls (P = 0.001). Genotypic frequencies of rs243865 were associated with the susceptibility of DCM in the codominant, dominant, and overdominant models (P < 0.05). Besides, rs243865-C allele presented a correlation with the poor prognosis of DCM patients in both dominant (HR = 2.0, 95% confidence interval [CI] = 1.14-3.57, P = 0.017) and additive (HR = 1.85, 95% CI = 1.09-3.13, P = 0.02) model. The statistical significance remained after adjustment for sex, age, hypertension, diabetes, hyperlipidaemia, and smoking status. There were significant differences in left ventricular end-diastolic diameter and left ventricular ejection fraction between rs243865-CC and CT genotypes. Functional analysis indicated that rs243865-C allele increased luciferase activity and the mRNA expression level of MMP2 by facilitating ZNF354C binding. CONCLUSIONS Our study suggested that MMP2 gene polymorphisms were associated with DCM susceptibility and prognosis in the Chinese Han population.
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Affiliation(s)
- Shiyang Li
- Division of Cardiology, Panzhihua Central Hospital, Panzhihua, China
| | - Xiaobin Zeng
- Division of Cardiology, Panzhihua Central Hospital, Panzhihua, China
| | - Shihai Wang
- Division of Cardiology, Panzhihua Central Hospital, Panzhihua, China
| | - Xiaoshuang Xie
- Division of Cardiology, Panzhihua Central Hospital, Panzhihua, China
| | - Jianjun Lan
- Division of Cardiology, Panzhihua Central Hospital, Panzhihua, China
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Abstract
The novel coronavirus disease 2019 (COVID-19) produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious infectious disease. In addition to typical flu-like symptoms, COVID-19 can also cause extrapulmonary spread and systemic inflammation, potentially causing multiorgan dysfunction, including thyroid dysfunction. Thyroid function changes in patients with COVID-19 have been widely reported, but the results are inconsistent. Based on available data, SARS-CoV-2 infection can lead to changes in thyroid function, and the degree of thyroid function changes was positively correlated with the severity of COVID-19, which involved multiple potential mechanisms. In contrast, current evidence was insufficient to prove that thyroid function changes could induce the progression of COVID-19 clinical deterioration.
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Affiliation(s)
- Wenjie Chen
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China
- Laboratory of Thyroid and Parathyroid Disease, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Jianyong Lei
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
| | - Zhihui Li
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
- Thyroid Surgery Center, West China Hospital of Sichuan University, Chengdu, 610041, China.
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Rodriguez L, Dinauer C, Francis G. Treatment of hypothyroidism in infants, children and adolescents. Trends Endocrinol Metab 2022; 33:522-532. [PMID: 35537910 DOI: 10.1016/j.tem.2022.04.007] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 04/11/2022] [Indexed: 11/22/2022]
Abstract
In 2014, treatment guidelines from the American Thyroid Association reflected the general consensus that levothyroxine (LT4), adjusted to maintain a normal thyrotropin (TSH) level, is the preferred method for treatment of hypothyroidism. Although this is generally applicable to children, there are subsets of children for whom the diagnosis and treatment of hypothyroidism are problematic. These include children with congenital hypothyroidism (CH), low birth weight (LBW) and very low birth weight (VLBW), Down syndrome (DS), subclinical hypothyroidism, and obesity. In this Review, we focus on the progress and remaining pitfalls in diagnosis and treatment of hypothyroidism in these and other groups.
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Affiliation(s)
- Luisa Rodriguez
- Assistant Professor of Pediatrics, Division of Endocrinology and Diabetes, University of Texas Health Science Center San Antonio, San Antonio, TX, USA
| | - Catherine Dinauer
- Associate Professor of Pediatrics, Division of Endocrinology, Yale University, New Haven, CT, USA
| | - Gary Francis
- Professor of Pediatrics, Division of Endocrinology and Diabetes, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
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Rao MJ, Zhang Y, Peng WZ, Pan PH. Association of thyroid hormones and thyroid-stimulating hormone with mortality in adults admitted to the intensive care unit: A systematic review and meta-analysis. J Chin Med Assoc 2022; 85:443-452. [PMID: 35125402 DOI: 10.1097/jcma.0000000000000697] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Thyroid hormones (THs) and thyroid-stimulating hormone (TSH) seem to show high potential in predicting the clinical death outcome of patients admitted to the intensive care unit (ICU). However, diverse studies on this topic are conflicting. METHODS A search was conducted by two investigators involved in this research in the PubMed, Embase, and Cochrane databases (all last launched on July 12, 2021). The quality of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS). Subgroup analyses were performed to determine the sources of heterogeneity. Sensitivity and publication bias analyses were also assessed. RESULTS A total of 27 studies (4970 participants) were included based on the eligibility criteria. Compared with survivors, nonsurvivors were found to have lower levels of THs (T3, T4, fT3, and fT4), whereas no significant difference was found in TSH levels (13 studies for T3: standardized mean differences [SMD], -0.78; 95% CI, -1.36 to -0.20; I2 = 96%; p = 0.008; 11 studies for T4: SMD = -0.79; 95% CI, -1.31 to -0.28; I2 =95%; p = 0.0002; 14 studies for fT3: SMD = -0.76; 95% CI, -1.21 to -0.32; I2 = 95%; p = 0.0008; 17 studies for fT4: SMD = -0.60; 95% CI, -0.99 to -0.22; I2 = 95%; p = 0.002; 20 studies for TSH: SMD = 0.00; 93% CI, -0.29 to 0.29; I2 = 93%; p = 0.98). CONCLUSION Nonsurvivors were associated with lower levels of THs (T3, T4, fT3, and fT4) than survivors. THs show great application potential in predicting ICU patients' death outcomes and improving already widely used prognostic scores in the ICU (ie, Acute Physiological and Chronic Health Evaluation [APACHE] II and Therapeutic Intervention Scoring System).
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Affiliation(s)
- Ming-Jun Rao
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Yan Zhang
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
| | - Wen-Zhong Peng
- Clinical Research Center for Respiratory Diseases in Hunan, Changsha, Hunan, China
| | - Pin-Hua Pan
- Department of Respiratory Medicine, National Key Clinical Specialty, Branch of National Clinical Research Center for Respiratory Disease, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Center of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China
- Clinical Research Center for Respiratory Diseases in Hunan, Changsha, Hunan, China
- Hunan Engineering Research Center for Intelligent Diagnosis and Treatment of Respiratory Disease, Changsha, Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, Hunan, China
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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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11
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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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12
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Téblick A, Langouche L, Van den Berghe G. Endocrine interventions in the intensive care unit. HANDBOOK OF CLINICAL NEUROLOGY 2021; 182:417-431. [PMID: 34266609 DOI: 10.1016/b978-0-12-819973-2.00028-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Following the onset of any life-threatening illness that requires intensive medical care, alterations within the neuroendocrine axes occur which are thought to be essential for survival, as they postpone energy-consuming anabolism, activate energy-producing catabolic pathways, and optimize immunological and cardiovascular functions. The hormonal changes present in the acute phase of critical illness at least partially resemble those of the fasting state, and recent evidence suggests that they are part of a beneficial, evolutionary-conserved adaptive stress response. However, a fraction of patients who survive the acute phase of critical illness remain dependent on vital organ support and enter the prolonged phase of critical illness. In these patients, the hypothalamic-pituitary-peripheral axes are functionally suppressed, which may have negative consequences by which recovery may be hampered and the risk of morbidity and mortality in the long-term increased. Most randomized controlled trials of critically ill patients that investigated the impact on the outcome of treatment with peripheral hormones did not reveal a robust morbidity or mortality benefit. In contrast, small studies of patients in the prolonged phase of critical illness documented promising results with the infusion of hypothalamic-releasing hormones. The currently available data corroborate the need for well-designed and adequately powered RCTs to further investigate the impact of these releasing factors on patient-centered outcomes.
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Affiliation(s)
- Arno Téblick
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University, Leuven, Belgium
| | - Lies Langouche
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University, Leuven, Belgium
| | - Greet Van den Berghe
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University, Leuven, Belgium.
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13
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Thilak MR, Shetty SM, Kotian CM, Mohammed AP, Dhunputh P, Umakanth S, Saraswat PP. Serum total triiodothyronine (T3) as a predictor of mortality and morbidity in critically ill patients and its correlation of predictability with acute physiology and chronic health evaluation II score: A prospective observational study. Int J Crit Illn Inj Sci 2021; 11:61-66. [PMID: 34395206 PMCID: PMC8318167 DOI: 10.4103/ijciis.ijciis_88_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 08/16/2020] [Accepted: 09/21/2020] [Indexed: 11/09/2022] Open
Abstract
Background: The aim is to assess the prognostic value of total T3, total T4, and thyroid-stimulating hormone among critically ill patients admitted to the medical intensive care unit (ICU) in association with mortality and its correlation with the acute physiology and chronic health evaluation II (APACHE II) score. METHODS : Our prospective observational study consists of 257 patients without known thyroid diseases admitted to the medical ICU. The baseline characteristics of the patients were recorded, including the APACHE II score and thyroid hormone levels at ICU admission. Based on the primary outcome of mortality, we analyzed the data by appropriate statistical methods. A P < 0.05 was considered significant. Results: Of the 257 patients included in the study, 47 (18.28%) succumbed to their illnesses. A significant difference in T3 levels (P < 0.001), T4 levels (P < 0.001), and APACHE II score (P < 0.001) was found between the survivors and the nonsurvivors. There was negative correlation observed between T3 and APACHE II score (r = −0.448, P < 0.001) and T4 and APACHE II score (r = −0.221, P ≤ 0.001). Multivariate logistic regression analysis determined T3 to be the only independent predictor of ICU mortality among thyroid hormones. The area under the curve (AUC) for T3 (0.811 ± 0.04) was almost equal to that of the APACHE II score (0.858 ± 0.029). The duration of ICU stay and hospital stay in patients with low T3 was significantly higher compared to patients with normal T3. Conclusion: Serum T3 is a good indicator for predicting mortality and morbidity among critically ill patients.
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Affiliation(s)
- M R Thilak
- Department of Medicine, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Seema M Shetty
- Department of Medicine, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Chitra M Kotian
- Department of Medicine, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Afsal P Mohammed
- Department of Medicine, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Pushwinder Dhunputh
- Department of Medicine, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Shashikiran Umakanth
- Department of Medicine, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Pallavi P Saraswat
- Department of Medicine, Melaka Manipal Medical College, Manipal Academy of Higher Education, Manipal, Karnataka, India
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14
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Grondman I, de Nooijer AH, Antonakos N, Janssen NAF, Mouktaroudi M, Leventogiannis K, Medici M, Smit JWA, van Herwaarden AE, Joosten LAB, van der Veerdonk FL, Pickkers P, Kox M, Jaeger M, Netea MG, Giamarellos-Bourboulis EJ, Netea-Maier RT. The Association of TSH and Thyroid Hormones With Lymphopenia in Bacterial Sepsis and COVID-19. J Clin Endocrinol Metab 2021; 106:1994-2009. [PMID: 33713408 PMCID: PMC7989224 DOI: 10.1210/clinem/dgab148] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Indexed: 11/19/2022]
Abstract
CONTEXT Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations. OBJECTIVE This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections. METHODS A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n = 224) and COVID-19 patients (n = 161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts. RESULTS Only T3 significantly correlated (ρ = 0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n = 56 per group). Severe lymphopenic COVID-19 patients (n = 17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n = 18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed. CONCLUSION Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved.
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Affiliation(s)
- Inge Grondman
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Aline H de Nooijer
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Nikolaos Antonakos
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Nico A F Janssen
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Maria Mouktaroudi
- 4th Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | | | - Marco Medici
- Department of Internal Medicine, Division of Endocrinology, Radboud University Nijmegen, GA, Nijmegen, the Netherlands
- Academic Center for Thyroid Diseases and Departments of Internal Medicine and Epidemiology, Erasmus Medical Centre, Rotterdam, Netherlands
| | - Jan W A Smit
- Department of Internal Medicine, Division of Endocrinology, Radboud University Nijmegen, GA, Nijmegen, the Netherlands
| | | | - Leo A B Joosten
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Frank L van der Veerdonk
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Peter Pickkers
- Department of Intensive Care Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
- Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Bonn, Germany
| | - Matthijs Kox
- Department of Intensive Care Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
- Department of Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, Bonn, Germany
| | - Martin Jaeger
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Mihai G Netea
- Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
- Department of Intensive Care Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
| | | | - Romana T Netea-Maier
- Department of Internal Medicine, Division of Endocrinology, Radboud University Nijmegen, GA, Nijmegen, the Netherlands
- Corresponding author (and to whom reprints should be addressed): Romana Netea-Maier, MD PhD, Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, The Netherlands, Tel: +31-24-3614599, Email
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15
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Bashkin A, Abu Saleh W, Shehadeh M, Even L, Ronen O. Subclinical hypothyroidism or isolated high TSH in hospitalized patients with chronic heart-failure and chronic renal-failure. Sci Rep 2021; 11:10976. [PMID: 34040018 PMCID: PMC8155051 DOI: 10.1038/s41598-021-90193-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 05/04/2021] [Indexed: 01/12/2023] Open
Abstract
Sub-clinical hypothyroidism (SCH) is common in heart failure (HF) and advanced renal failure (RF), but it is unclear whether there is a thyroid disease or a transient increase in TSH level. This is a retrospective study of hospitalized patients in medical departments. All patients with SCH and a TSH level up to less than 12 mIU/L were identified. Those who had at least one recurring admission within at least 6 months were included. A change in thyroid function during the last re-admission was determined and classified as an improvement, no change, or worsening of thyroid function. Overall, 126 cases of SCH met the inclusion criteria for re-admission. Analysis of the most recent hospitalization showed that in 100 (79.4%) patients thyroid function improved, in 15 (11.9%) patients thyroid function remained unchanged and only in 11 (8.7%) patients did thyroid function worsen. In most cases, worsening of hypothyroidism was determined by initiation of a low dose levothyroxine treatment. Of the 126 participants, 43 (34.1%) and 22 (17.5%) had a diagnosis of HF and RF (CKD stages 4 and 5), respectively. There was no association between HF or advanced RF and worsening of SCH. No association was found between worsening of hypothyroidism and gender, age, TSH, or creatinine levels in the first hospitalization. A borderline association between elevated CRP levels at first hospitalization and hypothyroidism worsening was found (p = 0.066). Mildly elevated TSH in hospitalized patients with HF and advanced RF is transient and most probably not related to thyroid disease and not associated with age or gender.
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Affiliation(s)
- Amir Bashkin
- Department of Endocrinology, Galilee Medical Center, POB 21, 2210001, Nahariya, Israel.
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
| | - Wagde Abu Saleh
- Department of Geriatric Medicine, Galilee Medical Center, Nahariya, Israel
| | - Mona Shehadeh
- Department of Biochemistry and Endocrinology Laboratory, Galilee Medical Center, Nahariya, Israel
| | - Lea Even
- Department of Pediatrics, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
| | - Ohad Ronen
- Department of Otolaryngology Head and Neck Surgery, Galilee Medical Center, Nahariya, Israel
- Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel
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16
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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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17
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Gao W, Guo W, Guo Y, Shi M, Dong G, Wang G, Ge Q, Zhu J, Zhou X. Thyroid hormone concentrations in severely or critically ill patients with COVID-19. J Endocrinol Invest 2021; 44:1031-1040. [PMID: 33140379 PMCID: PMC7605732 DOI: 10.1007/s40618-020-01460-w] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2020] [Accepted: 10/22/2020] [Indexed: 01/08/2023]
Abstract
OBJECTIVE COVID-19 is a new coronavirus infectious disease. We aimed to study the characteristics of thyroid hormone levels in patients with COVID-19 and to explore whether thyroid hormone predicts all-cause mortality of severely or critically ill patients. METHODS The clinical data of 100 patients with COVID-19, who were admitted to Wuhan Tongji Hospital from February 8 to March 8, 2020, were analyzed in this retrospective study. The patients were followed up for 6-41 days. Patients were grouped into non-severe illness and severe or critical illness, which included survivors and non-survivors. Multivariate Cox proportional hazards analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality in association with continuous and the lower two quartiles of thyroid hormone concentrations in severely or critically ill patients. RESULTS The means of free T3 (FT3) were 4.40, 3.73 and 2.76 pmol/L in non-severely ill patients, survivors and non-survivors, respectively. The lower (versus upper) two quartiles of FT3 was associated with all-cause mortality HR (95% CI) of 9.23 (2.01, 42.28). The HR (95% CI) for all-cause mortality in association with continuous FT3 concentration was 0.41 (0.21, 0.81). In the multivariate-adjusted models, free T4 (FT4), TSH and FT3/FT4 were not significantly related to all-cause mortality. Patients with FT3 less than 3.10 pmol/L had increased all-cause mortality. CONCLUSION FT3 concentration was significantly lower in patients with severe COVID-19 than in non-severely ill patients. Reduced FT3 independently predicted all-cause mortality of patients with severe COVID-19.
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Affiliation(s)
- W Gao
- Emergency Department, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China
| | - W Guo
- Trauma Center, Peking University People's Hospital, Beijing, China
| | - Y Guo
- Trauma Center, Peking University People's Hospital, Beijing, China
| | - M Shi
- Trauma Center, Peking University People's Hospital, Beijing, China
| | - G Dong
- Trauma Center, Peking University People's Hospital, Beijing, China
| | - G Wang
- Department of Critical Care Medicine, Peking University People's Hospital, Beijing, China
| | - Q Ge
- Department of Critical Care Unit, Peking University Third Hospital, Beijing, China
| | - J Zhu
- Emergency Department, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
| | - X Zhou
- Department of Endocrinology and Metabolism, Peking University People's Hospital, No.11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
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18
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Schwarz Y, Percik R, Oberman B, Yaffe D, Zimlichman E, Tirosh A. Sick Euthyroid Syndrome on Presentation of Patients With COVID-19: A Potential Marker for Disease Severity. Endocr Pract 2021; 27:101-109. [PMID: 33551316 PMCID: PMC7834506 DOI: 10.1016/j.eprac.2021.01.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/04/2021] [Accepted: 01/04/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Precise risk stratification and triage of coronavirus disease 2019 (COVID-19) patients are essential in the setting of an overwhelming pandemic burden. Clinical observation has shown a somewhat high prevalence of sick euthyroid syndrome among patients with COVID-19. This study aimed to evaluate the predictive value of free triiodothyronine (FT3) at the clinical presentation of COVID-19 for disease severity and death. METHODS This retrospective cohort study was based on electronic medical records. The study was conducted at Sheba Medical Centre, a tertiary hospital where several acute and chronic wards have been dedicated to the treatment of patients with COVID-19. The primary outcome measure was death during hospitalization; secondary outcomes included hospitalization in intensive care, mechanical ventilation, and length of hospitalization. RESULTS Of a total of 577 polymerase chain reaction-positive patients with COVID-19 hospitalized between February 27 and July 30, 2020, 90 had at least 1 measurement of thyroid-stimulating hormone, free thyroxine, and FT3 within 3 days of presentation. After applying strict exclusion criteria, 54 patients were included in the study. Patients in the lowest tertile of FT3 had significantly higher rates of mortality (40%, 5.9%, and 5.9%, P = .008), mechanical ventilation (45%, 29.4%, and 0.0%; P = .007) and intensive care unit admission (55%, 29.4%, and 5.9%, P = .006). In multivariate analyses adjusted for age, Charlson comorbidity index, creatinine, albumin, and white blood cell count. FT3 remained a significant independent predictor of death. CONCLUSION FT3 levels can serve as a prognostic tool for disease severity in the early presentation of COVID-19.
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Affiliation(s)
- Yair Schwarz
- Dalia and David Arabov Endocrinology and Diabetes Research Center, Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel.
| | - Ruth Percik
- Dalia and David Arabov Endocrinology and Diabetes Research Center, Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
| | - Bernice Oberman
- Gertner Institute for Epidemiology and Health Policy, Sheba Medical Center, Tel Hashomer, Israel
| | - Dana Yaffe
- MDClone, HaEnergia Street 77, Be'er Sheva, Israel
| | - Eyal Zimlichman
- Sackler Faculty of Medicine, Tel Aviv University, Israel; Central Management, Sheba Medical Center, Tel Hashomer, Israel
| | - Amir Tirosh
- Dalia and David Arabov Endocrinology and Diabetes Research Center, Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel
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Liu J, Xue Y, Jiang W, Zhang H, Zhao Y. Thyroid Hormone Is Related to Postoperative AKI in Acute Type A Aortic Dissection. Front Endocrinol (Lausanne) 2020; 11:588149. [PMID: 33312160 PMCID: PMC7708335 DOI: 10.3389/fendo.2020.588149] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2020] [Accepted: 10/12/2020] [Indexed: 01/16/2023] Open
Abstract
BACKGROUND Renal function is profoundly influenced by thyroid hormone levels. This study was designed to evaluate the association between preoperative thyroid hormones and postoperative acute kidney injury (AKI) in acute type A aortic dissection (ATAAD) patients. METHODS A total of 88 patients with ATAAD who underwent surgeries in Beijing Anzhen Hospital and 274 healthy controls from July 2016 to December 2016 were included in this study. Propensity-score matching was used to compare thyroid hormone levels. Additionally, in a cohort study of ATAAD patients, multivariable regression and stratification analyses were conducted to examine the association of preoperative thyroid hormones with postoperative AKI. RESULTS Compared with healthy controls, ATAAD patients presented with lower preoperative levels of total triiodothyronine (TT3) (P < 0.01), free triiodothyronine (FT3) (P < 0.01), and thyroid-stimulating hormone (TSH) (P < 0.01) and a higher preoperative level of free thyroxine (FT4) (P < 0.01). The overall occurrence of postoperative AKI was 45.5%. Multivariate regression revealed that low levels of TT3 (OR = 0.07, 95% CI, 0.01-0.86, P = 0.04) were independently associated with postoperative AKI. Subgroup analyses showed that the association between TT3 and AKI was significant in patients with normal TSH levels (OR = 0.001 95% CI, 0.001-0.16, P < 0.01) but not in patients with lower TSH levels (P = 0.12). CONCLUSION The present study showed that a low level of TT3 was a predictor of postoperative AKI in ATAAD patients, especially in patients with normal TSH. The thyroid function should be checked before surgical intervention of patients with ATAAD, and patients with low T3 might be at higher risk of postoperative AKI.
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Affiliation(s)
- Jihong Liu
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
- Beijing Lab for Cardiovascular Precision Medicine, Beijing, China
- Department of Cardiac Surgery, Affiliated Zhongshan Hospital of Dalian University, Dalian, China
| | - Yuan Xue
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
- Beijing Lab for Cardiovascular Precision Medicine, Beijing, China
| | - Wenjian Jiang
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
- Beijing Lab for Cardiovascular Precision Medicine, Beijing, China
- *Correspondence: Hongjia Zhang, ; Wenjian Jiang, ; Yuanfei Zhao,
| | - Hongjia Zhang
- Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China
- Beijing Lab for Cardiovascular Precision Medicine, Beijing, China
- *Correspondence: Hongjia Zhang, ; Wenjian Jiang, ; Yuanfei Zhao,
| | - Yuanfei Zhao
- Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, University of Sydney, Sydney, NSW, Australia
- *Correspondence: Hongjia Zhang, ; Wenjian Jiang, ; Yuanfei Zhao,
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Rothberger GD, Valestra PK, Knight K, Desai AK, Calixte R, Shapiro LE. Low Free T 3 Is Associated With Worse Outcomes in Patients in the ICU Requiring Invasive Mechanical Ventilation. J Intensive Care Med 2019; 36:313-318. [PMID: 31774023 DOI: 10.1177/0885066619890822] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
OBJECTIVE Critical illness causes a decrease in serum free triiodothyronine (T3) levels. This condition, known as nonthyroidal illness syndrome (NTIS), is associated with poor outcomes. The association of NTIS and outcomes in patients in the intensive care unit (ICU) requiring mechanical ventilation has not been well studied. This study aimed to determine the impact of NTIS on the outcomes of these patients. METHODS This prospective study included 162 patients in the ICU who underwent mechanical ventilation. Serum free T3 levels were tested on the day of initiation of mechanical ventilation. The rates of in-hospital mortality and ventilator-free days (VFDs) at day 28 after the initiation of mechanical ventilation were compared between patients with low (<2.3 pg/mL) and normal (≥2.3 pg/mL) free T3 levels. Patients who died while on mechanical ventilation were assigned a VFD of 0. RESULTS Low T3 was present in 60% of study patients. The in-hospital mortality rate of the entire cohort was 39%, and the mean and median VFDs at day 28 were 13.5 and 21 days, respectively. Compared to patients with normal free T3, patients with low free T3 had higher in-hospital mortality (52% vs 19%, P < .001) and less mean and median VFDs at day 28 (10.7 vs 18 and 0 vs 23, respectively. P < .001 for both mean and median VFDs). CONCLUSIONS The presence of low T3 due to NTIS in patients in the ICU requiring mechanical ventilation is associated with poor outcomes.
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Affiliation(s)
- Gary D Rothberger
- Division of Endocrinology, 24998NYU Winthrop Hospital, Mineola, NY, USA
| | - Paul K Valestra
- Department of Medicine, 24998NYU Winthrop Hospital, Mineola, NY, USA
| | - Khalilah Knight
- Division of Endocrinology, 24998NYU Winthrop Hospital, Mineola, NY, USA
| | - Anish K Desai
- Division of Pulmonary and Critical Care Medicine, 12302SUNY Upstate College of Medicine, Syracuse, NY, USA
| | - Rose Calixte
- Department of Community Health and Social Medicine, 465154CUNY School of Medicine, New York, NY, USA
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Langouche L, Jacobs A, Van den Berghe G. Nonthyroidal Illness Syndrome Across the Ages. J Endocr Soc 2019; 3:2313-2325. [PMID: 31745528 PMCID: PMC6853682 DOI: 10.1210/js.2019-00325] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 09/17/2019] [Indexed: 02/07/2023] Open
Abstract
In conditions of acute illness, patients present with reduced plasma T3 concentrations without a concomitant rise in TSH. In contrast, plasma concentrations of the inactive hormone rT3 increase, whereas plasma concentrations of T4 remain low-normal. This constellation of changes, referred to as nonthyroidal illness syndrome (NTIS), is present across all ages, from preterm neonates and over-term critically ill infants and children to critically ill adults. Although the severity of illness strongly correlates with the severity of the NTIS phenotype, the causality of this association remains debated, and pathophysiological mechanisms remain incompletely understood. In the acute phase of illness, NTIS appears to be caused predominantly by an increased peripheral inactivation of thyroid hormones, in which reduced nutritional intake plays a role. Current evidence suggests that these acute peripheral changes are part of a beneficial adaptation of the body to reduce expenditure of energy and to activate the innate immune response, which is important for survival. In contrast, in more severely ill and prolonged critically ill patients, an additional central suppression of the thyroid hormone axis alters and further aggravates the NTIS phenotype. Recent studies suggest that this central suppression may not be adaptive. Whether treatment of this central component of NTIS in prolonged critically ill patients, with the use of hypothalamic releasing factors, improves outcome remains to be investigated in large randomized control trials.
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Affiliation(s)
- Lies Langouche
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - An Jacobs
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Greet Van den Berghe
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
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Abstract
Thyroid hormone (TH) plays an essential role in human physiology and maintenance of appropriate levels is important for good health. Unfortunately, there are instances in which TH is misused or abused. Such misuse may be intentional such as when individuals take thyroid hormone for unapproved indications like stimulation of weight loss or improved energy. There are instances where healthcare providers prescribe thyroid hormone for controversial or out of date uses and sometimes in supraphysiologic doses. Othertimes, unintentional exposure may occur through supplements or food that unknowingly contain TH. No matter the reason, exposure to exogenous forms of TH places the public at risk for potential adverse side effects.
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Affiliation(s)
- Victor J Bernet
- Division of Endocrinology, Mayo Clinic, Mayo Clinic School of Medicine, Jacksonville, FL, 32224, USA.
- F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MA, USA.
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Abstract
PURPOSE OF REVIEW This review summarizes recent literature on nonthyroidal illness syndrome (NTI) and outcome of pediatric critical illness, to provide insight in pathophysiology and therapeutic implications. RECENT FINDINGS NTI is typically characterized by lowered triiodothyronine levels without compensatory TSH rise. Although NTI severity is associated with poor outcome of pediatric critical illness, it remains unclear whether this association reflects an adaptive protective response or contributes to poor outcome. Recently, two metabolic interventions that improved outcome also altered NTI in critically ill children. These studies shed new light on the topic, as the results suggested that the peripheral NTI component, with inactivation of thyroid hormone, may represent a beneficial adaptation, whereas the central component, with suppressed TSH-driven thyroid hormone secretion, may be maladaptive. There is currently insufficient evidence for treatment of NTI in children. However, the recent findings raised the hypothesis that reactivation of the central NTI component could offer benefit, which should be tested in RCTs. SUMMARY NTI in critically ill children can be modified by metabolic interventions. The peripheral, but not the central, component of NTI may be a beneficial adaptive response. These findings open perspectives for the development of novel strategies to improve outcome of critical illness in children.
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Affiliation(s)
- An Jacobs
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
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Nishii N, Okada R, Matsuba M, Takashima S, Kobatake Y, Kitagawa H. Risk factors for low plasma thyroxine and high plasma thyroid-stimulating hormone concentrations in dogs with non-thyroidal diseases. J Vet Med Sci 2019; 81:1097-1103. [PMID: 31204368 PMCID: PMC6715931 DOI: 10.1292/jvms.19-0169] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
The aim of the current study was to identify independent risk factors for thyroid axis alterations in dogs with non-thyroidal diseases. In this retrospective cross-sectional study, data and plasma samples from 207 dogs with non-thyroidal diseases was used. The involvement of various factors (disease severity, sex, age, breed, category and duration of disease, and medication) in the alteration of plasma thyroxine (T4) or thyroid-stimulation hormone (TSH) concentrations was analyzed using multivariate logistic regression. Among the 207 dogs analyzed, 99 (47.8%) had low plasma T4 concentrations, while 45 (21.7%) had high TSH concentrations. Intact male sex [odds ratio (OR), 3.25; 1.67-6.35; P<0.001], Labrador Retrievers (OR, 18.70; 2.32-151.00; P=0.006), moderate (OR, 2.39; 1.21-4.74; P=0.012) and severe diseases (OR, 6.84; 2.27-20.70; P<0.001) were associated with increased risk for low plasma T4 concentrations. Meanwhile, intact male (OR, 3.93; 1.51-10.30; P=0.005), spayed female (OR, 4.22; 1.59-11.20; P=0.004), older age (OR, 2.73; 1.28-5.84; P=0.009), and Miniature Dachshunds (OR, 5.39; 2.38-12.20; P<0.001) had increased risk for high plasma TSH concentrations. Disease severity had been determined as an independent risk factor for canine NTIS. In addition, sex, age and breed were also associated with thyroid axis alterations in dogs with non-thyroidal diseases.
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Affiliation(s)
- Naohito Nishii
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Rie Okada
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Moeka Matsuba
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Satoshi Takashima
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Yui Kobatake
- Joint Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan
| | - Hitoshi Kitagawa
- Department of Veterinary Medicine, Faculty of Veterinary Medicine, Okayama University of Science, 1-3 Ikoi-no-oka, Imabari, Ehime 794-8555, Japan
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Jacobs A, Derese I, Vander Perre S, van Puffelen E, Verstraete S, Pauwels L, Verbruggen S, Wouters P, Langouche L, Garcia Guerra G, Joosten K, Vanhorebeek I, Van den Berghe G. Non-Thyroidal Illness Syndrome in Critically Ill Children: Prognostic Value and Impact of Nutritional Management. Thyroid 2019; 29:480-492. [PMID: 30760183 PMCID: PMC6457888 DOI: 10.1089/thy.2018.0420] [Citation(s) in RCA: 20] [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] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Non-thyroidal illness (NTI), which occurs with fasting and in response to illness, is characterized by thyroid hormone inactivation with low triiodothyronine (T3) and high reverse T3 (rT3), followed by suppressed thyrotropin (TSH). Withholding supplemental parenteral nutrition early in pediatric critical illness (late-PN), thus accepting low/no macronutrient intake up to day 8 in the pediatric intensive care unit (PICU), accelerated recovery compared to initiating supplemental parenteral nutrition early (early-PN). Whether NTI is harmful or beneficial in pediatric critical illness and how it is affected by a macronutrient deficit remains unclear. This study investigated the prognostic value of NTI, the impact of late-PN on NTI, and whether such impact explains or counteracts the outcome benefit of late-PN in critically ill children. METHODS This preplanned secondary analysis of the Early versus Late Parenteral Nutrition in the Pediatric Intensive Care Unit randomized controlled trial quantified serum TSH, total thyroxine (T4), T3, and rT3 concentrations in 982 patients upon PICU admission versus 64 matched healthy children and in 772 propensity score-matched early-PN and late-PN patients upon admission and at day 3 or last PICU day for shorter PICU stay. Associations between thyroid hormone concentrations upon admission and outcome, as well as impact of late-PN on NTI in relation with outcome, were assessed with univariable analyses and multivariable logistic regression, linear regression, or Cox proportional hazard analysis, adjusted for baseline risk factors. RESULTS Upon PICU admission, critically ill children revealed lower TSH, T4, T3, and T3/rT3 and higher rT3 than healthy children (p < 0.0001). A more pronounced NTI upon admission, with low T4, T3, and T3/rT3 and high rT3 was associated with higher mortality and morbidity. Late-PN further reduced T4, T3, and T3/rT3 and increased rT3 (p ≤ 0.001). Statistically, the further lowering of T4 by late-PN reduced the outcome benefit (p < 0.0001), whereas the further lowering of T3/rT3 explained part of the outcome benefit of late-PN (p ≤ 0.004). This effect was greater for infants than for older children. CONCLUSION In critically ill children, the peripheral inactivation of thyroid hormone, characterized by a decrease in T3/rT3, which is further accentuated by low/no macronutrient intake, appears beneficial. In contrast, the central component of NTI attributable to suppressed TSH, evidenced by the decrease in T4, seems to be a harmful response to critical illness. Whether treating the central component with TSH releasing hormone infusion in the PICU is beneficial requires further investigation.
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Affiliation(s)
- An Jacobs
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Inge Derese
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Sarah Vander Perre
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Esther van Puffelen
- Intensive Care, Department of Pediatrics and Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Sören Verstraete
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Lies Pauwels
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Sascha Verbruggen
- Intensive Care, Department of Pediatrics and Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Pieter Wouters
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Lies Langouche
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Gonzalo Garcia Guerra
- Department of Pediatrics, Intensive Care Unit, University of Alberta, Stollery Children's Hospital, Edmonton, Canada
| | - Koen Joosten
- Intensive Care, Department of Pediatrics and Pediatric Surgery, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands
| | - Ilse Vanhorebeek
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
| | - Greet Van den Berghe
- Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven University Hospital, Leuven, Belgium
- Address correspondence to: Greet Van den Berghe, MD, Clinical Division and Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, Leuven 3000, Belgium
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Tyler PD, Du H, Feng M, Bai R, Xu Z, Horowitz GL, Stone DJ, Celi LA. Assessment of Intensive Care Unit Laboratory Values That Differ From Reference Ranges and Association With Patient Mortality and Length of Stay. JAMA Netw Open 2018; 1:e184521. [PMID: 30646358 PMCID: PMC6324400 DOI: 10.1001/jamanetworkopen.2018.4521] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
IMPORTANCE Laboratory data are frequently collected throughout the care of critically ill patients. Currently, these data are interpreted by comparison with values from healthy outpatient volunteers. Whether this is the most useful comparison has yet to be demonstrated. OBJECTIVES To understand how the distribution of intensive care unit (ICU) laboratory values differs from the reference range, and how these distributions are related to patient outcomes. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional study of a large critical care database, the Medical Information Mart for Intensive Care database, from January 1, 2001, to October 31, 2012. The database is collected from ICU data from a large tertiary medical center in Boston, Massachusetts. The data are collected from medical, cardiac, neurologic, and surgical ICUs. All patients in the database from all ICUs for 2001 to 2012 were included. Common laboratory measurements over the time window of interest were sampled. The analysis was conducted from March to June 2017. MAIN OUTCOMES AND MEASURES The overlapping coefficient and Cohen standardized mean difference between distributions were calculated, and kernel density estimate visualizations for the association between laboratory values and the probability of death or quartile of ICU length of stay were created. RESULTS Among 38 605 patients in the ICU (21 852 [56.6%] male; mean [SD] age, 74.5 [55.1] years), 8878 (23%) had the best outcome (ICU survival, shortest quartile length of stay) and 3090 (8%) had the worst outcome (ICU nonsurvival). Distribution curves based on ICU data differed significantly from the hospital standard range (mean [SD] overlapping coefficient, 0.51 [0.32-0.69]). All laboratory values for the best outcome group differed significantly from those in the worst outcome group. Both the best and worst outcome group curves revealed little overlap with and marked divergence from the reference range. CONCLUSIONS AND RELEVANCE The standard reference ranges obtained from healthy volunteers differ from the analogous range generated from data from patients in intensive care. Laboratory data interpretation may benefit from greater consideration of clinically contextual and outcomes-related factors.
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Affiliation(s)
- Patrick D. Tyler
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Hao Du
- Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore
| | - Mengling Feng
- Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore
| | - Ran Bai
- School of Computer Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
| | - Zenglin Xu
- School of Computer Science and Technology, University of Electronic Science and Technology of China, Chengdu, China
| | - Gary L. Horowitz
- Pathology and Laboratory Medicine, Tufts University School of Medicine, Boston, Massachusetts
| | - David J. Stone
- Departments of Anesthesiology and Neurosurgery, University of Virginia School of Medicine, Charlottesville
- Division of Health Sciences and Technology, Harvard–Massachusetts Institute of Technology, Cambridge
| | - Leo Anthony Celi
- Department of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts
- Division of Health Sciences and Technology, Harvard–Massachusetts Institute of Technology, Cambridge
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Abstract
OBJECTIVE The aim of this study was to determine the prevalence and type of thyroid hormone levels alterations in patients with acute pancreatitis (AP) and analyze if variations are useful AP progression predictors. METHODS Three groups of patients were analyzed: AP patients (n = 90), abdominal pain patients (n = 30), and healthy control subjects (n = 40). Usual blood parameters for AP diagnosis and prognosis, thyroid-stimulating hormone (or thyrotropin), FT4 (free thyroxine), FT3 (free triiodothyronine), and TT3 (total triiodothyronine) levels were analyzed. RESULTS Thyroid hormone level alterations were detected only within the AP group (41% of total cases), being the reduction in T3 levels the most frequently detected deviation (15.6% of FT3 and 8.3% of TT3 cases). Alterations were not influenced by age or sex. Free thyroxine average values were also significantly higher in the AP group, compared with the healthy control group (P = 0.0005), resulting as independent predictors of both severity and mortality. Mortality in this group was 50%, with deceased patients showing FT4 levels above the reference limit. CONCLUSIONS Our results show that FT4 level determination during the initial clinical evaluation of patients admitted to the emergency service with AP can be included as a severity indicator to help determine the differential care of these cases.
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Chaudhry MA, Grazette L, Fong MW. Myxedema Heart Disease: A Rare Disease Entity: Case Report and Brief Review of the Literature. Curr Hypertens Rev 2018; 15:13-16. [PMID: 30277162 DOI: 10.2174/1573402114666181001121108] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 09/09/2018] [Accepted: 09/10/2018] [Indexed: 11/22/2022]
Abstract
BACKGROUND Myxedema heart disease is an extremely rare disease entity and should be suspected in patients with unexplained heart failure refractory to conventional treatment. Myxedema coma with co- existent heart disease is not well known and very few cases have been reported. CONCLUSION Here, we present an interesting case of myxedema coma with severe valvular cardiomyopathy followed by a concise review of the literature with special emphasis on epidemiology, pathophysiology, diagnosis and therapeutic modalities.
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Affiliation(s)
- Muhammad Ali Chaudhry
- Division of Cardiovascular Medicine, Aultman Hospital, Canton, Ohio-44710, OH, United States
| | - Luanda Grazette
- Division of Cardiovascular Medicine, University of Southern California, Los Angeles-90033, LA, United States
| | - Michael W Fong
- Division of Cardiovascular Medicine, University of Southern California, Los Angeles-90033, LA, United States
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29
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Kim RB, Kim M, Cho YY, Kim SK, Jung JH, Jung J, Kim CY, Kang D, Hahm JR. Thyroid function tests in patients at the emergency department compared to a prior healthy setting. PLoS One 2018; 13:e0202422. [PMID: 30125325 PMCID: PMC6101387 DOI: 10.1371/journal.pone.0202422] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 07/09/2018] [Indexed: 02/06/2023] Open
Abstract
We examined the changes in thyroid hormone levels in patients with an acute clinical condition and compared these to levels in the healthy subjects. Serum total triiodothyronine (T3), thyroid stimulating hormone (TSH), and free thyroxine (fT4) measurements were recorded from 555 patients (mean age: 55.0 years, men: 65.9%) admitted to the emergency department (ED) 1-91 months (median: 34 months) after a regular health examination (HE). Serological data were analyzed; mean change in hormone levels was stratified by emergency classification system and quintiles of changes in inflammatory marker values, such as neutrophil lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (CRP). The mean decrease in T3 levels from HE and ED samples was 10.6 ng/dL (p< 0.001). Mean decrease in T3 levels was 21.6 ng/dL among patients classified as having an infection status and 11.0 ng/dL among patients classified as having an urgency status. A decrease 3.7 ng/dL among emergency patients was observed. TSH and fT4 levels did not change across all groups. When patients were stratified into quintiles according to changes in NLR values, mean decreases in T3 were 6.21, 8.14, 14.37, 12.76, and 21.98 ng/dL and showed significant linear reduction (p<0.001). For quintiles of changed CRP values, mean decreased T3 levels were 10.57, 3.05, 4.47, 7.68, and 28.07 ng/dL. TSH and fT4 were not associated with significant changes (p = 0.100, p = 0.561, respectively). In this study, thyroid function changes in individuals with an acute condition revealed that T3 significantly decreased, more markedly in infectious diseases compared to their healthy counterparts, and decline in T3 measurements correlated with inflammatory markers. TSH and fT4 levels remained stable. It is necessary to consider the severity of acute conditions when abnormal T3 levels are detected in subjects with emergent status.
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Affiliation(s)
- Rock Bum Kim
- Regional Cardiocerebrovascular Disease Center, Gyeongsang National University Hospital, Jinju, Korea
| | - Minji Kim
- Department of Endocrinology and Metabolism, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
| | - Yoon Young Cho
- Department of Endocrinology and Metabolism, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
| | - Soo Kyoung Kim
- Department of Endocrinology and Metabolism, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
| | - Jung Hwa Jung
- Department of Endocrinology and Metabolism, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
| | - Jaehoon Jung
- Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
- Department of Internal Medicine, Gyeongsang National University Changwon Hospital, Changwon, Korea
| | - Chi Yeon Kim
- Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
- Department of Dermatology, College of Medicine, Gyeongsang National University, Jinju, Korea
| | - Dawon Kang
- Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
- Department of Physiology, College of Medicine, Gyeongsang National University, Jinju, Korea
| | - Jong Ryeal Hahm
- Department of Endocrinology and Metabolism, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
- Institute of Health Sciences, Gyeongsang National University College of Medicine, Jinju, Korea
- Department of Internal Medicine, College of Medicine, Gyeongsang National University, Jinju, Korea
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Kanji S, Neilipovitz J, Neilipovitz B, Kim J, Haddara WMR, Pittman M, Meggison H, Patel R. Triiodothyronine replacement in critically ill adults with non-thyroidal illness syndrome. Can J Anaesth 2018; 65:1147-1153. [PMID: 29968209 DOI: 10.1007/s12630-018-1177-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2017] [Revised: 03/29/2018] [Accepted: 04/30/2018] [Indexed: 11/30/2022] Open
Abstract
PURPOSE Non-thyroidal illness syndrome is commonly encountered in critically ill patients, many of whom are treated with thyroid hormones despite uncertainty regarding their safety and effectiveness. This retrospective observational study sought to evaluate the utilization, safety, and effectiveness of triiodothyronine (T3) supplementation in critically ill adults admitted to either of two non-cardiac surgery mixed-medical/surgical intensive care units (ICU). METHODS Consecutive adults admitted to an ICU and treated with enterally administered T3 were identified over a two-year period. Data pertaining to demographics, T3 utilization, safety, and clinical outcomes were collected. RESULTS Data were extracted from the medical records of 70 consecutive patients. All had baseline serum free T3 concentrations below the lower limit of our laboratory's reference range and 22 (31%) patients also had low thyroxine (T4) concentrations. The most commonly prescribed replacement doses were 25 and 50 µg for a median of seven days and almost half of the patients also received concomitant T4 supplementation. Serum thyroid hormones were available in 48 of 70 patients (69%) at a median [interquartile range (IQR)] of 7 [6-38] days. Normalization of free T3 serum concentrations occurred in 30 of 48 patients (63%) at a median [IQR] of 8 [7-33] days. A dose-response relationship was identifiable. New adverse events (atrial fibrillation/flutter, hypertension, sinus tachycardia, myocardial infarction) during therapy were less frequent than at baseline. CONCLUSIONS This study suggests that with T3 supplementation there was evidence of serum free T3 normalization without evidence of associated harms. A definitive trial is needed to evaluate clinical effectiveness.
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Affiliation(s)
- Salmaan Kanji
- Department of Pharmacy, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada. .,The Ottawa Hospital Research Institute, Ottawa, ON, Canada.
| | - Jonathan Neilipovitz
- Department of Pharmacy, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada
| | - Benjamin Neilipovitz
- Department of Pharmacy, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada
| | - John Kim
- Department of Pharmacy, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada
| | - Wael M R Haddara
- Schulich School of Medicine, Western University, London, ON, Canada
| | - Michelle Pittman
- Department of Pharmacy, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada
| | - Hilary Meggison
- Department of Pharmacy, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada
| | - Rakesh Patel
- Department of Pharmacy, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON, K1H 8L6, Canada
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Liu YY, Brent GA. Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury. Pharmacol Ther 2018; 186:176-185. [PMID: 29378220 DOI: 10.1016/j.pharmthera.2018.01.007] [Citation(s) in RCA: 56] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation of thyroxine (T4) to triiodothyronine (T3) by the enzyme 5'-deiodinase Type 2 (Dio2), inactivation by the enzyme 5-deiodinase Type 3 (Dio3) to reverse T3 (rT3), which occurs in glial cells, and uptake by the Mct8 transporter in neurons. Traumatic brain injury (TBI) is associated with inflammation, metabolic alterations and neural death. In clinical studies, central hypothyroidism, due to hypothalamic and pituitary dysfunction, has been found in some individuals after brain injury. TH has been shown, in animal models, to be protective for the damage incurred from brain injury and may have a role to limit injury and promote recovery. Although clinical trials have not yet been reported, findings from in vitro and in vivo models inform potential treatment strategies utilizing TH for protection and promotion of recovery after brain injury.
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Affiliation(s)
- Yan-Yun Liu
- Departments of Medicine and Physiology, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States
| | - Gregory A Brent
- Departments of Medicine and Physiology, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, United States.
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Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, e Drigo RA, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N. Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function. Nat Med 2018; 24:39-49. [PMID: 29200204 PMCID: PMC5760280 DOI: 10.1038/nm.4447] [Citation(s) in RCA: 265] [Impact Index Per Article: 37.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Accepted: 10/23/2017] [Indexed: 12/15/2022]
Abstract
Thyroid hormone (TH) is critical for the maintenance of cellular homeostasis during stress responses, but its role in lung fibrosis is unknown. Here we found that the activity and expression of iodothyronine deiodinase 2 (DIO2), an enzyme that activates TH, were higher in lungs from patients with idiopathic pulmonary fibrosis than in control individuals and were correlated with disease severity. We also found that Dio2-knockout mice exhibited enhanced bleomycin-induced lung fibrosis. Aerosolized TH delivery increased survival and resolved fibrosis in two models of pulmonary fibrosis in mice (intratracheal bleomycin and inducible TGF-β1). Sobetirome, a TH mimetic, also blunted bleomycin-induced lung fibrosis. After bleomycin-induced injury, TH promoted mitochondrial biogenesis, improved mitochondrial bioenergetics and attenuated mitochondria-regulated apoptosis in alveolar epithelial cells both in vivo and in vitro. TH did not blunt fibrosis in Ppargc1a- or Pink1-knockout mice, suggesting dependence on these pathways. We conclude that the antifibrotic properties of TH are associated with protection of alveolar epithelial cells and restoration of mitochondrial function and that TH may thus represent a potential therapy for pulmonary fibrosis.
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Affiliation(s)
- Guoying Yu
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Argyris Tzouvelekis
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
- Division of Immunology, Biomedical Sciences Research Center
“Alexander Fleming”, Athens, Greece
| | - Rong Wang
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Jose D. Herazo-Maya
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Gabriel H. Ibarra
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Anup Srivastava
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Joao Pedro Werneck de Castro
- Division of Endocrinology/Metabolism, Rush University Medical
Center, Chicago IL
- Biophysics Institute, Federal University of Rio de Janeiro, RJ,
Brazil
| | - Giuseppe DeIuliis
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Farida Ahangari
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Tony Woolard
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Nachelle Aurelien
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Rafael Arrojo e Drigo
- The Salk Institute for Biological Studies, Molecular and Cell
biology laboratory, La Jolla, CA
| | - Ye Gan
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Morven Graham
- CCMI Electron Microscopy Core Facility, Yale University School of
Medicine, New Haven, CT
| | - Xinran Liu
- CCMI Electron Microscopy Core Facility, Yale University School of
Medicine, New Haven, CT
| | - Robert J. Homer
- Department of Pathology, Yale University School of Medicine, New
Haven, C
- Pathology and Laboratory Medicine Service, VA CT HealthCare System,
West Haven, CT
| | - Thomas S. Scanlan
- Department of Physiology and Pharmacology, Oregon Health and Science
University, Portland, Oregon, USA
| | - Praveen Mannam
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Patty J. Lee
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Erica L. Herzog
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
| | - Antonio C. Bianco
- Division of Endocrinology/Metabolism, Rush University Medical
Center, Chicago IL
| | - Naftali Kaminski
- Section of Pulmonary, Critical Care and Sleep Medicine, Department
of Internal Medicine, Yale School of Medicine, New Haven, CT
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Siroen MPC, van Bokhorst-de van der Schueren MAE, Richir MC, Sauerwein HP, Leemans CR, Quak JJ, van Leeuwen PAM. The Prognostic Value of Severe Malnutrition in the Development of Nonthyroidal Illness in Head and Neck Cancer Patients. JPEN J Parenter Enteral Nutr 2017; 30:415-20. [PMID: 16931610 DOI: 10.1177/0148607106030005415] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND Thyroid hormone metabolism is modulated by starvation and overfeeding but also by dietary composition. Unfortunately, little is known about the effect of malnutrition on disease-induced nonthyroidal illness (NTI). In this study, we investigated whether the degree of NTI after surgery differed between severely malnourished and well-fed patients with head and neck cancer. METHODS Plasma levels of the thyroid hormones 3',5-triiodothyronine (T(3)), reverse T(3) (rT(3)), free T(4) (FT(4)), and thyrotropin (TSH) were measured on the first day before the operation and on the first, fourth, and seventh day after the operation in 16 malnourished patients who were admitted for intentional curative surgery of T1-T4 carcinomas of the head and neck. Six well-fed head and neck cancer patients eligible for surgical treatment served as a control group. RESULTS In the malnourished group, rT(3) showed a significant increase, whereas T(3) and FT(4) decreased significantly due to the operation. TSH showed no significant change. During the postoperative course, it took 7 days until rT(3) and 4 days until T(3) and FT(4) were restored to their preoperative value. In contrast, well-fed patients did not develop NTI. CONCLUSIONS This study shows that peri- and postoperative rT(3), T(3), and FT(4) levels change significantly in malnourished patients compared with well-fed patients. Therefore, it can be concluded that nutrition status of patients undergoing major head and neck surgery should be optimized in order to prevent the development of NTI.
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Affiliation(s)
- M P C Siroen
- Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands
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Impairment of Thyroid Function in Critically Ill Patients in the Intensive Care Units. Am J Med Sci 2017; 355:281-285. [PMID: 29549931 DOI: 10.1016/j.amjms.2017.06.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 06/02/2017] [Accepted: 06/28/2017] [Indexed: 11/22/2022]
Abstract
Unexplained hypotension in the intensive care unit is commonly attributed to volume depletion, cardiorespiratory failure, sepsis, or relative adrenal insufficiency. In these acute conditions, thyroid hormone levels measured in blood, serum or plasma are often altered and solely attributed to critical illness. We report a series of 3 critically ill patients with prolonged respiratory failure, suppressed mental status and unexplained hypotension. Thyroid stimulating hormone levels ranged from normal to mildly elevated (2.36-7.65IU/mL; normal: 0.27-4.20), but free thyroxin was markedly suppressed (0.239-0.66ng/dL; normal: 0.93-1.70). After initiation of intravenous levothyroxine (75-100μg/day), the patients could be weaned off vasopressors and were successfully extubated shortly thereafter. These cases demonstrate that hypothyroid intensive care unit patients may exhibit even seemingly normal or mildly abnormal thyroid stimulating hormone values. Early recognition and treatment of a hypothyroid state superimposed on critical illness may contribute to recovery from hypotension or the need for mechanical ventilation.
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Orman S, Karaman K, Basok BI, Kisa U, Ceyran AB, Bostanci EB. Effects of Thyroid Hormone Therapy on Cut-Surface Healing of the Remnant Stomach with Short-Term Weight Loss Alterations after Sleeve Gastrectomy. J INVEST SURG 2017. [PMID: 28635514 DOI: 10.1080/08941939.2017.1280566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
BACKGROUND The hypothalamic-pituitary-tyhroid axis is directly affected by drastic changes in energy stores. The aim of the present study was to determine the effects of triiodothyronine (T3) treatment on cut-surface healing of remnant stomach with weight loss alterations after sleeve gastrectomy (SG). METHODS Thirty male Wistar Albino rats were divided into three groups: sham (n = 6), control (n = 12), and experimental (n = 12). Control and experimental group rats underwent sleeve gastrectomy. Experimental group rats received a single dose of T3 (400 mg/100 g) on the first postoperative day whereas control group rats received 0.9% NaCl. All rats were sacrificed on the seventh postoperative day. RESULTS In the group of rats receiving T3, levels of FT3 were significantly higher and that of FT4 were significantly lower compared with both the control and sham group rats (p <.05). No significant difference was found between control and T3 group rats in terms of weight loss (p >.05). Microscopic examination of the cut surface of remnant stomach in the control group rats revealed significantly more severe tissue necrosis, edema, and disruption of mucosal epithelium than in the T3 group rats (p <.05). On the other hand, bridging of the submucosal and muscular layers, tissue granulation, fibroblast accumulation, neoangiogenesis, and collagen deposition in the T3 group rats were significantly higher than in the control group rats (p <.05). CONCLUSIONS Sleeve gastrectomy did not significantly alter thyroid hormone levels in short term. T3 hormone therapy seems to deliver constructive therapeutic effects for wound healing while causing no adverse effect on weight reduction.
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Affiliation(s)
- Suleyman Orman
- a Department of Gastroenterological Surgery , Istanbul Medeniyet University Goztepe Teaching and Research Hospital , Istanbul , Turkey
| | - Kerem Karaman
- b Department of General Surgery , Sakarya University Faculty of Medicine , Sakarya , Turkey
| | - Banu Isbilen Basok
- c Department of Biochemistry , Istanbul Medeniyet University Goztepe Teaching and Research Hospital , Istanbul , Turkey
| | - Ucler Kisa
- d Department of Biochemistry , Kirikkale University Faculty of Medicine , Kirikkale , Turkey
| | - Ayse Bahar Ceyran
- e Department of Pathology , Istanbul Medeniyet University Goztepe Teaching and Research Hospital , Istanbul , Turkey
| | - Erdal Birol Bostanci
- b Department of General Surgery , Sakarya University Faculty of Medicine , Sakarya , Turkey
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Rothberger GD, Gadhvi S, Michelakis N, Kumar A, Calixte R, Shapiro LE. Usefulness of Serum Triiodothyronine (T3) to Predict Outcomes in Patients Hospitalized With Acute Heart Failure. Am J Cardiol 2017; 119:599-603. [PMID: 28017303 DOI: 10.1016/j.amjcard.2016.10.045] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2016] [Revised: 10/21/2016] [Accepted: 10/21/2016] [Indexed: 10/20/2022]
Abstract
Thyroid hormone plays an important role in cardiac function. Low levels of serum triiodothyronine (T3) due to nonthyroidal illness syndrome may have adverse effects in heart failure (HF). This study was designed to assess the ability of T3 to predict in-hospital outcomes in patients with acute HF. In total, 137 patients without thyroid disease or treatment with drugs which affect TH levels, who were hospitalized with acute HF were prospectively enrolled and studied. TH levels were tested upon hospital admission, and outcomes were compared between patients with low (<2.3 pg/ml) and normal (≥2.3 pg/ml) free T3 levels as well as between those with low (<0.6 ng/ml) and normal (≥0.6 ng/ml) total T3 levels. Low free T3 correlated with an increased length of stay in the hospital (median 11 vs 7 days, p <0.001) and higher rates of intensive care unit admission (31.8% vs 16.9%, p = 0.047), with a trend toward increased need for invasive mechanical ventilation (9.0% vs 1.4%, p = 0.056). Low total T3 correlated with an increased length of stay in the hospital (median 11 vs 7 days, p <0.001) and increased need for invasive mechanical ventilation (9.8% vs 1.3%, p = 0.045). In conclusion, low T3 predicts worse hospital outcomes in patients with acute HF and can be useful in the risk stratification of these patients.
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Chatzitomaris A, Hoermann R, Midgley JE, Hering S, Urban A, Dietrich B, Abood A, Klein HH, Dietrich JW. Thyroid Allostasis-Adaptive Responses of Thyrotropic Feedback Control to Conditions of Strain, Stress, and Developmental Programming. Front Endocrinol (Lausanne) 2017; 8:163. [PMID: 28775711 PMCID: PMC5517413 DOI: 10.3389/fendo.2017.00163] [Citation(s) in RCA: 98] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Accepted: 06/27/2017] [Indexed: 12/21/2022] Open
Abstract
The hypothalamus-pituitary-thyroid feedback control is a dynamic, adaptive system. In situations of illness and deprivation of energy representing type 1 allostasis, the stress response operates to alter both its set point and peripheral transfer parameters. In contrast, type 2 allostatic load, typically effective in psychosocial stress, pregnancy, metabolic syndrome, and adaptation to cold, produces a nearly opposite phenotype of predictive plasticity. The non-thyroidal illness syndrome (NTIS) or thyroid allostasis in critical illness, tumors, uremia, and starvation (TACITUS), commonly observed in hospitalized patients, displays a historically well-studied pattern of allostatic thyroid response. This is characterized by decreased total and free thyroid hormone concentrations and varying levels of thyroid-stimulating hormone (TSH) ranging from decreased (in severe cases) to normal or even elevated (mainly in the recovery phase) TSH concentrations. An acute versus chronic stage (wasting syndrome) of TACITUS can be discerned. The two types differ in molecular mechanisms and prognosis. The acute adaptation of thyroid hormone metabolism to critical illness may prove beneficial to the organism, whereas the far more complex molecular alterations associated with chronic illness frequently lead to allostatic overload. The latter is associated with poor outcome, independently of the underlying disease. Adaptive responses of thyroid homeostasis extend to alterations in thyroid hormone concentrations during fetal life, periods of weight gain or loss, thermoregulation, physical exercise, and psychiatric diseases. The various forms of thyroid allostasis pose serious problems in differential diagnosis of thyroid disease. This review article provides an overview of physiological mechanisms as well as major diagnostic and therapeutic implications of thyroid allostasis under a variety of developmental and straining conditions.
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Affiliation(s)
- Apostolos Chatzitomaris
- Medical Department I, Endocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Germany
- *Correspondence: Apostolos Chatzitomaris,
| | - Rudolf Hoermann
- Private Consultancy, Research and Development, Yandina, QLD, Australia
| | | | - Steffen Hering
- Department for Internal Medicine, Cardiology, Endocrinology, Diabetes and Medical Intensive Care Medicine, Krankenhaus Bietigheim-Vaihingen, Bietigheim-Bissingen, Germany
| | - Aline Urban
- Department for Anesthesiology, Intensive Care and Palliative Medicine, Eastern Allgäu-Kaufbeuren Hospitals, Kaufbeuren, Germany
| | | | - Assjana Abood
- Medical Department I, Endocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Germany
| | - Harald H. Klein
- Medical Department I, Endocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Germany
- Ruhr Center for Rare Diseases (CeSER), Ruhr University of Bochum and Witten/Herdecke University, Bochum, Germany
| | - Johannes W. Dietrich
- Medical Department I, Endocrinology and Diabetology, Bergmannsheil University Hospitals, Ruhr University of Bochum, Bochum, Germany
- Ruhr Center for Rare Diseases (CeSER), Ruhr University of Bochum and Witten/Herdecke University, Bochum, Germany
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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: 20] [Impact Index Per Article: 2.2] [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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Low Tri-Iodothyronine Syndrome in Neurosurgical Patients: A Systematic Review of Literature. World Neurosurg 2016; 95:197-207. [DOI: 10.1016/j.wneu.2016.07.035] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2016] [Revised: 07/10/2016] [Accepted: 07/11/2016] [Indexed: 11/21/2022]
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Wang Y, Zhou S, Bao J, Pan S, Zhang X. Low T 3 levels as a predictor marker predict the prognosis of patients with acute ischemic stroke. Int J Neurosci 2016; 127:559-566. [PMID: 27401927 DOI: 10.1080/00207454.2016.1211649] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Early and accurate prediction of outcome in acute stroke is important. The aim of this prospective study was to explore the correlation between serum triiodothyronine level and prognosis in acute ischemic stroke patients. METHODS A prospective observational study which included 359 consecutive patients with acute ischemic stroke from December 2014 to November 2015 was interrogated. Serum triiodothyronine (T3) concentrations were measured on admission to understand their value in predicting functional outcome within 90 d using multivariable models adjusted for confounding factors. Receiver operating characteristic (ROC) curves were calculated to define the best cut-off value of triiodothyronine to predict outcome. The accuracy of the test was assessed measuring the area under the ROC curve (AUROC). RESULTS Triiodothyronine was significantly decreased in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome within 90 d (p = 0.01). Binary logistic regression analyses revealed that lower triiodothyronine concentrations on admission were associated with a risk for poor outcomes (OR 0.05, 95% CI 0.01-0.25; p < 0.01). In addition, in ROC curve analysis, triiodothyronine may improve the National Institutes of Health Stroke Scale (NIHSS) score in predicting functional outcome. The combined model AUROC was 0.84 for 30 d and 0.91 for 90 d, which were both significantly higher than the AUROCs of original NIHSS (0.83 and 0.87), triiodothyronine (0.64 and 0.69) and age (0.57 and 0.68) (all p < 0.05). CONCLUSIONS Low serum triiodothyronine levels can be a predictive marker of short-term outcome after ischemic stroke. A combined model (triiodothyronine, age and NIHSS score) can add significant additional predictive information to the clinical score of the NIHSS.
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Affiliation(s)
- Yiping Wang
- a Department of neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | | | - Jianhong Bao
- a Department of neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Sipei Pan
- a Department of neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
| | - Xu Zhang
- a Department of neurology , The First Affiliated Hospital of Wenzhou Medical University , Wenzhou , China
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Fan J, Yan P, Wang Y, Shen B, Ding F, Liu Y. Prevalence and Clinical Significance of Low T3 Syndrome in Non-Dialysis Patients with Chronic Kidney Disease. Med Sci Monit 2016; 22:1171-9. [PMID: 27056188 PMCID: PMC4827515 DOI: 10.12659/msm.895953] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Background There are few data on the prevalence of low T3 (triiodothyronine) syndrome in patients with non-dialysis chronic kidney disease (CKD) and it is unclear whether low T3 can be used to predict the progression of CKD. Material/Methods We retrospectively studied 279 patients who had been definitively diagnosed with CKD, without needing maintenance dialysis. Thyroid function was analyzed in all enrolled subjects and the incidence of thyroid dysfunction (low T3 syndrome, low T4 syndrome, and subclinical hypothyroidism) in patients at different stages of CKD was determined. Results Glomerular filtration rate (GFR) of CKD patients was estimated as follows: 145 subjects (52%) had GFR <60 ml/min per 1.73 m2; 47 subjects (16.8%) had GFR between 30 and 59 ml/min per 1.73 m2, and 98 subjects (35.1%) had GFR <30 ml/min per 1.73 m2. Among all enrolled subjects, 4.7% (n=13) had subclinical hypothyroidism, 5.4% (n=15) had low T4 syndrome, and 47% (n=131) had low T3 syndrome. In 114 CKD patients in stages 3–5, serum T3 was positively related to protein metabolism (STP, PA, and ALB) and anemia indicators (Hb and RBC), and negatively related to inflammatory status (CRP and IL-6). Conclusions A high prevalence of low T3 syndrome was observed in CKD patients without dialysis, even in early stages (1 and 2). The increasing prevalence of low T3 as CKD progresses indicates its value as a predictor of worsening CKD. Furthermore, low T3 syndrome is closely associated with both malnutrition-inflammation complex syndrome (MICS) and anemia.
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Affiliation(s)
- Jingxian Fan
- Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Peng Yan
- , Shanghai Medical Association, Shanghai, China (mainland)
| | - Yingdeng Wang
- Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Bo Shen
- Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Feng Ding
- Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
| | - Yingli Liu
- Department of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (mainland)
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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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Fan S, Ni X, Wang J, Zhang Y, Tao S, Chen M, Li Y, Li J. Low Triiodothyronine Syndrome in Patients With Radiation Enteritis: Risk Factors and Clinical Outcomes an Observational Study. Medicine (Baltimore) 2016; 95:e2640. [PMID: 26871787 PMCID: PMC4753882 DOI: 10.1097/md.0000000000002640] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
The implications of low triiodothyronine syndrome (LT3S) in patients with radiation enteritis (RE) have not been properly investigated. As such, we conducted this cohort study to investigate the association between LT3S and RE, to explore the etiology of LT3S in RE, to evaluate the clinical features and clinical outcomes of LT3S patients, and to inspect the correlation of clinical variables and LT3S in RE.This prospective study included 39 RE patients. Medical records and various laboratory parameters (including thyroidal, tumorous, nutritional, and radiotherapy variables) were collected in all participants.Our results showed that the incidence of LT3S was 84.6% in patients with RE. Total protein (71.7 ± 5.7 vs 63.2 ± 9.6 g/L, P = 0.04) and albumin (ALB, 46.0 ± 4.6 vs 38.7 ± 5.3 g/L, P = 0.01) were significantly lower in LT3S group compared with those in euthyroid group. Standard thyroid-stimulating hormone index (-0.89 ± 2.11 vs -2.39 ± 1.33, P = 0.03) and sum activity of deiodinases (19.74 ± 4.19 vs 12.55 ± 4.32 nmol/L, P = 0.01) were significantly lower in LT3S group. Patients with LT3S suffered longer duration of hospitalization (48.25 ± 23.29 days in LT3S vs 26.75 ± 10.56 days in euthyroid, P = 0.036). Low serum ALB (β = 0.694, 95% CI = 0.007-0.190, P = 0.037) was the only significant predictor of LT3S.LT3S was common in RE patients. A hypodeiodination condition and a potential pituitary-thyrotroph dysfunction might play a role in the pathophysiology of LT3S in RE. Worse nutritional status and clinical outcomes were confirmed in RE patients with LT3S. Furthermore, total protein and ALB were observed as protective and differentiating parameters of LT3S in RE. In summary, this was the 1st investigation to evaluate the clinical correlation between RE and LT3S, investigate the prevalence of LT3S in RE, and explore the pathogenesis of LT3S, despite the limitation of a relatively small sample size. These results will hopefully encourage future research to place greater emphasis on early identification of LT3S in RE patients.
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Affiliation(s)
- Shengxian Fan
- From the Department of Surgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China
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Moura Neto A, Zantut-Wittmann DE. Abnormalities of Thyroid Hormone Metabolism during Systemic Illness: The Low T3 Syndrome in Different Clinical Settings. Int J Endocrinol 2016; 2016:2157583. [PMID: 27803712 PMCID: PMC5075641 DOI: 10.1155/2016/2157583] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2016] [Revised: 08/18/2016] [Accepted: 09/15/2016] [Indexed: 12/15/2022] Open
Abstract
Thyroid hormone abnormalities are common in critically ill patients. For over three decades, a mild form of these abnormalities has been described in patients with several diseases under outpatient care. These alterations in thyroid hormone economy are a part of the nonthyroidal illness and keep an important relationship with prognosis in most cases. The main feature of this syndrome is a fall in free triiodothyronine (T3) levels with normal thyrotropin (TSH). Free thyroxin (T4) and reverse T3 levels vary according to the underlying disease. The importance of recognizing this condition in such patients is evident to physicians practicing in a variety of specialties, especially general medicine, to avoid misdiagnosing the much more common primary thyroid dysfunctions and indicating treatments that are often not beneficial. This review focuses on the most common chronic diseases already known to present with alterations in serum thyroid hormone levels. A short review of the common pathophysiology of the nonthyroidal illness is followed by the clinical and laboratorial presentation in each condition. Finally, a clinical case vignette and a brief summary on the evidence about treatment of the nonthyroidal illness and on the future research topics to be addressed are presented.
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Affiliation(s)
- Arnaldo Moura Neto
- Division of Endocrinology, Department of Clinical Medicine, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil
- *Arnaldo Moura Neto:
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45
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Li R, Ren J, Wu Q, Wang G, Wu X, Chen J, Li G, Hong Z, Ren H, Zhao Y, Li J. Role of enteral nutrition in nonthyroidal illness syndrome: a retrospective observational study. BMC Endocr Disord 2015; 15:69. [PMID: 26531000 PMCID: PMC4632465 DOI: 10.1186/s12902-015-0061-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2015] [Accepted: 10/23/2015] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND The nonthyroidal illness syndrome (NTIS) is prevalent among patients with enterocutaneous fistula and is associated with poor outcomes. The present study aimed to explore the role of enteral nutrition (EN) therapy on thyroid function among patients with enterocutaneous fistula and NTIS. METHODS We conducted a retrospective observational study among patients with enterocutaneous fistula between January 2013 and April 2014. All enrolled patients received EN therapy. Thyroid function and other parameters were measured. RESULTS After administration of 4 weeks of EN therapy, NTIS was resolved in 66 patients (Group A), while it persisted in 14 patients (Group B). The overall treatment success rate was 82.50 %. There were no significant differences between groups A and B at baseline for all parameters, except for the time from admission to start of EN therapy. The logistic analysis revealed that the time from admission to start of EN therapy was a significant independent indicator for achieving resolution of NTIS in our cohort. CONCLUSIONS This retrospective observational cohort study demonstrated that EN therapy can aid in the resolution of NTIS among patients with enterocutaneous fistula. These findings confirm the benefit of EN in the treatment of enterocutaneous fistula.
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Affiliation(s)
- Ranran Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Jianan Ren
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Qin Wu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Gefei Wang
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Xiuwen Wu
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Jun Chen
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Guanwei Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Zhiwu Hong
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Huajian Ren
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Yunzhao Zhao
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
| | - Jieshou Li
- Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, 305 East Zhong Shan Road, Nanjing, 210002, China.
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Fliers E, Bianco AC, Langouche L, Boelen A. Thyroid function in critically ill patients. Lancet Diabetes Endocrinol 2015; 3:816-25. [PMID: 26071885 PMCID: PMC4979220 DOI: 10.1016/s2213-8587(15)00225-9] [Citation(s) in RCA: 253] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 01/14/2015] [Accepted: 01/19/2015] [Indexed: 12/20/2022]
Abstract
Patients in the intensive care unit (ICU) typically present with decreased concentrations of plasma tri-iodothyronine, low thyroxine, and normal range or slightly decreased concentration of thyroid-stimulating hormone. This ensemble of changes is collectively known as non-thyroidal illness syndrome (NTIS). The extent of NTIS is associated with prognosis, but no proof exists for causality of this association. Initially, NTIS is a consequence of the acute phase response to systemic illness and macronutrient restriction, which might be beneficial. Pathogenesis of NTIS in long-term critical illness is more complex and includes suppression of hypothalamic thyrotropin-releasing hormone, accounting for persistently reduced secretion of thyroid-stimulating hormone despite low plasma thyroid hormone. In some cases distinguishing between NTIS and severe hypothyroidism, which is a rare primary cause for admission to the ICU, can be difficult. Infusion of hypothalamic-releasing factors can reactivate the thyroid axis in patients with NTIS, inducing an anabolic response. Whether this approach has a clinical benefit in terms of outcome is unknown. In this Series paper, we discuss diagnostic aspects, pathogenesis, and implications of NTIS as well as its distinction from severe, primary thyroid disorders in patients in the ICU.
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Affiliation(s)
- Eric Fliers
- Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, AZ, Amsterdam, Netherlands
| | - Antonio C Bianco
- Division of Endocrinology and Metabolism, Rush University Medical Center, Chicago, IL, USA
| | - Lies Langouche
- Laboratory of Intensive Care Medicine, Department of Cellular and Molecular Medicine, University of Leuven, Leuven, Belgium
| | - Anita Boelen
- Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, AZ, Amsterdam, Netherlands.
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Pilarczyk K, Martini R, von der Brelie M, Haake N. Störungen des Endokriniums auf der herzchirurgischen Intensivstation. ZEITSCHRIFT FUR HERZ THORAX UND GEFASSCHIRURGIE 2015. [DOI: 10.1007/s00398-015-0027-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Kakavas S, Balis E, Papanikolaou A, Tatsis N, Kouvela M, Tatsis G. Triiodothyronine levels in acute pulmonary embolism predict in-hospital mortality. JOURNAL OF ACUTE DISEASE 2015. [DOI: 10.1016/j.joad.2015.04.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
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49
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Fragidis S, Sombolos K, Thodis E, Panagoutsos S, Mourvati E, Pikilidou M, Papagianni A, Pasadakis P, Vargemezis V. Low T3 syndrome and long-term mortality in chronic hemodialysis patients. World J Nephrol 2015; 4:415-422. [PMID: 26167466 PMCID: PMC4491933 DOI: 10.5527/wjn.v4.i3.415] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Revised: 02/03/2015] [Accepted: 04/14/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the predictive value of low freeT3 for long-term mortality in chronic hemodialysis (HD) patients and explore a possible causative role of chronic inflammation.
METHODS: One hundred fourteen HD patients (84 males) consecutively entered the study and were assessed for thyroid function and two established markers of inflammation, high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). Monthly blood samples were obtained from all patients for three consecutive months during the observation period for evaluation of thyroid function and measurement of inflammatory markers. The patients were then divided in two groups based on the cut-off value of 1.8 pg/mL for mean plasma freeT3, and were prospectively studied for a mean of 50.3 ± 30.8 mo regarding cumulative survival. The prognostic power of low serum fT3 levels for mortality was assessed using the Kaplan-Meier method and univariate and multivariate regression analysis.
RESULTS: Kaplan-Meier survival curve showed a negative predictive power for low freeT3. In Cox regression analysis low freeT3 remained a significant predictor of mortality after adjustment for age, diabetes mellitus, hypertension, hsCRP, serum creatinine and albumin. Regarding the possible association with inflammation, freeT3 was correlated with hsCRP, but not IL-6, and only at the first month of the study.
CONCLUSION: In chronic hemodialysis patients, low plasma freeT3 is a significant predictor of all-cause mortality. Further studies are required to identify the underlying mechanisms of this association.
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50
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Novitzky D, Mi Z, Collins JF, Cooper DKC. Increased Procurement of Thoracic Donor Organs After Thyroid Hormone Therapy. Semin Thorac Cardiovasc Surg 2015; 27:123-32. [PMID: 26686437 DOI: 10.1053/j.semtcvs.2015.06.012] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/17/2015] [Indexed: 12/17/2022]
Abstract
Hormonal therapy to the brain-dead organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), antidiuretic hormone, corticosteroids, or insulin. There has been a controversy on whether thyroid hormone enables more organs to be procured. Data on 63,593 donors of hearts and lungs (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in all donors (study 1), and in 40,124 details of all 4 hormones were recorded (study 2). In this cohort, group A (23,022) received T3/T4 and group B (17,102) no T3/T4. Univariate analyses and multiple regressions were performed. Posttransplant graft and recipient survival at 1 and 12 months were compared. In study 1, 30,962 donors received T3/T4, with 36.59% providing a heart and 20.05% providing 1 or both lungs. Of the 32,631 donors who did not receive T3/T4, only 29.62% provided a heart and 14.61% provided lungs, an increase of 6.97% hearts and 5.44% lungs from T3/T4-treated donors (both P < 0.0001). In study 2, 34.99% of group A provided a heart and 20.99% provided lungs. In group B only 25.76% provided a heart and 15.09% provided lungs, an increase of 9.23% (hearts) and 5.90% (lungs), respectively, in group A (both P < 0.0001). The results of multiple regression analyses indicated a beneficial effect of T3/T4 on heart (P < 0.0001) and lung (P < 0.0001) procurement independent of other factors. T3/T4 therapy to the donor was associated with either improved posttransplant graft and recipient survival or no difference in survival. T3/T4 therapy results in more transplantable hearts and lungs, with no detriment to posttransplant graft or recipient survival.
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Affiliation(s)
- Dimitri Novitzky
- Cardiothoracic Surgery, University of South Florida, Tampa, Florida
| | - Zhibao Mi
- Cooperative Studies Program Coordinating Center, VA Medical Center, Perry Point, Maryland
| | - Joseph F Collins
- Cooperative Studies Program Coordinating Center, VA Medical Center, Perry Point, Maryland
| | - David K C Cooper
- Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
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