Low triiodothyronine (T3) state: a predictor of outcome in respiratory failure? Results of a clinical pilot study

Scoscia, Elvio; Baglioni, Stefano; Eslami, Akbar; Iervasi, Giorgio; Monti, Simonetta; Todisco, Tommaso

doi:10.1530/eje.0.1510557

Cited by 85 publications

(78 citation statements)

References 13 publications

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“…1). The decreased T 3 and TSH and the increased rT 3 serum levels observed in this model of acute inflammatory lung injury are in agreement with those seen in the clinical setting of critical illness in patients with acute lung injury (ALI) and in animal models of acute illness (27)(28)(29)(30)(31)(32)(33)(34).…”

Section: Resultssupporting

confidence: 83%

Role of type 2 deiodinase in response to acute lung injury (ALI) in mice

Barca-Mayo

Liao

DiCosmo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Thyroid hormone (TH) metabolism, mediated by deiodinase types 1, 2, and 3 (D1, D2, and D3) is profoundly affected by acute illness. We examined the role of TH metabolism during ventilator-induced lung injury (VILI) in mice. Mice exposed to VILI recapitulated the serum TH findings of acute illness, namely a decrease in 3,5,3′-triiodothyronine (T 3 ) and thyroid-stimulating hormone and an increase in reverse T 3 . Both D2 immunoreactivity and D2 enzymatic activity were increased significantly. D1 and D3 activity did not change. Using D2 knockout (D2KO) mice, we determined whether the increase in D2 was an adaptive response. Although similar changes in serum TH levels were observed in D2KO and WT mice, D2KO mice exhibited greater susceptibility to VILI than WT mice, as evidenced by poorer alveoli integrity and quantified by lung chemokine and cytokine mRNA induction. These data suggest that an increase in lung D2 is protective against VILI. Similar findings of increased inflammatory markers were found in hypothyroid WT mice exposed to VILI compared with euthyroid mice, indicating that the lungs were functionally hypothyroid. Treatment of D2KO mice with T 3 reversed many of the lung chemokine and cytokine profiles seen in response to VILI, demonstrating a role for T 3 in the treatment of lung injury. We conclude that TH metabolism in the lung is linked to the response to inflammatory injury and speculate that D2 exerts its protective effect by making more TH available to the injured lung tissue.nonthyroidal illness | euthyroid sick | reverse triiodothyronine | bronchial alveolar lavage | sepsis T hyroid hormone [TH, here denoting the active hormone 3,5,3′-triiodothyronine (T 3 ) and its precursor thyroxine (T 4 )] is necessary for the normal development and function of virtually every vertebrate tissue. Although the thyroid gland is predominantly responsible for the production and release of T 4 , the cellular bioavailability of the active T 3 depends on TH-specific transporters and tissue TH metabolism. Metabolism of TH is regulated by three iodothyronine deiodinases. Both type 1 (D1) and type 2 (D2) deiodinases serve to generate bioactive T 3 by outer-ring deiodination of T 4 . D2 has a major role in the intracellular generation of the active TH in mouse; the role of the D1, with its broad substrate specificity and ability to carry out both outer-and inner-ring deiodination, is less well understood. In contrast, type 3 iodothyronine deiodinase (D3) inactivates TH by inner-ring deiodination of T 4 to reverse T 3 (3′,5,3-triiodothyronine; rT 3 ) and T 3 to 3,3′-diiodothyronine (T 2 ), both biologically inactive compounds (1).Studies have elucidated the dynamic effects of TH action on brain, bone, liver (2-5), and maturation of the fetal lung (6, 7), but little is known regarding the role of TH in adult lung physiology. Until now, evidence suggesting that TH influences adult lung physiology has been indirect and based on the presence of TH receptors (8), deiodinases (9-12), and measured TH concentrations (10,13,14) i...

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Section: Resultssupporting

confidence: 83%

Role of type 2 deiodinase in response to acute lung injury (ALI) in mice

Barca-Mayo

Liao

DiCosmo

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…This entity is characterized by a constant decrease in T 3 serum concentrations, and variable abnormalities of other thyroid hormone levels (4). It is secondary to severe acute (e.g., septic shock, myocardial infarction) (8,9) or chronic (e.g., cancer, advanced acquired immunodeficiency syndrome) (23)(24)(25) diseases and it has been demonstrated to be a predictor of increased mortality (6,18). As expected in our population of independently-living non-severely ill people, ESS was rare, occurring in only 3.4%.…”

Section: Discussionsupporting

confidence: 55%

“…In acute ESS, it was shown that the decrease in T 3 and the increase in rT 3 are related to mortality (5)(6)(7)(8)(9)(10). In nonacutely ill elderly, T 3 and rT 3 are often decreased and increased respectively, but many questions remain as to whether these disturbances are due solely to aging or to poor health status (11,12).…”

Section: Introductionmentioning

confidence: 99%

Increased reverse triiodothyronine is associated with shorter survival in independently-living elderly: the Alsanut study

Forestier¹,

Vinzio²,

Sapin³

et al. 2009

European Journal of Endocrinology

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Objective: Increased reverse tritiodothyronine (T 3 ) used to be described as a part of euthyroid sick syndrome (ESS). It was demonstrated to be associated with increased mortality in acutely ill patients. It can also be found with low or normal T 3 in non-severely ill subjects but its significance remains unclear. Patients and design: The Alsanut study included a representative sample of 440 independently-living subjects aged 65 or over constituted between January 1988 and September 1989. Past and current medical history and nutritional data were collected at inclusion. Baseline thyroid hormone (TSH, FT 4 , FT 3 and rT 3 ) serum levels were measured. Life status was determined on 1 December 2005. Results: Of the 374 elderly subjects included in the final analysis, 52 had abnormal TSH (43 with hyperthyroidism, nine with hypothyroidism) and 80.7% had died by 1 December 2005. There was no statistical difference in survival between subjects according to thyroid function (PZ0.54). Of the 322 elderly subjects with normal TSH, mortality rate was 81.1%. ESS was found in 3.4%, whereas 8.1% of the participants displayed elevated rT 3 with normal FT 3 . Time to death was strongly related to rT 3 (P!0.0001) and FT 3 (P!0.0001) in a univariate analysis. After adjusting for other confounding variables, rT 3 was the only thyroid hormone associated with shorter survival (PZ0.014). Conclusions: RT 3 was the only thyroid hormone associated with shorter survival in a representative population of independently-living elderly. In these subjects, isolated elevated rT 3 might be an equivalent of ESS, reflecting declining health.

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“…Accumulating evidence has indicated that low T 3 is associated with clinical outcomes in patients with various chronic diseases, including congestive heart failure, respiratory failure, and liver cirrhosis (13,14,15,16). Since low T 3 is the most common disturbance of thyroid hormone levels in ESRD patients, the adverse impact of low T 3 on patient survival has been widely explored in patients on maintenance hemodialysis (HD) and peritoneal dialysis (PD) (17,18).…”

Section: Introductionmentioning

confidence: 99%

The impact of low triiodothyronine levels on mortality is mediated by malnutrition and cardiac dysfunction in incident hemodialysis patients

Koo

Kim

Doh

et al. 2013

European Journal of Endocrinology

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Objective: Little is known about the impact of low triiodothyronine (T 3 ) levels on mortality in end-stage renal disease (ESRD) patients starting hemodialysis (HD) and whether this impact is mediated by malnutrition, inflammation, or cardiac dysfunction. Design and methods: A prospective cohort of 471 incident HD patients from 36 dialysis centers within the Clinical Research Center for ESRD in Korea was selected for this study. Based on the median value of T 3 , patients were divided into 'higher' and 'lower' groups, and all-cause and cardiovascular (CV) mortality rates were compared. In addition, associations between T 3 levels and various nutritional, inflammatory, and echocardiographic parameters were determined. Results: Compared with those in the 'higher' T 3 group, albumin, cholesterol, and triglyceride levels, lean body mass estimated by creatinine kinetics (LBM-Cr), and normalized protein catabolic rate (nPCR) were significantly lower in patients with 'lower' T 3 levels. The 'lower' T 3 group also had a higher left ventricular mass index (LVMI) and a lower ejection fraction (EF). Furthermore, correlation analysis revealed significant associations between T 3 levels and nutritional and echocardiographic parameters. All-cause and CV mortality rates were significantly higher in patients with 'lower' T 3 levels than in the 'higher' T 3 group (113.4 vs 18.2 events per 1000 patient-years, P!0.001, and 49.8 vs 9.1 events per 1000 patient-years, PZ0.001, respectively). The Kaplan-Meier analysis also showed significantly worse cumulative survival rates in the 'lower' T 3 group (P!0.001). In the Cox regression analysis, low T 3 was an independent predictor of all-cause mortality even after adjusting for traditional risk factors (hazard ratioZ3.76, PZ0.021). However, the significant impact of low T 3 on all-cause mortality disappeared when LBM-Cr, nPCR, LVMI, or EF were incorporated into the models. Conclusion: Low T 3 has an impact on all-cause mortality in incident HD patients, partly via malnutrition and cardiac dysfunction.

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Low triiodothyronine (T3) state: a predictor of outcome in respiratory failure? Results of a clinical pilot study

Cited by 85 publications

References 13 publications

Role of type 2 deiodinase in response to acute lung injury (ALI) in mice

Role of type 2 deiodinase in response to acute lung injury (ALI) in mice

Increased reverse triiodothyronine is associated with shorter survival in independently-living elderly: the Alsanut study

The impact of low triiodothyronine levels on mortality is mediated by malnutrition and cardiac dysfunction in incident hemodialysis patients

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