Relationship of Altered Thyroid Hormone Indices to Survival in Nonthyroidal Illnesses

Kaptein, Elaine M.; Weiner, John M.; Robinson, William J.; Wheeler, William; Nicoloff, John T.

doi:10.1111/j.1365-2265.1982.tb03173.x

Cited by 153 publications

(63 citation statements)

References 26 publications

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“…These results emphasize the prognostic importance of low-T4-T3 syndrome in the period after BMT that has also been shown in various other diseases. 19,20 Free-T4 concentrations, as in our study, are usually normal in patients with NTI. 14,33 In our study the degree of T4 to T3 conversion inhibition and subsequent decrease in T3 seems to be a good discriminator with respect to mortality after BMT and may therefore be valuable in the clinical setting.…”

Section: Discussionmentioning

confidence: 84%

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Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation

Schulte

Reinhardt

Beelen³

et al. 1998

Bone Marrow Transplant

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Summary:Bone marrow transplantation is known to be associated with considerable morbidity and mortality. The aim of this study was to determine the influence of nutritional status and development of sick euthyroid syndrome as prognostic factors for outcome after BMT. In 100 patients who underwent transplantation the following parameters were assessed before and at day 14 and 28 after transplantation: anthropometric data (body weight, body mass index, body composition, grip strength), rapid turnover proteins transferrin and prealbumin, T4, T3, free T4, reverse T3, thyroid-stimulating hormone and thyroglobulin. Following bone marrow transplantation, 22 patients died in the short-term follow-up (group A) before day 140 after BMT, 21 patients died during further follow-up between days 140 and 365 (group B) and 57 patients survived longer than 365 days (group C). All patients experienced a significant decrease of transferrin and T3, accompanied by an increase of rT3 and rT3/T3 ratio at day 14 after BMT. At day 28 after BMT, patients in group C showed recovery from these changes with an increase of transferrin and a fall in rT3 and the rT3/T3-ratio, which was not seen in patients who died during further follow-up (groups A and B). The observed changes were independent of other prognostically relevant factors (type of disease, HLA-match, immunosuppression). Impaired nutritional status and development of a sick euthyroid syndrome, without tendency to recovery, are associated with a higher probability of fatal outcome after bone marrow transplantation and have prognostic relevance in this group of patients.

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Section: Discussionmentioning

confidence: 84%

“…This hormone constellation has been called low-T3/ low-T4 syndrome and is correlated with a bad prognosis. 19,20 The relevance of these observations is still unclear. Typically, thyroid hormone parameters return to normal with recovery from the underlying illness.…”

mentioning

confidence: 99%

Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation

Schulte

Reinhardt

Beelen³

et al. 1998

Bone Marrow Transplant

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“…An inverse relationship between serum thyroxine (T4) and mortality in critically ill patients has previously been observed (2), but several controlled trials have reported no benefit (3) or even worsened outcome (4) with thyroid hormone supplementation. This has led to the hypothesis that the nonthyroidal illness syndrome is an adaptive process that promotes survival during life-threatening illness by reducing metabolic rate and energy cost.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats

Simonides¹,

Mulcahey²,

Redout³

et al. 2008

J. Clin. Invest.

153

172

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Thyroid hormone is a critical determinant of cellular metabolism and differentiation. Precise tissue-specific regulation of the active ligand 3,5,3′-triiodothyronine (T3) is achieved by the sequential removal of iodine groups from the thyroid hormone molecule, with type 3 deiodinase (D3) comprising the major inactivating pathway that terminates the action of T3 and prevents activation of the prohormone thyroxine. Using cells endogenously expressing D3, we found that hypoxia induced expression of the D3 gene DIO3 by a hypoxiainducible factor-dependent (HIF-dependent) pathway. D3 activity and mRNA were increased both by hypoxia and by hypoxia mimetics that increase HIF-1. Using ChIP, we found that HIF-1α interacted specifically with the DIO3 promoter, indicating that DIO3 may be a direct transcriptional target of HIF-1. Endogenous D3 activity decreased T3-dependent oxygen consumption in both neuronal and hepatocyte cell lines, suggesting that hypoxia-induced D3 may reduce metabolic rate in hypoxic tissues. Using a rat model of cardiac failure due to RV hypertrophy, we found that HIF-1α and D3 proteins were induced specifically in the hypertrophic myocardium of the RV, creating an anatomically specific reduction in local T3 content and action. These results suggest a mechanism of metabolic regulation during hypoxic-ischemic injury in which HIF-1 reduces local thyroid hormone signaling through induction of D3.

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“…This has been documented previously in critically ill children (32). It was once felt that the euthyroid sick syndrome was a physiologic adaptive mechanism limiting hypermctabolism, but this seems an unlikely explanation for a condition whose severity has been shown to have a close association with a poor outcome (33).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Severe Head Injury on Whole Body Energy Expenditure and Its Possible Hormonal Mediators in Children

Matthews

Aynsley-Green²,

Matthews³

et al. 1995

Pediatr Res

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This study examines the effects of severe head injury in children on whole body energy expenditure and the mediators that influence this. One hundred five serial measurements of whole body energy expenditure and plasma adrenaline, triiodothyronine, glucagon, cortisol, insulin, and growth hormone concentrations were made in 18 children aged 2-15 y receiving neurointensive care for severe head injury. Energy expenditure was mcasured using indirect calorimetry by a modified Douglas bag technique, and hormones were measured by RIA or radioenzymatic assay. Energy expenditure varied markedly betwcen and within children (mean 97% of predicted, range 60-137%) and was significantly lower in the four children with a poor outcome ( p = 0.03). Within each child there were statistically significant positive relationships between energy expenditure and adrenaline Head injury is the most important cause of mortality and long-term morbidity in children over 1 y of age in the Western world, accounting for 25% of all deaths between the ages of 5 and 15 y (1). However, little is known of the effects of severe head injury on whole body energy expenditure and the mediators that determine this. Both elevated and depresscd levels of energy expenditure may be disadvantageous to the critically injured child. Elevated metabolic rates increase nutritional demands, which, being difficult to meet, result in tissue wasting and an increased susceptibility to infection (2). Of equal importance, depressed metabolic rates are associated with a poor prognosis in critically ill adults (3). A greater understanding of the metabolic changes occurring in critically injured children could give rise to therapeutic interventions to aid management and improve outcome. The aims of the current study, therefore, Abbreviations ISS, injury severity score GCS, Glasgow coma score Fio,, proportion of 0, in inspiratory gas T3, triiodothyronine were to measure serially whole body energy expenditure in children after severe head injury and to investigate the relationship between energy expenditure and possible hormonal mediators. METHODS Subjects.The study was performed in 18 children who had sustained a severe head injury and were receiving neurointensive care. The mean age was 8.2 y with a range of 2-15 y. Sixteen children had isolated head injuries, and two children had other associated injuries. Associated injuries were defined as injuries severe enough to warrant hospital admission in their own right, which is approximately equivalent to an ISS of 2 9 (4). In all cases the head injury was the most serious injury sustained. The criterion for admission to the study was a GCS equal to or less than 8 (5). In children aged less than 4 y, the

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Relationship of Altered Thyroid Hormone Indices to Survival in Nonthyroidal Illnesses

Cited by 153 publications

References 26 publications

Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation

Low T3-syndrome and nutritional status as prognostic factors in patients undergoing bone marrow transplantation

Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats

The Effect of Severe Head Injury on Whole Body Energy Expenditure and Its Possible Hormonal Mediators in Children

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