Euthyroid sick syndrome in paediatric and adult patients requiring extracorporeal circulatory support and the role of thyroid hormone supplementation: a review.

Non-thyroid disorders may modify thyroid hormone metabolism, resulting in an 'euthyroid sick syndrome'. Studies determining the association of cardiopulmonary bypass to thyroid function showed changes in line with this euthyroid sick syndrome. In some cases, cardiovascular dysfunction after cardiac surgery with cardiopulmonary bypass is comparable to that noticed in hypothyroidism associated with low cardiac output and elevated systemic vascular resistance. Numerous lines of research have proposed that triiodothyronine can behave acutely as a positive inotropic and vasodilator agent. The aim of this review is to present an update on the current literature about in what clinical situations the use of thyroid supplementation during the perioperative period of extracorporeal circulation in the adult and paediatric populations may impact outcome to any appreciable degree. The contribution of thyroid function in patients undergoing a ventricular assist device implantation is additionally reviewed and future study directions are proposed. This is a narrative review, where the search strategy consisted on retrieving the articles through an extensive literature search performed using electronic databases from January 1978 up to September 2019. All controlled trials randomly allocating to perioperative thyroid hormone administration in children and adults undergoing extracorporeal circulation for cardiac surgery were considered. Thyroid hormone supplementation may be recommended particularly in selected paediatric sub-populations. There is currently no firm evidence regarding the benefits of routine use of thyroid hormone administration in cardiac adult patients. Further studies are required to assess the beneficial effect of thyroid hormone on patients with end-stage heart failure supported by ventricular assist devices.

Euthyroid sick syndrome and nutritional status are correlated with hyposelenemia in hemodialysis patients.

BACKGROUND: Maintenance hemodialysis (HD) patients have altered levels of thyroid hormone (TH) in euthyroid sick syndrome, along with low T3 levels and several nutritional metabolic disturbances. Selenium (Se) is an essential trace element for living organisms, which has been shown to play a major role in thyroid hormone levels and the nutritional metabolism. The aims of the present study were to assess the changes in serum levels of selenium and their correlation with disorders of the endocrine and nutritional metabolism in HD patients. METHODS: Fifty-three uremic patients with hemodialysis were evaluated; 30 healthy volunteers served as controls. Baseline serum concentrations of total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), and free thyroxine (FT4) were determined by radioimmunoassay (RIA). Serum levels of thyroid-stimulating hormone (TSH) and intact parathyroid hormone (iPTH) were measured by a sensitive immunoradiometric assay (IRMA). Serum selenium was analyzed using Hitachi Z- 2000 polarized Zeeman atomic absorption spectrometry. Other metabolic variables were measured in all patients and control subjects. Multiple correlation analysis was performed among variables. RESULTS: Higher serum triglyceride, LDL-C, ApoB and lower albumin, HDL-C levels were found in subjects with HD. Mean serum selenium concentration was significantly lower in the HD group than in the control group (p<0.01). The levels of serum TT3 and FT3 in HD patients were significantly lower than in healthy control subjects (p<0.01; p<0.05, respectively), but TT4, FT4 and TSH were not different. However, serum iPTH levels were significantly higher in patients than in controls (p<0.01). In the group of HD patients, serum selenium levels were significantly positively correlated with albumin, HDL-C, TT3 and FT3 ; and negatively correlated with triglyceride (TG), LDL-C, ApoB and iPTH. Both serum TT3 and FT3 levels were significantly positively correlated with HDL-C; and negatively correlated with TG, LDL-C and ApoB. CONCLUSIONS: These data suggest that hyposelenemia in HD patients correlated with euthyroid sick syndrome with low T3 levels, and nutritional status with hyperlipidemia and hypoalbuminemia which might be involved in dysfunction in the endocrine and nutrition metabolism in dialysis patients.

Is euthyroid sick syndrome a defensive mechanism against oxidative stress?

The body has a hierarchy of defence strategies to deal with oxidative stress. Among these arrays of defence mechanisms, the over expression and increased activity of glutathione peroxidases has been suggested as the first line of defence. The two main cofactors required for glutathione peroxidase activity are selenium and reduced glutathione. These two factors have been shown to be required for the deiodinase activity also. In vitro and in vivo studies have shown that oxidative stress decreases the activity of deiodinase. Thus, a decrease in deiodinase activity would facilitate the use of these cofactors by glutathione peroxidase in combating oxidative stress. Lowering of serum T3 is generally regarded as a valuable calorie-sparing economy. A decreased metabolic state of the cells as found in euthyroid sick syndrome indicates a decreased free radical generation from the mitochondria. For this reason, euthyroid sick syndrome could be considered as a physiological mechanism activated in response to oxidative stress.

Influence of selenium supplements on the post-traumatic alterations of the thyroid axis: a placebo-controlled trial.

OBJECTIVE: To investigate whether early selenium (Se) supplementation can modify the post-traumatic alterations of thyroid hormone metabolism, since the first week after trauma is characterised by low plasma Se and negative Se balances. DESIGN: Prospective, placebo-controlled randomised supplementation trial. SETTING: Surgical ICU in a tertiary university hospital. PATIENTS: Thirty-one critically ill trauma patients aged 42 +/- 16 years (mean +/- SD), with severe multiple injury (Injury Severity Score 30 +/- 7). INTERVENTION: Supplementation during the first 5 days after injury with either Se or placebo. The selenium group was further randomised to receive daily 500 microg Se, with or without 150 mg alpha-tocopherol (AT) and 13 mg zinc supplements. The placebo group received the vehicle. Circulating Se, AT, zinc, and thyroid hormones were determined on D0 (= day 0, admission), D1, D2, D5, D10, and D20. RESULTS: Plasma Se, low on D0, normalised from D1 in the selenium group; total T4 and T3 increased more and faster after D2 (P = 0.04 and 0.08), reverse T3 rising less between D0 and D2 (P = 0.05). CONCLUSIONS: Selenium supplements increased the circulating Se levels. Supplementation was associated with modest changes in thyroid hormones, with an earlier normalisation of T4 and reverse T3 plasma levels. The addition of AT and zinc did not produce any additional change.

Sick euthyroid syndrome. What to do when thyroid function tests are abnormal in critically ill patients.

Abnormal thyroid hormone concentrations are common in patients with serious nonthyroidal illnesses. Early evidence suggests that thyroid hormone levels may predict the prognosis for some patients. Abnormal thyroid function is usually reversible, but thyroid function tests should be repeated when the nonthyroidal illness is resolved. Whether active intervention using thyroid hormone supplements is beneficial or not remains controversial and requires future large-scale investigation.

[Therapy of euthyroid iron deficiency goiter. Effectiveness of a combination of L-thyroxine and 150 micrograms iodine in comparison with mono-L-thyroxine]. / Therapie der euthyreoten Jodmangelstruma. Wirksamkeit der Kombination aus L-Thyroxin und 150 micrograms Jodid im Vergleich zu Mono-L-Thyroxin.

BACKGROUND: In terms of the pathomechanism, TSH and intrathyroid iodine deficiency are the interconnecting elements between alimentary iodine deficiency and the growth and genesis of goiter. L-Thyroxine treatment for suppression of hypophyseal TSH production and supplementary iodide have a synergistic effect in reducing the size of goiter. An individual adaptation of the L-Thyroxine dose is necessary for optimal TSH suppression. Excessive suppression of the TSH level prevents uptake of iodine by the thyroid and thus compensation of the intrathyroid iodine deficiency. Combination therapy of an individually adjusted amount of L-Thyroxine with a small, mostly constant amount of iodine is a recognized concept of goiter therapy today. Administration of a combination preparation with an individually adjustable dose of L-Thyroxine and 150 micrograms iodine complies with these recommendations and improves compliance since only one tablet is required. PATIENTS AND METHODS: In the present study, the thyroid iodine supply, efficacy and tolerance of such a combination preparation was tested for the first time in 49 patients with euthyroid iodine deficiency goiter (group A). 45 patients receiving an individual L-Thyroxine therapy served as controls (group B). RESULTS: Supplementation of individually dosable L-Thyroxine with 150 micrograms iodide leads to a markedly raised iodine excretion in the urine (p < 0.005). This is an indirect indication of an improved thyroid iodine supply. Patients of group A showed a greater reduction of the thyroid volume (18.5% as compared to 16.8%, p = n. s.) and a more persistent TSH suppression (lowering by 39% [group A] as compared to a rise of 17% [group B]) in relation to the initial value (p < 0.004). This is attributable to the improved supply of iodine. CONCLUSION: The combination therapy tested was tolerated just as well as the mono-L-Thyroxine treatment with better efficacy.

Relations between the selenium status and the low T3 syndrome after major trauma.

OBJECTIVE: Thyroxine (T4) is deiodinated to triiodothyronine (T3) by the hepatic type I iodothyronine deiodinase, a selenoprotein that is sensitive to selenium (Se) deficiency. After severe injury, T4 deiodination is decreased, leading to the low T3 syndrome. Injury increases free radical production, which inactivates the iodothyronine deiodinase. The aims were to study the Se status after major trauma and to investigate its relation to the low T3 syndrome. DESIGN: Preliminary prospective descriptive study. SETTING: Intensive care unit at a university teaching hospital. PATIENTS AND METHODS: 11 patients aged 41 +/- 4 years (mean +/- SEM), with severe multiple injuries (Injury Severity Score 29 +/- 2 points). A balance study was performed from day 1 to day 7. Serum and urine samples were collected from the time of admission until day 7, then on days 10, 15, 20, 25 and 30. Non-parametric tests and Pearson's correlation coefficients were used for analysis. RESULTS: Cumulated Se losses were 0.88 +/- 0.1 mumol/24h. Serum Se was decreased from admission to day 7. T3, free T3, and the T3/T4 ratio were low until day 5, being lowest on day 2; T4 and thyroid stimulating hormone were normal. Serum Se was correlated with T3 (r = 0.55, p = 0.0001), and with free T3 (r = 0.35). CONCLUSION: Se status is altered after trauma, with decreased Se serum levels upon admission to the ICU but with no major Se losses. Se is probably redistributed to the tissues. The correlation between Se and T3, along with the parallel decrease in T4 deiodination, indicates that reduced deiodination might be related to the transient decrease in serum Se.