Role of cytokines in the pathogenesis of the euthyroid sick syndrome

Bartalena, Luigi; Bogazzi, Fausto; Brogioni, Sandra; Grasso, Lucia; Martino, Enio

doi:10.1530/eje.0.1380603

Cited by 85 publications

(63 citation statements)

References 107 publications

(106 reference statements)

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“…The concomitant changes and the significant negative correlation of serum IL-6 with serum T 3 and the positive correlation with serum rT 3 , raises again the issue that cytokines may be one of the causative factors of NTIS. In vitro experiments with human thyrocytes or in vivo with rats have shown that TNF-a, IL-1b, IL-6 and interferon-a (IFN-a) inhibit several thyroid cell functions (4). Administration of recombinant IL-6 to humans induced significant decrease in serum T 3 and TSH concentrations in association with an increase in serum rT 3 , and no changes in T 4 and FT 4 concentrations (19).…”

Section: Discussionmentioning

confidence: 99%

“…The normal range (NR) values for our adult population are 62-165 nmol/l for T 4 with intra-assay coefficient of variation (CV) 2.6% at the 84.1 nmol/l level; for T 3 NR is 0.8-2.7 nmol/l, and CV 1.5% at the 1.48 nmol/l level. Serum free (F)T 4 was measured by two different methods (both from Nichols Institute Diagnostics, San Juan Capistrano, CA, USA): (1) a direct equilibrium dialysis method (FT 4 Eq) with NR 10.3-34.7 pmol/l and with CV 10.7% at 12 pmol/l; (2) by a one-site chemiluminescence immunometric assay (FT 4 Ch) with NR 9-23 pmol/l and CV 5.6% for the FT 4 Ch value of 17 pmol/l. For the determination of TSH, a third generation two-site chemiluminescence immunoassay was used (Nichols Institute Diagnostics, Nijmegen, The Netherlands) with NR 0.4-3 mU/ml, with CV 4.8% for a TSH value of 1.28 mU/ml.…”

Section: Measurement Of Hormones and Cytokinesmentioning

confidence: 99%

“…These changes are related mainly to the inhibition of the 5 0 -monodeiodinase activity that leads to the decreased conversion of thyroxine (T 4 ) to triiodothyronine (T 3 ) in peripheral tissues, but other mechanisms may also be responsible for this syndrome (3). Recently, several proinflammatory cytokines which are elevated during the acute phase response have been implicated in the pathogenesis of the NTIS, although their role is still unclear (2)(3)(4). Cytokines are products of immune response acting not only as local factors but also as systemic hormones affecting the function of different endocrine glands such as pituitary or thyroid (4,5).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, several proinflammatory cytokines which are elevated during the acute phase response have been implicated in the pathogenesis of the NTIS, although their role is still unclear (2)(3)(4). Cytokines are products of immune response acting not only as local factors but also as systemic hormones affecting the function of different endocrine glands such as pituitary or thyroid (4,5).…”

Section: Introductionmentioning

confidence: 99%

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The role of cytokines and cortisol in the non-thyroidal illness syndrome following acute myocardial infarction

Karga

Papaioannou

Venetsanou

et al. 2000

European Journal of Endocrinology

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Objective: A number of different hormone changes have been described during the acute myocardial infarction (AMI), including those of the non-thyroidal illness syndrome (NTIS). Design and methods:We assessed the alterations of serum thyroid hormones, cytokines and cortisol levels in 30 patients with a first episode of AMI 4, 24, 48 h and 10 days (240 h) after the onset of the chest pain and we investigated the possible relationship of these alterations with the severity of AMI. Results: Fifteen patients had left ventricular ejection fraction (LVEF) Յ 50% (group I) and 15 patients had LVEF > 50% (group II). A transient decrease of total tri-iodothyronine (T 3 ), more prominent in group I (P < 0.05, t-test) with a concomitant rise of reverse T 3 (rT 3 ) occurred at 24 h. Total thyroxine (T 4 ), free T 4 (FT 4 ) and free T 4 index did not change significantly, but tended to be higher in group I patients, whereas TSH significantly increased in group II at 48 h. Interleukin-6 (IL-6) increased significantly at 24 h only in group I and declined thereafter (24 vs 240 h, P < 0.001) and this temporal change of IL-6 was associated with similar changes of creatine phosphokinase and creatine kinase isoenzyme MB (CK-MB). Tumor necrosis factor-a and IL-1b remained low in both groups. Cortisol was higher at 4 h and in 12 patients was above the normal values. Negative correlation was found between LVEF and IL-6 (P < 0.001), whereas T 3 , T 4 or cortisol levels were not correlated with the LVEF. Conclusions: Our data indicate that NTIS, in association with increase of IL-6, occurs in the early postinfarction period. In the NTIS following AMI the high level of IL-6 is the best predictor, among several parameters, of the severity of AMI as assessed by the LVEF and the rise of CK-MB.

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Section: Discussionmentioning

confidence: 99%

Section: Measurement Of Hormones and Cytokinesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The role of cytokines and cortisol in the non-thyroidal illness syndrome following acute myocardial infarction

Karga

Papaioannou

Venetsanou

et al. 2000

European Journal of Endocrinology

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“…26 Increased circulating cytokine levels are associated with several complications of BMT, such as GVHD or infectious episodes. [27][28][29] However, no study has been undertaken on the relation between thyroid hormone changes and cytokines in patients undergoing BMT.…”

Section: Discussionmentioning

confidence: 99%

Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation

Lee

Kang

et al. 2004

Bone Marrow Transplant

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Summary:The relation between thyroid hormone changes and cytokines in bone marrow transplantation (BMT) patients has not been studied. This prospective study was designed to determine the relation between thyroid hormones and cytokine levels after BMT and their effects on the mortality. We studied 80 patients undergoing allogeneic BMT. Serum thyroid hormone parameters and cytokine levels were measured before and serially during 6 months after BMT. Serum T 3 decreased to a nadir 3 weeks post-BMT and serum T 4 was lowest at 3 months post-BMT. Serum thyroid stimulating hormone (TSH) sharply decreased to a nadir at 1 week and recovered. Serum interleukin-6 increased for 2 weeks after BMT and declined thereafter. Serum tumor necrosis factor-a increased for 3 weeks after BMT and declined thereafter. After 3 weeks post-BMT, both cytokine levels were negatively correlated with serum T 3 and T 4 levels. A total of 29 patients died before 1 year post-BMT and 51 patients survived longer than 1 year. Those patients who died before 1 year post-BMT had significantly lower levels of T 4 at 3 weeks, 3 and 6 months than surviving patients. In conclusion, increased levels of serum IL-6 and TNF-a were negatively correlated with thyroid hormone concentrations in BMT recipients suggesting the role of these cytokines in euthyroid sick syndrome.

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Primary and Secondary Hypogonadism

Santi¹,

Corona²

2017

Endocrinology

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Role of cytokines in the pathogenesis of the euthyroid sick syndrome

Cited by 85 publications

References 107 publications

The role of cytokines and cortisol in the non-thyroidal illness syndrome following acute myocardial infarction

The role of cytokines and cortisol in the non-thyroidal illness syndrome following acute myocardial infarction

Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation

Primary and Secondary Hypogonadism

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