Tumor Necrosis Factor: A Putative Mediator of the Sick Euthyroid Syndrome in Man*
Abstract
Tumor necrosis factor-alpha (TNF) is believed to be an important mediator in many diseases that are associated with the sick euthyroid syndrome. To investigate the effect of TNF on thyroid hormone metabolism, we performed a controlled study in six healthy postabsorptive males, in whom plasma thyroid hormones and TSH were sequentially measured after iv bolus injections of recombinant human TNF (50 micrograms/m2) and isotonic saline. During the 10.5-h study TNF produced the characteristic changes in circulating thyroid hormones and TSH observed in the sick euthyroid syndrome. Compared with the control experiment, TNF induced significant decreases in T3 (-36 +/- 2%; saline, -20 +/- 3%; P less than 0.05) and TSH levels (-68 +/- 3%; saline, -44 +/- 8%; P less than 0.05) and a significant increase in rT3 values (+48 +/- 11%; saline, -12 +/- 7%; P less than 0.05). T4 and free T4 index were not affected by TNF. Free T4 showed a mean transient increase of 18% in five subjects (nonsignificant), which occurred synchronically with a transient 3.5-fold rise in circulating FFA levels. Our results suggest that TNF is involved, either directly or indirectly, in the pathogenesis of the sick euthyroid syndrome.
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TSH may be a poor indicator of peripheral thyroid levels in conditions such as chronic stress, chronic illness, diabetes, insulin resistance, obesity, leptin resistance, depression, chronic fatigue syndrome, fibromyalgia, premenstrual syndrome, and dieting or weight gain.
“As a result, TSH may be a poor indicator of peripheral thyroid levels in the presence of such conditions.”
From Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report (2017) · cites this paper as [35]
While serum T3 levels may decline by 30% and remain within the normal range, tissue T3 may decline by 70-80%, resulting in profound cellular hypothyroidism with normal serum TSH, FT4, and FT3 levels.
“While serum T3 levels may decline by 30%, which is significant, but still within the so-called “normal range”, tissue T3 may decline by 70–80%, resulting in profound cellular hypothyroidism with normal serum TSH, FT4, and FT3 levels”
From Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report (2017) · cites this paper as [35]
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References 23 · Cited by 270
- Authors
- POLL, T. V. D., ROMIJN, J. A., WIERSINGA, W. M., & SAUERWEIN, H. P.
- Affiliations
- University of Amsterdam (NL)
- Amsterdam UMC Location University of Amsterdam (NL)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 1990-12
- Volume
- 71
- Issue
- 6
- Pages
- 1567-1572
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2008122954
- Cited by
- 270
- References
- 23
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 6 · 2017: 4 · 2016: 9 · 2015: 8 · 2014: 12 · 2013: 8 · 2012: 6
- FWCI
- 5.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- TNF-α, low T3 syndrome, thyroid hormone metabolism, triiodothyronine, thyroxine, reverse T3, thyroid-stimulating hormone, free thyroxine, free fatty acids, recombinant human TNF
- MeSH terms
- Adult, Euthyroid Sick Syndromes, Fatty Acids, Nonesterified, Humans, Kinetics, Male, Recombinant Proteins, Thyroid Hormones, Thyrotropin, Thyroxine, Triiodothyronine, Triiodothyronine, Reverse, Tumor Necrosis Factor-alpha
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