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Cited by 145Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersHormonal and reproductive studies

Tissue Thyroid Hormone Levels in Critical Illness

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Peeters, Robin P., van der Geyten, Serge, Wouters, Pieter J., Darras, Veerle M., van Toor, Hans, Kaptein, Ellen, Visser, Theo J., Van den Berghe, Greet·2005·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2005-1013
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Abstract

Context: Pronounced alterations in serum thyroid hormone levels occur during critical illness. T3 decreases and rT3 increases, the magnitudes of which are related to the severity of disease. It is unclear whether these changes are associated with decreased tissue T3 concentrations and, thus, reduced thyroid hormone bioactivity. Patients and Study Questions: We therefore investigated, in 79 patients who died after intensive care and who did or did not receive thyroid hormone treatment, whether total serum thyroid hormone levels correspond to tissue levels in liver and muscle. Furthermore, we investigated the relationship between tissue thyroid hormone levels, deiodinase activities, and monocarboxylate transporter 8 expression. Results: Tissue iodothyronine levels were positively correlated with serum levels, indicating that the decrease in serum T3 during illness is associated with decreased levels of tissue T3. Higher serum T3 levels in patients who received thyroid hormone treatment were accompanied by higher levels of liver and muscle T3, with evidence for tissue-specific regulation. Tissue rT3 and the T3/rT3 ratio were correlated with tissue deiodinase activities. Monocarboxylate transporter 8 expression was not related to the ratio of the serum over tissue concentration of the different iodothyronines. Conclusion: Our results suggest that, in addition to changes in the hypothalamus-pituitary-thyroid axis, tissue-specific mechanisms are involved in the reduced supply of bioactive thyroid hormone in critical illness.

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  • A study involving patients who were critically ill and received TH treatment clearly showed that normalizing serum TH does not equal normalizing tissue TH.

    “This was clearly shown in a study involving patients who were critically ill and received TH treatment [84].”

    From An update on non-thyroidal illness syndrome (2021) · cites this paper as [84]

    The Discussion reports that treated critically ill patients had higher serum T3, accompanied by higher tissue T3, but the increase in liver T3 was twice the increase in serum T3. This supports a tissue-specific response to treatment. It does not clearly demonstrate the stated comparison between normalized serum and normalized tissue hormone levels: serum T3 in treated patients remained in the low-normal range, and the paper does not establish whether tissue levels normalized. (LLM, conf=0.84)

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  • 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 [29]

  • 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 [29]

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Authors
Peeters, R. P., van der Geyten, S., Wouters, P. J., Darras, V. M., van Toor, H., Kaptein, E., Visser, T. J., & Van den Berghe, G.
Affiliations
  • Erasmus MC (NL)
  • Laboratory of Comparative Endocrinology, Zoological Institute (S.v.d.G., V.M.D.), B-3000 Leuven, Belgium
  • KU Leuven (BE)
  • Department of Internal Medicine (R.P.P., H.v.T., E.K., T.J.V.), Erasmus University Medical Center, Rotterdam, The Netherlands;
  • Department of Intensive Care Medicine (P.J.W., G.V.d.B.), Katholieke Universiteit Leuven, B-3000 Leuven, Belgium
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2005-12-01
Volume
90
Issue
12
Pages
6498-6507
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2005-1013
OpenAlex
W2119065033
Cited by
145
References
41
Citations by year
2026: 2 · 2025: 5 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 7 · 2017: 8 · 2016: 8 · 2015: 10 · 2014: 10 · 2013: 6 · 2012: 7
FWCI
5.17
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • Lirias (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 › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords
critical illness, thyroid hormones, triiodothyronine, reverse T3, thyroid hormone deiodinases, MCT8, liver, skeletal muscle, thyroid hormone replacement, ICU mortality, iodothyronines
MeSH terms
Aged, Female, Humans, Insulin, Iodide Peroxidase, Liver, Male, Middle Aged, Triiodothyronine, Triiodothyronine, Reverse, Randomized Controlled Trials as Topic, Critical Illness, Muscle, Skeletal, Monocarboxylic Acid Transporters, Symporters

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