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Cited by 69Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersGrowth Hormone and Insulin-like Growth Factors

The hypothalamic-pituitary-thyroid axis in critical illness

Fliers, E., Alkemade, A., Wiersinga, W.M.·2001·Best Practice & Research Clinical Endocrinology & Metabolism
DOI 10.1053/beem.2001.0163
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Abstract

In severe illness, profound changes occur in the hypothalamic-pituitary-thyroid axis. The observed decrease in serum concentration of both thyroid hormones and thyrotropin (TSH) are not compatible with a negative feedback loop and suggest a major change in setpoint regulation of the hypothalamic-pituitary-thyroid axis. This is supported by post mortem studies showing a decreased expression of thyrotropin-releasing hormone in the hypothalamic paraventricular nucleus of patients with a decreased serum T3 level. In critical illness, serum T3 may even become undetectable without giving rise to an elevated concentration of serum TSH. It is currently not clearly established whether this reflects an adaptation of the organism to illness or instead a potentially harmful condition leading to hypothyroidism at tissue level. There is thus a need for randomized clinical trials in critically ill patients to investigate whether they may benefit from a normalization of thyroid hormone concentration. Recent clinical studies in these patients involving the administration of hypothalamic peptides open up new ways of achieving this.

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Crossref · 10.1053/beem.2001.0163

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  • Serum TSH may be relatively low in critically ill patients with concomitant hypothyroidism as a result of a variety of drugs, for example dopamine which inhibits TSH release.

    “As a potential complicating factor, serum TSH may be relatively low in critically ill patients with concomitant hypothyroidism as a result of a variety of drugs, for example dopamine which inhibits TSH release (for review see Fliers et al. [81]).”

    From An update on non-thyroidal illness syndrome (2021) · cites this paper as [81]

  • 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 [32]

  • 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 [32]

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Authors
Fliers, E., Alkemade, A., & Wiersinga, W. M.
Affiliations
Amsterdam UMC Location University of Amsterdam (NL)
ORCID
Venue
Best Practice & Research Clinical Endocrinology & Metabolism
Publisher
Elsevier BV
Published
2001-12
Volume
15
Issue
4
Pages
453-464
ISSN
1521-690X (ISSN-L)
DOI
10.1053/beem.2001.0163
OpenAlex
W2156519573
Cited by
69
References
43
Citations by year
2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2020: 3 · 2019: 2 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 5
FWCI
0.19
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Best Practice & Research 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 › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
hypothalamic-pituitary-thyroid axis, critical illness, thyroid-stimulating hormone, thyroid hormones, T3, negative feedback loop, paraventricular nucleus, thyrotropin-releasing hormone, hypothyroidism, hypothalamic neuropeptides, thyroid hormone replacement
MeSH terms
Humans, Hypothalamo-Hypophyseal System, Neuropeptides, Thyroid Diseases, Thyroid Gland, Thyroid Hormones, Critical Illness

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