Alterations in thyroid function in patients with systemic illness: the euthyroid sick syndrome

WARTOFSKY, LEONARD; BURMAN, KENNETH D.

doi:10.1210/edrv-3-2-164

Cited by 920Thyroid Disorders and TreatmentsGrowth Hormone and Insulin-like Growth FactorsAdrenal Hormones and Disorders

Alterations in thyroid function in patients with systemic illness: the euthyroid sick syndrome

WARTOFSKY, LEONARD, BURMAN, KENNETH D.·1982·Endocrine Reviews

DOI 10.1210/edrv-3-2-164

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Abstract

GENERALLY, the purpose of assessing thyroid function in a given patient is to determine his metabolic status. In patients with systemic nonthyroidal illness, as well as in those undergoing a variety of other stresses, this determination is complicated by effects at all levels of the hypothalamic-pituitary-thyroid axis. With the availability of thyrptropin releasing hormone (TRH) and the recent development of sensitive methods for the direct measurement of serum 3,5,3′-triiodothyronine (T3) and 3,3′,5′-triiodothyronine (reverse T3 (rT3)), considerable progress has been made in gaining an understanding of the significance of the alterations in thyroid hormone economy that accompany nonthyroidal illness, stress, and the administration of certain pharmacological agents. According to basic tenets of negative feedback control of thyrotropin (TSH) secretion by circulating free thyroid hormones, alterations in hormone binding in nonthyroidal illness that produce increases in free hormone should result in predictably decreased TSH responses to TRH stimulation. Indeed, the magnitude of TSH response to TRH is often taken to be the most specific clue to the true metabolic state of the organism, and the recent publication of studies that examined the status of TRH responsiveness in nonthyroidal illness has provided critical information in this regard.

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NTIS is characterized by normal or decreased serum TSH levels, low serum T3 levels, and serum free T4 levels that may be normal, increased, or decreased.
“In general terms, this syndrome is characterized by normal or even decreased serum TSH levels in the presence of low serum T3 levels and serum levels of free T4 that may be normal, increased, or decreased.”
From Can Reverse T3 Assay Be Employed to Guide T4 vs. T4/T3 Therapy in Hypothyroidism? (2019) · cites this paper as [6]
The alterations in thyroid hormone levels in euthyroid sick syndrome or non-thyroidal illness syndrome (NTIS) are based on reduced conversion of T4 to T3 and increased conversion to rT3 in critical conditions.
“This is the basis of the alterations in thyroid hormone levels in the euthyroid sick syndrome or non-thyroidal illness syndrome (NTIS) (6).”
From Can Reverse T3 Assay Be Employed to Guide T4 vs. T4/T3 Therapy in Hypothyroidism? (2019) · cites this paper as [6]

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Authors: WARTOFSKY, L., & BURMAN, K. D.
Affiliations: Uniformed Services University of the Health Sciences (US)
Corresponding author: WARTOFSKY, LEONARD
ORCID: WARTOFSKY, LEONARD
BURMAN, KENNETH D.
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 1982-04
Volume: 3
Issue: 2
Pages: 164-217
ISSN: 0163-769X (ISSN-L)
1945-7189
DOI: 10.1210/edrv-3-2-164
OpenAlex: W1993358990
Cited by: 916
References: 0
Citations by year: 2026: 4 · 2025: 9 · 2024: 8 · 2023: 11 · 2022: 12 · 2021: 13 · 2020: 12 · 2019: 14 · 2018: 14 · 2017: 19 · 2016: 9 · 2015: 14 · 2014: 17 · 2013: 16 · 2012: 11
FWCI: 29.14
Type: journal article
Language: en
Open access: closed
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: low T3 syndrome, thyroid function, hypothalamic-pituitary-thyroid axis, thyroid-stimulating hormone, triiodothyronine, reverse T3, thyroid hormone binding, TRH stimulation test, metabolic stress, free thyroid hormones
MeSH terms: Adult, Age Factors, Aged, Amiodarone, Animals, Anorexia Nervosa, Mental Disorders, Contrast Media, Diabetes Mellitus, Dopamine, Fasting, Glucocorticoids, Humans, Infant, Newborn, Iodine Radioisotopes, Kidney Diseases, Liver Diseases, Middle Aged, Myocardial Infarction, Neoplasms, Obesity, Protein-Energy Malnutrition, Starvation, Stress, Physiological, Thyroid Gland, Thyroid Hormones, Thyrotropin, Thyrotropin-Releasing Hormone

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Alterations in thyroid function in patients with systemic illness: the euthyroid sick syndrome

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