CoChat
Sign Up
Cited by 505Thyroid Disorders and TreatmentsAdrenal Hormones and DisordersHormonal and reproductive studies

The DOI matches its Crossref record; 101 of the 107 references it cites were found in a registry or an index.

Dangerous Dogmas in Medicine: The Nonthyroidal Illness Syndrome

De Groot, Leslie J.·1999·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jcem.84.1.5364
Open this paper in CoChat — free account

Abstract

For more than 3 decades it has been known that serum thyroid hormone levels drop during starvation and illness. In mild illness, this involves only a decrease in serum T3 levels. However, as the severity of the illness increases, there is a drop in both serum T3 and T4 (1). This decrease in serum thyroid hormone levels is seen in starvation (2), sepsis (3, 4), surgery (5), myocardial infarction (6, 7), bypass (8), bone marrow transplantation (9), and, in fact, probably any severe illness. Based on the conviction that patients with these abnormalities are not hypothyroid despite the low hormone levels in blood, the condition has been called the euthyroid sick syndrome. An alternative designation, which does not presume the metabolic status of the patient, is nonthyroidal illness syndrome (NTIS). NTIS seems a preferable name in light of present knowledge and will be used in this review. Starvation in man and animals causes a prompt decline in serum T3 and serum free T3 along with a drop in basal metabolic rate (BMR). As noted previously, almost any severe infection, trauma, or illness likewise causes a drop in serum T3 levels, but it is often difficult to differentiate the effects of these problems from short term starvation. Starvation, more precisely carbohydrate deprivation, appears to rapidly inhibit deiodination of T4 to T3 by type 1 iodothyronine deiodinase in the liver, thus inhibiting the generation of T3 and preventing the metabolism of rT3 (10). Consequently, there is a drop in serum T3 and an elevation in rT3. As starvation induces a decrease in the BMR (11), it has been argued, teleologically, that this decrease in thyroid hormone represents an adaptive response by the body to spare calories and protein by inducing hypothyroidism. This would logically be a beneficial response for an otherwise well animal or man facing temporary starvation. Patients who have only a drop in serum T3, representing the mildest form of NTIS, do not show clinical signs of hypothyroidism, nor has it been shown that this decrease in serum T3 has an adverse physiological effect on the body or that it is associated with increased mortality. As the severity of illness, and often the associated starvation, progresses, there is the gradual development of a more complex syndrome associated with low T3 and low T4 levels. In this state serum free T4 levels are commonly below normal, but may be normal or above normal, as described below. Generally, TSH levels are low or normal despite the low serum hormone levels, and rT3 levels are normal or elevated. The depression of serum T3 alone represents the least marked abnormality in NTIS, but there is no clear separation of this response from the more severe syndrome. Rather, there seems to be a gradual progression from a low T3 level to the most advanced condition in serious illness, associated with extremely low T3 and T4 levels. Most patients with serious illness in the hospital have low serum T3 levels. A large proportion of patients in an intensive care have of severity of NTIS with low T3 and T4 levels. The for in this syndrome is not to A marked decrease in serum T4 is associated with a of serum T4 levels drop below the of is with serum T4 levels below the of this the of of thyroid hormone would be beneficial in patients and of The in and by most in the the 3 decades has been that this is a beneficial physiological response and that is difficult to or of However, as described there is no for this of NTIS be the The abnormalities and would a The serum thyroid hormone abnormalities are to of T4 to and do not free hormone levels. of this may or may not the that a is present body than in and that the may inhibit of hormone by or to T3 and thus inhibit the of In NTIS, T3 levels in the are normal of the is the of the body is This deiodination as the hormone levels in fact, and the patients are but this is a beneficial physiological response and not be by the serum and hormone levels are is this is probably to the patient, and be serum T4 levels are below the level of T3 and free on NTIS that serum T3 and free T3 levels are low and have that free T3 levels low in a normal However, it is to that in the the patients with serum T4 levels that above the normal it is which be it is clear that most of the in the not have severe T3 in of as by In this patients with NTIS have free T3 levels than in normal T4 levels are in NTIS in proportion to the severity and probably the of the illness In short term trauma, as bypass or short term starvation there is no drop in serum However, with severity of trauma, illness, or infection, there is a drop in which may As serum T4 levels below are associated with a marked increased of to and T4 is below the extremely free The in the NTIS is in on the level of free T4 is by most to hormone to The of free T4 in NTIS are and may be by a of present in serum or the effect of as or free in the serum or that a to free hormone low for free T4 in T3 in the levels that

Overview

Integrity signals

Registry

Crossref · 10.1210/jcem.84.1.5364

Cites

101 of 101 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Research works printed but not linked: 6

  1. Maldonado, 1992, 2, 119
  2. 1997, Clinical relevance of thyroid hormone alterations in nonthyroidal illness., Thyroid Int, 4, 22
  3. Welle, 1986, Decrease in resting metabolic rate during rapid weight loss is reversed by low dose thyroid hormone treatment., Metabolism, 35, 289, 10.1016/0026-0495(86)90142-3 · DOI
  4. Osburne, 1983, Adaptation to hypocaloric feeding: physiologic significance of the fall in serum T3 as measured by the pulse wave arrival time., Metabolism, 32, 9, 10.1016/0026-0495(83)90148-8 · DOI
  5. Chopra, 1987, Evidence against benefit from replacement doses of thyroid hormones in nonthyroidal illness: studies using turpentine oil-injected rat., J Endocrinol Invest, 10, 559, 10.1007/BF03346994 · DOI
  6. Shigematsu, 1988, The effect of triiodothyronine and reverse triiodothyronine on canine hemorrhagic shock., Nippon Geka Gakkai Zasshi, 89, 1587

Cited by

Sorted by citations

See all 505

Related

See all

Metadata

Authors
De Groot, L. J.
Affiliations
Thyroid Study Unit, University of Chicago, Chicago, Illinois 60637
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
1999-01-01
Volume
84
Issue
1
Pages
151-164
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jcem.84.1.5364
OpenAlex
W2098580669
Cited by
505
References
107
Citations by year
2026: 7 · 2025: 2 · 2024: 2 · 2023: 9 · 2022: 16 · 2021: 14 · 2020: 13 · 2019: 16 · 2018: 11 · 2017: 10 · 2016: 16 · 2015: 15 · 2014: 23 · 2013: 28 · 2012: 17
FWCI
14.98
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
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
low T3 syndrome, thyroid hormone metabolism, serum T3, reverse T3, thyroxine, iodothyronine deiodinase, starvation, sepsis, basal metabolic rate, thyroid-stimulating hormone, hypothyroidism, diagnostic criteria
MeSH terms
Adaptation, Physiological, Euthyroid Sick Syndromes, Humans, Hypothyroidism, Thyrotropin, Thyroxine, Triiodothyronine, Cytokines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review