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Cited by 86Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryThyroid Cancer Diagnosis and Treatment

Clinical Parameters Are More Likely to Be Associated with Thyroid Hormone Levels than with Thyrotropin Levels: A Systematic Review and Meta-Analysis

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Fitzgerald, Stephen P., Bean, Nigel G., Falhammar, Henrik, Tuke, Jono·2020·Thyroid®
DOI 10.1089/thy.2019.0535PMC PMC7757573
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Abstract

Background: Though the functional states of other endocrine systems are not defined on the basis of levels of controlling hormones, the assessment of thyroid function is based on levels of the controlling hormone thyrotropin (TSH). We, therefore, addressed the question as to whether levels of thyroid hormones [free thyroxine (fT4), total triiodothyronine (TT3)/free triiodothyronine (fT3)], or TSH levels, within and beyond the reference ranges, provide the better guide to the range of clinical parameters associated with thyroid status. Methods: A PubMed/MEDLINE search of studies up to October 2019, examining associations of levels of thyroid hormones and TSH, taken simultaneously in the same individuals, with clinical parameters was performed. We analyzed atrial fibrillation, other cardiac parameters, osteoporosis and fracture, cancer, dementia, frailty, mortality, features of the metabolic syndrome, and pregnancy outcomes. Studies were assessed for quality by using a modified Newcastle–Ottawa score. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. A meta-analysis of the associations was performed to determine the relative likelihood of fT4, TT3/fT3, and TSH levels that are associated with the clinical parameters. Results: We identified 58 suitable articles and a total of 1880 associations. In general, clinical parameters were associated with thyroid hormone levels significantly more often than with TSH levels—the converse was not true for any of the clinical parameters. In the 1880 considered associations, fT4 levels were significantly associated with clinical parameters in 50% of analyses. The respective frequencies for TT3/fT3 and TSH levels were 53% and 23% ( p < 0.0001 for both fT4 and TT3/fT3 vs. TSH). The fT4 and TT3/fT3 levels were comparably associated with clinical parameters ( p = 0.71). More sophisticated statistical analyses, however, indicated that the associations with TT3/fT3 were not as robust as the associations with fT4. Conclusions: Thyroid hormones levels, and in particular fT4 levels, seem to have stronger associations with clinical parameters than do TSH levels. Associations of clinical parameters with TSH levels can be explained by the strong negative population correlation between thyroid hormones and TSH. Clinical and research components of thyroidology currently based on the measurement of the thyroid state by reference to TSH levels warrant reconsideration.

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  • Clinical parameters are associated with FT4 or FT3 significantly more often than with TSH levels (50% vs 23%, P<0.0001).

    “In accordance, a systematic review found that clinical parameters are associated with FT4 or FT3 significantly more often than with TSH levels (50% and 23% respectively, P<0.0001) [50].”

    From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [50]

    The Results report significant associations in 50% of analyses for fT4 versus 23% for TSH (p < 0.0001), supporting that comparison. The corresponding figure for T3 is 53% for the combined TT3/fT3 category, not 50% for fT3 alone; the cited percentage therefore does not support the sentence's fT3-specific wording. (LLM, conf=0.83)

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Research works printed but not linked: 2

  1. [15]Khosla S 2015 Chapter 65: Hypercalcemia and hypocalcemia. In: Kasper DL, Hauser SL, Jameson JL, Fauci AS, Longo DL, Loscalzo J (eds) Harrison's Principles of Internal Medicine, 19th ed. McGraw Hill, New York, pp, 313– 314
  2. [16]Arlt W 2015 Chapter 406: Disorders of the adrenal cortex. In: Kasper DL, Hauser SL, Jameson JL, Fauci AS, Longo DL, Loscalzo J (eds) Harrison's Principles of Internal Medicine, 19th ed. McGraw Hill, New York, pp. 2316

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Authors
Fitzgerald, S. P., Bean, N. G., Falhammar, H., & Tuke, J.
Affiliations
  • Royal Adelaide Hospital (AU)
  • ARC Centre of Excellence for Mathematical and Statistical Frontiers (AU)
  • Karolinska University Hospital (SE)
Corresponding author
Fitzgerald, Stephen P.
ORCID
Venue
Thyroid®
Publisher
SAGE Publications
Published
2020-12
Volume
30
Issue
12
Pages
1695-1709
ISSN
  • 1050-7256 (ISSN-L)
  • 1557-9077
DOI
10.1089/thy.2019.0535
PMC
PMC7757573
OpenAlex
W3021924627
Cited by
86
References
128
Citations by year
2026: 2 · 2025: 11 · 2024: 14 · 2023: 14 · 2022: 21 · 2021: 14 · 2020: 10
FWCI
2.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Thyroid (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords
free thyroxine, total triiodothyronine, free triiodothyronine, thyroid-stimulating hormone, thyroid function assessment, clinical features, atrial fibrillation, cancer, dementia, frailty, mortality, metabolic syndrome, pregnancy outcomes, TSH reference range
MeSH terms
Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Prognosis, Thyroid Diseases, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, Triiodothyronine, Reproducibility of Results, Biomarkers, Young Adult, Asymptomatic Diseases

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