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Cited by 26Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryClinical Laboratory Practices and Quality Control

Effect of Thyroid Function Variations Within the Laboratory Reference Range on Health Status, Mood, and Cognition in Levothyroxine-Treated Subjects

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Samuels, Mary H., Kolobova, Irina, Smeraglio, Anne, Niederhausen, Meike, Janowsky, Jeri S., Schuff, Kathryn G.·2016·Thyroid®
DOI 10.1089/thy.2016.0141PMC PMC5036318
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Abstract

Background: There has been recent debate within the thyroid field regarding whether current upper limits of the thyrotropin (TSH) reference range should be lowered. This debate can be better informed by investigation of whether variations in thyroid function within the reference range have clinical effects. One important target organ for thyroid hormone is the brain, but little is known about variations in neurocognitive measures within the reference range for thyroid function. Methods: This was a cross-sectional study of 132 otherwise healthy hypothyroid subjects receiving chronic replacement therapy with levothyroxine (LT4) who had TSH levels across the full span of the laboratory reference range (0.34–5.6 mU/L). Subjects underwent detailed tests of health status, mood, and cognitive function, with an emphasis on memory and executive functions. Results: Subjects with low-normal (≤2.5 mU/L) and high-normal (>2.5 mU/L) TSH levels did not differ on most tests of health status, mood, or cognitive function, and there were no correlations between TSH, free T4, or free T3 levels and most outcomes. There was, however, a suggestion that thyroid function affected performance on the Iowa Gambling Task, which mimics real life decision-making. Subjects with low-normal TSH levels made more advantageous decisions than those with high-normal TSH levels. Conclusions: Variations in thyroid function within the laboratory reference range do not appear to have clinically relevant effects on health status, mood, or memory in LT4 treated subjects. However, decision making, which encompasses many executive functions, may be affected. Unless further studies strengthen this finding, these data do not support narrowing the TSH reference range.

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  • Hypothyroid patients treated with levothyroxine monotherapy tend to have lower serum T3 concentrations and higher T4 levels than healthy people.

    “Hypothyroid patients treated with levothyroxine monotherapy tend to have lower serum T3 concentrations and higher T4 levels than healthy people. 42,50”

    From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [50]

    The Results (page unavailable) report low free T3 in 70 of 132 levothyroxine-treated subjects, supporting the low-T3 portion of the claim. The study compares treated subjects by TSH level, not with healthy people, and reports no finding that their T4 levels are higher than healthy people's. (LLM, conf=0.87)

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Research works printed but not linked: 11

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Authors
Samuels, M. H., Kolobova, I., Smeraglio, A., Niederhausen, M., Janowsky, J. S., & Schuff, K. G.
Affiliations
  • Oregon Health & Science University (US)
  • East Carolina University (US)
  • Stanford Medicine (US)
  • Saturday Academy (US)
Corresponding author
Samuels, Mary H.
ORCID
Venue
Thyroid®
Publisher
SAGE Publications
Published
2016-09
Volume
26
Issue
9
Pages
1173-1184
ISSN
  • 1050-7256 (ISSN-L)
  • 1557-9077
DOI
10.1089/thy.2016.0141
PMC
PMC5036318
OpenAlex
W2485397563
Cited by
26
References
45
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 3
FWCI
4.02
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Thyroid (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Oregon Health and Science University
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK075496)
  • National Center for Research Resources (K01RR024120)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
Keywords
TSH reference range, levothyroxine, hypothyroidism, thyroid function, cognitive function, memory, executive function, mood, health status, Iowa Gambling Task, decision-making, free thyroxine, free T3
MeSH terms
Affect, Cognition, Cross-Sectional Studies, Female, Health Status, Humans, Hypothyroidism, Male, Memory, Neuropsychological Tests, Reference Values, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, Triiodothyronine, Hormone Replacement Therapy, Executive Function

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