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Cited by 124Thyroid Disorders and TreatmentsClinical Laboratory Practices and Quality ControlThyroid and Parathyroid Surgery

DIAGNOSIS OF ENDOCRINE DISEASE: How reliable are free thyroid and total T3 hormone assays?

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Welsh, Kerry J, Soldin, Steven J·2016·European Journal of Endocrinology
DOI 10.1530/eje-16-0193PMC PMC5113291
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Abstract

Hypothyroidism is a very common disorder worldwide, for which the usual treatment is monotherapy with levothyroxine (L-T 4 ). However, a number of patients treated with L-T 4 continue to report symptoms of hypothyroidism despite seemingly normal levels of thyroid-stimulating hormone (TSH), free-T 3 (FT 3 ) and free-T 4 (FT 4 ) measured by immunoassay. This review summarizes the limitations of the immunoassays commonly used to measure thyroid hormone levels and emphasizes the advantages of the role of liquid chromatography-tandem mass spectrometry (LC-MS/MS). Immunoassays for free thyroid hormone are affected by alterations in serum binding proteins that occur in many physiological and disease states. Multiple studies show falsely normal values for T 3 , FT 3 and FT 4 by immunoassay that are below the reference interval when measured by (ultrafiltration) LC-MS/MS, a reference method. We suggest evaluation of thyroid hormone levels by ultrafiltration LC-MS/MS for patients who continue to experience hypothyroid symptoms on LT-4. This may help identify the approximately 20% subset of patients who would benefit from addition of T 3 to their treatment regimen (combination therapy).

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  • Several laboratories have developed procedures to accurately determine total T4 and total T3 in human plasma or serum and largely agree on concentration ranges, but this consensus has not been achieved for most other TH metabolites.

    “While meanwhile several laboratories developed procedures to accurately determine total T4 and total T3 in human plasma or serum and largely agree on concentrations ranges (25, 67–73), this consensus has not been achieved yet for most of the other TH metabolites, which occur at much lower concentrations.”

    From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [68]

    The Emerging role of LC-MSMS section describes sensitive, precise methods for measuring thyroid hormones, and the Clinical implications section says LC-MSMS measurement is available at most major reference laboratories. The paper does not establish that laboratories largely agree on total T4 and total T3 concentration ranges, or compare that agreement with results for most other thyroid-hormone metabolites. It instead reports discrepancies between commonly used immunoassays and LC-MSMS, particularly at low concentrations. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Authors
Welsh, K. J., & Soldin, S. J.
Affiliations
National Institutes of Health (US)
Corresponding author
Soldin, Steven J
ORCID
Welsh, Kerry J
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2016-12
Volume
175
Issue
6
Pages
R255-R263
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje-16-0193
PMC
PMC5113291
OpenAlex
W2531703351
Cited by
124
References
11
Citations by year
2026: 8 · 2025: 15 · 2024: 12 · 2023: 8 · 2022: 17 · 2021: 14 · 2020: 19 · 2019: 12 · 2018: 11 · 2017: 7 · 2016: 1
FWCI
1.45
Type
journal article
Language
en
Open access
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • NIH Clinical Center (ZIACL010355)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Physiology › Clinical Laboratory Practices and Quality Control
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
Keywords
hypothyroidism, levothyroxine, free T3, free thyroxine, combination thyroid hormone therapy
MeSH terms
Chromatography, Liquid, Endocrine System Diseases, Humans, Hypothyroidism, Thyroxine, Triiodothyronine, Reproducibility of Results, Tandem Mass Spectrometry

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