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Cited by 17Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryHormonal and reproductive studies

Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study

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Schmidt, Ulla, Nygaard, Birte, Jensen, Ebbe Winther, Kvetny, Jan, Jarløv, Anne, Faber, Jens·2013·Endocrine Connections
DOI 10.1530/ec-12-0064PMC PMC3680960
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Abstract

BACKGROUND: A recent randomized controlled trial suggests that hypothyroid subjects may find levothyroxine (l-T4) and levotriiodothyronine combination therapy to be superior to l-T4 monotherapy in terms of quality of life, suggesting that the brain registered increased T3 availability during the combination therapy. HYPOTHESIS: Peripheral tissue might also be stimulated during T4/T3 combination therapy compared with T4 monotherapy. METHODS: Serum levels of sex hormone-binding globulin (SHBG), pro-collagen-1-N-terminal peptide (PINP), and N-terminal pro-brain natriuretic peptide (NT-proBNP) (representing hepatocyte, osteoblast, and cardiomyocyte stimulation respectively) were measured in 26 hypothyroid subjects in a double-blind, randomized, crossover trial, which compared the replacement therapy with T4/T3 in combination (50 μg T4 was substituted with 20 μg T3) to T4 alone (once daily regimens). This was performed to obtain unaltered serum TSH levels during the trial and between the two treatment groups. Blood sampling was performed 24 h after the last intake of thyroid hormone medication. RESULTS: TSH remained unaltered between the groups ((median) 0.83 vs 1.18 mU/l in T4/T3 combination and T4 monotherapy respectively; P=0.534). SHBG increased from (median) 75 nmol/l at baseline to 83 nmol/l in the T4/T3 group (P=0.015) but remained unaltered in the T4 group (67 nmol/l); thus, it was higher in the T4/T3 vs T4 group (P=0.041). PINP levels were higher in the T4/T3 therapy (48 vs 40 μg/l (P<0.001)). NT-proBNP did not differ between the groups. CONCLUSIONS: T4/T3 combination therapy in hypothyroidism seems to have more metabolic effects than the T4 monotherapy.

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  • T3 may enhance metabolic effects in peripheral tissues more directly than T4, thus ameliorating hypothyroid symptoms.

    “T3, the more active hormone, may enhance metabolic effects in peripheral tissues more directly than T4, a prohormone, thus ameliorating hypothyroid symptoms [29].”

    From Evaluating the effectiveness of combined T4 and T3 therapy or desiccated thyroid versus T4 monotherapy in hypothyroidism: a systematic review and meta-analysis (2024) · cites this paper as [29]

    The Introduction describes T3 as the main metabolically active thyroid hormone, and the Abstract Conclusions report greater metabolic effects with T4/T3 combination therapy than with T4 alone. The Introduction also reports better quality-of-life, depression, and anxiety ratings in an earlier trial, but this paper does not establish that peripheral metabolic effects caused those improvements; its Conclusion says the benefits of its findings remain unclear. (LLM, conf=0.83)

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  • Some studies comparing combination T3/T4 treatment to L-T4 monotherapy have evaluated other parameters such as serum SHBG or markers of bone turnover, but a practical and useful marker has not been identified.

    “Some studies comparing physiologic effects of combination T3/T4 treatment to L-T4 monotherapy have evaluated other parameters reflective of thyroid status such as serum SHBG or markers of bone turnover (18) but a practical and useful marker has not been identified.”

    From Can Reverse T3 Assay Be Employed to Guide T4 vs. T4/T3 Therapy in Hypothyroidism? (2019) · cites this paper as [18]

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Research works printed but not linked: 2

  1. [1]Visser TH. Biosynthesis, transport, metabolism and actions of thyroid hormones. In Oxford Textbook of Endocrinology and Diabetes, 1st edn, ch 3, pp 287–301. Eds JAH Wass & SM Shalet. New York, NY: Oxford University Press, 2002.
  2. [2]Ingbar SH & Borges M. Peripheral metabolism of the thyroid hormones. In International Symposium on Free Thyroid Hormones, 1st edn, pp 17–27. Ed RP Ekins. Amsterdam: Excerpta Medica, 1978.

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Authors
Schmidt, U., Nygaard, B., Jensen, E. W., Kvetny, J., Jarløv, A., & Faber, J.
Affiliations
University of Copenhagen (DK)
Corresponding author
Faber, Jens
ORCID
Venue
Endocrine Connections
Publisher
Bioscientifica
Published
2013-03
Volume
2
Issue
1
Pages
55-60
ISSN
2049-3614 (ISSN-L)
DOI
10.1530/ec-12-0064
PMC
PMC3680960
OpenAlex
W2164628897
Cited by
17
References
22
Citations by year
2025: 1 · 2024: 2 · 2021: 5 · 2020: 2 · 2019: 1 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 2
FWCI
1.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine Connections (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
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 › Hormonal and reproductive studies
Keywords
hypothyroidism, levothyroxine, thyroid hormone replacement, sex hormone-binding globulin, NT-proBNP, thyroid-stimulating hormone, bone turnover, cardiac function

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