Evidence map›Paper›PMID 34185829›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2021

Comparative Effectiveness of Levothyroxine, Desiccated Thyroid Extract, and Levothyroxine+Liothyronine in Hypothyroidism.

Mohamed K M Shakir, Daniel I Brooks, Elizabeth A McAninch, Tatiana L Fonseca, Vinh Q Mai, Antonio C Bianco, Thanh D Hoang

Abstract readComparative StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 5 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

50 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
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  3. Treatment Preferences in Patients With Hypothyroidism.The Journal of clinical endocrinology and metabolism · 2025
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  9. Genetics of Thyroid Function: Relevance for Biology and Disease Management.The Journal of clinical endocrinology and metabolism · 2025
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Mohamed K M ShakirWalter Reed National Military Medical Center, Bethesda, MD 20889-5600, USA.
Daniel I BrooksWalter Reed National Military Medical Center, Bethesda, MD 20889-5600, USA.
Elizabeth A McAninchDivision of Endocrinology and Metabolism, Rush University Medical Center, Chicago, IL 60612, USA.
Tatiana L FonsecaSection of Adult and Pediatric Endocrinology, University of Chicago, Chicago, IL 60637, USA.
Vinh Q MaiWalter Reed National Military Medical Center, Bethesda, MD 20889-5600, USA.
Antonio C BiancoSection of Adult and Pediatric Endocrinology, University of Chicago, Chicago, IL 60637, USA.ORCID 0000-0001-7737-6813
Thanh D HoangWalter Reed National Military Medical Center, Bethesda, MD 20889-5600, USA.ORCID 0000-0001-7437-5604

Funding

Thyroid-adrenergic synergism and adaptive thermogenesisR01DK065055 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BIANCO, ANTONIO C · 2005 to 2021
$4.4M
NIDDK NIH HHS R01 DK065055
6 · The paper itself

Abstract

introductionStudies comparing levothyroxine (LT4) therapy with LT4 + liothyronine (LT3) or desiccated thyroid extract (DTE) did not detect consistent superiority of either treatment. Here, we investigated these therapies, focusing on the whole group of LT4-treated hypothyroid patients, while also exploring the most symptomatic patients. METHODOLOGY: Prospective, randomized, double-blind, crossover study of 75 hypothyroid patients randomly allocated to 1 of 3 treatment arms, LT4, LT4 + LT3, and DTE, for 22 weeks. The primary outcomes were posttreatment scores on the 36-point thyroid symptom questionnaire (TSQ-36), 12-point quality of life general health questionnaire (GHQ-12), the Wechsler memory scale-version IV (VMS-IV), and the Beck Depression Inventory (BDI). Secondary endpoints included treatment preference, biochemical and metabolic parameters, etiology of hypothyroidism, and Thr92Ala-DIO2 gene polymorphism. Analyses were performed with a linear mixed model using subject as a random factor and group as a fixed effect.

resultsSerum TSH remained within reference range across all treatment arms. There were no differences for primary and secondary outcomes, except for a minor increase in heart rate caused by DTE. Treatment preference was not different and there were no interferences of the etiology of hypothyroidism or Thr92Ala-DIO2 gene polymorphism in the outcomes. Subgroup analyses of the 1/3 most symptomatic patients on LT4 revealed strong preference for treatment containing T3, which improved performance on TSQ-36, GHQ-12, BDI, and visual memory index (VMS-IV component).

conclusionsAs a group, outcomes were similar among hypothyroid patients taking DTE vs LT4 + T3 vs LT4. However, those patients that were most symptomatic on LT4 preferred and responded positively to therapy with LT4 + LT3 or DTE.

Indexed as

AdultAgedCross-Over StudiesDesiccationDouble-Blind MethodFemaleHormone Replacement TherapyHumansHypothyroidismMaleMiddle AgedPlacebosProspective StudiesQuality of LifeSurveys and QuestionnairesThyroid GlandPlacebosThyroxineTissue ExtractsTriiodothyroninedesiccated thyroid extracthypothyroidismlevothyroxineliothyroninequality of life

Identifiers

PMID34185829
PMCPMC8530721

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.