rT3 and Inflammation in Hashimoto's Thyroiditis

April 3, 2026 updated by: Esra Yıldırım Demirçin, Ankara City Hospital Bilkent

Investigation of Systemic Inflammation Markers and Reverse T3 Levels in Patients With Hashimoto's Thyroiditis

Hashimoto's thyroiditis (HT) is characterized by an enlarged thyroid gland infiltrated with lymphocytes. The incidence of HT is estimated to be 0.3-1.5 cases per 1000 people, with a female/male predominance of 7-10:1. It has a strong association with other autoimmune diseases. The autoimmune presentation of HT relies on the interaction between environmental factors and genetic background such as human leukocyte antigen (HLA), T lymphocyte-associated 4 (CTLA-4), protein tyrosine phosphatase, non-receptor type 22 (PTPN22) genes, and X chromosome inactivation patterns, leading to an imbalance between self-tolerance mechanisms maintained by regulatory T and B lymphocytes. Furthermore, genetic polymorphisms in self antigens, cytokines and their receptors (e.g., interleukin 2 receptor IL2R), estrogen receptors, adhesion molecules (CD14, CD40), the promoter region of selenoprotein S, and apoptosis-related gene products have been associated with thyroid autoimmunity. Genetic factors account for 70-80% of the risk in the development of Hashimoto's disease, while environmental factors account for 20-30%. HT is diagnosed based on clinical symptoms, antithyroid antibodies, and histological features. Ultrasound imaging of the thyroid gland can aid in differential diagnosis, especially in patients with thyroid peroxidase antibody (TPOAb) negative HT. Ultrasound features of HT include decreased echogenicity, heterogeneity, hypervascularity, and the presence of small cysts. Hashimoto's disease can have stages presenting with hyperthyroidism, euthyroidism, and hypothyroidism. In diagnosis, hyperthyroidism, euthyroidism, and hypothyroidism are determined based on measurements of thyroid-stimulating hormone (TSH), free T4 (sT4), and free T3 (sT3), which are biochemical parameters used.

Hashimoto's thyroiditis is an inflammatory condition affecting the thyroid gland, and patients develop clinical thyroid dysfunction depending on the duration of the disease. HT causes atrophy of the thyroid parenchyma through autoimmune processes and chronic inflammation. This leads to an increase in inflammatory load in patients with Hashimoto's. Studies have shown that inflammation associated with HT may not be limited to the thyroid gland and can trigger a systemic inflammatory process even in patients with normal thyroid function.

Reverse T3 (3,3',5'-triiodothyronine or rT3) is the third most abundant iodothyronine circulating in human blood and is produced by deiodination of the inner ring of the prohormone thyroxine (T4). Unlike the more abundant and active metabolite T3, serum rT3 measurement has not yet found routine clinical application. While rT3 has little effect on nuclear thyroid hormone receptors (THR), it has been shown to interact with more recently identified non-nuclear thyroid hormone receptors. rT3 analysis is useful in confirming the diagnosis of non-thyroid disease syndrome, in measuring the T3/rT3 ratio in insulin-resistant patients, and in hemangiomas where iodothyronine deiodinase type 3 (DIO3) overexpression causes an increase in rT3. rT3 analysis also has the potential to identify situations where the diagnosis of hypothyroidism may be masked by concomitant drug treatment or potentially function as a marker of drug effect.

The aim of this study is to compare rT3 levels in anti-TPO-positive euthyroid Hashimoto's patients with or without thyroid hormone replacement therapy. The impact of drug use on hormone levels in these patient groups will be investigated. Additionally, systemic inflammatory markers derived from the complete blood count will be examined to determine the systemic inflammatory load in these patients.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

179

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Healthy Control

Description

Inclusion Criteria:

  • Between the ages of 18-50, anti-TPO negative, normal thyroid hormone levels, not pregnant or breastfeeding, no chronic disease or acute infection.

Exclusion Criteria:

  • Patients with positive anti-TPO results,

TSH, sT4, and sT3 hormone levels outside the reference range,

pregnant or breastfeeding patients,

those with chronic diseases,

those with signs of acute infection

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Healty control
anti-TPO negative, no chronic disease, euthyroid
Use medicine with Hashimoto thyroiditis
diagnosed with Hashimoto's thyroiditis, anti-TPO positive, euthyroid, thyroid hormone replacement therapy recipient
Not use medicine with Hashimoto thyroiditis
diagnosed with Hashimoto's thyroiditis, anti-TPO positive, euthyroid, not receiving thyroid hormone replacement therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
reverse T3 investigation inflammatory marker investigation
Time Frame: one month after ethics committee approval
one month after ethics committee approval

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ankara City Hospital Bilkent

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 20, 2025

Primary Completion (Actual)

September 22, 2025

Study Completion (Actual)

September 22, 2025

Study Registration Dates

First Submitted

March 30, 2026

First Submitted That Met QC Criteria

March 30, 2026

First Posted (Actual)

April 3, 2026

Study Record Updates

Last Update Posted (Actual)

April 8, 2026

Last Update Submitted That Met QC Criteria

April 3, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TABED 2-25-1436

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The study involves limited participant-level data and no plan exists for external data sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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