3,3'-Diiodothyronine concentrations in hospitalized or thyroidectomized patients: results from a pilot study
Open accessAbstract
Objective To determine if various medical conditions affect the serum concentrations of 3,3'-diiodothyronine (3,3'-T2). Methods A total of 100 patients who were recruited from a group of inpatients and outpatients with a diverse range of medical conditions, donated a single blood sample that was assayed for thyroid hormone derivatives using liquid-chromatography tandem mass spectrometry (LC-MS/MS). The associations between 3,3'-T2 concentrations and physiologic data and medical conditions were assessed. Results Higher quartiles of 3,3'-T2 concentrations (quartile 1: 2.01-7.48, quartile 2: 7.74-12.4, quartile 3: 12.5-17, quartile 4: 17.9-45.8 pg/mL) were associated with decreasing occurrence of critical illness (58%, 11%, 0%, 8%), stroke (29%, 7.7%, 4%, 0%), critical care unit hospitalization (75%, 39%, 8.3 %, 12%), and inpatient status (83%, 42%, 8%, 12%) (all P<.001). The same quartiles were associated with increasing frequency of thyroidectomy (4%, 12%, 17%, 60%). In multivariate analyses, after adjustment for age and sex, inpatient status was associated with decreasing concentrations of 3,3'-T2 (46% decrease for inpatients with 95% confidence interval [CI] 32-57%, P<.0001). Thyroidectomy was associated with increasing concentrations of 3,3'-T2 (29% increase (CI 0.5-66%, P = .049). Conclusion We observed associations between inpatient status and reduced 3,3'-T2 concentrations. This appears to be a global change associated with illness, rather than an association with specific medical conditions. We also observed higher 3,3'-T2 concentrations in athyreotic outpatients receiving thyroid-stimulating hormone (TSH) suppression therapy. This demonstrates that there is production of 3,3'-T2 from levothyroxine (LT4) in extrathyroidal tissues. Conversion of thyroxine (T4) to 3,3'-T2 via both triiodothyronine (T3) and reverse triiodothyronine (rT3) pathways may prevent excessive T3 concentrations in such patients.
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Reported serum concentrations for 3,3′-T2 covered a very narrow concentration range between 36 and 68 pM.
“Reported serum concentrations covered a very narrow concentration range between 36 and 68 pM for 3,3′-T2 (see Table 1) (23–29, 32–34).”
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 [27]
The Abstract’s Results report observed 3,3′-T2 concentrations from 2.01 to 45.8 pg/mL across four quartiles—a more than 20-fold span, not the narrow 36–68 pM range claimed. The Methods’ assay methodology also gives a different, narrower reference interval of 6.7–23 pg/mL; it is not presented as the full range of reported concentrations. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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Experimental — accuracy not yet measuredOther groups previously reported major deviations between immunoassay- and LC-MS-based methods for T3, rT3, or 3,3′T2 in human serum.
“Previously, other groups already reported major deviations between immunoassay- and LC-MS-based methods, if T3, rT3, or 3,3′T2 were analyzed in human serum (27, 76, 77).”
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 [27]
The Introduction (page unavailable) says that human serum 3,3′-T2 has been detected by both radioimmunoassay and mass spectrometry. The Methods (page unavailable) describe mass-spectrometry measurements of T3, rT3, and 3,3′-T2, but neither passage reports major deviations between the methods. Searches for assay comparisons and discrepancies found no passage establishing the claimed deviations. (LLM, conf=0.73)
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Cites
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Total and free thyroxine and triiodothyronine: measurement discrepancies, particularly in inpatients
Jonklaas, J., Sathasivam, A., Wang, H., Gu, J., Burman, K. D., & Soldin, S. J. (2014) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2014.06.007 · Cited by 40 · see citing works
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Self-citationBinding Characteristics of Thyroid Hormone Distributor Proteins to Thyroid Hormone Metabolites
Jongejan, R. M. S., Meima, M. E., Visser, W. E., Korevaar, T. I. M., van den Berg, S. A. A., Peeters, R. P., & de Rijke, Y. B. (2022) · Thyroid® · doi:10.1089/thy.2021.0588 · Cited by 20 · see citing works
- Authors
- Jonklaas, J., Sathasivam, A., Wang, H., Finigan, D., Soldin, O. P., Burman, K. D., & Soldin, S. J.
- Affiliations
- Georgetown University (US)
- MedStar Washington Hospital Center (US)
- MedStar Health Research Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Jonklaas, Jacqueline
- Venue
- Endocrine Practice
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 20
- Issue
- 8
- Pages
- 797-807
- ISSN
- 1530-891X (ISSN-L)
- PMC
- PMC4185286
- OpenAlex
- W2061080049
- Cited by
- 15
- References
- 4
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 1 · 2017: 1 · 2016: 2 · 2014: 2
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Endocrine Practice (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR000101)
- National Institute on Aging (R01AG033867)
- National Center for Research Resources (UL1RR031975)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Keywords
- thyroid hormone metabolism, thyroidectomy, inpatient status, levothyroxine, stroke, critical illness, hospitalized patients
- MeSH terms
- Adult, Aged, Diiodothyronines, Female, Hospitalization, Humans, Male, Middle Aged, Pilot Projects, Thyroidectomy, Triiodothyronine, Tandem Mass Spectrometry
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