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Increases in thyrotropin within the near-normal range are associated with increased triiodothyronine but not
Gilad Karavani1, David Strich, Shalom Edri
1Hebrew University Hadassah School of Medicine (G.K.), Jerusalem 91120, Israel; Clalit Health Services (D.S.), Jerusalem 95146, Israel; Shaare Zedek Medical Center (D.S.), Jerusalem 91031, Israel; Health Information Center (S.E.), Clalit Health Services, Jerusalem 95146, Israel; and Hadassah-Hebrew University Medical Center (D.G.), Jerusalem 91120, Israel.
Insights
Thyroid-stimulating hormone (TSH) in near-euthyroid individuals is linked to higher free triiodothyronine (FT3) levels, but not free thyroxine (FT4). This suggests TSH may preferentially boost FT3 production or secretion in vivo.
Area of Science:
- Endocrinology
- Thyroid Physiology
- Hormone Regulation
Background:
- In vitro studies suggest TSH increases T4 to T3 conversion and thyroidal T3 secretion.
- The in vivo significance of these TSH effects, outside of obesity, remains unclear.
Purpose of the Study:
- To investigate if TSH preferentially enhances serum free triiodothyronine (FT3) levels in vivo.
- To analyze the relationship between TSH, free thyroxine (FT4), and FT3 in a pediatric and adolescent population.
Main Methods:
- Analysis of a large database of thyroid test results from children and adolescents without known thyroid disease.
- Exclusion of individuals with thyroid autoantibodies, thyroid hormone use, or medications affecting thyroid function.
- Correlation of FT3, FT4, and FT3/FT4 ratios with TSH, stratified by TSH quartile and body mass index.
Main Results:
- A significant positive linear correlation was found between TSH and FT3 (P < .0001).
- TSH also correlated positively with FT3/FT4 ratios (P < .0001).
- No significant correlation was observed between TSH and FT4.
Conclusions:
- In near-euthyroid subjects, elevated TSH is associated with increased FT3 but not FT4.
- These findings provide in vivo evidence supporting TSH's role in preferentially enhancing T3 production and/or secretion.
Context:
TSH has been shown in vitro to increase conversion of T4 to T3 and to preferentially increase thyroidal T3 secretion. Whether or not these effects are significant in vivo, other than in obesity, is unclear.
Objective:
To test whether the incremental relationships between free T4 (FT4), free T3 (FT3), and TSH are compatible with TSH enhancement of a preferential increase in serum FT3.
Design And Setting:
A large database of pediatric and adolescent thyroid test results drawn in community clinics from children and adolescents without known thyroid disease was analyzed.
Patients And Methods:
RESULTS of FT3, FT4, and TSH were studied anonymously. They were crossed with electronic charts to exclude a history of positive thyroid autoantibodies and use of thyroid hormone preparations, antithyroid medication, or drugs known to affect thyroid function. All samples from patients appearing more than once in the database were removed. After exclusions, 3276 samples remained. FT4, FT3, and the FT3/FT4 ratios were correlated with TSH for the entire group, and the same parameters were segregated by TSH quartile. RESULTS were stratified for body mass index and studied separately in a normal-weight subgroup.
Main Outcome Measures:
Stepwise correlations of FT4, FT3, and FT3/FT4 ratios with TSH.
Results:
There was a significant positive linear correlation of TSH with FT3 and FT3/FT4 ratios (R = 0.12; P < .0001 in both), but not with FT4.
Conclusion:
Within the near-euthyroid range, increasing TSH levels are associated with increasing FT3 levels, without an increase in FT4. This provides in vivo support for TSH enhancing preferentially T3 production and/or secretion.
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