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Cited by 87Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryRegulation of Appetite and Obesity

Effects of levothyroxine replacement or suppressive therapy on energy expenditure and body composition

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Samuels, Mary H., Kolobova, Irina, Smeraglio, Anne, Peters, Dawn, Purnell, Jonathan Q., Schuff, Kathryn G.·2016·Thyroid
DOI 10.1089/thy.2015.0345PMC PMC4790206
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Abstract

BACKGROUND: Thyrotropin (TSH)-suppressive doses of levothyroxine (LT4) have adverse effects on bone and cardiac function, but it is unclear whether metabolic function is also affected. The objective of this study was to determine whether women receiving TSH-suppressive LT4 doses have alterations in energy expenditure or body composition. METHODS: This study was a cross-sectional comparison between three groups of women: 26 women receiving chronic TSH-suppressive LT4 doses, 80 women receiving chronic replacement LT4 doses, and 16 untreated euthyroid control women. Subjects underwent measurements of resting energy expenditure (REE), substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity energy expenditure by accelerometer; caloric intake by 24-hour diet recall; and body composition by dual X-ray absorptiometry. RESULTS: REE per kilogram lean body mass in the LT4 euthyroid women was 6% lower than that of the LT4-suppressed group, and 4% lower than that of the healthy control group (p = 0.04). Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with the other two groups (p = 0.007). The groups of subjects did not differ in other measures of energy expenditure, caloric intake, or body composition. CONCLUSIONS: LT4 suppression therapy does not adversely affect energy expenditure or body composition in women. However, LT4 replacement therapy is associated with a lower REE, despite TSH levels within the reference range. This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.

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Written from the paper’s full text.

TL;DR

In women, chronic TSH-suppressive levothyroxine (LT4) therapy did not adversely affect energy expenditure or body composition compared with healthy controls. However, LT4 replacement at euthyroid TSH levels was associated with lower resting energy expenditure (REE), possibly related to lower free triiodothyronine (fT3) levels.

Key findings

  • REE per kilogram lean body mass was 6% lower in LT4 euthyroid women than in LT4-suppressed women and 4% lower than in healthy controls (28.9 ± 0.3 vs. 30.7 ± 0.8 and 30.2 ± 0.7 kcal/kg/day; p = 0.04 in Table 2; text reports p = 0.03 for the contrast).
  • fT3 levels were 10% lower in LT4 euthyroid women than in the other two groups (216 ± 5 vs. 238 ± 7 and 240 ± 11 pg/dL; p = 0.007), and REE/kg was positively correlated with fT3 (p = 0.03) but not with fT4 or TSH.
  • LT4-suppressed women had similar metabolic parameters to healthy controls, with no differences among groups in substrate oxidation, thermic effect of food, caloric intake, physical activity, or body composition.
  • LT4-suppressed women took higher LT4 doses (1.92 ± 0.10 vs. 1.50 ± 0.07 µg/kg/day) and had lower TSH (0.14 ± 0.02 vs. 2.08 ± 0.14 and 2.13 ± 0.22 mIU/L) and higher fT4 (2.27 ± 0.09 vs. 1.63 ± 0.04 and 1.41 ± 0.07 ng/dL) than the other groups.

Methods

  • Cross-sectional comparison of three groups of women: 26 receiving chronic TSH-suppressive LT4 doses, 80 receiving chronic replacement LT4 doses, and 16 untreated euthyroid controls, matched by age and menstrual status.
  • Measurements included REE, substrate oxidation, and thermic effect of food by indirect calorimetry; physical activity by accelerometer; caloric intake by 24-hour diet recall; body composition by dual X-ray absorptiometry; and serum TSH, fT4, and fT3.
  • Main analysis used linear models for repeated measures (Proc Mixed) adjusted for age and estrogen status, with TEF models also adjusted for lean body mass, percent fat, and meal size; a staged multiple-comparison approach was used.

Limitations

  • Stated: the cross-sectional single-time-point design does not allow determination of causality or trends over time.
  • Stated: the LT4-treated groups were heterogeneous in underlying diagnosis, severity and duration of hypothyroidism, and LT4 dose requirements; some subjects had minor dose adjustments 3–6 months before study, 10 LT4-suppressed subjects were over-treated for benign disease, TSH suppression levels varied, residual thyroid tissue may have contributed endogenous T3, and limited sample size prevented subgroup analyses.
  • Stated: the healthy control and LT4-suppressed groups were relatively small, raising the possibility of missed true differences; selection bias is possible; only women were studied, so findings may not apply to men. Evident: total energy expenditure in free-living subjects was not measured, as the paper notes.

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Crossref · 10.1089/thy.2015.0345

Cites

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Claims the paper makes

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  • Findingown data
    § Energy expenditure and body composition

    Among the three groups of women, there were no differences in body composition (lean body mass, fat mass, % fat mass).

    “There were no differences in substrate oxidation rates, TEF parameters (total daily TEF, peak TEF, time to peak TEF), or body composition (lean body mass, fat mass, % fat mass) between the three groups.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Energy expenditure and body composition

    In women, resting energy expenditure per kilogram lean body mass was not correlated with serum free thyroxine (fT4) or thyrotropin (TSH) levels.

    “REE (REE/kg) was positively correlated with serum fT3 levels ( p = 0.03), but not with fT4 or TSH levels.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition

    In women, mean free triiodothyronine (fT3) levels were lower in the LT4 euthyroid group than in the healthy control and LT4-suppressed groups.

    “Free triiodothyronine (fT3) levels were directly correlated with REE, and were 10% lower in the LT4 euthyroid women compared with the other two groups ( p = 0.007).”
    • Also stated in: § Clinical parameters and thyroid function tests · plain
      “Mean fT3 levels were lower in the LT4 euthyroid group compared with the other two groups (216 -5 vs. 240 -11 and 238 -7 pg/dL).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Energy expenditure and body composition

    Among the three groups of women, there were no differences in thermic effect of food (TEF) parameters.

    “There were no differences in substrate oxidation rates, TEF parameters (total daily TEF, peak TEF, time to peak TEF), or body composition (lean body mass, fat mass, % fat mass) between the three groups.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Effects of Levothyroxine Replacement or Suppressive Therapy on Energy Expenditure and Body Composition

    In women, resting energy expenditure per kilogram lean body mass was lower in the LT4 euthyroid group than in the healthy control group.

    “and 4% lower than that of the healthy control group ( p = 0.04).”
    • Also stated in: § Energy expenditure and body composition · plain
      “Significant differences were seen for REE corrected for lean body mass (30.2 -0.7 kcal/kg/day in controls, 28.9 -0.3 in LT4 euthyroid, and 30.7 -0.8 in LT4suppressed groups; p = 0.03 for difference between the LT4 euthyroid and the other two groups).”
    Quote in the paperSubstantial claim
  • May combine two claims. 26
  • Classified as probably not a substantial claim. 23

  • May combine two claims.

    Findingown data
    § Discussion

    LT4 euthyroid women had lower REE/kg lean body mass than LT4-suppressed women (6% lower) and healthy control women (4% lower).

    “An unexpected finding was the lower REE/kg lean body mass observed in LT4 euthyroid women, which was 6% lower than in the LT4-suppressed group and 4% lower than in the healthy control group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    Mean BMI was 27.5 kg/m2 in the healthy control group and 27.3 kg/m2 in the LT4 euthyroid group.

    “However, mean BMIs were 27.5 kg/m 2 in the healthy control group and 27.3 kg/m 2 in the LT4 euthyroid group”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    LT4 euthyroid women had lower REE than LT4-suppressed women and a trend toward lower REE than healthy controls.

    “On the other hand, LT4 euthyroid women had lower REE than LT4-suppressed women had, as well as a trend toward lower REE than healthy controls.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data
    § Clinical parameters and thyroid function tests

    LT4-suppressed women were taking higher LT4 doses than LT4 euthyroid women.

    “As expected, LT4-suppressed subjects were taking higher LT4 doses than LT4 euthyroid subjects were (1.50 -0.07 vs. 1.92 -0.10 l g/kg/day).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Study design and conductnone given
    § Discussion

    Subjects were well matched for age, sex, menopausal status, TSH levels, and baseline BMI.

    “Subjects were well matched for age, sex, menopausal status, TSH levels, and baseline BMI.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Statistical methods

    To limit the effect of multiple comparisons, an initial assessment of whether there was evidence of a difference among groups for any of the related measures was obtained before pairwise comparisons.

    “To limit the effect of multiple comparisons, two assessments were made prior to conducting pairwise comparisons between groups: An initial assessment of whether there was evidence of a difference among groups for any of the related measures was obtained.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Clinical parameters and thyroid function tests

    TSH levels were not significantly different at the baseline visit compared to levels over the previous three months.

    “TSH levels were not significantly different at the baseline visit compared to levels over the previous three months, including at the screening visit (data not shown).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Discussion

    Most subjects had been on stable doses of LT4 for at least six months, but a few had minor dose adjustments three to six months prior to the study.

    “Most of the subjects had been on stable doses of LT4 for at least six months, but a few had minor dose adjustments three to six months prior to the study”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given
    § Discussion

    The relatively large number of comparisons for the number of subjects was accounted for by performing group analyses together, progressing to pairwise comparisons only in the presence of significant group effects and examining subscales only when there was evidence of interaction.

    “While there is a relatively large number of comparisons for the number of subjects, this was accounted for by performing group analyses together, progressing to pairwise comparisons only in the presence of significant group effects and examining subscales only when there was evidence of interaction.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given
    § Discussion

    The present data represent the largest group of LT4-treated subjects studied using specific measures of energy expenditure and body composition to date, and the only study to compare LT4-treated euthyroid subjects with matched controls and LT4-suppressed subjects.

    “Although not a prospective study, the present data represent the largest group of LT4-treated subjects studied using specific measures of energy expenditure and body composition to date, and the only study to compare LT4-treated euthyroid subjects with matched controls and LT4-suppressed subjects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation
    § Discussion

    Serum T3 levels are higher in endogenous subclinical hyperthyroidism, which may explain the differing effects on metabolic function and body composition compared with exogenous LT4 suppression.

    “Serum T3 levels are higher in endogenous subclinical hyperthyroidism, which may explain the differing effects on metabolic function and body composition compared with exogenous LT4 suppression (20).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Study design and conductnone given
    § Discussion

    Sensitive, validated measures were utilized to provide a metabolic phenotype of the subjects.

    “Sensitive, validated measures were utilized to provide a ''metabolic phenotype'' of these subjects.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    Short-term studies of supraphysiologic thyroid hormone doses uniformly showed increased resting and 24-hour energy expenditure, but were too brief to document changes in body composition.

    “These studies uniformly showed increased resting and 24-hour energy expenditure, but were too brief to document changes in body composition.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [3] source

      Not checked in the free run.

    • cites [4] Barbe P, 2001, FASEB J source

      Not checked in the free run.

    • cites [5] source

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    • cites [6] source

      Not checked in the free run.

    • cites [7] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Discussion

    LT4-treated subjects had received LT4 for variable time periods, and the mean duration of therapy was longer in the LT4 euthyroid group compared with the LT4-suppressed group.

    “LT4-treated subjects had received LT4 for variable time periods, and the mean duration of therapy was longer in the LT4 euthyroid group compared with the LT4-suppressed group.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given
    § Discussion

    Two carefully matched control groups were included: healthy euthyroid women on no LT4 therapy, and women with normal TSH levels on LT4 therapy for hypothyroidism.

    “Two carefully matched control groups were included: healthy euthyroid women on no LT4 therapy, and women with normal TSH levels on LT4 therapy for hypothyroidism.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data
    § Clinical parameters and thyroid function tests

    Body mass index, blood pressure, and heart rate were not different among the three groups.

    “Body mass index (BMI), blood pressure, and heart rate were not different among the groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning
    § Discussion

    The study's cross-sectional design at a single time point does not allow for determination of causality or trends over time.

    “The major limitation is its cross-sectional design at a single time point, which does not allow for determination of causality or trends over time.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Diet intake and physical activity

    Moderate and vigorous activity measures were combined because energy expenditure and percent time spent in vigorous activity were very low in all groups.

    “Moderate and vigorous activity measures were combined because energy expenditure and percent time spent in vigorous activity were very low in all groups.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Diet intake and physical activity

    Mixed models were adjusted for age and menstrual status.

    “Mixed models were adjusted for age and menstrual status.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Diet intake and physical activity

    Physical activity values were available for 15 healthy controls, 79 LT4 euthyroid subjects, and all 26 LT4-suppressed subjects due to technical limitations with an Actical device.

    “Physical activity values were available for 15 healthy controls, 79 LT4 euthyroid subjects, and all 26 LT4-suppressed subjects due to technical limitations with an Actical device.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    Thyroid hormone plays a critical role in determining energy expenditure, body mass, and body composition.

    “LT4 suppression therapy may also affect metabolic function, since thyroid hormone plays a critical role in determining energy expenditure, body mass, and body composition (2).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Discussion

    The limited sample size did not allow for subgroup analysis of these variables.

    “The limited sample size did not allow for subgroup analysis of these variables, which would be important to investigate in the future.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Introduction

    Prior long-term LT4 suppression studies did not find significant changes in resting energy expenditure, but some demonstrated effects on body weight or composition.

    “While significant changes in resting energy expenditure (REE) were not found, some did demonstrate effects on body weight or composition.”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [8] source

      Not checked in the free run.

    • cites [9] source

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    • cites [10] source

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    • cites [11] source

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    • cites [12] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Statistical methods

    All statistical models included adjustments for age and estrogen status.

    “All models included adjustments for age and estrogen status.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Diet intake and physical activity

    Diet intake values were available for all 16 healthy controls, 79 LT4 euthyroid subjects, and 25 LT4-suppressed subjects due to limitations in scheduling diet recalls.

    “Diet intake values were available for all 16 healthy controls, 79 LT4 euthyroid subjects, and 25 LT4-suppressed subjects due to limitations in scheduling diet recalls.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Diet intake and physical activity

    Daily physical activity energy expenditure for sedentary activities is not shown because the Actical software sets sedentary activities at zero energy expenditure.

    “Daily physical activity energy expenditure for sedentary activities is not shown because the Actical software sets sedentary activities at zero energy expenditure.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data
    § Statistical methods

    Analyses of thermic effect of food variables included adjustments for lean body mass, percent fat, and meal size.

    “In addition, adjustments for lean body mass, percent fat, and meal size were included in the analyses of TEF variables.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Discussion

    The study has strengths including two well-matched control groups and sensitive measures of energy expenditure, body composition, diet intake, and physical activity.

    “There are a number of strengths to this study, including the two well-matched control groups and sensitive measures of energy expenditure, body composition, diet intake, and physical activity.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Discussion

    Among subjects in the LT4-suppressed group, 10 had TSH levels < 0.1 mIU/L, while 16 had TSH levels between 0.1 and 0.33 mIU/L.

    “Among the subjects in the LT4-suppressed group, 10 had TSH levels &lt; 0.1 mIU/L, while 16 had TSH levels between 0.1 and 0.33 mIU/L.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Discussion

    Only women were studied, and it is not clear whether the findings would apply to men treated with LT4.

    “Finally, only women were studied, and it is not clear whether the findings would apply to men treated with LT4.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given
    § Discussion

    The two LT4-treated groups were heterogeneous in underlying diagnosis, severity and duration of hypothyroidism, and LT4 dose requirements.

    “These two groups were heterogeneous in terms of underlying diagnosis, severity and duration of hypothyroidism, and LT4 dose requirements.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Discussion

    Population-based studies in non-LT4-treated euthyroid subjects have reported that resting, sleeping, or 24-hour energy expenditure are directly correlated with free or total thyroid hormone levels, and that TSH is inversely correlated with basal oxygen consumption.

    “Population-based studies in non-LT4-treated euthyroid subjects have reported that resting, sleeping, or 24-hour energy expenditure are directly correlated with free or total thyroid hormone levels (21-23), and that TSH is inversely correlated with basal oxygen consumption, a marker of energy expenditure (24).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [21] Astrup A, 1992, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [22] source

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    • cites [23] Toubro S, 1996, J Clin Endocrinol Metab

      Not checked in the free run.

    • cites [24] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    Compared with euthyroid controls, LT4-treated thyroidectomized subjects gained an excess of 1.8 kg over one year, and LT4-treated hypothyroid subjects gained an excess of 0.9 kg.

    “Compared with euthyroid controls, LT4-treated thyroidectomized subjects gained an excess of 1.8 kg over one year, and LT4-treated hypothyroid subjects gained an excess of 0.9 kg.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Discussion

    None of the studies examining body weight and composition in LT4-treated subjects have shown significant differences in these parameters compared to control subjects or when LT4 doses were altered to lower TSH within the reference range.

    “None have shown significant differences in these parameters compared to control subjects (47,48) or when LT4 doses were altered to lower TSH within the reference range (14,41).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [47] source

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    • cites [48] source

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    • cites [14] Frayn KN, 1983, J Appl Physiol Respir Environ Exercise Physiol

      Not checked in the free run.

    • cites [41] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion

    Past studies have reported increased resting or 24-hour energy expenditure and whole body oxygen consumption with exogenous administration of pharmacologic doses of LT4 or LT3 to healthy humans due to increased expression of uncoupling proteins and decreased mitochondrial efficiency.

    “Past studies have reported increased resting or 24-hour energy expenditure and whole body oxygen consumption with exogenous administration of pharmacologic doses of LT4 or LT3 to healthy humans (3-7) due to increased expression of uncoupling proteins and decreased mitochondrial efficiency (3,4,7).”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [3] source

      Not checked in the free run.

    • cites [4] Barbe P, 2001, FASEB J source

      Not checked in the free run.

    • cites [5] source

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    • cites [6] source

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    • cites [7] source

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  • May combine two claims.

    Premisecitation
    § Discussion

    A third study randomly assigned DTC patients to continue LT4 suppressive therapy versus lowering LT4 doses for six months, and found no changes in body composition, despite an increase in mean TSH levels from 0.07 to 4.35 mIU/L.

    “A third study randomly assigned DTC patients to continue LT4 suppressive therapy versus lowering LT4 doses for six months, and found no changes in body composition, despite an increase in mean TSHlevels from 0.07 to 4.35 mIU/L (8).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [8] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation
    § Discussion

    Subjects lost 1.4 kg after 16 weeks of desiccated thyroid extract and 1.8 kg after six weeks of LT3, although there was no change in REE in the LT3 study.

    “Subjects lost 1.4 kg after 16 weeks of desiccated thyroid extract and 1.8 kg after six weeks of LT3, although there was no change in REE in the LT3 study (30).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    Another study found no change in lean body mass but a 9% decrease in muscle mass in the DTC group.

    “while the other found no change in lean body mass but a 9% decrease in muscle mass in the DTC group (9).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    These studies utilized doses of thyroid hormone that caused increases in thyroid hormones well above the physiologic range for short periods of time, and are not relevant for long-term therapy with lower doses of LT4.

    “These studies utilized doses of thyroid hormone that caused increases in thyroid hormones well above the physiologic range for short periods of time, and are not relevant for long-term therapy with lower doses of LT4.”
    Quote in the paperSubstantial claim
39 of 39

  • The paper relies on this without support.

    The study had adequate statistical power to detect differences in energy expenditure and body composition.

    “LT4 suppression therapy does not adversely affect energy expenditure or body composition in women.”

  • The paper relies on this without support.

    Free triiodothyronine (fT3) levels reflect tissue thyroid hormone status.

    “This may be due to lower fT3 levels, suggesting relative tissue hypothyroidism may contribute to impaired energy expenditure in LT4 therapy.”
2 of 2

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Cites

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Research works printed but not linked: 3

  1. Frayn KN, 1983, J Appl Physiol Respir Environ Exercise Physiol, 55, 628
  2. Astrup A, 1992, J Clin Endocrinol Metab, 74, 279
  3. Toubro S, 1996, J Clin Endocrinol Metab, 81, 2670

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Authors
Samuels, M. H., Kolobova, I., Smeraglio, A., Peters, D., Purnell, J. Q., & Schuff, K. G.
Affiliations
  • Oregon Health & Science University (US)
  • Stanford Medicine (US)
Corresponding author
Samuels, Mary H.
ORCID
Venue
Thyroid
Publisher
SAGE Publications
Published
2016-03
Volume
26
Issue
3
Pages
347-355
ISSN
  • 1050-7256 (ISSN-L)
  • 1557-9077
DOI
10.1089/thy.2015.0345
PMC
PMC4790206
OpenAlex
W2199136101
Semantic Scholar
a2726550ba9bc93bbe1960ebd610a171804e1da8
Cited by
87
References
51
Citations by year
2026: 5 · 2025: 8 · 2024: 9 · 2023: 3 · 2022: 10 · 2021: 9 · 2020: 14 · 2019: 11 · 2018: 10 · 2017: 4 · 2016: 4
FWCI
5.20
Type
journal article
Language
en
Open access
Licence
www.liebertpub.com/nv/resources-tools/text-and-data-mining-policy/121/ (tdm)
Locations
  • Thyroid (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Oregon Health and Science University
  • Georgia Clinical and Translational Science Alliance
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK075496)
  • National Center for Research Resources (UL1 RR 024120)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
levothyroxine, TSH suppression, levothyroxine replacement therapy, energy expenditure, resting energy expenditure, body composition, free triiodothyronine, substrate oxidation, thermic effect of food, physical activity energy expenditure, energy intake, women
MeSH terms
Adult, Body Composition, Energy Intake, Calorimetry, Indirect, Cross-Sectional Studies, Energy Metabolism, Female, Humans, Hypothyroidism, Middle Aged, Oxidation-Reduction, Surveys and Questionnaires, Antithyroid Agents, Thyrotropin, Thyroxine, Biomarkers, Absorptiometry, Photon, Case-Control Studies, Treatment Outcome, Hormone Replacement Therapy, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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