FGF-21 Levels and RMR in Children and Adolescents With Hashimoto's Thyroiditis (THYROMETABOL): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for FGF-21 Levels and RMR in Children and Adolescents With Hashimoto's Thyroiditis (THYROMETABOL) (NCT02725879), a registered phase not stated study. The primary outcome is Fibroblast Growth Factor 21 (FGF-21).

2. Clinical Question

The study’s stated rationale is that thyroid hormones and FGF-21 are both involved in metabolic pathways, while evidence about FGF-21 in pediatric chronic autoimmune thyroiditis is described as scarce. Its central question is therefore associational: how do serum FGF-21 levels in children and adolescents with Hashimoto’s thyroiditis relate to RMR and treatment status, and how might they relate to other clinical or biochemical parameters? The record does not identify a single treatment-effect comparison as the primary question.

The groups represent different thyroid-status categories and a healthy-control group. The subclinical hypothyroid group is described as receiving routine LT4 treatment, while the euthyroid and control groups have no special intervention. Because allocation is not stated and the groups differ by clinical status, comparisons should not be read as randomized estimates of treatment effects. The registry record supplies no outcome estimates with which to assess the proposed relationships.

3. Trial Design

The registry lists a completed study with an enrollment of 90. It describes three groups: children and adolescents with subclinical hypothyroidism due to Hashimoto’s thyroiditis, children and adolescents with chronic autoimmune thyroiditis and euthyroidism, and healthy individuals with normal thyroid function and no chronic autoimmune thyroiditis. Each group is described as containing 30 participants. The control and euthyroid groups are described as age- and sex-matched with the subclinical hypothyroid group.

This is not described as a randomized trial. Allocation is not stated in the registry record, and the groups are not a like-for-like control comparison. Instead, the design compares people classified by thyroid and autoimmune status. The subclinical hypothyroid group received routine LT4 treatment and was to be reassessed at 6 months. The registry describes no special intervention for the other groups and no 6-month reassessment for them.

The listed primary measure is serum FGF-21 after overnight fasting, with a baseline and 6-month timeframe. The registry specifies median and interquartile range as the planned summary format, but does not report the corresponding values. It also states that control-group data were not collected at 6 months and that baseline and 6-month data were not collected for the AIT euthyroid group. These gaps constrain the comparisons that can be assessed from the record.

The study description says it aims to investigate relationships with RMR, LT4 treatment, and other clinical and biochemical parameters. The registered secondary outcomes include anthropometric and thyroid-related measures. The registry record identifies 27 outcome measures but reports 0 analyses. It does not report the statistical analysis plan, participant flow, eligibility criteria in detail, or the method used to assign participants to groups. Those design details are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Data have not been collected for the "Control Group" at the 6 month time point. Data have not been collected for the "AIT Euthyroid Group" for the baseline and 6 month time points.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: AIT Subclinical Hypothyroid group: diagnosed with chronic autoimmune thyroiditis (AIT) and subclinical hypothyroidism (SCH), receiving standard levothyroxine (LT4) treatment. Control group: Healthy, no chronic autoimmune thyroiditis (AIT) and normal thyroid function (age- and sex-matched with AIT Subclinical Hypothyroid Group). AIT Euthyroid group: diagnosed with chronic autoimmune thyroiditis (AIT) and euthyroidism (age- and sex-matched with AIT Subclinical Hypothyroid Group).

6. Primary Endpoint

The registry lists the primary outcome as Fibroblast Growth Factor 21 (FGF-21), measured over baseline and 6 months.

The primary outcome is serum fibroblast growth factor 21 (FGF-21), measured in pg/mL after an overnight fast. The registry specifies median and interquartile range as its summary format and lists baseline and 6 months as the measurement timeframe. FGF-21 is the biomarker at the center of the study’s stated question about metabolic associations in children and adolescents with Hashimoto’s thyroiditis.

In general, a biomarker can be summarized to describe its distribution within a group and compared across groups or measurement times. The median identifies the middle of an ordered set of measurements, while the interquartile range describes the spread of the middle portion of that set. These summaries can be useful when the distribution is asymmetric or contains values far from the center. The registry’s choice of these summaries does not establish what the observed distribution looked like.

The study description also identifies RMR as an intended association of interest, but the primary outcome stated in the record is FGF-21. The record does not provide RMR values or a numerical estimate relating RMR to FGF-21. Nor does it provide FGF-21 values by group or time point. The absence of those results means the relationship under study cannot be quantified from the registry record.

The record explicitly notes missing collections for some group-time combinations: there are no control-group data at 6 months, and no baseline or 6-month data for the AIT euthyroid group. It does not explain whether other planned measurements were collected or how missing values were handled. The primary outcome’s observed values, variability, and analysis results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record specifies the primary outcome and its descriptive summary but does not report the statistical analysis methods or any results. The concepts below explain how methods of this kind are generally interpreted; they are not claims about analyses actually performed in this study.

What does a median and interquartile range describe?

In general, the median is the value at the center of an ordered distribution. The interquartile range describes the spread between the lower and upper quartiles. Together, these summaries convey a typical value and variation without assuming that measurements are symmetrically distributed around a mean. This can be useful for biomarker measurements, whose distributions may be skewed. However, a median and interquartile range do not by themselves show the difference between groups or the uncertainty around that difference.

The registry identifies FGF-21 as the primary measure and specifies median and interquartile range. It does not give the actual summaries. Without the observed values, it is not possible to describe the scale or variability of FGF-21 in any group, or to judge whether the distributions overlap substantially.

How would an association be interpreted?

In general, an association describes how measurements vary together. An association between FGF-21 and RMR would quantify whether FGF-21 tends to change alongside RMR in the study population, according to a chosen statistical model or correlation measure. It would not by itself show that changes in one cause changes in the other. A causal interpretation would require design and analysis assumptions beyond the existence of an association.

The study description names RMR, LT4 treatment, and clinical and biochemical parameters as topics of interest. The registry record does not identify the specific association measures, models, covariates, or comparison procedures used. It also does not report numerical estimates. No particular model or statistical test can therefore be attributed to the study from this record.

What would a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. It can show which effect sizes are reasonably compatible with the observed data and model, rather than presenting only a single estimate. A narrow interval indicates greater precision than a wide interval, although precision does not establish that an effect is important or free from bias. The registry record does not report confidence intervals for the primary outcome or any association.

A p-value, when reported, addresses how compatible the data are with a specified statistical null model under its assumptions. It does not measure the probability that a hypothesis is true, and it does not describe the magnitude or practical importance of an association. No p-values or hypothesis tests are reported in the registry record. It is therefore not possible to classify any proposed relationship as statistically significant or not significant using this record.

Why do group definitions matter?

In general, comparisons across nonrandomized groups can be affected by differences in characteristics that relate to both group membership and the measured outcome. Matching on age and sex, as described for the control and euthyroid groups relative to the subclinical hypothyroid group, addresses those matching factors in the design, but does not establish that all relevant characteristics are comparable. The registry does not report further adjustment methods or covariate balance.

The groups are defined by thyroid and autoimmune status, and one group receives routine LT4 treatment. Because allocation is not stated, comparisons involving treatment cannot be interpreted as randomized treatment effects. A statistical adjustment might address measured differences in some circumstances, but its adequacy depends on information about the variables, model, and data. Such details are not reported in the registry record.

How should repeated measurements be considered?

In general, repeated measurements from the same participant are related rather than independent. A longitudinal analysis should account for that within-participant dependence when estimating change or comparing change between groups. The registry describes baseline and 6-month FGF-21 measurement and reassessment for the subclinical hypothyroid group. It does not report a repeated-measures model, a paired analysis, or any estimate of change. The record also identifies missing group-time data, limiting what can be inferred about a complete longitudinal comparison.

What is the role of over-dispersion?

In general, over-dispersion refers to variation in data that exceeds what a statistical model assumes. If it is ignored, standard errors and uncertainty intervals can be too small, making results appear more precise than warranted. The relevance of over-dispersion depends on the outcome type and model. The primary outcome is a continuous serum concentration summarized by median and interquartile range; the registry does not describe a model for it or any over-dispersion assessment. This concept is therefore general statistical context, not a finding about this study.

Finally, an analysis requires clarity about which participants contribute to each estimate, how missing measurements are handled, and whether planned comparisons were selected in advance. Those details are important for judging precision and potential bias, but they are not reported in the registry record. No statistical result can be reconstructed from the group descriptions alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 27 outcome measures and 0 analyses. It identifies FGF-21 as the primary outcome and lists secondary measures including SDS BMI, waist circumference, hip circumference, MUAC, body-fat percentage, FMI, FFMI, and TSH. The record does not report which outcomes were analyzed, which comparisons were planned, or whether any multiplicity procedure was used.

In general, testing many outcomes or comparisons can increase the chance of obtaining apparently noteworthy results by chance. Statistical approaches to multiplicity can control or describe that risk, but the appropriate approach depends on the research question and analysis plan. No correction, hierarchical testing strategy, or prespecified family of comparisons is reported in the registry record. Because no analysis results are reported, multiplicity cannot be evaluated from the posted record.

The record states that control-group data were not collected at 6 months and that AIT euthyroid-group data were not collected at baseline or 6 months for the primary outcome. These are specified absences of collection, rather than documented missing values caused by participant dropout. The record does not explain whether any other measurements were missing, why they were missing, or whether imputation or another missing-data method was used.

Analysis populations are also not reported. Although enrollment and group descriptions are recorded, the number contributing to each outcome or analysis is not specified in the results information. No intention-to-treat, per-protocol, complete-case, or other population definition appears in the registry record. The impact of missing measurements on estimates and uncertainty therefore cannot be assessed.

11. What the Result Does, and Does Not, Mean

The record establishes that a completed study was registered to measure fasting serum FGF-21 in children and adolescents with Hashimoto’s thyroiditis and to investigate possible relationships with RMR, LT4 treatment, and other parameters. It specifies a primary outcome, group descriptions, a planned summary format, and some absent group-time measurements. These details define the intended research question and parts of the design.

The record does not establish what FGF-21 levels were, whether they differed by group or time, or whether they were associated with RMR. It also does not establish an effect of LT4 treatment. No numerical outcome estimates, uncertainty intervals, or analysis results are reported. The study’s completed status does not resolve these gaps.

In general, an observed association would not by itself demonstrate cause and effect. Here, the groups are not described as randomized, and treatment is part of the clinical group description. A difference between groups could reflect factors other than treatment or thyroid status. The registry record does not provide the results or adjustment details needed to explore that possibility.

The absence of results should not be interpreted as evidence that there was no association, no difference, or no effect. It means those quantities cannot be evaluated from the record. Likewise, the adverse-event entries listing zero counts do not establish that no events occurred in the underlying study; they report zeros in the registry fields, without further information on ascertainment or completeness.

For a substantive interpretation, readers would need the observed FGF-21 summaries, estimates for the intended comparisons or associations, measures of uncertainty, and descriptions of the analysis populations and missing-data handling. Until such information is available in the registry record, the defensible conclusion is limited to the study’s stated aims and recorded design.

12. Why This Trial Matters Statistically

This study raises a useful statistical question about how a metabolic biomarker relates to thyroid status and RMR in a pediatric population. Its three-group structure distinguishes subclinical hypothyroidism, euthyroidism with autoimmune thyroiditis, and healthy controls. That design can frame descriptive and associational questions, while also making clear why group definition and comparability matter.

The registry record highlights a distinction between a completed study and an interpretable result. Enrollment, group descriptions, outcome definitions, and a measurement timeframe are recorded, but the primary outcome summaries and analyses are not. Without estimates and uncertainty, readers cannot assess the magnitude or precision of the relationships the study set out to examine. This is a central statistical limitation, not merely a missing presentation detail.

The unequal availability of outcome measurements across group and time combinations also matters. The intended baseline and 6-month timeframe is not populated for every group, according to the record. This restricts the comparisons that can be made from the stated measurement plan and makes it important to define which question each analysis addresses. The registry does not report how that limitation was handled.

Finally, the observational group structure cautions against treating associations as causal effects. Matching is described for age and sex, but further comparability and adjustment details are not reported. The study is therefore statistically relevant both for its stated biomarker question and as an example of why results, analysis methods, and missing-data information are essential for interpreting a completed clinical study.

13. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation of the registry record for interpreting this study is that it does not report primary-outcome values or analyses. The FGF-21 median and interquartile range are specified as the summary format, but neither those summaries nor estimates of association with RMR are included. The registry lists 0 analyses. As a result, no conclusion about the observed direction, magnitude, or precision of the study’s proposed relationships can be drawn from this record.

The comparison structure is nonrandomized as described: allocation is not stated, and group membership reflects thyroid and autoimmune status. The AIT subclinical hypothyroid group received routine LT4 treatment, so comparisons involving that group do not isolate a randomized treatment effect. Matching on age and sex is described for the control and euthyroid groups, but the registry does not report other baseline characteristics, covariate adjustment, or balance across groups.

Primary-outcome collection is incomplete across the listed groups and time points. There are no 6-month control data and no baseline or 6-month AIT euthyroid data. The registry does not report how these absent measurements affected the analyses, whether other measurements were unavailable, or how missing data were handled. It also does not identify analysis populations or outcome-specific participant counts.

Other design and analysis details are not reported in the registry record, including detailed eligibility criteria, the statistical plan, the rationale for the enrollment target, and whether interim analyses were conducted. These omissions limit assessment of the planned comparisons and potential sources of bias. The adverse-event fields contain zero counts, but the registry does not provide event-collection methods or further context for interpreting those entries.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: FGF-21 Levels and RMR in Children and Adolescents With Hashimoto's Thyroiditis (THYROMETABOL) — NCT02725879.
• Registry record last updated 2024-02-20; status last verified 2024-02.
• Results first posted 2024-02-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

17. Record Summary

The registry record concerns a completed study of FGF-21 in children and adolescents with Hashimoto’s thyroiditis. It lists enrollment of 90 and describes an AIT subclinical hypothyroid group, an AIT euthyroid group, and a healthy control group, with 30 participants described in each. The subclinical hypothyroid group received routine LT4 treatment and was to be reassessed at 6 months.

The primary outcome is fasting serum FGF-21 in pg/mL, summarized as median and interquartile range, with baseline and 6-month time points. The record notes that 6-month control data and baseline and 6-month AIT euthyroid data were not collected. It lists 27 outcome measures and 0 analyses.

The study description proposes examining relationships with RMR, LT4 treatment, and other clinical and biochemical parameters. However, outcome values, analysis methods, and statistical results are not reported in the registry record. The group allocation method is not stated, and the design is not described as randomized.