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

February 17, 2024 updated by: Assimina Galli-Tsinopoulou, Aristotle University Of Thessaloniki

Association of Serum Fibroblast Growth Factor 21 (FGF-21) Levels With Resting Metabolic Rate (RMR), in Children and Adolescents With Hashimoto's Thyroiditis.

It is well documented that thyroid hormones (THs) are involved in energy and lipid metabolism, thermogenesis, and body weight control, acting on several tissues. Thus, any change in thyroid status may affect body weight and metabolic rate. On the other hand, fibroblast growth factor 21 (FGF-21) is a complex hormone involved in energy, lipid, and glucose metabolism, sharing common biochemical pathways and sites of action with THs. FGF-21 is synthesized and acts primarily on the liver, but weaker expression has also been described in muscle, pancreas, and adipose tissue. In addition, FGF-21 acts through endocrine and paracrine mechanisms, regulating metabolic pathways such as fatty acid oxidation, glucose uptake, and thermogenesis. Recent animal and human studies have highlighted a close bidirectional relationship between FGF-21 and THs, partially elucidated. Thyroid hormones regulate the expression of the FGF-21 gene in the liver and can also increase FGF-21 levels in vivo. However, it has also been suggested that some of their key actions are largely independent. Data on FGF-21 levels and their metabolic role in pediatric patients with chronic autoimmune thyroiditis (AIT) are scarce. This study aims to measure FGF-21 serum levels in children and adolescents with Hashimoto's thyroiditis and investigate any possible associations between FGF-21 serum levels and resting metabolic rate (RMR) and levothyroxine (LT4) treatment, or other clinical and biochemical parameters.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Children and adolescents, aged 5-18 years, will undergo routine screening for chronic autoimmune thyroiditis (AIT) at the Pediatric Endocrinology Outpatient Clinic of "Papageorgiou" General Hospital and "AHEPA" University Hospital of Thessaloniki, Greece. The diagnosis of AIT will be based on the presence of anti-thyroid autoantibodies (Anti-TPOAb and/or Anti-TgAb) and one or more of the following: clinical symptoms of thyroid dysfunction, goiter, or diffuse/irregular hypoechogenicity of the thyroid gland during an ultrasound examination.

All participants should have a normal body mass index (BMI) for their age and sex, be drug-naive for at least 3 months, follow no special diet, and have no chronic and/or acute disease or menstrual disorder. Only those subjects that will start routine LT4 treatment will be reassessed at six months (not the rest participants), with no specific intervention to take place during those six months.

For all participants, a detailed medical history will be recorded. The following parameters will be measured and calculated: age and pubertal stage according to Tanner, height, body weight, Body Mass Index (BMI), waist circumference, hip circumference, mid-upper arm circumference (MUAC), and skinfolds measurement in order to estimate the percentage of body fat (%BF). The resting metabolic rate (RMR) will be measured with a portable device applying indirect calorimetry. Blood samples will be collected after overnight fasting.

The following parameters will be tested in serum: thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), anti-thyroid peroxidase antibody (Anti-TPOAb) titers, thyroglobulin antibody (Anti-TgAb) titers, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γglutamyltransferase (γ-GT), alkaline phosphatase (ALP), applying an automatic chemical analyzer or immunoassay system and analogs reagents that already exist at the hospital. Serum FGF-21 levels will be determined in pg/mL using the Solid Phase Sandwich Enzyme-linked Immunosorbent Assay (ELISA) method according to the manufacturer's protocol.

Additionally, all participants, with the help of their parents and/or caregivers, will complete the Mediterranean Diet Index (KIDMED) at their first visit.

Study Type

Observational

Enrollment (Actual)

90

Contacts and Locations

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

Study Contact

  • Name: Assimina Galli-Tsinopoulou, MD,PhD
  • Phone Number: +30 2310994801
  • Email: agalli@auth.gr

Study Locations

  • Greece
      • Thessaloniki, Greece, 546 21
        • 2nd Department of Paediatrics, School of Medicine Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA Hospital Thessaloniki, Greece

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

5 years to 18 years (Child, Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Probability Sample

Study Population

Children and Adolescents of Greek origin who attend the Pediatric Endocrinology Outpatient Units of 4th and 2nd Departments of Pediatrics, Medical School, Aristotle University of Thessaloniki for testing thyroid autoimmunity, as well as healthy controls.

Description

Inclusion Criteria:

For patients

  • Subjects 5 to 18 years old.
  • First diagnosis of chronic autoimmune thyroiditis (high levels of serum antithyroid autoantibodies anti-TPO, anti-TgAb).

For Controls:

  • Healthy individuals 5 to 18 years old.
  • BMI for age between 15th and 85th percentile (z-score between -1 and +1).

Exclusion Criteria:

For patients

  • Pre-existing medical treatment for thyroid disease
  • Taking other medications (eg growth hormone, corticosteroids) in the last 3 months.
  • Taking food supplements (eg omega-3 fatty acids, amino acids) in the last 3 months.
  • Concomitant endocrine, metabolic, degenerative, and/or chronic diseases other than obesity (eg diabetes, hyper/ hypercortisolemia, cardiovascular diseases, kidney diseases, myasthenia, neurological diseases, psychiatric disorders eg anorexia nervosa, cancer, anemia, celiac disease, chromosomal abnormalities eg syndrome Turner, Down, etc).
  • Participation in any daily organized physical activity (sport), more than 1 hour per day.
  • Presence of menstrual disorders in adolescent girls.
  • Having any kind of nutrition/dietary intervention (eg weight loss diet, hypocaloric, ketogenic, low-protein diet), in the last 6 months.

For Controls:

  • Presence of any form of thyroid disease.
  • Presence of any endocrine, metabolic, degenerative, and/or chronic disease (eg diabetes, hyper/ hypercortisolemia, obesity, metabolic syndrome, cardiovascular diseases, kidney diseases, myasthenia, neurological diseases, psychiatric disorders eg anorexia nervosa, cancer, anemia, celiac disease, chromosomal abnormalities eg syndrome Turner, Down, etc).
  • Taking any medication (eg growth hormone, corticosteroids) in the last 3 months.
  • Taking food supplements (eg omega-3 fatty acids, amino acids) in the last 3 months.
  • Participation in any daily organized physical activity (sport), more than 1 hour per day. Presence of menstrual disorders in adolescent girls.
  • Having any kind of nutrition/dietary intervention (eg weight loss diet, hypocaloric, ketogenic, low-protein diet), in the last 6 months.

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

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
AIT Subclinical Hypothyroid Group

30 children and adolescents with subclinical hypothyroidism due to Hashimoto's thyroiditis.

No special intervention is to be administered, only routine LT4 treatment. Reassessment at 6 months.
Control Group

30 healthy individuals with no chronic autoimmune thyroiditis and normal thyroid function (age- and sex-matched with the AIT Subclinical Hypothyroid Group).

No special intervention is to be administered. No reassessment at 6 months.
AIT Euthyroid Group

30 children and adolescents with chronic autoimmune thyroiditis and euthyroidism (age- and sex-matched with the AIT Subclinical Hypothyroid Group).

No special intervention is to be administered. No reassessment at 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fibroblast Growth Factor 21 (FGF-21)
Time Frame: baseline and 6 months
serum fibroblast growth factor 21 (FGF-21) levels after an overnight fasting
baseline and 6 months
RMR/Weight/Day
Time Frame: baseline and 6 months
Resting Metabolic Rate (RMR) per kilogram of body weight per day
baseline and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
SDS BMI
Time Frame: baseline and 6 months

Standard Deviation Score (SDS) for Body Mass Index (BMI). The standard deviation is a measure of the amount of variation or spread of a set of values around the mean or average. The mean or average value is given an SDS of "0". A negative SDS indicates that the value is below the average or mean and a positive value means it is above the average or mean. SDS correspond to growth chart percentiles as follow:

-2.68 = 0.4th percentile, -2.01 = 2nd percentile, -1.34 = 9th percentile, -0.67 = 25th percentile, 0 (mean or average) = 50th percentile, +0.67 = 75th percentile, +1.34 = 91st percentile, +2.01 = 98th percentile, +2.68 = 99.6th percentile.

These percentiles help us understand whether a measurement falls within the normal range for children of the same age and sex. A lower SDS value (closer or lower to -2.68) and a higher SDS value (closer or above +2.68) mean a worst outcome, while a SDS value closer to 0 (mean or average), mean a better outcome.
baseline and 6 months
WAIST C.
Time Frame: baseline and 6 months
Waist Circumference
baseline and 6 months
HIP C.
Time Frame: baseline and 6 months
Hip circumference
baseline and 6 months
MUAC
Time Frame: baseline and 6 months
mid-upper arm circumference
baseline and 6 months
%BF
Time Frame: baseline and 6 months
Body fat percentage (%BF), is the total mass of fat divided by total body mass. The total body fat includes essential body fat and stored body fat.
baseline and 6 months
FMI
Time Frame: baseline and 6 months
Fat mass index (FMI) is calculated by dividing the fat weight in kilograms by the height in metres squared.
baseline and 6 months
FFMI
Time Frame: baseline and 6 months
Fat free mass index (FFMI) is calculated by dividing the free fat weight in kilograms by the height in metres squared.
baseline and 6 months
TSH
Time Frame: baseline and 6 months
thyroid-stimulating hormone (TSH) after an overnight fasting
baseline and 6 months
FT3
Time Frame: baseline and 6 months
free triiodothyronine after an overnight fasting
baseline and 6 months
FT4
Time Frame: baseline and 6 months
free thyroxine (FT4) after an overnight fasting
baseline and 6 months
Glucose
Time Frame: baseline and 6 months
glucose serum level after an overnight fasting
baseline and 6 months
Insulin
Time Frame: baseline and 6 months
insulin serum level after an overnight fasting
baseline and 6 months
TC
Time Frame: baseline and 6 months
Total Cholesterol (TC) serum level after an overnight fasting
baseline and 6 months
TG
Time Frame: baseline and 6 month
Triglyceride (TG) serum level after an overnight fasting
baseline and 6 month
HDL
Time Frame: baseline and 6 months
high-density lipoprotein (HDL) serum level after an overnight fasting
baseline and 6 months
LDL
Time Frame: baseline and 6 months
low-density lipoprotein (LDL) serum level after an overnight fasting
baseline and 6 months
AST
Time Frame: baseline and 6 months
aspartate aminotransferase (AST) serum level after an overnight fasting
baseline and 6 months
ALT
Time Frame: baseline and 6 months
alanine aminotransferase (ALT) serum level after an overnight fasting
baseline and 6 months
γ-GT
Time Frame: baseline and 6 months
gamma gloutamyltransferase (γ-GT) serum level after an overnight fasting
baseline and 6 months
ALP
Time Frame: baseline and 6 months
alkaline phosphatase (ALP) serum level after an overnight fasting
baseline and 6 months
Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
Time Frame: baseline and 6 months

HOMA-IR stands for Homeostatic Model Assessment of Insulin Resistance, using fasting insulin and blood glucose levels after an overnight fastιng. The meaningful part of the acronym is "insulin resistance". It marks for both the presence and extent of any insulin resistance that you might currently express. It is a way to reveal the dynamic between the baseline (fasting) blood sugar and the responsive hormone insulin.

Healthy Range: 1.0 (0.5-1.4) Less than 1.0 means you are insulin-sensitive which is optimal. Above 1.9 indicates early insulin resistance. Above 2.9 indicates significant insulin resistance.
baseline and 6 months
Mediterranean Diet Index (KIDMED) Score
Time Frame: baseline

Mediterranean diet index (KIDMED) score is a questionnaire used to evaluate adherence to the Mediterranean diet in children and adolescents. The KIDMED assesses how well an individual's dietary habits align with the Mediterranean diet.

Scoring System: 16 questions, each associated with a specific value. The total score ranges from -4 to 12.

Interpretation:

≤3: Very-low-quality diet. 4-7: Need to improve the food pattern to align with the Mediterranean diet.

≥8: Optimal adherence to the Mediterranean diet. A lower overall score (≤3) mean a worst outcome (adherence); while a higher overall score (≥8) mean a better outcome (adherence).
baseline
Mediterranean Diet Index (KIDMED) Analysis
Time Frame: baseline
specific foods frequency consumption based on the KIDMED questionnaire
baseline
Anti-TPOAb
Time Frame: baseline and 6 months
antithyroid peroxidase antibody (Anti-TPOAb) titers
baseline and 6 months
Anti-TgAb
Time Frame: baseline and 6 months
thyroglobulin antibody (Anti-TgAb) titers
baseline and 6 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparisons between initial and after 6 months levothyroxine treatment of FGF-21 serum levels and RMR.
Time Frame: 1 year
Comparison between the patient's group initial FGF-21 serum levels and RMR before and after levothyroxine treatment. Similar comparison will be done in the control group. Furthermore, a final comparison between patients and controls will be held.
1 year

Collaborators and Investigators

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

Sponsor

Aristotle University Of Thessaloniki

Investigators

  • Principal Investigator: Assimina Galli-Tsinopoulou, MD,PhD, 2nd Department of Paediatrics, AΗEPA Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

October 1, 2015

Primary Completion (Actual)

March 1, 2020

Study Completion (Actual)

March 1, 2020

Study Registration Dates

First Submitted

January 9, 2016

First Submitted That Met QC Criteria

March 29, 2016

First Posted (Estimated)

April 1, 2016

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 17, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PEDIATRIC ENDOCRINOLOGY

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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