Clinical trial NCT02725879: FGF-21 Levels and RMR in Children and Adolescents With Hashimoto's Thyroiditis (THYROMETABOL)
Official title: Association of Serum Fibroblast Growth Factor 21 (FGF-21) Levels With Resting Metabolic Rate (RMR), in Children and Adolescents With Hashimoto's Thyroiditis.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hashimoto Disease
Keywords: fibroblast growth factor 21
resting metabolic rate
chronic autoimmune thyroiditis
L-thyroxin
children
adolescents
Lead sponsor: Aristotle University Of Thessaloniki
Sponsor class: OTHER
First posted: 2016-04-01
Enrollment: 90
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
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.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Fibroblast Growth Factor 21 (FGF-21)
timeFrame: baseline and 6 months
measure: RMR/Weight/Day
timeFrame: baseline and 6 months
Secondary outcomes:
measure: SDS BMI
timeFrame: baseline and 6 months
measure: WAIST C.
timeFrame: baseline and 6 months
measure: HIP C.
timeFrame: baseline and 6 months
measure: MUAC
timeFrame: baseline and 6 months
measure: %BF
timeFrame: baseline and 6 months
measure: FMI
timeFrame: baseline and 6 months
measure: FFMI
timeFrame: baseline and 6 months
measure: TSH
timeFrame: baseline and 6 months
measure: FT3
timeFrame: baseline and 6 months
measure: FT4
timeFrame: baseline and 6 months
measure: Glucose
timeFrame: baseline and 6 months
measure: Insulin
timeFrame: baseline and 6 months
measure: TC
timeFrame: baseline and 6 months
measure: TG
timeFrame: baseline and 6 month
measure: HDL
timeFrame: baseline and 6 months
measure: LDL
timeFrame: baseline and 6 months
measure: AST
timeFrame: baseline and 6 months
measure: ALT
timeFrame: baseline and 6 months
measure: γ-GT
timeFrame: baseline and 6 months
measure: ALP
timeFrame: baseline and 6 months
measure: Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
timeFrame: baseline and 6 months
measure: Mediterranean Diet Index (KIDMED) Score
timeFrame: baseline
measure: Mediterranean Diet Index (KIDMED) Analysis
timeFrame: baseline
measure: Anti-TPOAb
timeFrame: baseline and 6 months
measure: Anti-TgAb
timeFrame: baseline and 6 months
Other outcomes:
Locations:
city: Thessaloniki
country: Greece
facility: 2nd Department of Paediatrics, School of Medicine Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA Hospital Thessaloniki, Greece
Study officials:
affiliation: 2nd Department of Paediatrics, AΗEPA Hospital
name: Assimina Galli-Tsinopoulou, MD,PhD
role: PRINCIPAL_INVESTIGATOR
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