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

Completed

Conditions: Hashimoto Disease

Registration Number: NCT02725879

Lead Sponsor: Aristotle University Of Thessaloniki

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 90

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 & Design

Study Type: OBSERVATIONAL

Study Design: Not specified

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
TC	baseline and 6 months	Total Cholesterol (TC) serum level after an overnight fasting
HDL	baseline and 6 months	high-density lipoprotein (HDL) serum level after an overnight fasting
LDL	baseline and 6 months	low-density lipoprotein (LDL) serum level after an overnight fasting
Anti-TgAb	baseline and 6 months	thyroglobulin antibody (Anti-TgAb) titers
FT3	baseline and 6 months	free triiodothyronine after an overnight fasting
HIP C.	baseline and 6 months	Hip circumference
FT4	baseline and 6 months	free thyroxine (FT4) after an overnight fasting
ALT	baseline and 6 months	alanine aminotransferase (ALT) serum level after an overnight fasting
Mediterranean Diet Index (KIDMED) Analysis	baseline	specific foods frequency consumption based on the KIDMED questionnaire
γ-GT	baseline and 6 months	gamma gloutamyltransferase (γ-GT) serum level after an overnight fasting
ALP	baseline and 6 months	alkaline phosphatase (ALP) serum level after an overnight fasting
SDS BMI	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.
MUAC	baseline and 6 months	mid-upper arm circumference
%BF	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.
TSH	baseline and 6 months	thyroid-stimulating hormone (TSH) after an overnight fasting
Insulin	baseline and 6 months	insulin serum level after an overnight fasting
AST	baseline and 6 months	aspartate aminotransferase (AST) serum level after an overnight fasting
Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)	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.
WAIST C.	baseline and 6 months	Waist Circumference
Mediterranean Diet Index (KIDMED) Score	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).
Anti-TPOAb	baseline and 6 months	antithyroid peroxidase antibody (Anti-TPOAb) titers
FMI	baseline and 6 months	Fat mass index (FMI) is calculated by dividing the fat weight in kilograms by the height in metres squared.
FFMI	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.
Glucose	baseline and 6 months	glucose serum level after an overnight fasting
TG	baseline and 6 month	Triglyceride (TG) serum level after an overnight fasting

Trial Locations

Locations (1): 2nd Department of Paediatrics, School of Medicine Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA Hospital Thessaloniki, Greece
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Thessaloniki, Greece