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

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.

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.