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

NCT02725879 | Completed Results

• 1 other identifier: PEDIATRIC ENDOCRINOLOGY
• Study Type: observational
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Hashimoto Disease

Keywords

fibroblast growth factor 21; resting metabolic rate; chronic autoimmune thyroiditis; L-thyroxin; children; adolescents

Outcome Measures

Primary Outcomes (2)

• Fibroblast Growth Factor 21 (FGF-21)

  serum fibroblast growth factor 21 (FGF-21) levels after an overnight fasting

  baseline and 6 months

• RMR/Weight/Day

  Resting Metabolic Rate (RMR) per kilogram of body weight per day

  baseline and 6 months

Secondary Outcomes (25)

• SDS BMI

  baseline and 6 months

• WAIST C.

  baseline and 6 months

• HIP C.

  baseline and 6 months

• MUAC

  baseline and 6 months

• %BF

  baseline and 6 months

Study Arms (3)

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.

Eligibility Criteria

• Age: 5 Years - 18 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• 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.

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Aristotle University Of Thessaloniki: lead

Study Sites (1)

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

Thessaloniki, 546 21, Greece

Location

Related Publications (24)

• Adams AC, Astapova I, Fisher FM, Badman MK, Kurgansky KE, Flier JS, Hollenberg AN, Maratos-Flier E. Thyroid hormone regulates hepatic expression of fibroblast growth factor 21 in a PPARalpha-dependent manner. J Biol Chem. 2010 May 7;285(19):14078-82. doi: 10.1074/jbc.C110.107375. Epub 2010 Mar 17.

  PMID: 20236931 BACKGROUND

• Astrup A, Buemann B, Toubro S, Ranneries C, Raben A. Low resting metabolic rate in subjects predisposed to obesity: a role for thyroid status. Am J Clin Nutr. 1996 Jun;63(6):879-83. doi: 10.1093/ajcn/63.6.879.

  PMID: 8644681 BACKGROUND

• Barbesino G, Chiovato L. The genetics of Hashimoto's disease. Endocrinol Metab Clin North Am. 2000 Jun;29(2):357-74. doi: 10.1016/s0889-8529(05)70136-5.

  PMID: 10874534 BACKGROUND

• Coskun T, Bina HA, Schneider MA, Dunbar JD, Hu CC, Chen Y, Moller DE, Kharitonenkov A. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology. 2008 Dec;149(12):6018-27. doi: 10.1210/en.2008-0816. Epub 2008 Aug 7.

  PMID: 18687777 BACKGROUND

• Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med. 1996 Jul 11;335(2):99-107. doi: 10.1056/NEJM199607113350206. No abstract available.

  PMID: 8649497 BACKGROUND

• Dostalova I, Kavalkova P, Haluzikova D, Lacinova Z, Mraz M, Papezova H, Haluzik M. Plasma concentrations of fibroblast growth factors 19 and 21 in patients with anorexia nervosa. J Clin Endocrinol Metab. 2008 Sep;93(9):3627-32. doi: 10.1210/jc.2008-0746. Epub 2008 Jun 17.

  PMID: 18559909 BACKGROUND

• Griffiths M, Payne PR, Stunkard AJ, Rivers JP, Cox M. Metabolic rate and physical development in children at risk of obesity. Lancet. 1990 Jul 14;336(8707):76-8. doi: 10.1016/0140-6736(90)91592-x.

  PMID: 1975323 BACKGROUND

• Hanks LJ, Casazza K, Ashraf AP, Wallace S, Gutierrez OM. Fibroblast growth factor-21, body composition, and insulin resistance in pre-pubertal and early pubertal males and females. Clin Endocrinol (Oxf). 2015 Apr;82(4):550-6. doi: 10.1111/cen.12552. Epub 2014 Aug 8.

  PMID: 25039824 BACKGROUND

• Iglesias P, Selgas R, Romero S, Diez JJ. Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21. Eur J Endocrinol. 2012 Sep;167(3):301-9. doi: 10.1530/EJE-12-0357. Epub 2012 Jun 27.

  PMID: 22740503 BACKGROUND

• Kim KH, Lee MS. FGF21 as a Stress Hormone: The Roles of FGF21 in Stress Adaptation and the Treatment of Metabolic Diseases. Diabetes Metab J. 2014 Aug;38(4):245-51. doi: 10.4093/dmj.2014.38.4.245.

  PMID: 25215270 BACKGROUND

• Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, Perron RM, Werner CD, Phan GQ, Kammula US, Kebebew E, Pacak K, Chen KY, Celi FS. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014 Feb 4;19(2):302-9. doi: 10.1016/j.cmet.2013.12.017.

  PMID: 24506871 BACKGROUND

• Lee Y, Park YJ, Ahn HY, Lim JA, Park KU, Choi SH, Park DJ, Oh BC, Jang HC, Yi KH. Plasma FGF21 levels are increased in patients with hypothyroidism independently of lipid profile. Endocr J. 2013;60(8):977-83. doi: 10.1507/endocrj.ej12-0427. Epub 2013 Jun 12.

  PMID: 23759753 BACKGROUND

• Mai K, Schwarz F, Bobbert T, Andres J, Assmann A, Pfeiffer AF, Spranger J. Relation between fibroblast growth factor-21, adiposity, metabolism, and weight reduction. Metabolism. 2011 Feb;60(2):306-11. doi: 10.1016/j.metabol.2010.02.016. Epub 2010 Apr 1.

  PMID: 20362303 BACKGROUND

• McAninch EA, Bianco AC. Thyroid hormone signaling in energy homeostasis and energy metabolism. Ann N Y Acad Sci. 2014 Apr;1311:77-87. doi: 10.1111/nyas.12374. Epub 2014 Feb 20.

  PMID: 24697152 BACKGROUND

• Mraz M, Bartlova M, Lacinova Z, Michalsky D, Kasalicky M, Haluzikova D, Matoulek M, Dostalova I, Humenanska V, Haluzik M. Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clin Endocrinol (Oxf). 2009 Sep;71(3):369-75. doi: 10.1111/j.1365-2265.2008.03502.x. Epub 2008 Dec 11.

  PMID: 19702724 BACKGROUND

• Muller TD, Tschop MH. Play down protein to play up metabolism? J Clin Invest. 2014 Sep;124(9):3691-3. doi: 10.1172/JCI77508. Epub 2014 Aug 18.

  PMID: 25133420 BACKGROUND

• Nakamura MT, Yudell BE, Loor JJ. Regulation of energy metabolism by long-chain fatty acids. Prog Lipid Res. 2014 Jan;53:124-44. doi: 10.1016/j.plipres.2013.12.001. Epub 2013 Dec 18.

  PMID: 24362249 BACKGROUND

• Pyrzak B, Demkow U, Kucharska AM. Brown Adipose Tissue and Browning Agents: Irisin and FGF21 in the Development of Obesity in Children and Adolescents. Adv Exp Med Biol. 2015;866:25-34. doi: 10.1007/5584_2015_149.

  PMID: 26022904 BACKGROUND

• Santini F, Marzullo P, Rotondi M, Ceccarini G, Pagano L, Ippolito S, Chiovato L, Biondi B. Mechanisms in endocrinology: the crosstalk between thyroid gland and adipose tissue: signal integration in health and disease. Eur J Endocrinol. 2014 Oct;171(4):R137-52. doi: 10.1530/EJE-14-0067.

  PMID: 25214234 BACKGROUND

• Skarpa V, Kousta E, Tertipi A, Anyfandakis K, Vakaki M, Dolianiti M, Fotinou A, Papathanasiou A. Epidemiological characteristics of children with autoimmune thyroid disease. Hormones (Athens). 2011 Jul-Sep;10(3):207-14. doi: 10.14310/horm.2002.1310.

  PMID: 22001131 BACKGROUND

• Vaidya B, Kendall-Taylor P, Pearce SH. The genetics of autoimmune thyroid disease. J Clin Endocrinol Metab. 2002 Dec;87(12):5385-97. doi: 10.1210/jc.2002-020492. No abstract available.

  PMID: 12466323 BACKGROUND

• Woelnerhanssen B, Peterli R, Steinert RE, Peters T, Borbely Y, Beglinger C. Effects of postbariatric surgery weight loss on adipokines and metabolic parameters: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy--a prospective randomized trial. Surg Obes Relat Dis. 2011 Sep-Oct;7(5):561-8. doi: 10.1016/j.soard.2011.01.044. Epub 2011 Mar 22.

  PMID: 21429816 BACKGROUND

• Xu J, Lloyd DJ, Hale C, Stanislaus S, Chen M, Sivits G, Vonderfecht S, Hecht R, Li YS, Lindberg RA, Chen JL, Jung DY, Zhang Z, Ko HJ, Kim JK, Veniant MM. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure, and improves insulin sensitivity in diet-induced obese mice. Diabetes. 2009 Jan;58(1):250-9. doi: 10.2337/db08-0392. Epub 2008 Oct 7.

  PMID: 18840786 BACKGROUND

• Zhang A, Sieglaff DH, York JP, Suh JH, Ayers SD, Winnier GE, Kharitonenkov A, Pin C, Zhang P, Webb P, Xia X. Thyroid hormone receptor regulates most genes independently of fibroblast growth factor 21 in liver. J Endocrinol. 2015 Mar;224(3):289-301. doi: 10.1530/JOE-14-0440. Epub 2014 Dec 11.

  PMID: 25501997 BACKGROUND

Biospecimen

Retention: NONE RETAINED

Serum samples

MeSH Terms

Conditions

Hashimoto Disease

Condition Hierarchy (Ancestors)

Thyroiditis, Autoimmune; Thyroiditis; Thyroid Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

No randomization; relative small sample size; serum FGF-21 levels were not measured in AIT euthyroid patients, as previous animal studies revealed that exogenous FGF-21 administration to hypothyroid animal models led to similar serum and liver lipid metabolites and gene expression changes in both hypothyroid and euthyroid mice. Patients did not have severe long-standing hypothyroidism.

Results Point of Contact

• Title: Professor Assimina Galli-Tsinopoulou
• Organization: 2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki,

agalli@auth.gr

+302310994802

Study Officials

• Assimina Galli-Tsinopoulou, MD,PhD

  2nd Department of Paediatrics, AΗEPA Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 9, 2016
• First Posted: April 1, 2016
• Study Start: October 1, 2015
• Primary Completion: March 1, 2020
• Study Completion: March 1, 2020
• Last Updated: February 20, 2024
• Results First Posted: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

GR (1)