TY - JOUR
T1 - Childhood Thyroid Function Reference Ranges and Determinants
T2 - A Literature Overview and a Prospective Cohort Study
AU - Önsesveren, Ibrahim
AU - Barjaktarovic, Mirjana
AU - Chaker, Layal
AU - de Rijke, Yolanda B
AU - Jaddoe, Vincent W V
AU - Van Santen, Hanneke M.
AU - Visser, Theo J.
AU - Peeters, Robin P
AU - Korevaar, Tim I.M.
N1 - Funding Information:
This work was supported by a clinical fellowship from ZonMw, project number 90 700 412 (to R.P.P.) and by a fellowship from ERAWEB, a project funded by the European Commission (to M.B.).
Funding Information:
The contributions of the endocrine laboratory technicians are highly appreciated. The Generation R study is conducted by the Erasmus Medical Center (Rotterdam) in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam; the Municipal Health Service Rotterdam area, Rotterdam; the Rotterdam Homecare Foundation, Rotterdam; and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond, Rotterdam. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals, midwives, and pharmacies in Rotterdam. The general design of the Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam; the Erasmus University Rotterdam; The Netherlands Organization for Health Research and Development; The Netherlands Organisation for Scientific Research; the Ministry of Health, Welfare, and Sport; and the Ministry of Youth and Families. Furthermore, we gratefully acknowledge W.M. Bramer for his contribution to the systematical search through different libraries in order to find eligible studies for the systematic review.
Publisher Copyright:
© Copyright 2017, Mary Ann Liebert, Inc. 2017.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - BACKGROUND: Reported cut-offs for childhood TSH and FT4 reference ranges vary widely and the knowledge on the determinants of childhood thyroid function is sparse. We aimed to summarize the existing studies on thyroid function reference ranges in children. Furthermore, our objective was to investigate the determinants of childhood TSH and FT4 concentration in a population based-prospective cohort.METHODS: First, to identify studies on childhood thyroid reference ranges, we systematically searched The National Library of Medicine's PubMed, Embase, Ovid Medline, Web of Science and Google Scholar databases. Second, in a non-selected sample of 4273 children (median age 6.0 years, range 4.9 - 9.1 years) from our cohort, we studied the associations of age, sex, anthropometric characteristics, ethnicity, maternal education, time and season at venipuncture with TSH and FT4 concentrations. We also investigated to what extent between-individual variations in the determinants of TSH and FT4 could influence the calculation of reference ranges.RESULTS: Published reference ranges for TSH and FT4 differ per age range and within age ranges (cut-offs low TSH: 0.13 to >1 mU/L; high TSH: 2.36 to >10 mU/L; low FT4: 7.0 to >10 pmol/L; high FT4: 15.5 to >30 pmol/L). In our cohort, weight, sex and ethnicity were determinants of TSH (P≤0.03) and FT4 concentrations (P≤0.01), height and time at venipuncture were determinants of TSH only (P<0.0001). The between-individual variation depending on clinical determinants for TSH ranged between 0.64 and 0.96 mU/L (total population 0.87 mU/L) for the lower limit and 4.30 and 5.62 mU/L (total population 5.20 mU/L) for the upper limit, whereas for FT4, the lower limit ranged between 13.6 and 14.2 pmol/L (total population 13.8 pmol/L) and the upper limit ranged between 20.2 and 23.0 pmol/L (total population 20.8 pmol/L).CONCLUSIONS: Considerable differences exist in the reported reference ranges for childhood TSH and FT4 across and within age ranges and assays. In our cohort, we show only a minimal association between TSH and FT4 suggesting that the hypothalamus-pituitary-thyroid axis remains unaffected by thyroid interfering factors. We identified various determinants of TSH and FT4 in children which accounted for a considerable variation of reference range cut-offs.
AB - BACKGROUND: Reported cut-offs for childhood TSH and FT4 reference ranges vary widely and the knowledge on the determinants of childhood thyroid function is sparse. We aimed to summarize the existing studies on thyroid function reference ranges in children. Furthermore, our objective was to investigate the determinants of childhood TSH and FT4 concentration in a population based-prospective cohort.METHODS: First, to identify studies on childhood thyroid reference ranges, we systematically searched The National Library of Medicine's PubMed, Embase, Ovid Medline, Web of Science and Google Scholar databases. Second, in a non-selected sample of 4273 children (median age 6.0 years, range 4.9 - 9.1 years) from our cohort, we studied the associations of age, sex, anthropometric characteristics, ethnicity, maternal education, time and season at venipuncture with TSH and FT4 concentrations. We also investigated to what extent between-individual variations in the determinants of TSH and FT4 could influence the calculation of reference ranges.RESULTS: Published reference ranges for TSH and FT4 differ per age range and within age ranges (cut-offs low TSH: 0.13 to >1 mU/L; high TSH: 2.36 to >10 mU/L; low FT4: 7.0 to >10 pmol/L; high FT4: 15.5 to >30 pmol/L). In our cohort, weight, sex and ethnicity were determinants of TSH (P≤0.03) and FT4 concentrations (P≤0.01), height and time at venipuncture were determinants of TSH only (P<0.0001). The between-individual variation depending on clinical determinants for TSH ranged between 0.64 and 0.96 mU/L (total population 0.87 mU/L) for the lower limit and 4.30 and 5.62 mU/L (total population 5.20 mU/L) for the upper limit, whereas for FT4, the lower limit ranged between 13.6 and 14.2 pmol/L (total population 13.8 pmol/L) and the upper limit ranged between 20.2 and 23.0 pmol/L (total population 20.8 pmol/L).CONCLUSIONS: Considerable differences exist in the reported reference ranges for childhood TSH and FT4 across and within age ranges and assays. In our cohort, we show only a minimal association between TSH and FT4 suggesting that the hypothalamus-pituitary-thyroid axis remains unaffected by thyroid interfering factors. We identified various determinants of TSH and FT4 in children which accounted for a considerable variation of reference range cut-offs.
KW - childhood
KW - determinant
KW - fT4
KW - literature overview
KW - reference range
KW - TSH
UR - http://www.scopus.com/inward/record.url?scp=85032740405&partnerID=8YFLogxK
U2 - 10.1089/thy.2017.0262
DO - 10.1089/thy.2017.0262
M3 - Article
C2 - 28942709
AN - SCOPUS:85032740405
SN - 1050-7256
VL - 27
SP - 1360
EP - 1369
JO - Thyroid
JF - Thyroid
IS - 11
ER -