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Assessment of Iodine Status Using Dried Blood Spot Thyroglobulin: Development of Reference Material and Establishment of an International Reference Range in Iodine-Sufficient Children

Laboratory for Human Nutrition (M.B.Z.), Swiss Federal Institute of Technology, CH-8092 Zürich, Switzerland; Department of Nutrition for Health and Development (B.d.B.), World Health Organization, 1211 Geneva, Switzerland; Endocrine and Metabolism Unit (S.C., E.A.P.), High Altitude Research Institute, Cayetano Heredia Peruvian University, 430 Lima, Peru; Nutritional Intervention Research Unit (P.L.J.), Medical Research Council, Cape Town 7505, South Africa; Child Development Center (L.M.), University Children’s Hospital, CH-8032 Zürich, Switzerland; Nutrition Department (K.M., Z.S.A.-D.), Ministry of Health, Manama, Bahrain; Dalian Center for Disease Control and Prevention (Y.W.), Dalian 116023, The People’s Republic of China; Institute of Endocrinology (C.Z.-P.), Tianjin Medical University, Tianjin 300060, The People’s Republic of China; and Department of Endocrinology (T.T.), Children’s Hospital, The University of Zürich, CH-8032 Zurich, Switzerland

Address all correspondence and requests for reprints to: Michael B. Zimmermann, M.D., Laboratory for Human Nutrition, Swiss Federal Institute of Technology, LFV E19, Schmelzbergstrasse 7, CH-8092 Zürich, Switzerland. E-mail: michael.zimmermann{at}ilw.agrl.ethz.ch.

Context: Thyroglobulin (Tg) may be a valuable indicator of improving thyroid function in children after salt iodization. A recently developed Tg assay for use on dried whole blood spots (DBS) makes sampling practical, even in remote areas.

Objective: The study aim was to develop a reference standard for DBS-Tg, establish an international reference range for DBS-Tg in iodine-sufficient children, and test the standardized DBS-Tg assay in an intervention trial.

Design, Participants, and Interventions: Serum Tg reference material of the European Community Bureau of Reference (CRM-457) was adapted for DBS and its stability tested over 1 yr. DBS-Tg was determined in an international sample of 5- to 14-yr-old children (n = 700) who were euthyroid, anti-Tg antibody negative, and residing in areas of long-term iodine sufficiency. In a 10-month trial in iodine-deficient children, DBS-Tg and other indicators of iodine status were measured before and after introduction of iodized salt.

Results: Stability of the CRM-457 Tg reference standard on DBS over 1 yr of storage at –20 and –50 C was acceptable. In the international sample of children, the third and 97th percentiles of DBS-Tg were 4 and 40 µg/liter, respectively. In the intervention, before introduction of iodized salt, median DBS-Tg was 49 µg/liter, and more than two thirds of children had DBS-Tg values greater than 40 µg/liter. After 5 and 10 months of iodized salt use, median DBS-Tg decreased to 13 and 8 µg/liter, respectively, and only 7 and 3% of children, respectively, had values greater than 40 µg/liter. DBS-Tg correlated well at baseline and 5 months with urinary iodine and thyroid volume.

Conclusions: The availability of reference material and an international reference range facilitates the use of DBS-Tg for monitoring of iodine nutrition in school-age children.