ORIGINAL ARTICLE Trimester- and method-specific reference intervals for thyroid tests in pregnant Chinese women: methodology, euthyroid definition and iodine status can influence the setting of reference intervals Yu-Qin Yan*, Zuo-Liang Dong†, Ling Dong‡, Feng-Rui Wang§, Xue-Ming Yang–, Xing-Yi Jin**, Lai-Xiang Lin*, Yi-Na Sun* and Zu-Pei Chen* *Institute of Endocrinology, and Key Laboratory of Hormone and Development of China Ministry of Health, †Laboratory Center of General Hospital, Tianjin Medical University, ‡Tianjin Women’s and Children’s Health Center, Tianjin, §Center for Disease Control and Prevention of Xinjiang Autonomous Region, Urumchi, –Center for Disease Control and Prevention of Beijing, Beijing and **Center for Disease Control and Prevention of Hangzhou, Hangzhou, China Summary Objective The importance of diagnosis and treatment of thyroid dysfunction during pregnancy has been widely recognized. We therefore established trimester- and method-specific reference intervals for thyroid testing in pregnant women according to the NACB recommended criteria. Several factors can affect the setting of reference intervals, in particular manufacturer’s methodology, euthyroid definition and iodine status. Design Cross-sectional dataset analysis. Subjects Five hundred and five normal pregnant women at differ- ent stages of gestation were rigorously selected for setting reference intervals. All were healthy, iodine sufficient, euthyroid and negative for both serum thyroid peroxidase antibody (TPOAb) and thyro- globulin antibody (TgAb). Measurements Thyrotrophin (TSH), total and free thyroxine (TT4 and FT4), total and free triiodothyronine (TT3 and FT3) and anti-TPOAb and anti-TgAb were measured using the Bayer ADVIA Centaur system. Iodine content in drinking water, salt and urine was determined by national standard methods. The 2Æ5th and 97Æ5th percentiles were calculated as the reference intervals for thy- roid hormone levels during each trimester. Results All participants had long-term consumption of iodized salt and median urinary iodine of 150–200 lg/l during each three trimester. The reference intervals for the first, second and third tri- mesters were, respectively, TSH 0Æ03–4Æ51, 0Æ05–4Æ50 and 0Æ47– 4Æ54 mIU/l and FT4 11Æ8–21Æ0, 10Æ6–17Æ6 and 9Æ2–16Æ7 pmol/l. The manufacturer’s method, euthyroid definition and iodine status may influence TSH and FT4 reference intervals. Alterations in thy- roid hormone concentrations during pregnancy differed at differ- ent stage of gestation and to those of a nonpregnant state. Conclusions The trimester- and method-based reference inter- vals for thyroid tests during pregnancy are clinically appropriate. Some variables should be controlled when establishing reference intervals. (Received 11 July 2010; returned for revision 30 July 2010; finally revised 7 September 2010; accepted 18 October 2010) Introduction Many studies have demonstrated that maternal thyroid dysfunc- tion can have an adverse impact on both mother and child. Recent publications have shown that early maternal thyroid insufficiency, even subclinical hypothyroidism [elevated thyrotrophin (TSH) with normal free thyroxine (FT4)] and isolated hypothyroxinemia (normal TSH with lower FT4) have the potential to impair foetal neurodevelopment. 1–5 Increasing attention has therefore focused on the diagnosis and treatment of maternal thyroid dysfunction during pregnancy. A recent consensus statement on clinical guide- lines for the management of thyroid problems during pregnancy and the postpartum period has been endorsed by several important societies. During pregnancy, increased thyroxine-binding globulin (TBG) and human chorionic gonadotrophin (hCG) can respec- tively affect total thyroxine (TT4) and total triiodothyronine (TT3), and TSH concentrations. The rise in TBG can increase TT4 and TT3 levels to approximately 1Æ5 times the nonpregnant level by 16 weeks of gestation. A decline in serum TSH is usually seen dur- ing the first trimester and is often associated with a modest increase in FT4 level owing to the thyroid-stimulating effect of hCG. Levels of FT4 peak at 10–12 weeks of gestation and together with free tri- iodothyronine (FT3) concentration decline thereafter during the second and third trimester to levels 20–40% below the normal mean level. These changes differ between stages of gestation and to Correspondence: Yu-Qin Yan, Institute of Endocrinology, and Key Labora- tory of Hormone and Development of China Ministry of Health, Tianjin Medical University, 22 Qixiangtai Road, Heping District, Tianjin 300070, China. Tel.: 86 022 23542619; Fax: 86 022 23340048; E-mail: yanyuqin2005 @yahoo.com.cn Clinical Endocrinology (2011) 74, 262–269 doi: 10.1111/j.1365-2265.2010.03910.x 262 Ó 2011 Blackwell Publishing Ltd