Chenling Fan

Abnormalities of maternal thyroid function during pregnancy affect neuropsychological development of their children at 25–30 months

Objective  To examine the relationship between specific thyroid abnormalities (subclinical hypothyroidism, hypothyroxinaemia or elevated thyroid peroxidase antibody titres) in women during pregnancy and the subsequent neuropsychological development of their offspring.

Antithyroperoxidase and antithyroglobulin antibodies in a five-year follow-up survey of populations with different iodine intakes.

OBJECTIVE In a follow-up study, we determined the prevalence, incidence, and natural course of positive antithyroperoxidase antibodies (TPOAbs) and antithyroglobulin antibodies (TgAbs) in the general population and examined the influences of iodine intake. DESIGN The study was conducted in Panshan, Zhangwu, and Huanghua, regions with mildly deficient, more than adequate, and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 3018 participated in the 5-yr follow-up study. Serum TSH, TPOAb, and TgAb levels were measured. RESULTS Among subjects in Panshan, Zhangwu, and Huanghua, the prevalence of positive TPOAbs was 11.23, 11.83 and 12.02%, respectively, whereas 11.23, 11.17, and 11.26% of subjects were TgAb positive, respectively. In the older population (> or =45 yr), TgAb-positive individuals were more frequent in Huanghua than Panshan and Zhangwu (P < 0.05). The 5-yr cumulative incidence of positive TPOAb was 2.08, 3.84, and 2.84% in Panshan, Zhangwu, and Huanghua, respectively, whereas 2.91, 3.64, and 5.07% of subjects were TgAb positive, respectively (P < 0.05), corresponding to the increase in iodine intake. Subjects who were TPOAb and/or TgAb positive at baseline developed thyroid dysfunctions more frequently than those without antibodies (14.44 vs. 3.31%, P < 0.01); their incidence of elevated TSH levels was 1.32, 8.46, and 15.38% in Panshan, Zhangwu, and Huanghua, respectively (P < 0.05). CONCLUSIONS Subjects who were TPOAb and TgAb positive at baseline developed thyroid dysfunctions more frequently than seronegative subjects. High iodine intake was a risk factor for developing hypothyroidism in antibody-positive subjects. A constant exposure to excessive iodine intake increased the incidence of positive TgAb.

Assessment of Thyroid Function During First-Trimester Pregnancy: What Is the Rational Upper Limit of Serum TSH During the First Trimester in Chinese Pregnant Women?

CONTEXT Guidelines of the American Thyroid Association (ATA) proposed that the upper limit of the TSH reference range should be 2.5 mIU/L in first trimester, but the reported ranges in China are significantly higher. OBJECTIVE Our objective was to establish a rational reference range of serum TSH for diagnosis of subclinical hypothyroidism in the first trimester of pregnant women in China. DESIGN We screened 4800 pregnant women in the first trimester and 2000 women who planned to become pregnant and evaluated 535 pregnant women in follow-up visits during the second and third trimester. RESULTS Median concentrations of serum TSH decreased significantly from the seventh week of gestation. The median of TSH from 4 to 6 weeks was significantly higher than from 7 to 12 weeks (2.15 [0.56-5.31] mIU/L vs 1.47 [0.10-4.34] mIU/L, P<.001); however, there was no significant difference compared with nonpregnant women (2.07 [0.69-5.64] mIU/L; P=.784). The median of free T4 was not significantly altered in the first trimester. The prevalence of subclinical hypothyroidism in the 4800 pregnant women was 27.8% on the diagnostic criteria of TSH>2.5 mIU/L and 4.0% using the reference interval derived by our laboratory (0.14-4.87 mIU/L).Additionally, of 118 pregnant women who had serum TSH>2.5 mIU/L in the first trimester, only 30.0% and 20.3% of them at the 20th and 30th week of gestation had TSH>3.0 mIU/L. CONCLUSIONS The reference range for nonpregnant women can be used for the assessment of pregnant women at 4 to 6 weeks of gestation. The upper limit of serum TSH in the first trimester was much higher than 2.5 mIU/L in Chinese pregnant women.

More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels.

OBJECTIVE With the introduction of iodized salt worldwide, more and more people are exposed to more than adequate iodine intake levels with median urinary iodine excretion (MUI 200-300 μg/l) or excessive iodine intake levels (MUI >300 μg/l). The objective of this study was to explore the associations between more than adequate iodine intake levels and the development of thyroid diseases (e.g. thyroid dysfunction, thyroid autoimmunity, and thyroid structure) in two Chinese populations. DESIGN A population-based cross-sectional study was conducted in two areas in which people are exposed to different levels of iodine intake (Rongxing, MUI 261 μg/l; Chengshan, MUI 145 μg/l). A total of 3813 individuals were recruited by random sampling. Thyroid hormones, thyroid autoantibodies in serum, and iodine levels in urine were measured. B-mode ultrasonography of the thyroid was also performed for each participant. RESULTS The prevalence of subclinical hypothyroidism was significantly higher for subjects who live in Rongxing than those who live in Chengshan (5.03 vs 1.99%, P<0.001). The prevalence of positive anti-thyroid peroxidase antibody (TPOAb) and positive anti-thyroglobulin antibody (TgAb) was significantly higher for subjects in Rongxing than those in Chengshan (TPOAb: 10.64 vs 8.4%, P=0.02; TgAb: 10.27 vs 7.93%, P=0.01). The increase in thyroid antibodies was most pronounced in the high concentrations of TPOAb (TPOAb: ≥500 IU/ml) and low concentrations of TgAb (TgAb: 40-99 IU/ml) in Rongxing. CONCLUSIONS More than adequate iodine intake could be a public health concern in terms of thyroid function and thyroid autoimmunity in the Chinese populations.

A study for maternal thyroid hormone deficiency during the first half of pregnancy in China

Background  Maternal thyroid hormone deficiency is the most common disorder of thyroid function during pregnancy and can influence the outcome for mother and foetus. The purpose of this study was to investigate the prevalence of thyroid hormone deficiency during the first half of pregnancy in iodine sufficient areas of China.

The prevalence of thyroid disorders during early pregnancy in China: the benefits of universal screening in the first trimester of pregnancy

CONTEXT Maternal thyroid disorders during early pregnancy can influence pregnancy outcome and fetal development. The recent Endocrine Society Clinical Practice Guideline recommends a case-finding approach in which pregnant women who are at high risk for developing thyroid disease are tested. OBJECTIVE The purpose of this study was to use the first trimester-specific reference intervals of thyroid-related hormones to explore the prevalence of thyroid dysfunction during early pregnancy and to analyze effectiveness of different screening strategies. DESIGN A multicenter cohort study. METHOD A total of 2899 pregnant women were enrolled in this study during their first trimester of gestation. Levels of TSH, free thyroxine, free triiodothyronine, and thyroid peroxidase antibodies (TPOAb) were measured and thyroid disorders of pregnant women were diagnosed based on the first trimester-specific reference intervals. RESULTS The prevalence of hypothyroidism was significantly higher in the high-risk group than in the non-high-risk group (10.9 vs 7.0%, χ²=7.1, P = 0.008). The prevalence of hyperthyroidism was not significantly different between the high-risk group and the non-high-risk group (2.7 vs 1.6%, χ²=2.27, P=0.13). Elevated levels of TPOAb and a personal history of thyroid disease increased the risk of thyroid dysfunction. CONCLUSIONS A case-finding strategy for screening thyroid function in the high-risk group would miss about 81.6% pregnant women with hypothyroidism and 80.4% pregnant women with hyperthyroidism.

Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes

Objective  The aim of the present study was to evaluate whether the status of iodine nutrition influences the TSH concentration in a selected Chinese reference population according to the criteria proposed by National Academy of Clinical Biochemistry (NACB) and regular thyroid ultrasonography, to establish a new reference interval of TSH based on the wide variation of iodine nutrition in populations, and to identify an optimal interval of TSH by following up the cohort with normal TSH concentrations at baseline.

Chronic iodine excess does not increase the incidence of hyperthyroidism: a prospective community-based epidemiological survey in China

OBJECTIVE An increasing incidence of hyperthyroidism has been observed when iodine supplementation has been introduced to an iodine-deficient population. Moreover, the influence of chronic more than adequate or excessive iodine intake on the epidemiological features of hyperthyroidism has not been widely and thoroughly described. To investigate the influences of different iodine intake levels on the incidence of hyperthyroidism, we conducted a prospective community-based survey in three communities with mild-deficient, more than adequate (previously mild deficient iodine intake), and excessive iodine intake. SUBJECTS AND METHODS In three rural Chinese communities, a total of 3761 unselected inhabitants aged above 13 years participated in the original investigation and 3018 of them received identical examinations after 5 years. Thyroid function, levels of thyroid peroxidase antibody (TPOAb), thyroglobulin antibody and urinary iodine excretion were measured and thyroid ultrasound examination was also performed. RESULTS In three communities, median urinary iodine excretion was 88, 214, and 634 microg/l (P<0.05) respectively. The cumulative incidence of hyperthyroidism was 1.4, 0.9, and 0.8% (P>0.05) respectively. Autoimmune hyperthyroidism was predominant in thyroid hyperfunction in all the three cohorts. Either positive TPOAb (>50 U/ml) or goiter in original healthy participants was associated with the occurrence of unsuspected hyperthyroidism in 5 years (logistic regression, OR=4.2 (95% CI 1.7-8.8) for positive TPOAb, OR=3.1 (95% CI 1.4-6.8) for goiter). CONCLUSION Iodine supplementation may not induce an increase in hyperthyroidism in a previously mildly iodine-deficient population. Chronic iodine excess does not apparently increase the risk of autoimmune hyperthyroidism, suggesting that excessive iodine intake may not be an environmental factor involved in the occurrence of autoimmune hyperthyroidism.

High iodine intake is a risk factor of post-partum thyroiditis: Result of a survey from Shenyang, China

The aim of the present study is to obtain the epidemiological data on post-partum thyroiditis (PPT) firstly in Chinese women, and to try to evaluate whether excessive intake of iodine in post-partum women imposes any danger of occurring PPT. Sixty hundred and ten pregnant women were involved in the cohort just before delivery. Four hundred and eighty-eight (80%) of them accepted taking part in follow-ups more than 6 months post-partum. A blood sample was taken from participants before delivery and every 3 months post-partum for testing of serum TSH, thyroid autoantibodies. Free T3 (FT3), free T4 (FT4) and TSH receptor antibody (TRAb) were detected if TSH was abnormal. The iodine nutrition was evaluated according to the mean level of the fasting urinary iodine excretions at different times during the studying period, and participants were subgrouped into 3 categories with low, adequate and high iodine intake. For those participants who had thyroid dysfunction within 6 months post-partum, the follow-up persisted for 1 yr. Of 488 preg- nant women, PPT developed in 11.9% (58/488). Given overt and subclinical PPT, the prevalence was 7.17% (no.=35) and 4.71% (no.=23), respectively. There was a strong association between the presence of thyroid peroxidase antibody (TPOAb) at delivery and the risk of developing PPT [RR=6.76, 95% (CI) 4.42–10.34]. Overt cases had much higher titers of TPOAb than subclinical patients (all p<0.05). The median urinary iodine (MUI) of patients with PPT was significantly higher than that of healthy women (231.93 vs 199.88 μg/l p=0.00153). Both the prevalence of PPT and positive TPOAb rise with the increment of iodine intakes. Pregnant women with high iodine intake had more risk of developing PPT when compared with those with low iodine intake (RR=2.92, 95%CI 1.31–6.50). We concluded that positive TPOAb was of value for predicting the occurrence and severity of PPT, and a high iodine intake was a risk factor triggering PPT.

The effect of maternal subclinical hypothyroidism during pregnancy on brain development in rat offspring.

BACKGROUND Maternal thyroid hormones (THs), especially thyroxine (T(4)), are crucial to early brain development in the mammalian embryo. Epidemiological studies and case reports have shown that maternal subclinical hypothyroidism may result in significant negative effects on pregnancy and neurodevelopment of the fetus. To understand the mechanism responsible for these neurological alterations, we induced maternal subclinical hypothyroidism in pregnant rats. Behavior and several genes that are under the control of THs were evaluated in the offspring of TH-deficient rats. METHODS A total of 60 female rats were divided into three groups: (i) maternal subclinical hypothyroidism (total thyroidectomy with T(4) infusion), (ii) maternal hypothyroidism (total thyroidectomy without T(4) infusion), and (iii) control (sham operated). All rats were mated 10 days after the start of infusion. The infusion continued until 10 days postpartum. Pups were sacrificed at postnatal day 3 (PND 3), PND 7, and PND 21. The hippocampus was collected and tested for brain-derived neurotrophic factor (BDNF) and Rap1 protein expression by Western blotting and for BDNF and neural cell adhesion molecule mRNA expression by real-time polymerase chain reaction. On PND 41-PND 49, rat pups explored the Morris water maze. Time spent in the quadrant previously containing the platform was recorded. RESULTS This study found decreases in BDNF mRNA expression (on PND 3) and protein level (on PND 3 and PND 7) in hippocampi of pups from subclinical hypothyroidism dams (p < 0.05). Rap1 protein expression was higher in maternal subclinical hypothyroidism offspring than in control offspring at PND 7 and PND 21. No change was observed in neural cell adhesion molecule mRNA expression in the maternal subclinical hypothyroidism offspring. In addition, results from the Morris water maze revealed that pups from the subclinical hypothyroidism dams showed deficits in long-term memory, spending less time in the platform quadrant (p < 0.05) during testing. There was a trend toward a deficit in short-term memory (p > 0.05) in this group as well. CONCLUSIONS The long-term memory deficits of pups born to maternal subclinical hypothyroidism dams likely related with decreasing in BDNF mRNA expression and protein level as well as increasing in Rap1 protein expression in hippocampi.