Xiaohui Yu

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.

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.

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.

Iron deficiency, an independent risk factor for isolated hypothyroxinemia in pregnant and nonpregnant women of childbearing age in China.

CONTEXT Isolated hypothyroxinemia during early pregnancy may irreversibly damage the neurodevelopment of offspring. However, the causes are not well clarified. OBJECTIVE To explore the association of iron deficiency (ID) with hypothyroid function of women in early pregnancy and nonpregnant women. DESIGN A total of 7953 pregnant women of ≤ 12 weeks gestation and 2000 childbearing-aged women were recruited. A subpopulation including 3340 pregnant women and 1052 nonpregnant women with sufficient iodine intake and negative thyroid peroxidase antibody were studied. Mild and severe cases of hypothyroxinemia were defined as free T4 levels below the 10th percentile and the 5th percentile, respectively, with normal TSH. Total body iron, serum ferritin, and serum transferrin receptor were used as indicators for iron nutrition. RESULTS Serum free T4 levels were significantly lower in both pregnant and nonpregnant women with ID compared with the corresponding groups without ID (both P < .05). The prevalence of mild and severe hypothyroxinemia was markedly higher in women with ID than those without, in both pregnant and nonpregnant women (all P < .01). Logistic regression indicated that ID was an independent risk factor for both mild and severe hypothyroxinemia in pregnancy (odds ratio [OR] = 2.440, 95% confidence interval [CI]: 1.324-4.496, P = .004; and OR = 3.278, 95% CI: 1.443-7.446, P = .005, respectively) and nonpregnancy (OR = 2.662, 95% CI: 1.330-5.329, P = .006; and OR = 3.254, 95% CI: 1.375-7.700, P = .007, respectively). CONCLUSIONS An association between ID and isolated hypothyroxinemia was found in both pregnant and nonpregnant childbearing-aged women, independent of the effects of iodine and thyroid autoimmunity. We speculate that ID may be a pathogenic factor for hypothyroxinemia, even in pregnant women during the first trimester.

Aberrant Overexpression of Pyruvate Kinase M2 Is Associated With Aggressive Tumor Features and the BRAF Mutation in Papillary Thyroid Cancer

CONTEXT Many tumor cells predominantly generate energy through high rates of glycolysis. Pyruvate kinase M2 (PKM2) has been identified as being necessary for aerobic glycolysis. OBJECTIVE The aim of this study was to investigate the expression pattern of PKM2 in papillary thyroid cancer (PTC) and the possible role of PKM2 in PTC. DESIGN The expression of PKM2 in human thyroid tissues was examined using immunocytochemistry. PKM2 expression in PTC correlated with clinicopathological features and the BRAF mutation. PTC cells were transfected with small interfering RNA against PKM2. PKM2 expression in cells was analyzed by Western blotting and real-time RT-PCR. Cell growth was evaluated both in vitro and in vivo. Lactate and ATP production and glucose consumption by cells were determined using commercial assay kits. RESULTS PKM2 was aberrantly overexpressed in PTC. This overexpression was associated with poor clinicopathological features including advanced tumor stages and lymph node metastasis. More intensive immunostaining of PKM2 was detected in PTCs harboring the BRAF mutation. Specific small interfering RNA against PKM2 in PTC cell lines retarded cell growth both in vitro and in xenograft mouse models. PKM2 knockdown also reduced lactate and ATP production and glucose consumption by PTC cells. CONCLUSIONS We conclude that overexpression of PKM2 provides a selective growth advantage for PTC cells through activation of glycolysis. Aberrant PKM2 overexpression may serve as a novel biomarker and a potential treatment target for PTC. The BRAF mutation may contribute to alterations in the expression pattern of glycolytic enzymes such as PKM2.

A five-year follow-up study of goiter and thyroid nodules in three regions with different iodine intakes in China

Objective: The association between iodine status and the prevalence of goiter and thyroid nodules has been well established but the extent to which different iodine intake levels influence the incidence of goiter and thyroid nodules is unclear. The aim of the study was to determine the incidence of goiter and thyroid nodules in 3 regions with different iodine intake levels: mildly deficient, more than adequate, and excessive. Design, patients and measurements: Of the 3385 un-selected subjects enrolled in 1999 in Panshan, Zhangwu, and Huanghua where median urinary iodine excretion (UIE) was 83.5 μg/l, 242.9 μg/l, and 650.9 μg/l, respectively, 2708 (80.0%) participated in the follow-up study in 2004. The examinations of thyroid ultrasonography, thyroid function, thyroid autoantibodies and UIE were performed at baseline and follow-up. Results: The cumulative incidence of diffuse goiter was 7.1 %, 4.4%, and 6.9%, respectively, higher in Panshan and Huanghua than in Zhangwu (p=0.013 and p=0.015) and that of nodular goiter was 5.0%, 2.4%, and 0.8%, respectively, declining with increasing iodine intake levels (p<0.001). Mild iodine deficiency, chronic iodine excess as well as positive thyroid autoantibodies were associated with the occurrence of goiter [Logistic regression: odds ratio (OR)=1.83 (95% confidence interval (CI) 1.26–2.65), OR=1.46 (95% CI 1.01–2.11 ) and OR=1.68 (95% CI 1.14–2.48), respectively]. The cumulative incidence of single nodule was 4.0%, 5.7%, and 5.6%, respectively and that of multiple nodules was 0.4%, 1.2%, and 1.0%, respectively. Conclusions: The relationship between iodine and the risk for the occurrence of diffuse goiter shows a U-shaped curve. Nodular goiters are more prevalent in iodine-deficient areas.