Objective: To investigate the risk factors of childhood systemic lupus erythematosus (SLE) with thyroid dysfunction and to explore the relationship between thyroid hormone and kidney injury of lupus nephritis (LN). Methods: In this retrospective study, 253 patients who were diagnosed with childhood SLE and hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2021 were enrolled in the case group, and 70 healthy children were the control cases. The patients in the case group were divided into the normal thyroid group and the thyroid dysfunction group. Independent t-test, χ² test, and Mann-Whitney U test were used for comparison between the groups, Logistic regression analysis was used for multivariate analysis, and Spearman correlation. Results: A total of 253 patients, there were 44 males and 209 females in the case group, and the age of onset was 14 (12, 16) years; a total of 70 patients, 24 males and 46 females were in the control group, and the age of onset was 13 (10, 13) years. The incidence of thyroid dysfunction in the case group was higher than that in the control group (48.2% (122/253) vs. 8.6% (6/70), χ²=36.03, P<0.05). Of the 131 patients, there were 17 males and 114 females in the normal thyroid group, and the age of onset was 14 (12, 16) years. Of the 122 patients in the thyroid dysfunction group, 28 males and 94 females were in the thyroid dysfunction group, and the age of onset was 14 (12, 16) years. Of the 122 had thyroid dysfunction, including 51 cases (41.8%) with euthyroid sick syndrome, 25 cases (20.5%) with subclinical hypothyroidism, 18 cases (14.8%) patients with sub-hyperthyroidism, 12 cases (9.8%) with hypothyroidism, 10 cases (8.2%) with Hashimoto's thyroiditis, 4 cases (3.3%) with hyperthyroidism, and 2 cases (1.6%) with Graves disease. Compared to patients with normal thyroid function, the serum level of triglyceride, total cholesterol, urine white blood cell, urine red blood cell, 24 h urine protein, D-dimer, and fibrinogen, ferritin and systemic lupus erythematosus disease activity Index-2000 (SLEDAI-2K) score were higher in patients with thyroid dysfunction (Z=3.07, 3.07, 2.48, 3.16, 2.40, 3.99, 2.68, 2.55, 2.80, all P<0.05), while the serum level of free thyroxine and C3 were lower in thyroid disfunction patients (10.6 (9.1, 12.7) vs. 11.3 (10.0, 12.9) pmol/L, and 0.46 (0.27, 0.74) vs. 0.57 (0.37, 0.82) g/L, Z=2.18, 2.42, both P<0.05). The higher level of triglyceride and D-dimer were the independent risk factors for childhood SLE with thyroid dysfunction (OR=1.40 and 1.35, 95%CI 1.03-1.89 and 1.00-1.81, respectively, both P<0.05). There were 161 patients with LN in the case group, all of which were conducted with renal biopsies, including 11 cases (6.8%) with types Ⅰ LN, 11 cases (6.8%) with typesⅡLN, 31 cases (19.3%) with types Ⅲ LN, 92 cases (57.1%) with types Ⅳ LN, and 16 cases (9.9%) with types Ⅴ LN. There were significant differences in the level of free triiodothyronine and thyroid stimulating hormone among different types of kidney pathology (both P<0.05); compared with types I LN, the serum level of free triiodothyronine was lower in types Ⅳ LN (3.4 (2.8, 3.9) vs. 4.3 (3.7, 5.5) pmol/L, Z=3.75, P<0.05). The serum level of free triiodothyronine was negatively correlated with the acute activity index score of lupus nephritis (r=-0.228, P<0.05), while the serum level of thyroid stimulating hormone was positively correlated with the renal pathological acute activity index score of lupus nephritis (r=0.257, P<0.05). Conclusions: There is a high incidence of thyroid dysfunction in childhood SLE patients. The higher SLEDAI and more severe renal damage were found in SLE patients with thyroid dysfunction compared to these with normal thyroid functions. The risk factors of childhood SLE with thyroid dysfunction are the higher level of triglyceride and D-dimer. The serum level of thyroid hormone is possibly related to the kidney injury of LN.
Child ; Female ; Male ; Humans ; Lupus Nephritis/epidemiology* ; Triiodothyronine ; Retrospective Studies ; Lupus Erythematosus, Systemic/complications* ; Hypothyroidism/epidemiology* ; Hyperthyroidism ; Risk Factors

BACKGROUND: Although congenital hypothyroidism (CH) has been widely studied in Western countries, CH incidence at different administrative levels in China during the past decade remains unknown. This study aimed to update the incidence and revealed the spatial pattern of CH incidence in the mainland of China, which could be helpful in the planning and implementation of preventative measures. METHODS: The data used in our study were derived from 245 newborns screening centers that cover 30 provinces of the Chinese Newborn Screening Information System. Spatial auto-correlation was analyzed by Global Moran I and Getis-Ord Gi statistics at the provincial level. Kriging interpolation methods were applied to estimate a further detailed spatial distribution of CH incidence at city level throughout the mainland of China, and Kulldorff space scanning statistical methods were used to identify the spatial clusters of CH cases at the city level. RESULTS: A total of 91,921,334 neonates were screened from 2013 to 2018 and 42,861 cases of primary CH were identified, yielding an incidence of 4.66 per 10,000 newborns screened (95% confidence interval [CI]: 4.62-4.71). Neonates in central (risk ratio [RR] = 0.84, 95% CI: 0.82-0.85) and western districts (RR = 0.71, 95% CI: 0.69-0.73) had lower probability of CH cases compared with the eastern region. The CH incidence indicated a moderate positive global spatial autocorrelation (Global Moran I value = 0.394, P  < 0.05), and the CH cases were significantly clustered in spatial distribution. A most likely city-cluster (log-likelihood ratio [LLR] = 588.82, RR = 2.36, P  < 0.01) and 25 secondary city-clusters of high incidence were scanned. The incidence of each province and each city in the mainland of China was estimated by kriging interpolation, revealing the most affected province and city to be Zhejiang Province and Hangzhou city, respectively. CONCLUSION This study offers an insight into the space clustering of CH incidence at provincial and city scales. Future work on environmental factors need to focus on the effects of CH occurrence.
China/epidemiology* ; Cluster Analysis ; Congenital Hypothyroidism/epidemiology* ; Humans ; Incidence ; Infant, Newborn ; Retrospective Studies ; Spatial Analysis

Adult ; Asymptomatic Diseases/epidemiology* ; Autoimmune Diseases/etiology* ; China/epidemiology* ; Female ; Humans ; Hypothyroidism/etiology* ; Male ; Metabolic Syndrome/epidemiology* ; Middle Aged ; Obesity/epidemiology* ; Risk Factors ; Thyroid Diseases/etiology* ; Young Adult

OBJECTIVE: To investigate the prevalence rate of hypothyroidism in children with β-thalassemia major (β-TM) and its risk factors. METHODS: A total of 86 children with β-TM treated and followed up in the Department of Pediatrics of the Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai Municipal Maternal and Child Health Care Hospital from August 2018 to August 2020 were enrolled. The clinical data of the children were analyzed to investigate the prevalence rate of hypothyroidism in children with β-thalassemia major (β-TM) and its risk factors. RESULTS: The prevalence rate of hypothyroidism in children with β-TM in Zhuhai area was 17.4%. The level of serum ferritin(SF) (4948.27±1225.33 μg/L) in hypothyroidism children was significantly increased(t=10.273，P<0.05). The prevalence rate of hypothyroidism was significantly higher in β-TM children(age ≥10 years old, SF ≥2 500 μg/L and irregular iron removal) (P<0.05). Logistic regression result showed that age ≥10 years old was the independent risk factor affecting the increasing of hypothyroidism rate in the children. The levels of SF(3880.60±1269.17 μg/L), TSH(4.43±1.52 mIU/L) and the prevalence rate of hypothyroidism(37.14%)(P<0.05) were higher for the children in irregular iron removal group. CONCLUSION The prevalence rate of hypothyroidism in children with β-TM in Zhuhai area is high, and it is related to the age ≥10 years old, SF ≥2 500 μg/L and irregular iron removal of the children.
Child ; Humans ; Hypothyroidism/epidemiology* ; Iron Overload ; Prevalence ; Risk Factors ; beta-Thalassemia/epidemiology*

OBJECTIVE: To describe the thyroid function abnormality of first-trimester twin pregnant women according to different references, and to explore its association with preterm delivery. METHODS: Participants, first-trimester twin pregnant women, were recruited at Peking University Third Hospital from March 2017 to February 2020. The thyroid hormone reference for ordinary adults identified on the assay kits by Siemens incorporation, thyroid hormone reference specifically for singleton pregnancy established previously, and thyroid hormone reference specifically for twin pregnancy established previously were used in the description of hypothyroidism and hyperthyroidism for first-trimester twin pregnant women. Thyroid autoantibody reference identified on the assay kits by Siemens incorporation was used in the description of positive thyroid autoantibody. Multivariable log-binomial regression was conducted to examine the association between thyroid function and preterm delivery, in which normal pregnant women according to the three references and normal pregnant women according to twin pregnancy reference accompanied with negative thyroid autoantibody were taken as control respectively. RESULTS: A total of 570 twin pregnant women were finally included. Rates of hypothyroidism according to the three references were 1.2%, 1.6% and 3.5%, respectively. Rates of hyperthyroidism according to the three references were 32.6%, 18.1% and 1.1%, respectively. After adjustment for potential confounding factors, risk of preterm delivery significantly increased in pregnant women with hyperthyroidism according to the twin specific pregnancy reference [adjusted relative risk (ARR)=1.41, 95%CI: 1.14-1.75], while no significant increase was found in those with normal thyroid function according to the twin specific pregnancy reference but hyperthyroidism according to the singleton specific pregnancy reference (ARR=1.00, 95%CI: 0.81-1.25) and in those with hyperthyroidism purely according to the ordinary adult reference (ARR=1.06, 95%CI: 0.85-1.32), compared with those normal according to all the references. Risks of preterm delivery almost significantly or significantly increased in pregnant women with hypothyroidism according to the ordinary adult or singleton specific pregnancy reference (ARR=1.40, 95%CI: 0.88-2.22) and those with hypothyroidism according to the twin specific pregnancy reference (ARR=1.53, 95%CI: 1.03-2.28). Overall analysis of thyroid function according to the twin specific pregnancy reference and thyroid autoantibody showed that risks of preterm delivery almost significantly or significantly increased in pregnant women with simple hypothyroidism (ARR=1.46, 95%CI: 0.93-2.27), simple positive thyroid autoantibody (ARR=1.32, 95%CI: 1.15-1.52), and hypothyroidism accompanied with positive thyroid autoantibody (ARR=1.78, 95%CI: 1.30-2.44), compared with those normal according to the twin specific pregnancy reference with negative thyroid autoantibody. CONCLUSION The ordinary adult reference and that of singleton pregnancy may lead to under-diagnosis of hypothyroidism and over-diagnosis of hyperthyroidism in first-trimester twin pregnant women. Compared with pregnant women with normal thyroid function, those missed in the diagnosis of hypothyroidism were at a higher risk of preterm delivery, while those over-diagnosed as hyperthyroidism had a similar risk of preterm delivery, indicating a need to develop and generalize twin-pregnancy-specific reference on common indicators of thyroid function. Moreover, the thyroid autoantibody should be taken into consideration in the prenatal diagnosis and treatment to twin pregnant women with hypothyroidism.
Adult ; Female ; Humans ; Hypothyroidism/epidemiology* ; Infant, Newborn ; Pregnancy ; Pregnancy Complications/epidemiology* ; Pregnancy Trimester, First ; Pregnant Women ; Premature Birth/epidemiology*

Objective: To investigate the effects of high iodine intake on thyroid function in pregnant and lactating women. Methods: A cross sectional epidemiological study was conducted among 130 pregnant women and 220 lactating women aged 19-40 years in areas with high environment iodine level (>300 μg/L) or proper environment iodine level (50-100 μg/L) in Shanxi in 2014. The general information, urine samples and blood samples of the women surveyed and water samples were collected. The water and urine iodine levels were detected with arsenic and cerium catalysis spectrophotometric method, the blood TSH level was detected with electrochemiluminescence immunoassay, and thyroid stimulating hormone (FT(4)), antithyroid peroxidase autoantibody (TPOAb) and anti-thyroglobulin antibodies (TGAb) were detected with chemiluminescence immunoassay. Results: The median urine iodine levels of the four groups were 221.9, 282.5, 814.1 and 818.6 μg/L, respectively. The median serum FT(4) of lactating women in high iodine area and proper iodine area were 12.96 and 13.22 pmol/L, and the median serum TSH was 2.45 and 2.17 mIU/L, respectively. The median serum FT(4) of pregnant women in high iodine area and proper iodine area were 14.66 and 16.16 pmol/L, and the median serum TSH was 2.13 and 1.82 mIU/L, respectively. The serum FT(4) levels were lower and the abnormal rates of serum TSH were higher in lactating women than in pregnant women in both high iodine area and proper iodine area, the difference was statistically significant (FT(4): Z=-6.677, -4.041, P<0.01; TSH: Z=8.797, 8.910, P<0.01). In high iodine area, the abnormal rate of serum FT(4) in lactating women was higher than that in pregnant women, the difference was statistically significant (Z=7.338, P=0.007). The serum FT(4) level of lactating women in high iodine area was lower than that in proper iodine area, the difference was statistically significant (Z=-4.687, P=0.000). In high iodine area, the median serum FT(4) in early pregnancy, mid-pregnancy and late pregnancy was 16.26, 14.22 and 14.80 pmol/L, respectively, and the median serum TSH was 1.74, 1.91 and 2.38 mIU/L, respectively. In high iodine area, the serum FT(4) level in early pregnancy was higher than that in mid-pregnancy and late pregnancy, and the serum TSH level was lower than that in mid-pregnancy and late pregnancy, the difference was statistically significant (FT(4): Z=-2.174, -2.238, P<0.05; TSH: Z=-2.985, -1.978, P<0.05). There were no significant differences in the positive rates of serum thyroid autoantibodies among the four groups of women and women in different periods of pregnancy (P>0.05). The morbidity rates of subclinical hyperthyroidism in pregnant women and lactating women in high iodine area were obviously higher than those in proper iodine areas, the difference was statistically significant (χ(2)=5.363, 5.007, P<0.05). Conclusions: Excessive iodine intake might increase the risk of subclinical hypothyroidism in pregnant women and lactating women. It is suggested to strengthen the iodine nutrition and thyroid function monitoring in women, pregnant women and lactating women in areas with high environmental iodine.
Adult ; China/epidemiology* ; Cross-Sectional Studies ; Female ; Humans ; Hypothyroidism/epidemiology* ; Iodides/administration & dosage* ; Iodine/urine* ; Lactation ; Nutritional Status ; Pregnancy ; Prevalence ; Thyroid Diseases/epidemiology* ; Thyroid Function Tests ; Thyroid Gland/physiology* ; Young Adult

BACKGROUND: Most cases with congenital hypothyroidism (CH) are usually sporadic, while about 20% of the cases are caused by genetic defects. Little information is available regarding the mutation incidence and genetic heterogeneity of CH in Koreans. We aimed to determine the mutation incidence of CH in newborn screenings (NBS) and to evaluate the frequency and spectrum of mutations underlying CH. METHODS: A total of 112 newborns with thyroid dysfunction were enrolled from 256,624 consecutive NBS. Furthermore, 58 outpatients with primary CH were added from an endocrine clinic. All coding exons of TSHR, PAX8, TPO, DUOX2, DUOXA2, and SCL5A5 were sequenced. RESULTS: The mutation incidence of CH was estimated to be 1 in 6,580 newborns. A total of 36 different mutations were identified in 53 cases. The overall mutation positive rate was 31%. The DUOX2 mutations were the most prevalent in both newborns and outpatients. Seven different recurrent mutations [p.G488R (n=13), p.A649E (n=3), p.R885Q (n=3), p.I1080T (n=2), and p.A1206T (n=2) in DUOX2; p.Y138X (n=9) in DUOXA2; and p.R450H (n=5) in TSHR) were identified as the mutations underlying CH. CONCLUSIONS: The mutation incidence of CH was considerably higher than expected in the Korean newborn population. This study revealed seven different recurrent mutations underlying CH. We conclude that DUOX2 mutations are a frequent cause of CH in the Korean population.
Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Congenital Hypothyroidism/epidemiology/*genetics/pathology ; Exons ; Female ; Genetic Association Studies ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; NADPH Oxidase/*genetics ; Polymorphism, Single Nucleotide ; Republic of Korea/epidemiology ; Sequence Analysis, DNA ; Thyrotropin/blood

BACKGROUND/AIMS: Hypothyroidism is reported to contribute to the development of nonalcoholic fatty liver disease (NAFLD). We compared the risk of the development of NAFLD among three groups with different thyroid hormonal statuses (control, subclinical hypothyroidism, and overt hypothyroidism) in a 4-year retrospective cohort of Korean subjects. METHODS: Apparently healthy Korean subjects without NAFLD and aged 20-65 years were recruited (n=18,544) at health checkups performed in 2008. Annual health checkups were applied to the cohort for 4 consecutive years until December 2012. Based on their initial serum-free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels, they were classified into control, subclinical hypothyroidism (TSH >4.2 mIU/L, normal fT4), and overt hypothyroidism (TSH >4.2 mIU/L, fT4 <0.97 ng/dL) groups. NAFLD was diagnosed on the basis of ultrasonography findings. RESULTS: NAFLD developed in 2,348 of the 18,544 subjects, representing an overall incidence of 12.7%: 12.8%, 11.0%, 12.7% in the control, subclinical hypothyroidism, and overt hypothyroidism groups, respectively. The incidence of NAFLD did not differ significantly with the baseline thyroid hormonal status, even after multivariate adjustment (subclinical hypothyroidism group: hazard ratio [HR]=0.965, 95% confidence interval [CI]=0.814-1.143, P=0.67; overt hypothyroidism group: HR=1.255, 95% CI=0.830-1.899, P=0.28). CONCLUSIONS: Our results suggest that the subclinical and overt types of hypothyroidism are not related to an increased incidence of NAFLD.
Adult ; Aged ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Hypothyroidism/*complications/*diagnosis ; Incidence ; Kaplan-Meier Estimate ; Liver/ultrasonography ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*complications/*diagnosis/epidemiology ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Thyrotropin/analysis ; Thyroxine/analysis

OBJECTIVETo summarize and analyze neonatal screening results for congenital hypothyroidism (CH) in parts of Yunnan Province, China.

METHODSA total of 236 218 newborns (121 463 males and 114 755 females) who were born in Zhaotong City, Qujing City, Lijiang City, and Diqing Tibetan Autonomous Prefecture of Yunnan Province, China, between July 2012 and April 2014 were screened for CH. The original blood smear was re-tested if the thyroid stimulating hormone (TSH) level in heel blood was ≥8 μIU/L in the initial screening. The newborns with positive TSH results were called back for further diagnosis by measuring blood TSH and free thyroxine (FT4) levels.

RESULTSAmong 236 218 newborns, the pass rate of blood smears, re-acquisition rate of unqualified blood smears, and recall rate of suspected cases were 96.67%, 81.75%, and 73.02%, respectively. Sixty-six cases of CH were confirmed, among which 36 were male infants and 30 were female infants (P>0.05). The incidence rate of CH was 1/3 579, which was significantly lower than the national average rate (1/2 034; P<0.01). The gestational age of CH newborns was mostly between 37 to 42 weeks, and only 3% were born at a gestational age of >42 weeks. Most of the CH newborns had normal birth weight. The CH newborns with a body length of <50 cm accounted for 32%.

CONCLUSIONSThe incidence of CH in Yunnan Province is lower than the national average. There are no specific clinical features in CH newborns. The neonatal screening in Yunnan Province needs further improvement.

China ; epidemiology ; Congenital Hypothyroidism ; blood ; epidemiology ; Female ; Humans ; Infant, Newborn ; Male ; Neonatal Screening ; Thyrotropin ; blood

OBJECTIVETo understand the relationship between perinatal factors and congenital hypothyroidism (CH) and provide scientific evidence for the prevention of CH.

METHODSA case-control study was conducted among 125 neonates with CH (case group) and 375 neonates without CH (control group) in Fujian Neonatal Screening Center from January in 2012 to December in 2013. Univariate and multivariate logistic regression analysis were performed to identify the risk factors to CH during perinatal period.

RESULTSUnivariate logistic regression analysis indicated that compared with control group, gestational hypertension, gestational diabetes mellitus, gestational thyroid disease and older age of mother were the risk factors to CH, the difference was statistically significant (P < 0.05) and the risk of CH was higher in female babies, preterm babies, post-term babies low birth weight babies, macrosomia, twins, babies with birth defects and infection in cases group than those in control group, the difference was statistically significant (P < 0.05). Multivariate logistic analysis showed that older age of mother (OR = 2.518, 95% CI: 1.186-5.347), gestational diabetes mellitus (OR = 1.904, 95% CI: 1.190-3.045), gestational hypothyroidism or hyperthyroidism (OR = 12.883 and 30.797, 95% CI: 2.055-80.751 and 3.309-286.594), preterm birth (OR = 4.238, 95% CI: 1.269-14.155), and post-term birth (OR = 12.799, 95% CI: 1.257-130.327), low birth weight (OR = 3.505, 95% CI: 1.059-11.601), macrosomia (OR = 3.733, 95% CI: 1.415-9.851), twin or multiparous delivery (OR = 5.493, 95% CI: 1.701-17.735), birth defects (OR = 3.665, 95% CI: 1.604-8.371) and fetal distress (OR = 3.130, 95% CI: 1.317-7.440) were the high risk factors to CH (P < 0.05).

CONCLUSIONCH was correlated with mother's age, gestational diabetes, gestational thyroid disease as well as neonate's birth weight and gestational age, foetus number, fetal distress and other complicated birth defects at certain degree. More attention should be paid to perinatal care to reduce risk factors and the incidence of CH.

Birth Weight ; Case-Control Studies ; Congenital Hypothyroidism ; epidemiology ; Diabetes, Gestational ; epidemiology ; Female ; Gestational Age ; Humans ; Hypertension, Pregnancy-Induced ; epidemiology ; Incidence ; Infant, Newborn ; Infant, Premature ; Maternal Age ; Neonatal Screening ; Pregnancy ; Pregnancy Complications ; epidemiology ; Premature Birth ; Risk Factors ; Twins