Gestational hypothyroxinemia and offspring autism / 中华内分泌代谢杂志

Hypothyroxinemia is a common subclinical thyroid dysfunction in pregnant women. Epidemiological studies have shown that the offspring of maternal hypothyroxinemia have a significantly increased risk of autism, but mechanisms remain unclear. Studies from clinical and animals suggest that thyroid hormone deficiency may lead to irreversible damage to brain development, which may contribute to autism. This review explores the clinical evidence of gestational hypothyroxinemia and autism in offspring and the underlying mechanisms that promote the development and progression of autism. It also emphasizes the importance of early diagnosis and treatment of thyroid disease in pregnancy for the prevention of neurodevelopmental abnormalities in offspring.

Effects of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy on complications and adverse outcomes of pregnancy / 中华内分泌代谢杂志

Objective:To investigate the effects of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy on complications and adverse outcomes of pregnancy.Methods:A retrospective analysis was conducted in 784 pregnant women including 111 cases of persistent isolated hypothyroxinemia in the first and second trimester of pregnancy and 673 pregnant women with normal thyroid function as control group. All women were registered and delivered in the Department of Obstetrics of our hospital from April 2016 to April 2017. The complications and adverse outcomes of pregnancy in the two groups were analyzed.Results:Age, body weight before pregnancy, body mass index(BMI), 1 h plasma glucose and 2 h plasma glucose during oral glucose tolerance test in persistent isolated hypothyroxinemia group were higher than those in control group( P<0.05), with increased incidence of anemia during pregnancy( P<0.05). However, there were no significant differences in the incidences of gestational diabetes mellitus and gestational hypertension between the two groups( P>0.05). No significant statistical differences were found in macrosomia, stillbirth, neonatal malformation, postpartum hemorrhage, acute delivery, premature delivery, fetal intrauterine development delay, and small full-term infants between the two groups( P>0.05). Logistic regression analysis showed that age( OR=1.1, 95% CI 1.0-1.1, P=0.002) and pre-pregnancy body weight( OR=1.0, 95% CI 1.0-1.1, P=0.046) were risk factors for the occurrence of persistent isolated hypothyroxinemia in the first and second trimesters of pregnancy. Persistent isolated hypothyroxinemia in the first and second trimesters was associated with anemia during pregnancy( OR=1.9, 95% CI 1.1-3.2, P=0.024). Conclusions:Pregnant women who are older and heavier before pregnancy should pay more attention to their thyroid function. Pregnant women with persistent isolated hypothyroxinemia in the first and second trimesters should be concerned for anemia.

Transient hypothyroxinemia of prematurity and its risk factors in an extramural neonatal intensive care unit

ABSTRACT Objective: Thyroid functions in preterm newborns may be altered in the first week of life. Hypothyroxinemia has been commonly reported in these babies, which could be due to the immaturity of the hypothalamic pituitary thyroid axis or acute illness. It could have a long-term impact on the developing brain of these babies. We conducted this study to estimate the incidence of transient hypothyroxinemia of prematurity (THOP) and to determine its risk factors. Materials and methods: We analyzed thyroid stimulating hormone (TSH) and free T4 levels of 64 preterm neonates admitted in the neonatal intensive care unit. TSH and free T4 levels were measured in the first week and then at 14-21 days of life to estimate the incidence of THOP and determine its risk factors. We also estimated the incidence of congenital hypothyroidism (CH) and delayed TSH elevation in CH. Risk analysis was conducted using simple and multiple logistic regression, and numerical data was compared using the Mann Whitney U test and t test. Results: THOP was seen in 25% of the preterm babies. Caesarean delivery, presence of one or more morbidities, mechanical ventilation, birth weight ≥ 1,500 g, and gestational age ≥ 32 weeks were identified as risk factors for THOP based on simple logistic regression. In multiple regression, mechanical ventilation and gestational age ≥ 32 weeks were significantly associated with THOP. CH was seen in 2 (3.1%) babies, and 1 of these cases had delayed TSH elevation. Conclusion: Thyroid abnormalities are common in preterm admitted neonates. Mechanical ventilation is an independent risk factor for development of THOP.

Severe hypothyroxinemia in a young adult with Carbimazole-TreatedT3-Predominant Graves’ hyperthyroidism, Reversed with L-Thyroxine Loading Immediately Post-Total Thyroidectomy / Journal of the ASEAN Federation of Endocrine Societies

@#Patients with triiodothyronine (T3)-predominant Graves’ hyperthyroidism with markedly elevated serum thyroid stimulating immunoglobulin (TSI) levels and massive goitre may display discordant hypothyroxinemia with eutriiodothyroninemia or hypertriiodothyroninemia while on anti-thyroid drug therapy. A 25-year-old female with the above was started on oral carbimazole therapy for 9 months before total thyroidectomy. Preoperatively, her serum free T4 was reduced to below detection limit, and total T4 reduced to 11% of lower limit of normal, while T3 levels remained normal, and TSH remained largely suppressed. Immediately after total-thyroidectomy, a loading dose of L-thyroxine (L-T4) was administered intravenously. She was extubated without any postoperative complications. Serum free and total T4, and TSH normalized within the next 24 hours. The peculiar thyroid axis dynamics and use of L-T4 postoperative loading in such a rare clinical scenario are discussed.

Effect of thyroxine level on gestational diabetes mellitus and pregnancy outcome / 解放军医学杂志

Objective: To investigate the effect of thyroxine level on the onset of gestational diabetes mellitus (GDM), pregnancy outcome and the basic conditions of neonates. Methods: The related information of 1903 cases of pregnant women were prospectively collected from the Department of Obstetrics, Shanghai Changhai Hospital. Selecting group A (gravida with low thyroxinemia, n=36), group B (gravida with pure thyroid peroxidase antibody (TPOAb) positive, n=113) and group C (gravida with normal thyroid function, n=1539) according to the results of thyroid function test in newly constructed card. The incidence of GDM and the related index of thyroid function and glucose metabolism during the second trimester of pregnancy were compared among the three groups. Gravida with GDM in the three groups were group D (9 cases), group E (32 cases) and group F (367 cases), respectively. The differences of pregnancy outcome and the basic conditions of neonates among them were compared. Results: No significant differences existed (P>0.05) in the incidence of GDM during different pregnant period in groups A, B and C (First trimester: 50.00% vs. 25.00% vs. 34.69%; Second trimester: 21.88% vs. 28.71% vs. 22.70%). In the second trimester, the level of glycosylated hemoglobin (HbA1c) was significantly higher in group A than in group C [4.80%(4.60%, 5.00%) vs. 4.70%(4.40%, 4.90%)], w hi le the fasting glucose level was significantly higher in group B than those in group C [(4.69±0.59) mmol/L vs. (4.58±0.43) mmol/L, P0.05). Conclusions: Different levels of thyroxine have no significant effect on the incidence of GDM, but throw some effects on the glucose metabolism in the second trimester. In addition, positive TPOAb may increase the incidence of premature delivery and fetal distress in pregnant women with GDM, and affect fetal growth and development to some extent. Thyroid function status should be evaluated in the early stages of pregnancy, and regular follow-up should be conducted for patients with TPOAb positivity and timely intervention if necessary.

Establishment of reference range for specific thyroid function during pregnancy and analysis of influencing factors of hypothyroxinemia / 中华内分泌代谢杂志

Objective To establish a reference range for specific thyroid function during pregnancy and to explore the influencing factors of hypothyroxinemia during pregnancy.Methods A retrospective analysis of 2 996 cases of thyroid function in the pregnant women who were with single pregnancy and without thyroid diseases and family history of those diseases.Results (1) Establish a unified reference range for specific thyroid function during pregnancy;the early,middle,and late trimesters thyrotropin (TSH) ranges were 0.02-6.39,0.16-6.23,0.64-6.59 mU/L,respectively,while free thyroxine (FT4) ranges were 11.32-23.00,9.39-18.92,8.54-16.73 pmol/L respectively.The specific reference ranges of Han and Uygur pregnant women were established separately.There was no difference in the detection rates of various thyroid diseases when using their respective reference ranges and the unified reference range of the hospital (P ＞ 0.05).(2) The detection rate of various thyroid diseases (except subclinical hyperthyroidism) of our subjects with China guideline reference range was significantly higher than the reference range with the hospital (P＜0.05).(3) The detection rates of hypothyroxinemia in all pregnant women with FT4 cut points of P2.5 and P5 were 4.3％ and 7.4％,respectively,of which the Han population was 4.3％ and 7.1％,respectively,and the Uygur population was 4.3％ and 7.9％,respectively.(4) Comparing the mean age,gestational age,median urine iodine,and thyroid antibody positive rate between the hypothyroxinemia group and the control group,only the mean age and gestational age were different (P＜0.05);Logistic binary regression analysis showed that age was the risk factor for hypothyroxinemia during pregnancy (OR =1.035,95％ CI 1.006-1.066,P ＜ 0.05).Conclusions The Han and Uygur pregnant women in this area both can use the thyroid reference range of our hospital during pregnancy.The establishment of thyroid reference range may avoid over-diagnosis of thyroid disease during pregnancy.Age is a possible influencing factor of hypothyroxinemia during pregnancy.

Maternal hypothyroxinemia in the first trimester of gestation and association with obstetric and neonatal outcomes and iron deficiency: a prospective Brazilian study

ABSTRACT Objective: To evaluate the association of isolated hypothyroxinemia in the first trimester with obstetric and neonatal outcomes and iron deficiency. Subjects and methods: The study was prospective. Women who had become pregnant spontaneously were initially selected. Next, anti-thyroid peroxidase antibodies (TPOAb), free T4 (FT4), total T4 (TT4), TSH, and ferritin were measured. TPOAb-positive women were excluded. The final sample consisted of 596 women with serum TSH between 0.1 and 2.5 mIU/l. Hypothyroxinemia was defined as FT4 < 0.86 ng/dL and < 0.92 ng/dL, corresponding to the 5th and 10th percentiles, respectively, and TT4 < 7.8 ng/dL. None of the pregnant women was treated with levothyroxine until the end of pregnancy. Results: The women ranged in age from 18 to 36 years, with a median gestation of 9 weeks. T4 levels were not correlated with BMI or maternal TSH. Isolated hypothyroxinemia was observed in 4.3% (FT4 < 0.86 ng/dL), 9% (FT4 < 0.92 ng/dL), and 7% (TT4 < 7.8 ng/dL) of the pregnant women. The frequencies of obstetric and neonatal outcomes were similar in women with versus without hypothyroxinemia. In women without iron deficiency, 8.4%, 3.9%, and 6.5% had FT4 < 0.92 ng/dl, FT4 < 0.86 ng/dL and TT4 < 7.8 ng/dL, respectively. These frequencies of hypothyroxinemia were significantly higher among women with iron deficiency (20.7%, 14.8% and 17.2%, respectively). Conclusions: This prospective Brazilian study found no association between isolated hypothyroxinemia in the first trimester of gestation and obstetric or neonatal outcomes, but an association was demonstrated with iron deficiency.

Retrospective analysis of the effect of gestational hypothyroxinemia on pregnancy outcomes / 解放军医学杂志

Objective To discuss the influence of gestational hypothyroxinemia to the pregnancy outcomes and fetus development,and find the evidence of hormone replacement therapy.Methods The clinical data of 1141 gravida admitted from Nov.2014 to Oct.2015 were retrospectively analyzed,including the data of systematic antenatal examination,all the data of pregnancy,the materials of delivery,the last ultrasound examination,production status and the thyroid stimulating hormone (TSH) of the newborn etc.,to find the difference of related index.Results Of the 1141 gravida with integral data,200 had past history of thyroid disease,189 showed below normal of free thyroxine (FT4) and 752 were normal ones.The 189 gravida with normal TSH but lower FT4 were divided into group A (0-5％ lower than the normal FT4 value,n=60),group B (5％-10％ lower than the normal FT4 value,n=40) and group C (10％ and above lower than the normal FT4 value,n=89).The ones with both normal TSH and FT4 value served as control group.Compared to the control group,the higher premature delivery rate,incidence of gestational diabetes mellitus and cesarean delivery rate (P＜0.05) were found in group C,and more gravida in group B had a history of hypertension and dyslipidemia during pregnancy (P＜0.05).The cesarean delivery rate of group B and C were higher than group A.Meanwhile,the rate of group B was higher than control group (P＞0.05).At delivery,the maternal weight,BMI,diastolic pressure,and head circumference of fetus in the last ultrasound examination were higher in group C than in control group (P＜0.01),but the gestational weeks of the newborn were shorter in group C (38.55 ± 1.86 weeks) than in control group (39.14 ± 1.57 weeks,P＜0.01).The 189 gravida with lower FT4 were divided into two groups according to the thyroid peroxidase antibody (TPOAb) level.The head circumference of fetus in the last ultrasound examination was higher in TPOAb(+) group than in TPOAb(-) group (45.99 ± 62.36cm vs.33.23 ± 2.08cm,P＜0.01).Conclusions The influence of gestational hypothyroxinemia to pregnancy outcomes and fetus development cannot be ignored,especially for the pregnant women with lower FT4 value (10％ and above lower than the normal) or with positive TPOAb.It is suggested to take the thyroid function test in the early stage of pregnancy for those pregnant women mentioned above.

Relationship of hypothyroxinemia to gestational diabetes mellitus during early pregnancy / 中华内分泌代谢杂志

Objective To investigate the relationship of hypothyroxinemia to gestational diabetes mellitus during early pregnancy. Methods A total of 11 365 cases of women with early singleton pregnancies were collected from Chongqing Health Center for Women and Children. The screening of thyroid function was performed. The postload glucose concentrations and the risks of gestational diabetes mellitus in hypothyroxinemia were investigated. The relationship of thyroid hormones to postload glucose concentration was evaluated. The association between thyroid peroxidase antibodies(TPOAb) and gestational diabetes mellitus was analyzed. Results Early pregnancy women with hypothyroxinemia had a higher postload glucose concentration. Comparing to normal pregnancy women, the prevalence of gestational diabetes mellitus in hypothyroxinemia was higher(42.2%vs18.4%, P<0.05). Free thyroxine(FT4) was significantly negatively correlated with postload glucose concentration. FT4 was associated with gestational diabetes mellitus. The risk of gestational diabetes mellitus was greater when FT4 was lower. The prevalence of gestational diabetes mellitus in early pregnancy women with TPOAb levels ≥500 IU/ml was significantly higher than that in normal pregnancy women (31.2%vs 18.4%, P<0.05). Conclusion Early pregnancy women with hypothyroxinemia and TPOAb≥500 IU/ml were related to the risk of gestational diabetes mellitus. Lower FT4 was the risk factor of gestational diabetes mellitus.

Effect of hypothyroxinemia on the emotion in developing rats / 国际儿科学杂志

Objective To investigate the effect of hypothyroxinemia on emotion and hippocampus neurons in developing rats.Methods Sixty-nine healthy postnatal day (PD) 1 rats were randomly divided into control group (n =36) and experimental group (n =33).On PD1,experimental group was bilaterally thyroidectomized to establish hypothyroxinemia model,the control group was only given thyroid exposure operation without thyroid resection.On PD10,21,40,serum triiodothyronine (T3),thyroxine (T4),thyrotropicstimulating hormone (TSH) were detected by radioimmunoassay.Tail suspension test,forced swimming test,the elevated-plus maze and open field were respectively employed to detect the anxiety/depression like behavior on PD30,31,32,33.Nisslg staining was used to determine the survival of neurons at PD10,21,40 in hippocampus CA1,CA3,DG regions.Results Serum T4 levels on PD10,21,40 in experimental group decreased significantly as compared with control group (P ＜0.01),while there was no significant difference in serum T3 or TSH level (P ＞ 0.05).In the tail suspension test,immobility time of experimental group [(197.00 ± 19.50) s] was longer than control group [(158.33 ± 32.90) s,P ＜0.05].In the forced swimming test,immobility time of experimental group[(92.11 ± 35.24) s] was longer than control group [(62.00 ± 23.73) s,P ＜ 0.05].In the elevated plus-maze test,total number of arm entries and closed arm entries in experimental group were increased as compared with control group(P ＜ 0.05),percentage of closed arm/total time of experimental group was decreased as compared with control group(P ＜ 0.05).In the open field,there was no obvious difference between the two groups(P ＞ 0.05).On PD10,21,40,the amount of neurons in DG region of experimental group were less than control group(P ＜0.05),while there was no significant difference in CA1 or CA3 on PD10,21,40(P ＞0.05).Contusions Hypothyroxinemia can cause depression,hyperactivity and hippocampus neuron damage of developing rats.

Neurodevelopmental Evaluation of Very Low Birth Weight Infants With Transient Hypothyroxinemia at Corrected Age of 18-24 Months.

Objective: To perform neurodevelopmental evaluation at 18 to 24 months’ corrected age in very low birth infants (VLBW) with transient hypothyroxinemia. Design: Cohort study. Setting: Maternity teaching hospital. Patients: Premature infants who were previously evaluated for thyroid hormone values in the first weeks of life were included. Intervention: Data of these infants who weighed ≤1500 g and ≤32 weeks of gestation were retrieved for the current study. Available subjects (n=56) were evaluated for neurodevelopmental status at 18 to 24 months of corrected age. Bayley Scales of Infant Development –Second Edition (BSID-II) was performed to define Mental developmental index (MDI) and Psychomotor developmental index (PDI). Results: The mean MDI and PDI scores were similar between the infants with and without transient hypothyroxinemia of prematurity (THOP) [79.9 ± 14.9 vs 70 ± 20.7, respectively (P=0.54); and 92.2 ± 16.4 vs 85.6 ± 18.9, respectively (P=0.68)]. After adjustment for gestational age and multiple prenatal, perinatal, and early and late neonatal variables, THOP was not associated with an increased risk of disabling cerebral palsy, or a reduction of MDI and PDI scores. Conclusions: THOP may not be an important cause of problems in neurologic and mental development detected at the age of 18 to 24 months’ corrected age.

A Case of Hypothyroxinemia with Thyroxine-Binding-Globulin Deficiency

The transport proteins such as thyroxine-binding-globulin (TBG), albumin and transthyretin carry over 99% of circulating thyroid hormones. TBG is a major thyroid hormone transport protein in serum. Although TBG deficiency does not have metabolic consequences, it has diagnostic implications as it can lead to an incorrect interpretation of thyroid function tests. We experienced a case that a man who had an abnormal thyroid function showed unexpectedly low concentrations of serum total thyroxine. We detected the low TBG in his serum and he was diagnosed the TBG deficiency. We report this case along with a review of the related literature.

Transient hypothyroxinemia, brain injury and neuroethology in preterm infants / 中国小儿急救医学

Objective To analyse the associativity among serum thyroid hormone level,brain injury and neuroethology in preterm infants by testing the thyroid hormone level and neuro-behaviour assessment.Methods Fifty-two preterm infants were continuously admitted in neonatal department of Shanghai Children's Hospital from Dec 2009 to Apr 2010. Radio-immunity was used to determine the serum level of T3,T4, TSH within 6 h after birth. Each case received cranial ultrasonic examination within 3 d after birth and rechecked every week. Before discharge, every infant received a cranial MRI examination. The 52 cases were devided into three groups according to the result of ultrasound and MRI:no brain damage group (33 cases),intraventricular hemorrhage greup (10 cases) ,and white matter injury group (9 cases). At the corrected gestation age 40±2 weeks,every infant received a neonatal behavioral neurological assessment (NBNA). Results The level of serum TSH in all the three groups of preterm infants were normal, which could reject congenital hypothyroidism. Eight preterm infants(15.4% ,8/52) had normal thyroid hormone level,another 44 preterm infants(84. 6% ,44/52) got lower thyroid functions. The levels of T3 and T4 were higher in the no brain damage group than those in intraventricular hemorrhage group and white matter injury group. And the preterm infants who had white mauer injury got the lowest level of thyroine hormone T3 and T4. Thyroxine hormone levels had significant difference among three groups (P ＜ 0. 05). The preterm infants who had no brain damage got higher scores in capability, passive muscle tonus,initiative muscle tonus and total score than the other two groups. Intraventricular hemorrhage group always got higher scores in NBNA than the white matter injury group (P ＜ 0. 05). The NBNA scores had significant difference among three groups (P ＜ 0. 05). Conclusion Premature infant who has more severe brain injury always has lower levels of thyroxine hormone. Premature infants with brain injury get lower scores in NBNA test than those without brain injury.

Clinical trials with thyroid hormone supplementation in preterm infants with transient hypothyroidism / 国际儿科学杂志

The morbidity of transient hypothyroxinemia of prematurity (THOP) was high. There is controversial about thyroid hormone supplementation in THOP. Clinical studies suggest that thyroid hormone supplementation can reduce the incidence of patent ductus arteriosus,but no effect on the mortality and the incidence of respiratory disease.Thyroid hormone supplementation can improve the neurodevelopmental outcomes in infants with gestational age less than 28 weeks with THOP, but no effect on infants with gestational age more than 28 weeks. Future research should focus on the normal range of thyroid hormone according to gestational age in preterm infants,and randomized clinical trial welldesigned stratified according to gestational age to study the long-term neurodevelopmental outcome of thyroid hormone replacement therapy in infants with THOP

An epidemiologic survey of hypothyroidism during the first half of pregnancy / 中华内分泌代谢杂志

Objective To investigate the prevalence of hypothyrodism during the first half of pregnancy in the Han nationality women in iodine-adequate area. Methods TSH, FT4 and thyroid peroxidase antibody (TPOAb) levels were detected in 4 800 pregnant women during the first half of pregnancy. Both gestational age-specific reference intervals and population-based reference intervals of thyroid function were applied and the corresponding prevalences of hypothyroidism were compared with each other. Results Based on the gestational age-specific reference intervals, the prevalences of overt hypothyroidism at 4th and 8th weeks of gestation were 1.03%, 0.37% respectively. At 4th, 8th, 12th, 16th and 20th weeks of gestation, the prevalences of subclinical hypothyroidism were 4.59%, 6.15% , 4.68%, 4.53%, 5.96% respectively, while those of hypothyroxinemia were 3.69%, 1.11%, 2.92% , 1.29%, 2.29%, respectively. According to the pepulation-based reference intervals, the rates of missed diagnosis of subclinical hypothyroidism were 0.18%, 2.85%, 4.10%, 3.24%, 3.21% while those of hypothyroxinemia were 3.45%, 0.66%, 2.34%, 1.29%, 1.83%, respectively. During 4th, 8th, 16th weeks of gestation, the positive rates of TPOAb in the group with subclinical hypothyroidism were significantly higher than those with euthyroidism. The prevalences of subclinical hypothyroidism in TPOAb positive group were obviously higher than those in TPOAb negative group at 4th, 8th, 12th, 16th gestational weeks. Conclusion The rates of missed diagnosis of subclinical hypothyroidism and hypothyroxinemia during the first half of pregnancy were decreased by applying the gestational age-specific reference intervals in this prospective study. Positive TPOAb is a risk factor for subclinical hypothyroidism during the first half of pregnancy.

The Influence of Gestational Age, Birth Weight and Disease on Thyroid Function in Preterm Infants / 대한소아내분비학회지

PURPOSE: To evaluate the influence of gestational age(GA) and disease on thyroid hormone concentration in preterm neonates(preterm), we measured thyroxine (T4) and thyroid stimulating hormone(TSH) concentrations and analyzed the relation to GA and diseases. Additionally, we calculated the reference ranges of T4 in preterm for future investigation. METHODS: Serum T4 and TSH were measured by radioimmunoassay for 107 preterm who admitted neonatal intensive care unit during 1994. We sampled from preterm on 5th day of life. We analysed the relationship of GA and birth weight with the levels of T4 and TSH, and prospectively compared them with each neonatal disease. RESULTS: Serum T4 concentration correlated positively with GA(r=0.62, P<0.001) and birth weight(r=0.29, P<0.01). After controlling GA, birth weight did not correlate to the levels of T4. But after controlling birth weight, GA had correlation with T4(r=0.58, P<0.001). In preterm less than 32 weeks of GA, there was no difference of T4 level between healthy and the diseased(respiratory distress syndrome, patent ductus arteriosus, sepsis, intraventricular hemorrhage, and cerebral palsy). Group of bronchopulmonary dysplasia had significant lower level of T4 compared control group(P<0.01). The reference range of T4 in GA 32-36 weeks is 5.56-15.58 microgdL (9.82+/-.40 microgdL). CONCLUSION: GA positively correlated with serum T4 in preterm, but not to TSH. The measurement of TSH level, using in most of the neonatal care unit as neonatal thyroid screening test, in Korea, is not an adequate test to diagnosis hypothyroidism early in preterm. We recommend serial follow up of TSH and T4 in preterm.