Urinary haloacetic acid concentrations and thyroid function among women: Results from the TREE study.

BACKGROUND: Disinfection byproducts (DBPs) have been shown to impair thyroid function in experimental models. However, epidemiological evidence is scarce. METHODS: This study included 1190 women undergoing assisted reproductive technology (ART) treatment from the Tongji Reproductive and Environmental (TREE) cohort from December 2018 to August 2021. Serum thyrotropin (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured as indicators of thyroid function. FT4/FT3 and TSH/FT4 ratios were calculated as markers of thyroid hormone homeostasis. Dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA), the two most abundant HAAs, in urine were detected to assess individual DBP exposures. RESULTS: After adjusting for relevant covariates, positive associations were observed between urinary TCAA concentrations and serum TSH and TSH/FT4 levels (e.g., percent change = 5.82 %, 95 % CI: 0.70 %, 11.21 % for TSH), whereas inverse associations were found for serum FT3 and FT4 (e.g., percent change = -1.29 %, 95 % CI: -2.49 %, -0.07 % for FT3). There also was a negative association between urinary DCAA concentration and serum FT4/FT3 (percent change = -2.49 %, 95 % CI: -4.71 %, -0.23 %). These associations were further confirmed in the restricted cubic spline and generalized additive models with linear or U-shaped dose-response relationships. CONCLUSION: Urinary HAAs were associated with altered thyroid hormone homeostasis among women undergoing ART treatment.

Variations in thyroid hormone levels in endangered St. Lawrence Estuary belugas: Potential linkage with stress and organohalogen contaminant exposure.

The St. Lawrence Estuary (SLE) beluga (Delphinapterus leucas) population is highly exposed to an array of contaminants that were identified as one of the causes to the non-recovery of this endangered and declining population. In the last decade, an increasing number of parturition-associated complications and calf mortality has been reported in this population. It was suggested that elevated exposure to organohalogens (e.g., the halogenated flame retardants polybrominated diphenyl ethers [PBDEs]) and stress could play a role in this phenomenon by perturbing thyroid hormones. The objective of this study was to investigate the impact of concentrations of organohalogen contaminants and stress (cortisol levels) on thyroid hormone variations in adult male and female SLE belugas. Because plasma could not be collected in SLE belugas for ethical reasons, skin biopsy (n = 40) was used as a less-invasive alternative matrix to determine organohalogens (PBDEs and other halogenated flame retardants, polychlorinated biphenyls, and organochlorine pesticides), cortisol, and thyroid hormones (triiodothyronine [T3] and thyroxine [T4]), and their metabolites reverse T3 and 3,5-diiodothyronine [3,5-T2]). Cortisol and thyroid hormones were analyzed by ultra-performance liquid chromatography-multiple reactions monitoring mass spectrometry (UPLC-MRM/MS). This method was compared using skin and plasma samples obtained from Arctic belugas. Comparisons of linear models showed that cortisol was a weak predictor for T4, rT3 and 3,5-T2. Specifically, there was a weak significant negative association between T4 and cortisol levels. Moreover, in male SLE belugas, a weak significant positive association was found between T3 and Σ34PBDE concentrations in skin. Our findings suggest that stress (i.e., elevated skin cortisol levels) along with organohalogen exposure (mainly PBDEs) may be associated with thyroid hormone level perturbations in skin of cetaceans.

Free triiodothyronine to free thyroxine ratio as a marker of poor prognosis in euthyroid patients with acute coronary syndrome and diabetes after percutaneous coronary intervention.

Objectives: In recent years, the free triiodothyronine/free thyroxine (FT3/FT4) ratio, a new comprehensive index for evaluating thyroid function, which could reflect thyroid function more stably and truly than serum thyroid hormone level, has been demonstrated to correlate with the risks of diabetes and cardiovascular disease in euthyroid adults. However, the correlation between thyroid hormone sensitivity and long-term prognosis in euthyroid patients with acute coronary syndrome (ACS) and diabetes after percutaneous coronary intervention (PCI) remains unclear. Methods: A total of 1,786 euthyroid patients with ACS who successfully underwent PCI at Beijing Anzhen Hospital from August 2021 to April 2022 were included in our study, which was divided into three groups according to tertiles of thyroid hormone sensitivity index. Cox regression, Kaplan-Meier, and receiver operating characteristic analyses were applied to analyze the associations between the FT3/FT4 ratio with ACS and diabetes after PCI. Results: Our analysis indicated that a lower level of FT3/FT4 ratio in euthyroid patients with acute coronary syndrome (ACS) and diabetes after PCI showed significantly higher incidences of major adverse cardiac and cerebrovascular events (MACCE) when compared with a higher level of FT3/FT4 ratio. After adjusting for other covariates, patients with a lower level of FT3/FT4 ratio were negatively associated with the risk of MACCE than those with a higher level of FT3/FT4 ratio (adjusted OR =1.61, 95% CI 1.05-2.47, P = 0.028). In subgroup analyses, individuals were stratified by age, sex, BMI, ACS type, hypertension, and dyslipidemia, showing that there were no significant interactions between the FT3/FT4 ratio and all subgroups for MACCE. In addition, the FT3/FT4 ratio performed better on ROC analyses for cardiac death prediction [area under the curve (AUC), 0.738]. Conclusion: A reduced level of FT3/FT4 ratio was a potential marker of poor prognosis in euthyroid patients with ACS and diabetes after PCI.

Impact of methimazole-induced hypothyroidism on postnatal swine.

Thyroid hormones regulate metabolic rate, nutrient utilization, growth, and development. Swine are susceptible to thyroid suppression in response to disease or environmental conditions, but the physiological impact of such disruption has not been established. The objective of this study was to evaluate the impact of hypothyroidism induced with the antithyroid medication methimazole (MMI). 10 mg/kg MMI significantly decreased circulating triiodothyronine (T3) for the duration of treatment but had only a transient effect on circulating thyroxine (T4). Thyroid tissue weight was significantly increased by more than 3.5-fold in response to MMI treatment. Histologically, the eosinophilic colloid was largely absent from the thyroid follicle which displayed a disorganized columnar epithelium consistent with goiter. MMI induced hypothyroidism has no effect on growth rate over 28 days. Hepatic expression of genes associated with thyroid metabolism (DIO1, DIO2, and DIO3), lipid utilization (CD36, FASN, and ACACA), apoptosis (TP53, PERP, SIVA1, and SFN) and proliferation (CDK1, CDK2, CDK4, and CDKN1A) were unaffected by treatment. Collectively these results demonstrate that MMI induces mild systemic hypothyroidism and pronounced goiter, indicating a strong homeostatic central regulation within the hypothalamic pituitary thyroid axis. This combined with limited peripheral effects, indicates resilience to hypothyroidism in modern swine.

The Joint Effects of Bisphenols and Iodine Exposure on Thyroid during Pregnancy.

The aim of this research was to study the combined effects of bisphenols and iodine exposure on the thyroid gland during pregnancy. We included 162 pregnant women from a cohort established in Shanghai. Urinary concentrations of bisphenol A, bisphenol B(BPB), bisphenol C(BPC), bisphenol F, bisphenol S, and bisphenol AF(BPAF) were examined. Bayesian kernel machine regression (BKMR) and quantile g-computation models were used. The geometric means of BPA, BPB, BPC, BPF, BPS, BPAF, and ΣBPs levels in urine were 3.03, 0.24, 2.66, 0.36, 0.26, 0.72, and 7.55 µg/g creatinine, respectively. We observed a positive trend in the cumulative effects of BPs and iodine on serum triiodothyronine (FT3) and free thyroxine (FT4), as well as a U-shaped dose-response relationship between BPs and the probability of occurrence of thyroperoxidase autoantibody positivity in women with low urinary iodine concentration. In addition, a synergistic effect on the probability of occurrence of thyroid autoantibody positivity was observed between BPF and BPB, as well as between BPC and BPAF in this study. There were adverse health effects on the thyroid after co-exposure to BPs and iodine. Even if pregnant women were exposed to lower levels of BPs, women with iodine deficiency remained vulnerable to thyroid autoimmune disease.

Dioscin Ameliorates Experimental Autoimmune Thyroiditis via the mTOR and TLR4/NF-κB Signaling.

Background: Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear. Methods: The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC-P), respectively. Results: Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group. Conclusion: Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.

Establishment of reference intervals for fT3, fT4, and TSH levels in Japanese children and adolescents.

The present study aimed to establish new reference intervals (RIs) for serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in Japanese children and adolescents aged 4 to 19 years. A total of 2,036 (1,611 girls, 425 boys) participants were included over a 17-year period; they all tested negative for antithyroid antibodies (TgAb, TPOAb) and were found to have no abnormalities on ultrasonography. RIs were determined by nonparametric methods. The results showed that serum fT3 was significantly higher in the 4-15-year-olds than in the 19-year-olds. The serum fT4 was significantly higher in the 4-10-year-olds than in the 19-year-olds. The serum TSH was significantly higher in the 4-12-year-olds than in the 19-year-olds. All of them gradually decreased with age to approximate the adult levels. The upper limit of TSH was lower in those aged 13 to 19 years than in adults. The differences were examined by sex. The serum fT3 was significantly higher in boys than in girls between the ages of 11 and 19 years. The serum fT4 was significantly higher in boys than in girls between the ages of 16 and 19 years. There did not seem to be any sex difference in those under 10 years of age. In conclusion, serum fT3, fT4, and TSH levels in children and adolescents differ from those in adults. It is important to evaluate thyroid function using the new RIs that are appropriate for chronological age.

Laboratorio de función tiroidea en pediatría. Ventajas y limitaciones de los métodos indirectos para la obtención de intervalos de referencia / Thyroid function laboratory in pediatrics. Advantages and limitations of indirect methods to obtain reference intervals

Obtener intervalos de referencia (IRs) confiables para pruebas de laboratorio en pediatría es particularmente complejo y costoso. Una alternativa a este problema es el uso de métodos indirectos, donde se usan grandes bases de datos preexistentes de pacientes. Nuestros objetivos fueron: calcular IR para TSH y hormonas tiroideas (Perfil tiroideo, PT) en población pediátrica que asiste al Hospital de Pediatría Juan P. Garrahan, por método indirecto y verificar la confiabilidad de los mismos para su aplicación. Se recolectaron datos de 19.842 pacientes entre enero de 2020 y diciembre de 2021. Se aplicaron filtros para eliminar los pacientes que pudieran tener afectado el PT. Los 4.861 pacientes incorporados al análisis fueron divididos en 3 grupos: G1: 0-12 meses (n: 551), G2:13 meses- 7 años (n: 1347) y G3: 8 -18 años (n: 2963). Los IR fueron calculados por 2 métodos: el de Hoffman adaptado y el de CLSI EP28A3, para cada grupo de edad. TSH, TT3 y T4L se analizaron con Architect i4000-Abbott y TT4 con Immulite 2000XPi-Siemens. Para la primera etapa de verificación se utilizaron 20 sueros de pacientes provenientes de análisis prequirúrgicos. Los outliers se detectaron aplicando el método de Tukey. Los datos fueron procesados según CLSI EP28A3c. Los IR obtenidos fueron similares a los previamente publicados obtenidos por método directo. Los resultados de la verificación fueron en su mayoría aceptados. Por lo tanto, los métodos indirectos son una buena alternativa de cálculo de IR en pediatría (AU)

Obtaining reliable reference ranges (RRs) for laboratory tests in pediatrics is particularly complex and costly. An alternative to this problem is to use of indirect methods, where large pre-existing patient databases are used. Our aims were to calculate RRs for TSH and thyroid hormones (thyroid profile, PT) in children seen at Hospital de Pediatría Juan P. Garrahan by indirect methods and to verify their reliability for their application. Data were collected from 19,842 patients seen between January 2020 and December 2021. Filters were applied to eliminate patients in whom the PT was potentially affected. The remaining 4,861 patients included in the analysis were divided into 3 groups: G1: 0-12 months (n: 551), G2: 13 months-7 years (n: 1347) and G3: 8-18 years (n: 2963). RRs were calculated by 2 methods: the adapted Hoffman method and the CLSI EP28A3 method, for each age group. TSH, TT3, and FT4 were analyzed with Architect i4000-Abbott and TT4 with Immulite 2000XPi-Siemens. For the first stage of verification, 20 patient sera from pre-surgical analysis were used. Outliers were detected by applying the Tukey method. The data were processed according to CLSI EP28A3c. The RRs obtained were similar to those previously published using the direct method. The verification results were mostly acceptable. Therefore, indirect methods are a good option for calculating RRs in children (AU)

The associations between concentrations of gestational bisphenol analogues and thyroid related hormones in cord blood: A prospective cohort study.

Animal studies indicated that Bisphenol analogues (BPs) exhibited potential thyroid toxicity. However, little is known of the associations between maternal BPs exposure and offspring's thyroid related hormones in humans. On the basis of Shanghai-Minhang Birth Cohort study, we analyzed BPs in maternal urine collected at the third trimester of pregnancy. Thyroid related hormones (THs), including total triiodothyronine (TT3), free triiodothyronine (FT3), total thyroxine (TT4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured in cord blood samples. We performed multiple linear regression and Bayesian kernel machine regression (BKMR) models to explore the single and joint effects of gestational BPs exposure on thyroid related hormones in cord blood among 258 mother-child pairs. Statistically significant inverse associations of categorized BPA with FT3 and TT4 concentrations were observed. We also found a significant association between the mixture of BPs in maternal urine and increased concentration of TT3 in cord blood and a marginally significant association between BPs mixture and increased FT3 concentrations. Further associations of BPA with lower TT4/FT4 and of Bisphenol AF (BPAF) with higher TT3/FT3 were also suggestive, by BKMR model, when other BPs were fixed at 25th percentiles. It was concluded that prenatal BPs exposure was associated with THs in cord blood. Exposure to BPA and BPAF might have large contributions to the effects on thyroid function than other bisphenols.

Thyroxine changes in COVID-19 pandemic: A systematic review and meta-analysis.

Objective: COVID-19 infection may affect thyroid function. However, changes in thyroid function in COVID-19 patients have not been well described. This systematic review and meta-analysis assess thyroxine levels in COVID-19 patients, compared with non-COVID-19 pneumonia and healthy cohorts during the COVID-19 epidemic. Methods: A search was performed in English and Chinese databases from inception to August 1, 2022. The primary analysis assessed thyroid function in COVID-19 patients, comparing non-COVID-19 pneumonia and healthy cohorts. Secondary outcomes included different severity and prognoses of COVID-19 patients. Results: A total of 5873 patients were enrolled in the study. The pooled estimates of TSH and FT3 were significantly lower in patients with COVID-19 and non-COVID-19 pneumonia than in the healthy cohort (P < 0.001), whereas FT4 were significantly higher (P < 0.001). Patients with the non-severe COVID-19 showed significant higher in TSH levels than the severe (I2 = 89.9%, P = 0.002) and FT3 (I2 = 91.9%, P < 0.001). Standard mean differences (SMD) of TSH, FT3, and FT4 levels of survivors and non-survivors were 0.29 (P= 0.006), 1.11 (P < 0.001), and 0.22 (P < 0.001). For ICU patients, the survivors had significantly higher FT4 (SMD=0.47, P=0.003) and FT3 (SMD=0.51, P=0.001) than non-survivors. Conclusions: Compared with the healthy cohort, COVID-19 patients showed decreased TSH and FT3 and increased FT4, similar to non-COVID-19 pneumonia. Thyroid function changes were related to the severity of COVID-19. Thyroxine levels have clinical significance for prognosis evaluation, especially FT3.

Very young children with Prader-Willi syndrome are refractory to growth hormone-associated decreases in free thyroxine levels.

The earlier initiation of growth hormone (GH) treatment for patients with Prader-Willi syndrome (PWS) who are younger than 2 years has become more prevalent. Because free thyroxine (FT4) levels are low during this period, GH may induce further reductions; however, limited information is currently available on this issue. Therefore, we herein performed age-dependent and time-course analyses of thyroid hormone levels in GH-treated PWS children. This retrospective analysis included genetically diagnosed PWS patients (N = 37, median age of 26 months). An age-dependent analysis was performed by subdividing subjects based on age [a younger group aged between 1 and 24 months (N = 16) and an older group between 25 and 84 months (N = 21)] and was followed by a multiple regression analysis with adjustments for sex and the cumulative GH dose per bodyweight. A time-course analysis of subjects who had not received levothyroxine during the first 18 months of GH treatment (N = 28) was conducted. A one-month treatment with GH decreased FT4 levels in the older group, but not in the younger group, and this was associated with increases in thyroid-stimulating hormone levels. A positive correlation was noted between age and decreases in FT4 levels independent of the cumulative GH dose per bodyweight. The time-course analysis revealed no changes in FT4 levels in the younger group, while transient decreases were observed in the older group. In conclusion, GH treatment causes age-dependent changes in FT4 levels. This result will help clinicians establish a therapeutic strategy to decide the necessity of levothyroxine supplementation in GH-treated children with PWS.

The Free Triiodothyronine/Free Thyroxine Ratio Is Associated with Frailty in Older Adults: A Longitudinal Multisetting Study.

Background: Various models have been proposed to predict frailty, including those based on clinical criteria and phenotypes. However, a simple biomarker associated with frailty has been not yet identified. The aim of this study is to evaluate the relationship between free triiodothyronine (fT3)/free thyroxine (fT4) ratio value and the degree of frailty among three different cohorts of older individuals: (1) acutely ill hospitalized patients, (2) nursing-home (NH) residents, and (3) home-dwelling centenarians. Methods: We performed a secondary analysis of de-identified patient-level data from two prospective observational studies on acutely hospitalized older patients (Geriatric Acute Unit [GAU]), and home-dwelling centenarians (CENT), and a retrospective-prospective observational study on older NH residents. Demographic characteristics, along with a 30-items Frailty Index (FI) and serum thyrotropin, fT3 and fT4 measurements were obtained. Results: Six hundred fifteen individuals (aged 86.4 ± 8.9 years; 55.1% females) were included in the study, including 298 (48.5%) GAU, 250 (40.6%) NH, and 67 (10.9%) CENT. A significant inverse relationship between fT3/fT4 ratio and FI values was observed (ρs = -0.17 [confidence interval; CI: -0.092 to 0.252], p < 0.001), and this was confirmed by logistic multivariate analysis (ß = -0.44, odds ratio [OR]: 0.64 [CI: 0.47-0.87], p < 0.001) (after adjustment for age, sex, and cohorts). Moreover, a progressively decreased mortality risk was associated with rising fT3/fT4 ratio (OR 0.60 [CI: 0.44-0.80] ß = -0.51, p < 0.001]. Conclusions: The fT3/fT4 ratio value was inversely correlated with frailty degree and mortality risk in a large cohort of older individuals, including centenarians, regardless of their sex and clinical condition. fT3/fT4 ratio value could represent an easily measured independent biochemical marker of frailty degree in older people.

Optimized Replacement T4 and T4+T3 Dosing in Male and Female Hypothyroid Patients With Different BMIs Using a Personalized Mechanistic Model of Thyroid Hormone Regulation Dynamics.

Objective: A personalized simulation tool, p-THYROSIM, was developed (1) to better optimize replacement LT4 and LT4+LT3 dosing for hypothyroid patients, based on individual hormone levels, BMIs, and gender; and (2) to better understand how gender and BMI impact thyroid dynamical regulation over time in these patients. Methods: p-THYROSIM was developed by (1) modifying and refining THYROSIM, an established physiologically based mechanistic model of the system regulating serum T3, T4, and TSH level dynamics; (2) incorporating sex and BMI of individual patients into the model; and (3) quantifying it with 3 experimental datasets and validating it with a fourth containing data from distinct male and female patients across a wide range of BMIs. For validation, we compared our optimized predictions with previously published results on optimized LT4 monotherapies. We also optimized combination T3+T4 dosing and computed unmeasured residual thyroid function (RTF) across a wide range of BMIs from male and female patient data. Results: Compared with 3 other dosing methods, the accuracy of p-THYROSIM optimized dosages for LT4 monotherapy was better overall (53% vs. 44%, 43%, and 38%) and for extreme BMI patients (63% vs. ~51% low BMI, 48% vs. ~36% and 22% for high BMI). Optimal dosing for combination LT4+LT3 therapy and unmeasured RTFs was predictively computed with p-THYROSIM for male and female patients in low, normal, and high BMI ranges, yielding daily T3 doses of 5 to 7.5 µg of LT3 combined with 62.5-100 µg of LT4 for women or 75-125 µg of LT4 for men. Also, graphs of steady-state serum T3, T4, and TSH concentrations vs. RTF (range 0%-50%) for untreated patients showed that neither BMI nor gender had any effect on RTF predictions for our patient cohort data. Notably, the graphs provide a means for estimating unmeasurable RTFs for individual patients from their hormone measurements before treatment. Conclusions: p-THYROSIM can provide accurate monotherapies for male and female hypothyroid patients, personalized with their BMIs. Where combination therapy is warranted, our results predict that not much LT3 is needed in addition to LT4 to restore euthyroid levels, suggesting opportunities for further research exploring combination therapy with lower T3 doses and slow-releasing T3 formulations.

The Effect of Leptin on the Blood Hormonal Profile (Cortisol, Insulin, Thyroid Hormones) of the Ewe in Acute Inflammation in Two Different Photoperiodical Conditions.

As a day animal with sensitivity to inflammation similar to that of humans, the sheep may highly outperform the rodent model in inflammation studies. Additionally, seasonality makes sheep an interesting model in endocrinology research. Although there are studies concerning inflammation's influence on leptin secretion and vice versa, a ewe model, with its possible 'long-day leptin resistance', is still not examined enough. The present study aimed to examine whether leptin may modulate an acute inflammation influence on plasma hormones in two photoperiodical conditions. The experiment was conducted on 48 ewes divided into four groups (control, lipopolysaccharide (LPS), leptin, LPS + leptin) during short and long days. Blood sampling started 1 hour before and continued 3 h after LPS/saline administration for further hormonal analysis. The results showed that the photoperiod is one of the main factors influencing the basal concentrations of several hormones with higher values of leptin, insulin and thyroid hormones during long days. Additionally, the acute inflammation effect on cortisol, insulin and thyroid hormones was photoperiod-dependent. The endotoxemia may also exert an influence on leptin concentration regardless of season. The effects of leptin alone on hormone blood concentrations are rather limited; however, leptin can modulate the LPS influence on insulin or thyroxine in a photoperiod-dependent way.

Management of Hypothyroidism and Hypothyroxinemia During Pregnancy.

OBJECTIVE: To review the diagnosis and management of hypothyroidism during pregnancy, in the preconception period, and in the postpartum period. METHODS: A literature review of English-language papers published between 1982 and 2022, focusing on the most recent literature. RESULTS: During pregnancy, thyroid function laboratory tests need to be interpreted with regard to gestational age. Overt hypothyroidism, regardless of the thyroid-stimulating hormone (TSH) level, should always be promptly treated when it is diagnosed before conception or during pregnancy or lactation. Most women with pre-existing treated hypothyroidism require an increase in levothyroxine (LT4) dosing to maintain euthyroidism during gestation. LT4-treated pregnant patients need close monitoring of their serum TSH levels to avoid overtreatment or undertreatment. There is no consensus about whether to initiate LT4 in women with mild forms of gestational thyroid hypofunction. However, in light of current evidence, it is reasonable to treat women with subclinical hypothyroidism with LT4, particularly if the TSH level is >10 mIU/L or thyroperoxidase antibodies are present. Women who are not treated need to be followed up to ensure that treatment is initiated promptly if thyroid failure progresses. Additional studies are needed to better understand the effects of the initiation of LT4 in early gestation in women with subclinical hypothyroidism and hypothyroxinemia and determine optimal strategies for thyroid function screening in the preconception period and during pregnancy. CONCLUSION: The diagnosis and management of hypothyroidism in the peripregnancy period present specific challenges. While making management decisions, it is essential to weigh the risks and benefits of treatments for not just the mother but also the fetus.

Postnatal Serum Total Thyroxine Level Associated with Short- and Long-Term Anthropometric Outcomes in Very Preterm Infants.

Thyroxine (T4) importantly regulates the growth of newborns. Compared to fetuses with equivalent gestational ages, very preterm infants (VPIs) often experience relatively low thyroxinemia, with a normal thyroid-stimulating hormone (TSH) concentration < 10 µIU/mL. However, there is continued debate regarding postnatal thyroxine supplementation for VPIs with normal TSH and transitionally low thyroxinemia. Little research has explored the role of the postnatal total T4 (TT4) serum concentration on the growth of VPIs. In this study, we aim to clarify whether the postnatal thyroxine concentration is associated with the short- and long-term growth outcomes of VPIs. A total of 334 surviving VPIs in our previously reported cohort, born in the period August 2007−July 2016, were enrolled. The exposure variable was the postnatal TT4 concentration at 1 month old. The primary outcomes were body weight increments over 28 days after the screening and anthropometric outcomes at the corrected age of 24 months old. Infants with any hormonal replacement, severe brain injury, congenital anomaly, or cerebral palsy were excluded. In total, 290 (86.8%) VPIs were included for analysis. In the 28 days after thyroid function screening, the TT4 concentration was found to have a significant association with positive increments in body weight (mean increment: 25.7 g per 1 µg/dL; p < 0.001) and a positive body weight z-score (mean increment: 0.039 per 1 µg/dL; p = 0.037), determined by generalized estimating equation analysis. At the corrected age of 24 months old, a higher postnatal TT4 concentration was associated with a lower body mass index (mean coefficient: −0.136; 95% CI: −0.231 to −0.041, p = 0.005) and lower body mass index z-score (mean coefficient: −0.097; 95% CI: −0.170 to −0.024, p = 0.009). Infants with a TT4 concentration > 6.4 ug/dL had significantly lower odds of overweight status (odds ratio: 0.365; 95% CI: 0.177 to 0.754, p = 0.006). We conclude that the postnatal TT4 concentration is associated with a positive increment in body weight in the short term. At the same time, the postnatal TT4 concentration is associated with lower odds of overweight status after long-term follow-up.

Aging-related Characteristics of Subclinical Hypothyroidism Detected in General Practice.

Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 µU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH.

Iodine deficiency in pregnancy along a concentration gradient is associated with increased severity of preeclampsia in rural Eastern Cape, South Africa.

BACKGROUND: Preeclampsia is a leading cause of maternal mortality and morbidity in South Africa. Iodine deficiency in pregnancy, which is amenable to correction through iodine supplementation, has been reported to increase the risk of preeclampsia. However, the association of iodine nutrition status with preeclampsia in South Africa has not been studied. METHODS: We enrolled 51 randomly selected normotensive pregnant controls at term together with 51 consecutively selected cases of preeclampsia and 51 cases of severe preeclampsia/eclampsia, all in the third trimester, from Mthatha Regional and Nelson Mandela Academic Hospital in the Eastern Cape Province. Urinary iodine concentration (UIC), serum thyroid-stimulating hormone (TSH), triiodothyronine (FT3), thyroxine (FT4) and thyroglobulin (Tg) levels were compared between cases and controls. RESULTS: The respective chronological and gestational ages at enrolment for normotensive, preeclampsia and severe preeclampsia/eclampsia participants were: age 23, 24 and 19 years (p = 0.001), and gestational age 38, 34, and 35 weeks (p < 0.001). The median gravidity was 1 for all three groups. The median UIC, FT4, FT3 revealed a decreasing and Tg a rising trend with the severity of preeclampsia (p < 0.05). TSH had a non-significant rising trend (p > 0.05). The respective median values for normotensive, preeclampsia and severe preeclampsia/eclampsia participants were UIC 217.1, 127.7, and 98.8 µg/L; FT4 14.2, 13.7, and 12. pmol/L; FT3 4.8, 4.4, and 4.0 pmol//L; Tg 19.4, 21.4, and 32. Nine microgram per liter; TSH 2.3, 2.3, and 2.5 mIU/L. UIC < 100 µg/L, Tg > 16 µg/L and FT4 < 11.3 pmol/L were independent predictors of preeclampsia/eclampsia syndrome. CONCLUSION: Women with severe preeclampsia/eclampsia had significantly low UIC and high Tg, suggesting protracted inadequate iodine intake. Inadequate iodine intake during pregnancy severe enough to cause elevated Tg and FT4 deficiency was associated with an increased risk of severe preeclampsia/eclampsia.

Modulatory effects of lycopene and vitamin E on cloacal temperature, thyroid hormonal and reproductive performance responses in laying hens during the hot-dry season.

The aim of the study was to evaluate the effects of lycopene and vitamin E on cloacal temperature (CT), thyroid hormones and performance indices in laying hens (Gallus domesticus) during the hot-dry season. The dry-bulb temperature and temperature-humidity index in the pen and CT were measured in all hens twice weekly and thyroid hormones for five consecutive weeks. Ovarian and follicular activities were assessed at the end of the study after slaughter. The CT values in control hens at 09:00 h, 12:00 h and 15:00 h (41.20 ± 0.07 °C, 41.84 ± 1.8 °C and 42.1 ± 1.1 °C, respectively) were higher (P < 0.05), compared to the corresponding values recorded in lycopene (41.50 ± 0.07 °C, 41.50 ± 0.07 °C and 41.73 ± 0.08 °C, respectively), and lycopene + vitamin E (41.31 ± 0.07 °C, 41.40 ± 0.05 °C and 41.63 ± 0.09 °C, respectively). In lycopene + vitamin E laying hens, plasma thyroxine concentration (15.22 ± 1.74 nmol/L) was greater (P < 0.05) than in lycopene (7.64 ± 0.8 nmol/L), vitamin E hens (6.80 ± 1.3 nmol/L) and controls (6.5 ± 0.9 °C nmol/L). Plasma triiodothyronine concentration was highest (P < 0.05) in lycopene + vitamin E (4.80 ± 0.37 nmol/L), compared to lycopene (3.42 ± 0.4 nmol/L), vitamin E (1.96 ± 0.2 nmol/L) and control (1.2 ± 0.1 nmol/L) laying hens. Lycopene + vitamin E hens recorded higher (P < 0.05) count of preovulatory follicles (6.0 ± 0.2) than the controls (4.5 ± 0.3). Countable white follicles were higher (P < 0.05) in lycopene + vitamin E and lycopene hens (58.0 ± 1.4 and 48.5 ± 0.5, respectively) than controls (33.0 ± 2.5). In conclusion, lycopene and vitamin E, especially their combination, modulated the heat stress-induced responses in the laying hens by decreasing CT values, and increasing thyroid hormone concentrations, the count of hierarchical preovulatory and white ovarian follicles during the hot-dry season.