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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1983

Motion sickness susceptibility related to ACTH, ADH and TSH

The hypothesis that endogenous levels of certain hormones might be indicative of an individual's susceptibility to stressful motion is tested in a comparison of subjects classified as less prone to motion sickness with those of higher susceptibility. The levels of ACTH and vasopressin measured before exposure to stressful motion were twice as high in the less-suceptible group. No significant differences were noted in the levels of angiotensin, aldosterone, or TSH. The differences between the two groups were greater for a given hormone than for any of the changes induced by exposure to stressful motion.

Kohl, R. L.↗
NASA NTRS1984

Hypergravity effects on litter size, nursing activity, prolactin, TSH, T3, and T4 in the rat

In a recent study of the effects of hypergravity (HG) on the reproductive system of the rat, it was found that the estrous cycle is perturbed in a pseudopregnancy-like pattern upon first exposure of animals to HG. This can be prevented by previous exposure to HG or by administration of bromergo cryptin. Adapted rats can mate and deliver in HG. However, little is known of the condition of the individual pregnant rat, fetuses, and newborn pups in this environment. There are also questions regarding the effects of HG on the number of fetuses, the mortality rate in different HG levels, and the effects on production and secretion of PRL and TSH. The present investigation is concerned with such questions, taking into account possible approaches to avoid or minimize the lethal effects of HG. The obtained results suggest that peripartum plasma PRL levels and thyroid hormone levels are critical for the survival of the litter.

Megory, E.↗
DOE OSTI2018

Effects of sex, age, sampling time, and season on thyroid-stimulating hormone concentrations: A retrospective study

Highlights: • Serum TSH concentrations in women were significantly higher than in men. • TSH concentrations decreased during the summer while increased during the winter. • TSH concentrations decreased from 7 a.m. to 1 p.m. while increased from 1 p.m. to 4 p.m. • Sex, age, season, and sampling time affected serum TSH concentrations. • Sampling time was the major factor affecting serum TSH concentrations. Measuring thyroid-stimulating hormone (TSH) is essential for diagnosing and monitoring thyroid diseases. The aim of this study was to evaluate the effect of sex, age, sampling time and season on TSH in a large Chinese population and to determine which factor had the greatest impact on TSH measurement results.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Association between thyroid profile and perfluoroalkyl acids: Data from NHNAES 2007–2008

The effect of six perfluoroalkyl acids (PFAAs), namely, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDE), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamide) acetic acid (MPAH), and perfluorononanoic acid (PFNA) on the levels of six thyroid function variables, namely, thyroid stimulating hormone (TSH), free and total thyroxine (FT4, TT4), free and total triiodothyronine (FT3, TT3), and thyroglobulin (TGN) was evaluated. Data from National Health and Nutrition Examination Survey for the years 2007–2008 were used for this evaluation. TSH levels increased with increase in levels of PFOA (p<0.01). There were no statistically significant associations between the levels of FT3, and FT4 with the levels of any of the six PFAAs. Levels of TT3 were found to increase with the levels of PFOA (p=0.01) and TT4 levels were found to increase with increase in PFHxS levels (p<0.01). Males had statistically significantly higher levels of FT3 than females and females had statistically significantly higher levels of TT4 than males. As compared to non-Hispanics whites and Hispanics, non-Hispanic blacks had lower levels of TSH, FT3, TT3, and TT4 but Hispanics had the lowest levels of TGN. Age was negatively associated with FT3 and TT3 but positively associated with FT4 and TT4. Non-smokers had higher levels of TSH and TT4 than smokers and smokers had higher levels of FT3 and TGN than non-smokers. Iodine deficiency was associated with increased levels of TSH, TT3, TT4, and TGN. -- Highlights: • Levels of total triiodothyronine were found to increase with the levels of PFOA. • Total thyroxine increased with increase in levels of perfluorohexane sulfonic acid. • There was a positive association between the levels of PFOA and TSH. • Iodine deficiency was associated with elevated levels of TSH, total T3 and T4. • Iodine deficiency was associated with elevated levels of thyroglobulin.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Associations of maternal exposure to triclosan, parabens, and other phenols with prenatal maternal and neonatal thyroid hormone levels

Highlights: • Triclosan was associated with lower maternal total T4 during pregnancy. • 2,4-Dichlorophenol was associated with lower maternal free T4 during pregnancy. • Propyl paraben was associated with lower maternal TSH during pregnancy. • No chemicals were associated with neonatal TSH. Environmental phenols and parabens are commonly used in personal care products and other consumer products and human exposure to these chemicals is widespread. Although human and animal studies suggest an association between exposure to phenols and parabens and thyroid hormone levels, few studies have investigated the association of in utero exposure to these chemicals and thyroid hormones in pregnant women and their neonates. We measured four environmental phenols (triclosan, benzophenone-3, and 2,4- and 2,5-dichlorophenol), and three parabens (methyl-, propyl-, and butyl paraben) in urine collected from mothers at two time points during pregnancy as part of the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study. We measured free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in serum of the pregnant women (N = 454) and TSH in their neonates (N = 365). We examined potential confounding by a large number of additional chemical exposures and used Bayesian Model Averaging (BMA) to select the most influential chemicals to include in regression models. We observed negative associations of prenatal urinary concentrations of propyl paraben and maternal TSH (β for two-fold increase = −3.26%, 95% CI: −5.55, −0.90) and negative associations of 2,4-dichlorophenol and maternal free T4 (β for two-fold increase = −0.05, 95% CI: −0.08, −0.02), after controlling for other chemical exposures. We observed negative associations of triclosan with maternal total T4 after controlling for demographic variables, but this association became non-significant after controlling for other chemicals (β for two-fold increase = −0.05, 95% CI: −0.11, 0.00). We found evidence that environmental phenols and parabens are associated with lower TSH and free T4 in pregnant women after controlling for related chemical exposures.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

CO-occurring exposure to perchlorate, nitrate and thiocyanate alters thyroid function in healthy pregnant women

Background: Adequate maternal thyroid function during pregnancy is necessary for normal fetal brain development, making pregnancy a critical window of vulnerability to thyroid disrupting insults. Sodium/iodide symporter (NIS) inhibitors, namely perchlorate, nitrate, and thiocyanate, have been shown individually to competitively inhibit uptake of iodine by the thyroid. Several epidemiologic studies examined the association between these individual exposures and thyroid function. Few studies have examined the effect of this chemical mixture on thyroid function during pregnancy Objectives: We examined the cross sectional association between urinary perchlorate, thiocyanate and nitrate concentrations and thyroid function among healthy pregnant women living in New York City using weighted quantile sum (WQS) regression. Methods: We measured thyroid stimulating hormone (TSH) and free thyroxine (FreeT4) in blood samples; perchlorate, thiocyanate, nitrate and iodide in urine samples collected from 284 pregnant women at 12 (±2.8) weeks gestation. We examined associations between urinary analyte concentrations and TSH or FreeT4 using linear regression or WQS adjusting for gestational age, urinary iodide and creatinine. Results: Individual analyte concentrations in urine were significantly correlated (Spearman's r 0.4–0.5, p<0.001). Linear regression analyses did not suggest associations between individual concentrations and thyroid function. The WQS revealed a significant positive association between the weighted sum of urinary concentrations of the three analytes and increased TSH. Perchlorate had the largest weight in the index, indicating the largest contribution to the WQS. Conclusions: Co-exposure to perchlorate, nitrate and thiocyanate may alter maternal thyroid function, specifically TSH, during pregnancy. - Highlights: • Perchlorate, nitrate, thiocyanate and iodide measured in maternal urine. • Thyroid function (TSH and Free T4) measured in maternal blood. • Weighted quantile sum (WQS) regression examined complex mixture effect. • WQS identified an inverse association between the exposure mixture and maternal TSH. • Perchlorate indicated as the ‘bad actor’ of the mixture.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Gestational urinary bisphenol A and maternal and newborn thyroid hormone concentrations: The HOME Study

Bisphenol A (BPA), an endocrine disruptor used in consumer products, may perturb thyroid function. Prenatal BPA exposure may have sex-specific effects on thyroid hormones (THs). Our objectives were to investigate whether maternal urinary BPA concentrations during pregnancy were associated with THs in maternal or cord serum, and whether these associations differed by newborn sex or maternal iodine status. We measured urinary BPA concentrations at 16 and 26 weeks gestation among pregnant women in the HOME Study (2003–2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine (T{sub 4}) and triiodothyronine (T{sub 3}) were measured in maternal serum at 16 weeks (n=181) and cord serum at delivery (n=249). Associations between BPA concentrations and maternal or cord serum TH levels were estimated by multivariable linear regression. Mean maternal urinary BPA was not associated with cord THs in all newborns, but a 10-fold increase in mean BPA was associated with lower cord TSH in girls (percent change=−36.0%; 95% confidence interval (CI): −58.4, −1.7%), but not boys (7.8%; 95% CI: −28.5, 62.7%; p-for-effect modification=0.09). We observed no significant associations between 16-week BPA and THs in maternal or cord serum, but 26-week maternal BPA was inversely associated with TSH in girls (−42.9%; 95% CI: −59.9, −18.5%), but not boys (7.6%; 95% CI: −17.3, 40.2%; p-for-effect modification=0.005) at birth. The inverse BPA–TSH relation among girls was stronger, but less precise, among iodine deficient versus sufficient mothers. Prenatal BPA exposure may reduce TSH among newborn girls, particularly when exposure occurs later in gestation. - Highlights: • Examined associations of BPA with thyroid hormones in pregnant women and newborns. • Assessed effect modification of BPA–thyroid hormone associations by newborn sex. • Greater BPA related to decreased thyroid stimulating hormone in girls' cord serum. • Results may suggest window of susceptibility to BPA in later gestation. • BPA potentially has greatest adverse effect on girls with iodine deficient mothers.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Thyroid antagonists and thyroid indicators in U.S. pregnant women in the Vanguard Study of the National Children's Study

The sodium iodide-symporter (NIS) mediates uptake of iodide into thyroid follicular cells. This key step in thyroid hormone synthesis is inhibited by perchlorate, thiocyanate (SCN) and nitrate (NO{sub 3}) anions. When these exposures occur during pregnancy the resulting decreases in thyroid hormones may adversely affect neurodevelopment of the human fetus. Our objectives were to describe and examine the relationship of these anions to the serum thyroid indicators, thyroid stimulating hormone (TSH) and free thyroxine (FT4), in third trimester women from the initial Vanguard Study of the National Children's Study (NCS); and to compare urine perchlorate results with those in pregnant women from the National Health and Nutritional Examination Survey (NHANES). Urinary perchlorate, SCN, NO{sub 3}, and iodine, serum TSH, FT4, and cotinine were measured and a food frequency questionnaire (FFQ) was administered to pregnant women enrolled in the initial Vanguard Study. We used multiple regression models of FT4 and TSH that included perchlorate equivalent concentration (PEC, which estimates combined inhibitory effects of the anions perchlorate, SCN, and NO{sub 3} on the NIS). We used multiple regression to model predictors of each urinary anion, using FFQ results, drinking water source, season of year, smoking status, and demographic characteristics. Descriptive statistics were calculated for pregnant women in NHANES 2001–2012. The geometric mean (GM) for urinary perchlorate was 4.04 µg/L, for TSH 1.46 mIU/L, and the arithmetic mean for FT4 1.11 ng/dL in 359 NCS women. In 330 women with completed FFQs, consumption of leafy greens, winter season, and Hispanic ethnicity were significant predictors of higher urinary perchlorate, which differed significantly by study site and primary drinking water source, and bottled water was associated with higher urinary perchlorate compared to filtered tap water. Leafy greens consumption was associated with higher urinary NO{sub 3} and higher urinary SCN. There was no association between urinary perchlorate or PEC and TSH or FT4, even for women with urinary iodine <100 µg/L. GM urinary perchlorate concentrations in the full sample (n=494) of third trimester NCS women (4.03 µg/L) were similar to pregnant women in NHANES (3.58 µg/L). - Highlights: • Limited biomonitoring data are available in pregnant women. • We found no effect of perchlorate and related anions on thyroid indicators in third trimester women. • Leafy green vegetables were a dietary source for perchlorate, nitrate, and thiocyanate.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Synergism between exposure to mercury and use of iodine supplements on thyroid hormones in pregnant women

Objective: To evaluate the association between mercury exposure and thyroid-stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) levels during pregnancy as well as to explore if there is any synergic action between mercury and intake of iodine from different sources. Methods: The study population was 1407 pregnant women participating in the Spanish INMA birth cohort study. Total mercury concentrations were analyzed in cord blood. Thyroid hormones (THs) were measured in serum samples collected at 13.2±1.5 weeks of gestation. The association between mercury and TH levels was evaluated with multivariate linear regression models. Effect modification caused by iodine intake from supplements and diet was also evaluated. Results: The geometric means of TSH, TT3, FT4 and mercury were 1.1 μU/L, 2.4 nmol/L, 10.5 pmol/L and 7.7 μg/L, respectively. Mercury levels were marginally significantly associated with TT3 (β: −0.05; 95%CI: −0.10, 0.01), but were neither associated with TSH nor FT4. The inverse association between mercury and TT3 levels was stronger among the iodine supplement consumers (−0.08; 95%CI: −0.15, −0.02, interaction p-value=0.07). The association with FT4 followed the same pattern, albeit not significant. Conclusion: Prenatal mercury exposure was inversely associated with TT3 levels among women who took iodine supplements during pregnancy. These results could be of public health concern, although further research is needed. - Highlights: • We studied the relationship between mercury and thyroid hormones among pregnant. • Mercury was marginally significantly associated with TT3, but not with TSH or FT4. • This association was stronger among the iodine supplement. • These results could be of public health concern, but further research is needed.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Adaptive time steps in trajectory surface hopping simulations

Trajectory surface hopping (TSH) simulations are often performed in combination with active-space multi-reference configuration interaction (MRCI) treatments. Technical problems may arise in such simulations if active and inactive orbitals strongly mix and switch in some particular regions. We propose to use adaptive time steps when such regions are encountered in TSH simulations. For this purpose, we present a computational protocol that is easy to implement and increases the computational effort only in the critical regions. We test this procedure through TSH simulations of a GFP chromophore model (OHBI) and a light-driven rotary molecular motor (F-NAIBP) on semiempirical MRCI potential energy surfaces, by comparing the results from simulations with adaptive time steps to analogous ones with constant time steps. For both test molecules, the number of successful trajectories without technical failures rises significantly, from 53% to 95% for OHBI and from 25% to 96% for F-NAIBP. The computed excited-state lifetime remains essentially the same for OHBI and increases somewhat for F-NAIBP, and there is almost no change in the computed quantum efficiency for internal rotation in F-NAIBP. We recommend the general use of adaptive time steps in TSH simulations with active-space CI methods because this will help to avoid technical problems, increase the overall efficiency and robustness of the simulations, and allow for a more complete sampling.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
NASA NTRS2008

J-2X Fuel Turbopump Point of Departure: The Performance of the J-2s Fuel Turbopump Inducer

To aid the J-2X program design effort with detailed performance and environment information, the J-2S fuel turbopump (FTP) inducer has undergone a thorough test series in both water and hydrogen. The test series utilizes both inducer only and a complete pump configuration to assess the inducer interaction to the overall turbopump system. The test goals include verification of suction performance against heritage J-2S data, head production, effects of thermodynamic suppression head (TSH), and evaluation of the inducer dynamic pressure caused by cavitation instabilities. Test facilities at both Pratt & Whitney Rocketdyne (PWR) and NASA s Stennis Space Center (SSC) are employed for the testing. The inducer only water test effort conducted at PWR established performance curves for suction performance, head production, and efficiency over a wide operating range. Because the heritage J-2S suction performance data set is in hydrogen, it is desired to obtain current suction performance data in hydrogen as well, thus avoiding the reliance on a theoretical TSH correlation for direct comparison. This data then provides an empirically based TSH correlation allowing for the comparison of water test suction data to system suction requirements. The FTP testing performed at SSC provides these suction performance relationships as well as inlet duct dynamic pressures during liquid hydrogen operation. The test effort successfully confirms the heritage J-2S suction performance and establishes the amount of TSH between water and hydrogen operation at the design flow coefficient. Correlating data is also obtained for cavitating instability frequency content, illustrating the validity of using the wide flow range water test data to predict hydrogen performance.

Sargent, S. R.↗
DOE OSTI2013

Normal Tissue Complication Probability Modeling of Radiation-Induced Hypothyroidism After Head-and-Neck Radiation Therapy

Purpose: To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Methods and Materials: Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with {alpha}/{beta} = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Results: Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D{sub 50} estimated from the models was approximately 44 Gy. Conclusions: The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Soy isoflavones interfere with thyroid hormone homeostasis in orchidectomized middle-aged rats

We previously reported that genistein (G) and daidzein (D) administered subcutaneously (10 mg/kg) induce changes in the angio-follicular units of the thyroid gland, reduce concentration of total thyroid hormones (TH) and increase thyrotropin (TSH) in serum of orchidectomized middle-aged (16-month-old) rats. To further investigate these effects, we now examined expression levels of the thyroglobulin (Tg), thyroperoxidase (Tpo), vascular endothelial growth factor A (Vegfa) and deiodinase type 1 (Dio 1) genes in the thyroid; in the pituitary, genes involved in TH feedback control (Tsh β, Dio 1, Dio 2, Trh receptor); and in the liver and kidney, expression of T{sub 3}-activated genes Dio 1 and Spot 14, as well as transthyretin (Ttr), by quantitative real-time PCR. We also analyzed TPO-immunopositivity and immunofluorescence of T{sub 4} bound to Tg, determined thyroid T{sub 4} levels and measured deiodinase enzyme activities in examined organs. Decreased expression of Tg and Tpo genes (p < 0.05) correlated with immunohistochemical staining results, and together with decreased serum total T{sub 4} levels, indicates decreased Tg and TH synthesis following treatments with both isoflavones. However, expression of Spot 14 (p < 0.05) gene in liver and kidney was up-regulated, and liver Dio 1 expression and activity (p < 0.05) increased. At the level of pituitary, no significant change in gene expression levels, or Dio 1 and 2 enzyme activities was observed. In conclusion, both G and D impaired Tg and TH synthesis, but at the same time increased tissue availability of TH in peripheral tissues of Orx middle-aged rats. - Highlights: • We tested how genistein and daidzein interfere with thyroid hormone homeostasis. • Thyroid: decreased expression of Tg and TPO genes correlated with IHC results. • Serum: total T{sub 4} reduced and TSH increased. • Liver and kidney: expression of Spot 14 and liver Dio 1 activity increased. • Pituitary: expression of T{sub 3}-regulated genes and Dio 1 and 2 activities unchanged.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Exposure to perfluoroalkyl substances and associations with serum thyroid hormones in a remote population of Alaska Natives

Highlights: • Serum concentrations PFOA, PFNA, PFUnA and PFDA were positively associated with TSH in individual models. • No serum PFASs are associated with total or free T{sub 4}. • The associations between serum PFOA and PFNA and free T{sub 3,} as well as PFNA and total T3 are modified by sex. • The effect of PFAS exposure on thyroid hormone homeostasis differs between sexes. Perfluoroalkyl substances (PFASs) are known to accumulate in traditional food animals of the Arctic, and arctic indigenous peoples may be exposed via consumption of subsistence-harvested animals. PFASs are suspected of disrupting thyroid hormone homeostasis in humans. The aim of this study is to assess the relationship between serum PFASs and thyroid function in a remote population of Alaska Natives. Serum samples were collected from 85 individuals from St. Lawrence Island, Alaska. The concentrations of 13 PFASs, as well as free and total thyroxine (T{sub 4}), free and total triiodothyronine (T{sub 3}), and thyrotropin (TSH) were quantified in serum samples. The relationships between circulating concentrations of PFASs and thyroid hormones were assessed using multiple linear regression fit with generalized estimating equations. Several PFASs, including perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA), were positively associated with TSH concentrations when modeled individually. PFOS and PFNA were significantly associated with free T{sub 3} and PFNA was significantly associated with total T{sub 3} in models with PFAS*sex interactive terms; these associations suggested negative associations in men and positive associations in women. PFASs were not significantly associated with concentrations of free or total T{sub 4}. Serum PFASs are associated with circulating thyroid hormone concentrations in a remote population of Alaska Natives. The effects of PFAS exposure on thyroid hormone homeostasis may differ between sexes.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

The Cross-sectional and Longitudinal Association Between Thyroid Function and Depression: A Population-Based Study

Abstract Context An association of thyroid function with mood disorders has been widely suggested, but very few studies have examined this association longitudinally. Objective We assessed the cross-sectional and longitudinal association between thyroid function and depression in a population-based cohort. Methods A total of 9471 individuals were included in cross-sectional analyses, of whom 8366 had longitudinal data. At baseline, we assessed thyroid function using serum samples (thyrotropin [TSH], free thyroxine (FT4), and thyroid peroxidase antibodies) and depressive symptoms using the Centre for Epidemiologic Studies Depression (CES-D) scale. Incident depressive events (n = 1366) were continuously followed up with the CES-D and clinical interviews. We analyzed the cross-sectional association of thyroid function and thyroid disease with depressive symptoms using linear and logistic regression, and the longitudinal association with Cox proportional hazard models for depressive events. Results Lower TSH levels and lower and higher FT4 levels were cross-sectionally associated with more depressive symptoms with a B value of −0.07 per 1 unit increase of natural log-transformed TSH (95% CI −0.11; −0.04). Furthermore, hypothyroidism was cross-sectionally associated with less depressive symptoms and hyperthyroidism with more depressive symptoms. Longitudinally, there was a U-shaped association between FT4 and incident depressive events but only in euthyroid participants. Conclusion We show a cross-sectional association between thyroid (dys)function with depressive symptoms, and a U-shaped association between FT4 and incident depressive events in euthyroid individuals. Our findings suggest an association of thyroid function with the risk of developing depression, albeit small. Reverse causation and additional underlying factors may also contribute to the association.

Roa Dueñas, Oscar Hernando (ORCID:0000000207522261↗
NASA NTRS2000

Absence of detectable melatonin and preservation of cortisol and thyrotropin rhythms in tetraplegia

The human circadian timing system regulates the temporal organization of several endocrine functions, including the production of melatonin (via a neural pathway that includes the spinal cord), TSH, and cortisol. In traumatic spinal cord injury, afferent and efferent circuits that influence the basal production of these hormones may be disrupted. We studied five subjects with chronic spinal cord injury (three tetraplegic and two paraplegic, all neurologically complete injuries) under stringent conditions in which the underlying circadian rhythmicity of these hormones could be examined. Melatonin production was absent in the three tetraplegic subjects with injury to their lower cervical spinal cord and was of normal amplitude and timing in the two paraplegic subjects with injury to their upper thoracic spinal cord. The amplitude and the timing of TSH and cortisol rhythms were robust in the paraplegics and in the tetraplegics. Our results indicate that neurologically complete cervical spinal injury results in the complete loss of pineal melatonin production and that neither the loss of melatonin nor the loss of spinal afferent information disrupts the rhythmicity of cortisol or TSH secretion.

NASA Discipline Regulatory Physiology↗
DOE OSTI2018

Development of a functional thyroid model based on an organoid culture system

Highlights: • We developed a culture system for murine thyroid organoids. • TSH stimulated thyroid organoid formation and growth. • TSH-responsive thyroid organoids formed functional thyroid-like tissue in vivo. • NRAS{sup Q61R}-positive, p53{sup −/−} organoids gave rise to thyroid cancer. The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid–like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRAS{sup Q61R}) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Exposure to pyrethroids insecticides and serum levels of thyroid-related measures in pregnant women

Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10–12 gestational weeks recruited at a university hospital in Tokyo during 2009–2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self-administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06) μg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adult females. The range of serum fT4, TSH and TBG level was 0.83–3.41 ng/dL, 0.01–27.4 μIU/mL and 16.4–54.4 μg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected. -- Highlights: • Pyrethroid exposure and thyroid hormone status was examined in pregnant women. • Urinary 3-phenoxybenzoic acid was used as a biomarker of exposure. • Iodine nutrition, age and other covariates were included in statistical models. • No association was found between levels of thyroid hormone and pyrethroid exposure. • The result may be ascribed to lower exposure level.

54 ENVIRONMENTAL SCIENCES↗