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Sample records for neonatal thyroid-stimulating hormone

  1. Neonatal screening for congenital hypothyroidism by measurement of plasma thyroxine and thyroid stimulating hormone concentrations.

    PubMed Central

    Griffiths, K D; Virdi, N K; Rayner, P H; Green, A

    1985-01-01

    Neonatal screening for congenital hypothyroidism was introduced in the City of Birmingham in 1980 by measuring concentrations of both thyroid stimulating hormone and thyroxine in plasma. Over two years 30 108 babies were tested. Thirty one babies were recalled because of thyroid stimulating hormone concentrations greater than 40 mU/l, of whom 12 were treated with replacement thyroxine. Six babies were found to have low thyroxine concentrations because of reduced thyroxine binding globulin and five raised thyroxine values because of increased thyroxine binding globulin. As a result of this study screening was continued with measurement of thyroid stimulating hormone only as the primary test for congenital hypothyroidism, the thyroxine value being measured only when the concentration of thyroid stimulating hormone exceeded 20 mU/l. PMID:3926078

  2. Thyroid Stimulating Hormone Receptor

    PubMed Central

    Tuncel, Murat

    2017-01-01

    Thyroid stimulating hormone receptor (TSHR) plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases. PMID:28117293

  3. Thyroid Stimulating Hormone Receptor.

    PubMed

    Tuncel, Murat

    2016-01-05

    Thyroid stimulating hormone receptor (TSHR) plays a pivotal role in thyroid hormone metabolism. It is a major controller of thyroid cell function and growth. Mutations in TSHR may lead to several thyroid diseases, most commonly hyperthyroidism. Although its genetic and epigenetic alterations do not directly lead to carcinogenesis, it has a crucial role in tumor growth, which is initiated by several oncogenes. This article will provide a brief review of TSHR and related diseases.

  4. Perinatal factors associated with neonatal thyroid-stimulating hormone in normal newborns

    PubMed Central

    2016-01-01

    Purpose This study was to evaluate the effect of neonatal, maternal, and delivery factors on neonatal thyroid-stimulating hormone (TSH) of healthy newborns. Methods Medical records of 705 healthy infants born through normal vaginal delivery were reviewed. Neonatal TSH levels obtained by neonatal screening tests were analyzed in relation to perinatal factors and any associations with free thyroxine (FT4) and 17-α hydroxyprogesterone (17OHP) levels. Results An inverse relationship was found between TSH and sampling time after birth. Twin babies and neonates born by vacuum-assisted delivery had higher TSH levels than controls. First babies had higher TSH levels than subsequent babies. Birth weight, gestational age, maternal age and duration from the rupture of the membrane to birth were not related to neonatal TSH. There were no significant differences in TSH level according to sex, Apgar scores, labor induction, the presence of maternal disease and maternal medications. There was a positive association between TSH and 17OHP level but not between TSH and FT4 level. Multiple linear regression analyses showed that sampling time, mode of delivery, birth order, and 17OHP level were significant factors affecting neonatal TSH level. Conclusion Neonatal TSH levels of healthy normal newborns are related with multiple factors. Acute stress during delivery may influence the neonatal TSH level in early neonatal period. PMID:28164073

  5. Neonatal Thyroid-Stimulating Hormone Concentrations in Belgium: A Useful Indicator for Detecting Mild Iodine Deficiency?

    PubMed Central

    Vandevijvere, Stefanie; Coucke, Wim; Vanderpas, Jean; Trumpff, Caroline; Fauvart, Maarten; Meulemans, Ann; Marie, Sandrine; Vincent, Marie-Françoise; Schoos, Roland; Boemer, François; Vanwynsberghe, Timothy; Philips, Eddy; Eyskens, François; Wuyts, Brigitte; Selimaj, Valbona; Van Overmeire, Bart; Kirkpatrick, Christine; Van Oyen, Herman; Moreno-Reyes, Rodrigo

    2012-01-01

    It has been proposed that neonatal thyroid-stimulating hormone (TSH) concentrations are a good indicator of iodine deficiency in the population. A frequency of neonatal TSH concentrations above 5 mU/L below 3% has been proposed as the threshold indicating iodine sufficiency. The objective of the present study was to evaluate feasibility and usefulness of nation-wide neonatal TSH concentration screening results to assess iodine status in Belgium. All newborns born in Belgium during the period 2009–2011 (n = 377713) were included in the study, except those suffering from congenital hypothyroidism and premature neonates. The frequency of neonatal TSH concentrations above 5 mU/L from 2009 to 2011 in Belgium fluctuated between 2.6 and 3.3% in the centres using the same TSH assay. There was a significant inverse association between neonatal TSH level and birth weight. The longer the duration between birth and screening, the lower the TSH level. Neonatal TSH levels were significantly lower in winter than in spring or autumn and significantly lower in spring and summer than in autumn while significantly higher in spring compared to summer. In conclusion, despite that pregnant women in Belgium are mildly iodine deficient, the frequency of neonatal TSH concentrations above 5 mU/L was very low, suggesting that the neonatal TSH threshold proposed for detecting iodine deficiency needs to be re-evaluated. Although neonatal TSH is useful to detect severe iodine deficiency, it should not be recommended presently for the evaluation of iodine status in mildly iodine deficient regions. PMID:23112844

  6. Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Yau, Vincent M.; Lutsky, Marta; Yoshida, Cathleen K.; Lasley, Bill; Kharrazi, Martin; Windham, Gayle; Gee, Nancy; Croen, Lisa A.

    2015-01-01

    Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001 were identified: ASD (n = 78), developmental delay…

  7. Prenatal and Neonatal Thyroid Stimulating Hormone Levels and Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Yau, Vincent M.; Lutsky, Marta; Yoshida, Cathleen K.; Lasley, Bill; Kharrazi, Martin; Windham, Gayle; Gee, Nancy; Croen, Lisa A.

    2015-01-01

    Thyroid hormones are critical for normal brain development. This study examined autism spectrum disorders (ASD) and thyroid stimulating hormone (TSH) levels measured in mid-pregnancy maternal serum and infant blood after birth. Three groups of children born in Orange County, CA in 2000-2001 were identified: ASD (n = 78), developmental delay…

  8. Effect of maternal and neonatal factors on cord blood thyroid stimulating hormone

    PubMed Central

    Lakshminarayana, Sheetal G.; Sadanandan, Nidhish P.; Mehaboob, A. K.; Gopaliah, Lakshminarayana R.

    2016-01-01

    Background: Congenital hypothyroidism (CH) is most common preventable cause of mental retardation in children. Cord blood Thyroid Stimulating Hormone (CBTSH) level is an accepted screening tool for CH. Objectives: To study CBTSH profile in neonates born at tertiary care referral center and to analyze the influence of maternal and neonatal factors on their levels. Design: Cross retrospective sectional study. Methods: Study population included 979 neonates (males = 506 to females = 473). The CBTSH levels were estimated using electrochemiluminescence immunoassay on Cobas analyzer. Kit based cut-offs of TSH level were used for analysis. All neonates with abnormal CBSTH levels, were started on levothyroxine supplementation 10 μg/Kg/day and TSH levels were reassessed as per departmental protocol. Results: The mean CBTSH was 7.82 μIU/mL (Range 0.112 to 81.4, SD = 5.48). The mean CBTSH level was significantly higher in first order neonates, neonates delivered by assisted vaginal delivery and normal delivery, delivered at term or preterm, neonates with APGAR score <5 and those needing advanced resuscitation after birth. The CBTSH level >16.10 and <1.0 μIU/mL was found in 4.39 % and 1.02 % neonates respectively. The prevalence rate of CBTSH level >16.1 μIU/mL was significantly higher in neonates delivered by assisted vaginal delivery and normal delivery, term and preterm neonates, APAGR score of <5, presence of fetal distress, need for resuscitation beyond initial steps and in those with birth weight of <1.5 Kg. Three neonates were confirmed to have CH after retesting of TSH level. Conclusions: The CBTSH estimation is an easy, non-invasive method for screening for CH. The cutoff level of CB TSH (μIU/mL) >16.10 and <1.0 led to a recall of 5.41% of neonates which is practicable given the scenario in our Country. The mode of delivery and perinatal stress factors have a significant impact on CBTSH levels and any rise to be seen in the light of these factors. The prevalence

  9. Neonatal thyroid-stimulating hormone concentration and psychomotor development at preschool age

    PubMed Central

    Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vandevijvere, Stefanie

    2016-01-01

    Objective Thyroid hormones are essential for normal brain development. The aim of this study is to assess if high concentration of thyroid stimulating hormone (TSH) that is below the clinical threshold (5–15 mIU/L) at neonatal screening is linked to psychomotor development impairments in the offspring at preschool age. Design A total of 284 Belgian preschool children 4–6 years old and their mothers were included in the study. The children were randomly selected from the total list of neonates screened in 2008, 2009 and 2010 by the Brussels newborn screening centre. The sampling was stratified by gender and TSH range (0.45–15 mIU/L). Infants with congenital hypothyroidism (>15 mIU/L), low birth weight and/or prematurity were excluded. Psychomotor development was assessed using the Charlop-Atwell scale of motor coordination. The iodine status of children was determined using median urinary iodine concentration. Socioeconomic, parental and child potential confounding factors were measured through a self-administered questionnaire. Results TSH level was not significantly associated with total motor score (average change in z-score per unit increase in TSH is 0.02 (−0.03, 0.07), p=0.351), objective motor score (p=0.794) and subjective motor score (p=0.124). No significant associations were found using multivariate regression model to control confounding factors. Conclusions Mild thyroid dysfunction in the newborn—reflected by an elevation of TSH that is below the clinical threshold (5–15 mIU/L)—was not associated with impaired psychomotor development at preschool age. PMID:27402733

  10. Neonatal Thyroid-Stimulating Hormone Screening as a Monitoring Tool for Iodine Deficiency in Turkey.

    PubMed

    Çaylan, Nilgün; Tezel, Başak; Özbaş, Sema; Şahin, Nuran; Aydın, Şirin; Acıcan, Deniz; Keskinkılıç, Bekir

    2016-06-05

    Thyroid-stimulating hormone (TSH) level in neonates is recommended as an indicator for presence of iodine deficiency (ID) at a population level and as a monitoring tool in programs of iodine supplementation. The purpose of this study, based on data from the National Newborn Screening Program (NNSP) for congenital hypothyroidism (CH) in 2014, was to analyze neonatal TSH levels to predict the current status of iodine nutrition in Turkey. According to screening methodology, heel-prick blood samples of newborns were collected on filter paper cards usually on day 3-5 after birth (or shortly before discharge). Results of samples collected >48 h after birth were analyzed. The degree of severity of ID was assessed by using the epidemiologic criteria of the World Health Organization (WHO). Elevated TSH levels (>5 mIU/L) were processed and classified according to province, region, birth season, and sampling time. A total of 1,298531 newborns were registered in the NNSP for the CH database. Of those, 1,270311 newborns had screening results collected >48 h after birth and were included in the statistical analyses. The national prevalence of elevated TSH was 7.2%. While the Gaziantep sub-region had the highest TSH elevation rate (15.9%), the Tekirdağ sub-region had the lowest rate (4.0%; p<0.001). Seasonal variations were also significant, and the elevated TSH prevalence rate was highest in winter (7.4%; p<0.001). National CH screening results suggest that Turkey may still be mildly iodine deficient. Nationwide studies should be performed for direct assessment and monitoring of iodine status in vulnerable populations to confirm accuracy of our results.

  11. Increased iodine deficiency in Victoria, Australia: analysis of neonatal thyroid-stimulating hormone data, 2001 to 2006.

    PubMed

    Rahman, Ashequr; Savige, Gayle S; Deacon, Nicholas J; Francis, Ivan; Chesters, Janice E

    2010-11-01

    To use neonatal thyroid-stimulating hormone (TSH) concentration data to measure the iodine status of the population of the Australian state of Victoria. Retrospective analysis of the results of 368,552 neonatal heel-prick blood tests for TSH concentration in Victoria in the years 2001-2006. Iodine deficiency as indicated by a mean percentage of neonatal TSH concentrations > 5 mIU/L of over 3% in accordance with World Health Organization, United Nations Children's Fund and International Council for the Control of Iodine Deficiency Disorder criteria; comparison of findings for the nine Department of Human Services health regions in Victoria. The mean percentage of neonatal TSH concentrations > 5 mIU/L ranged from 4.07% in 2001 to 9.65% in 2006, and this increase was statistically significant (P < 0.001). The populations of all nine Victorian health regions showed increasing iodine deficiency over the study period. Metropolitan populations had higher iodine deficiency than non-metropolitan populations, and this difference was also statistically significant (P < 0.05). These results are consistent with urinary iodine excretion research in Victoria. The high percentage of elevated TSH concentrations among newborns is of concern and requires ongoing monitoring. Neonatal TSH assay is part of routine screening in Australia, and thus offers an effective and economical method of monitoring population iodine status.

  12. Thyroid-Stimulating Hormone (TSH) Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age

    PubMed Central

    Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vanderpas, Jean; Vandevijvere, Stefanie

    2015-01-01

    The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH) concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4–6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45–15 mIU/L). Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence—third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration—a surrogate marker for MID—was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10–15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children. PMID:26540070

  13. Thyroid-Stimulating Hormone (TSH) Concentration at Birth in Belgian Neonates and Cognitive Development at Preschool Age.

    PubMed

    Trumpff, Caroline; De Schepper, Jean; Vanderfaeillie, Johan; Vercruysse, Nathalie; Van Oyen, Herman; Moreno-Reyes, Rodrigo; Tafforeau, Jean; Vanderpas, Jean; Vandevijvere, Stefanie

    2015-11-02

    The main objective of the study was to investigate the effect of MID during late pregnancy, assessed by the thyroid-stimulating hormone (TSH) concentration at neonatal screening, on cognitive development of preschool children. A retrospective cohort study including 311 Belgian preschool children of 4-6 years old was conducted. Children were selected at random from the total list of neonates screened in 2008, 2009, and 2010 by the Brussels new-born screening center. Infants with congenital hypothyroidism, low birth weight, and/or prematurity were excluded from the selection. The selected children were stratified by gender and TSH-range (0.45-15 mIU/L). Cognitive abilities were assessed using Wechsler Preschool and Primary Scale of Intelligence-third edition. In addition, several socioeconomic, parental, and child confounding factors were assessed. Neonatal TSH concentration-a surrogate marker for MID-was not associated with Full Scale and Performance IQ scores in children. Lower Verbal IQ scores were found in children with neonatal TSH values comprised between 10-15 mIU/L compared to lower TSH levels in univariate analysis but these results did not hold when adjusting for confounding factors. Current levels of iodine deficiency among pregnant Belgian women may not be severe enough to affect the neurodevelopment of preschool children.

  14. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  15. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  16. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  17. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  18. 21 CFR 862.1690 - Thyroid stimulating hormone test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid stimulating hormone test system. 862.1690... Systems § 862.1690 Thyroid stimulating hormone test system. (a) Identification. A thyroid stimulating hormone test system is a device intended to measure thyroid stimulating hormone, also known...

  19. Cord blood thyroid-stimulating hormone and free T4 levels in Turkish neonates: is iodine deficiency still a continuing problem?

    PubMed

    Kişlal, Fatih; Cetinkaya, Semra; Dilmen, Uğur; Yaşar, Handan; Teziç, Tahsin

    2010-10-01

    The objectives of this study were to determine the cord blood thyroid-stimulating hormone (TSH) and free T(4) (FT(4) ) levels in Turkish neonates and to determine whether these variables reveal iodine deficiency. We collected 818 cords from healthy mothers at parturition and measured levels of FT(4) and TSH. We also measured cord blood FT(4) and TSH levels in different stages of gestation and gender. We grouped the neonates according to cord serum TSH levels, either being less (Group A) or greater (Group B) than 10 mIU/L. Group A included 589 neonates (300 girls [51%] and 289 boys [49%]) and Group B included 229 neonates (105 girls [45%] and 124 boys [55%]). The percentage of subjects with cord blood TSH < 10 mIU/L and >10 mIU/L was 72% and 28%, respectively. Although cord TSH levels in Group B were greater than those in Group A (P < 0.001), cord blood FT(4) levels in Group B were lower than those in Group A (P < 0.05). There was no difference between both sex in terms of birthweight and maternal age. TSH and FT(4) levels did not vary according to neonate sex during gestation, except for from week 37 to 41. TSH levels of male neonates at the 41st week of gestation were higher than those of female neonates (P < 0.05). There were no effects of birthweight on TSH and FT(4) levels if the neonate was lighter than 2500 g at birth. TSH levels of male neonates were higher than those of female neonates when their birthweights were <2500 g (P < 0.05). There was no significant difference in TSH levels according to birthweights in male neonates. Our data provide the normative data for cord blood TSH and FT(4) levels in Turkish neonates and show that iodine deficiency is a still a public health problem in Turkey. These measurements can be useful for detection and verification of hypothyroidism in a screening program for congenital hypothyroidism as well as evaluation of the success of the iodination program. © 2010 The Authors. Pediatrics International © 2010 Japan Pediatric

  20. Rabbits immunized with thyroid-stimulating hormone produce autoantiidiotypic thyroid-stimulating antibodies.

    PubMed

    Beall, G N; Rapoport, B; Chopra, I J; Kruger, S R

    1985-05-01

    We immunized rabbits with thyroid-stimulating hormone (TSH) to investigate the hypothesis that such immunization could result in production of thyroid-stimulating autoantiidiotypic antibodies to anti-TSH. Thyroid-stimulating immunoglobulin (TSI) appeared in the serum of several rabbits after immunization. At 160 d, TSI equivalent to 6-18 microU TSH/1.5 mg IgG was present in two of six human (h)TSH-, two of six hTSH beta chain-, and two of the four surviving bovine (b)TSH-immunized animals. Control (human serum albumin-immunized rabbits) serum TSI was 4.3 +/- 0.4 (mean +/- SD) at this time. Antiidiotypic antibodies that could bind to monoclonal anti-hTSH were found in the sera of the bTSH-immunized rabbits. The peak TSI activity occurred 3 mo after a TSH booster immunization and declined gradually during subsequent weeks. Evidence that antiidiotypic antibodies to anti-TSH can cause thyroid stimulation strengthens the notion that such antibodies may be the cause of Graves' hyperthyroidism.

  1. Association between borderline neonatal thyroid-stimulating hormone concentrations and educational and developmental outcomes: a population-based record-linkage study.

    PubMed

    Lain, Samantha J; Bentley, Jason P; Wiley, Veronica; Roberts, Christine L; Jack, Michelle; Wilcken, Bridget; Nassar, Natasha

    2016-09-01

    Congenital hypothyroidism causes intellectual delay unless identified and effectively treated soon after birth. Newborn screening has almost eliminated intellectual disability associated with congenital hypothyroidism. However, clinical uncertainty remains about infants with thyroid-stimulating hormone (TSH) concentrations less than the newborn screening cutoffs. We assessed the association between neonatal TSH concentrations and educational and developmental outcomes. We did a population-based record-linkage study of all liveborn infants undergoing newborn screening from 1994 to 2008 in New South Wales, Australia, with assessments of childhood development or school performance. Very-low-birthweight babies (<1500 g) were excluded. Developmental and educational outcomes were obtained and these were linked to individual records by the New South Wales Centre for Health Record Linkage. The primary educational outcome was the proportion of students with National Assessment Program Literacy and Numeracy (NAPLAN) results lower than the national minimum standard in reading or numeracy measured at all ages, and the primary developmental outcome was the proportion of children who were classified as being developmentally high risk (vulnerable in two or more of the five developmental domains assessed by the Australian Early Development Census) at age 4-6 years. The proportions of infants with each outcome were calculated per percentile (0-100) of TSH concentration. Multivariable logistic regression was used to account for potential confounding by maternal and fetal variables known to affect neonatal TSH concentrations or neurodevelopmental outcomes. 503 706 infants had a neonatal TSH result that linked to a developmental or educational outcome. 149 569 infants born between 2002 and 2008 were linked to an Australian Early Development Census developmental outcome and 354 137 were linked to a NAPLAN educational outcome. Median follow-up for educational outcome was 10 years

  2. Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroid-stimulating immunoglobulins

    PubMed Central

    Lytton, S D; Li, Y; Olivo, P D; Kohn, L D; Kahaly, G J

    2010-01-01

    Thyroid-stimulating immunoglobulins (TSI) are a functional biomarker of Graves' disease (GD). To develop a novel TSI bioassay, a cell line (MC4-CHO-Luc) was bio-engineered to constitutively express a chimeric TSH receptor (TSHR) and constructed with a cyclic adenosine monophosphate (cAMP)-dependent luciferase reporter gene that enables TSI quantification. Data presented as percentage of specimen-to-reference ratio (SRR%) were obtained from 271 patients with various autoimmune and thyroid diseases and 180 controls. Sensitivity of 96% and specificity of 99% for untreated GD were attained by receiver operating characteristic analysis, area under the curve 0·989, 95% confidence interval 0·969–0·999, P = 0·0001. Precision testing of manufactured reagents of high, medium, low and negative SRR% gave a percentage of coefficient-of-variation of 11·5%, 12·8%, 14·5% and 15·7%, respectively. There was no observed interference by haemoglobin, lipids and bilirubin and no non-specific stimulation by various hormones at and above physiological concentrations. TSI levels from GD patients without (SRR% 406 ± 134, mean ± standard deviation) or under anti-thyroid treatment (173 ± 147) were higher (P < 0·0001) compared with TSI levels of patients with Hashimoto's thyroiditis (51 ± 37), autoimmune diseases without GD (24 ± 10), thyroid nodules (30 ± 26) and controls (35 ± 18). The bioassay showed greater sensitivity when compared with anti-TSHR binding assays. In conclusion, the TSI-Mc4 bioassay measures the functional biomarker accurately in GD with a standardized protocol and could improve substantially the diagnosis of autoimmune diseases involving TSHR autoantibodies. PMID:21070207

  3. Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis

    EPA Science Inventory

    Serum thyroid hormone (TH) concentrations in anuran larvae rise rapidly during metamorphosis. Such a rise in an adult anuran would inevitably trigger a negative feedback response resulting in decreased synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary....

  4. Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Xenopus Metamorphosis

    EPA Science Inventory

    Serum thyroid hormone (TH) concentrations in anuran larvae rise rapidly during metamorphosis. Such a rise in an adult anuran would inevitably trigger a negative feedback response resulting in decreased synthesis and secretion of thyroid-stimulating hormone (TSH) by the pituitary....

  5. Protocol of the PSYCHOTSH study: association between neonatal thyroid stimulating hormone concentration and intellectual, psychomotor and psychosocial development at 4–5 year of age: a retrospective cohort study

    PubMed Central

    2014-01-01

    Background Several European countries, including Belgium, still suffer from mild iodine deficiency. Thyroid stimulating hormone (TSH) concentration in whole blood measured at birth has been proposed as an indicator of maternal iodine status during the last trimester of pregnancy. It has been shown that mild iodine deficiency during pregnancy may affect the neurodevelopment of the offspring. In several studies, elevated TSH levels at birth were associated with suboptimal cognitive and psychomotor outcomes among young children. This paper describes the protocol of the PSYCHOTSH study aiming to assess the association between neonatal TSH levels and intellectual, psychomotor and psychosocial development of 4–5 year old children. The results could lead to a reassessment of the recommended cut-off levels of 5 > mU/L used for monitoring iodine status of the population. Methods In total, 380 Belgian 4–5 year old preschool children from Brussels and Wallonia with a neonatal blood spot TSH concentration between 0 and 15 mU/L are included in the study. For each sex and TSH-interval (0–1, 1–2, 2–3, 3–4, 4–5, 5–6, 6–7, 7–8, 8–9 and 9–15 mU/L), 19 newborns were randomly selected from all newborns screened by the neonatal screening centre in Brussels in 2008–2009. Infants with congenital hypothyroidism, low birth weight and prematurity were excluded from the study. Neonatal TSH concentration was measured by the Autodelphia method in dried blood spots, collected by heel stick on filter paper 3 to 5 days after birth. Cognitive abilities and psychomotor development are assessed using the Wechsler Preschool and Primary Scale of Intelligence - third edition - and the Charlop-Atwell Scale of Motor coordination. Psychosocial development is measured using the Child Behaviour Check List for age 1½ to 5 years old. In addition, several socioeconomic, parental and child confounding factors are assessed. Conclusions This study aims to clarify the effect of

  6. Thyroid stimulating hormone and cognition during severe, transient hypothyroidism.

    PubMed

    Schraml, Frank V; Goslar, Pamela W; Baxter, Leslie; Beason-Held, Lori L

    2011-01-01

    The purpose of our pilot study was to explore the relationship between serum thyroid stimulating hormone (TSH) levels during overt hypothyroidism (OH) and hypothyroid-related neuropsychological symptoms. We hypothesized that TSH level may reflect the degree of 'brain hypothyroidism' such that an inverse correlation may exist between serum TSH and cognitive function in patients experiencing overt hypothyroidism (OH), and sought to explore this hypothesis. Eleven thyroidectomized patients underwent neuropsychological and thyroid function testing while overtly hypothyroid, and again following thyroid hormone replacement. Their test performance was compared with that of eleven healthy controls at a similarly separated two points in time, and the change over time for the patient group and the controls was likewise assessed and compared. The patients' neuropsychological test scores were then correlated with their serum TSH levels while hypothyroid. The patients' performance while hypothyroid was worse than that of the controls in only one neurocognitive measure--Working Memory Index. The subjects improved similarly or to a greater degree than the controls, when the subjects were thyroid hormone replaced, on all but one neurocognitive measure - Thurstone Word Fluency. TSH level during hypothyroidism was inversely proportional to the patients' performance on these same two measures, but no others. Serum TSH level during hypothyroidism was inversely proportional to performance on the only two neurocognitive measures evidencing an adverse effect from hypothyroidism in our cohort. This suggests that serum TSH level may reflect the severity of 'brain hypothyroidism' during the overt stage of this condition.

  7. Association of thyroid-stimulating hormone with insulin resistance and androgen parameters in women with PCOS.

    PubMed

    Dittrich, Ralf; Kajaia, Natia; Cupisti, Susanne; Hoffmann, Inge; Beckmann, Matthias W; Mueller, Andreas

    2009-09-01

    There is a relationship between thyroid function and insulin sensitivity and alterations in lipids and metabolic parameters. Little information is available regarding this relationship in women with polycystic ovary syndrome. However all those pathologies are also described as often affecting women with polycystic ovary syndrome. The association between thyroid-stimulating hormone <2.5 mIU/l and > or =2.5 mIU/l with insulin resistance and endocrine parameters in 103 women with polycystic ovary syndrome was studied. Clinical, metabolic and endocrine parameters were obtained and an oral glucose tolerance test was performed with calculation of insulin resistance indices. Women with thyroid-stimulating hormone > or =2.5 mIU/l had a significantly higher body mass index (P = 0.003), higher fasting insulin concentrations (P = 0.02) and altered insulin resistance indices (P = 0.007), higher total testosterone (P = 0.009) and free androgen indices (P = 0.001) and decreased sex hormone-binding globulin concentrations (P = 0.01) in comparison with women with thyroid-stimulating hormone <2.5 mIU/l. Generally, all of these parameters correlated significantly (P < 0.05) with thyroid-stimulating hormone only in women with thyroid-stimulating hormone > or =2.5 mIU/l. Women with polycystic ovary syndrome and with thyroid-stimulating hormone > or =2.5 mIU/l had significantly altered endocrine and metabolic changes.

  8. Thyroid stimulating hormone and prospective memory functioning in old age.

    PubMed

    Livner, Asa; Wahlin, Ake; Bäckman, Lars

    2009-11-01

    Alterations of thyroid functioning are common in old age. Even among persons free from thyroid disorders, subclinical variations in thyroid functioning may affect cognitive performance. However, it is unknown whether prospective memory (ProM) is related to thyroid stimulating hormone (TSH) variations. An association could be expected, as changes in the thyroid gland have been linked to alterations in frontal brain regions that play a key role in prospective remembering. Thus, the aim of this study was to examine whether subclinical variations in thyroid functioning affect ProM performance. We studied 103 participants, 75 years and older, who were free from thyroid disorders and had serum levels of TSH and thyroxine (T4) within normal ranges. Interestingly, we found a non-linear association between TSH and ProM performance, where persons with TSH levels above the fourth quartile performed substantially better than persons in the other quartiles. T4 levels were unrelated to ProM performance. This pattern suggests that the previously identified "normal-range" interval for TSH should be moved further up in old age, at least when cognitive functioning is considered.

  9. Thyroid stimulating hormone increases hepatic gluconeogenesis via CRTC2.

    PubMed

    Li, Yujie; Wang, Laicheng; Zhou, Lingyan; Song, Yongfeng; Ma, Shizhan; Yu, Chunxiao; Zhao, Jiajun; Xu, Chao; Gao, Ling

    2017-02-15

    Epidemiological evidence indicates that thyroid stimulating hormone (TSH) is positively correlated with abnormal glucose levels. We previously reported that TSH has direct effects on gluconeogenesis. However, the underlying molecular mechanism remains unclear. In this study, we observed increased fasting blood glucose and glucose production in a mouse model of subclinical hypothyroidism (only elevated TSH levels). TSH acts via the classical cAMP/PKA pathway and CRTC2 regulates glucose homeostasis. Thus, we explore whether CRTC2 is involved in the process of TSH-induced gluconeogenesis. We show that TSH increases CRTC2 expression via the TSHR/cAMP/PKA pathway, which in turn upregulates hepatic gluconeogenic genes. Furthermore, TSH stimulates CRTC2 dephosphorylation and upregulates p-CREB (Ser133) in HepG2 cells. Silencing CRTC2 and CREB decreases the effect of TSH on PEPCK-luciferase, the rate-limiting enzyme of gluconeogenesis. Finally, the deletion of TSHR reduces the levels of the CRTC2:CREB complex in mouse livers. This study demonstrates that TSH activates CRTC2 via the TSHR/cAMP/PKA pathway, leading to the formation of a CRTC2:CREB complex and increases hepatic gluconeogenesis.

  10. Thyroid Stimulating Hormone and Cognition during Severe, Transient Hypothyroidism

    PubMed Central

    Schraml, Frank V.; Goslar, Pamela W.; Baxter, Leslie; Beason-Held, Lori L.

    2011-01-01

    OBJECTIVE The purpose of our pilot study was to explore the relationship between serum thyroid stimulating hormone (TSH) levels during overt hypothyroidism (OH) and hypothyroid-related neuropsychological symptoms. We hypothesized that TSH level may reflect the degree of ‘brain hypothyroidism’ such that an inverse correlation may exist between serum TSH and cognitive function in patients experiencing overt hypothyroidism (OH), and sought to explore this hypothesis. METHODS Eleven thyroidectomized patients underwent neuropsychological and thyroid function testing while overtly hypothyroid, and again following thyroid hormone replacement. Their test performance was compared with that of eleven healthy controls at a similarly separated two points in time, and the change over time for the patient group and the controls was likewise assessed and compared. The patients’ neuropsychological test scores were then correlated with their serum TSH levels while hypothyroid. RESULTS The patients’ performance while hypothyroid was worse than that of the controls in only one neurocognitive measure--Working Memory Index. The subjects improved similarly or to a greater degree than the controls, when the subjects were thyroid hormone replaced, on all but one neurocognitive measure--Thurstone Word Fluency. TSH level during hypothyroidism was inversely proportional to the patients’ performance on these same two measures, but no others. CONCLUSION Serum TSH level during hypothyroidism was inversely proportional to performance on the only two neurocognitive measures evidencing an adverse effect from hypothyroidism in our cohort. This suggests that serum TSH level may reflect the severity of ‘brain hypothyroidism’ during the overt stage of this condition. PMID:21712772

  11. Thyroid-Stimulating Hormone Receptor Antibodies in Pregnancy: Clinical Relevance

    PubMed Central

    Bucci, Ines; Giuliani, Cesidio; Napolitano, Giorgio

    2017-01-01

    Graves’ disease is the most common cause of thyrotoxicosis in women of childbearing age. Approximately 1% of pregnant women been treated before, or are being treated during pregnancy for Graves’ hyperthyroidism. In pregnancy, as in not pregnant state, thyroid-stimulating hormone (TSH) receptor (TSHR) antibodies (TRAbs) are the pathogenetic hallmark of Graves’ disease. TRAbs are heterogeneous for molecular and functional properties and are subdivided into activating (TSAbs), blocking (TBAbs), or neutral (N-TRAbs) depending on their effect on TSHR. The typical clinical features of Graves’ disease (goiter, hyperthyroidism, ophthalmopathy, dermopathy) occur when TSAbs predominate. Graves’ disease shows some peculiarities in pregnancy. The TRAbs disturb the maternal as well as the fetal thyroid function given their ability to cross the placental barrier. The pregnancy-related immunosuppression reduces the levels of TRAbs in most cases although they persist in women with active disease as well as in women who received definitive therapy (radioiodine or surgery) before pregnancy. Changes of functional properties from stimulating to blocking the TSHR could occur during gestation. Drug therapy is the treatment of choice for hyperthyroidism during gestation. Antithyroid drugs also cross the placenta and therefore decrease both the maternal and the fetal thyroid hormone production. The management of Graves’ disease in pregnancy should be aimed at maintaining euthyroidism in the mother as well as in the fetus. Maternal and fetal thyroid dysfunction (hyperthyroidism as well as hypothyroidism) are in fact associated with several morbidities. Monitoring of the maternal thyroid function, TRAbs measurement, and fetal surveillance are the mainstay for the management of Graves’ disease in pregnancy. This review summarizes the biochemical, immunological, and therapeutic aspects of Graves’ disease in pregnancy focusing on the role of the TRAbs in maternal and fetal

  12. Serum thyroid-stimulating hormone and cognition in older people.

    PubMed

    Ojala, Anna K; Schalin-Jäntti, Camilla; Pitkälä, Kaisu H; Tilvis, Reijo S; Strandberg, Timo E

    2016-01-01

    high TSH concentrations and cognitive decline are both very common among older people and could be linked. to assess cognition in our cohort of 335 home-dwelling older people (75 years and older) and to cross-sectionally relate the results to thyroid-stimulating hormone (TSH) concentrations. Our special focus was on the upper normal TSH range and subclinical hypothyroidism. cognitive performance was evaluated using the Consortium to Establish a Registry for Alzheimer's disease neuropsychological battery (CERAD-nb). The Clinical Dementia Rating (CDR) scale was used to evaluate severity of cognitive disorder. The APOEε4 genotype was also defined. Subjects were divided into quartiles based on the TSH concentrations, and results were compared between these groups. expected relations were observed between CERAD domains and both educational level and APOEε4 genotype. Female sex significantly associated with better performance in Boston naming (OR = 0.48; 95% CI = 0.27-0.85). In the whole cohort, higher TSH concentrations tended to associate with better scores in most parts of the CERAD-nb tests, but differences were not statistically significant. However, subjects with the highest TSH concentration (90th TSH percentile, range 4.14-14.4 mU/l) had better CDR scores compared with subjects with the lowest TSH concentration (10th percentile, range 0.001-0.63 mIU/l; OR 0.10; 95% CI 0.014-0.76). our results do not support the notion that higher TSH concentrations, not even in the range of subclinical hypothyroidism, would adversely affect cognition among older people. © The Author 2015. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Normative Thyroid-Stimulating Hormone Values for Healthy Nigerian Newborns.

    PubMed

    Yarhere, Iroro E; Jaja, Tamunopriye; Oduwole, Abiola; Ibekwe, M Ugochi; Suwaid, Salma; Alkali, Yahaya; Adeniran, Kayode; Fetuga, Bolanle; Jarrett, Olumide O; Elusiyan, Jerome B; Adesiyun, Omotayo; Idris, Hafsat W; Blankenstein, Oliver; Akani, Nwadiuto A

    2016-01-01

    Congenital hypothyroidism is a common congenital endocrine disorder prevailing all over the world. No nationwide screening exists for any sub-Saharan country. We present normative cord and capillary thyroid-stimulating hormone (TSH) values for healthy Nigerian newborns. A cross-sectional study was carried out in 6 university hospitals in Nigeria between January 1 and December 31, 2013. Cord and heel blood placed on 4 concentric circles on a Whartman filter paper were analysed for TSH within 1 week of collection using AutoDelfia 1235 immunoassay (Perkin Elmer Wallace, Boston, Mass., USA) at Charité - Universitätsmedizin Berlin, Berlin, Germany. The mean TSH levels of the newborns were determined, considering their sex, birthweight, socioeconomic status, and birth city. The association between the mean TSH level and other parameters was determined by analysis of variance. A total of 2,014 subjects were recruited during the study period. The mean TSH value for the subjects was 1.86 μIU/ml, and 98.1% of the newborns were within the 2.5th and 97.5th percentiles (range: 0.09-7.90 μIU/ml) of the TSH levels. We collected 247 cord and 1,767 heel samples, respectively, and the range was slightly higher in samples from cord blood. The study highlights the normal reference values for capillary/cord TSH levels in term Nigerian newborns. TSH was higher in one region, attributable to earlier sampling, but was not influenced by gender, socioeconomic status, or birthweight. © 2015 S. Karger AG, Basel.

  14. Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx.

    PubMed

    Nishiike, Suetaka; Tatsumi, Ke-ita; Shikina, Takashi; Masumura, Chisako; Inohara, Hidenori

    2014-12-01

    Thyroid-stimulating hormone-secreting ectopic pituitary adenoma of the nasopharynx is highly unusual, with only three reported cases in the world literature. We describe the clinical presentation and radiologic findings in one patient with such rare lesions. A 46-year-old male with typical symptoms of Grave's disease was found to have a mass on magnetic resonance imaging. An otolaryngologic examination revealed a nasopharyngeal mass lesion, which was endoscopically resected. The results of immunohistochemical staining for thyroid-stimulating hormone were positive. After the resection, the patient's TSH was within normal limits. The clinical significance of the case and a brief literature review are presented.

  15. Thyroid-stimulating Hormone (TSH): Measurement of Intracellular, Secreted, and Circulating Hormone in Xenopus laevis and Xenopus tropicalis.

    EPA Science Inventory

    Thyroid Stimulating Hormone (TSH) is a hormone produced in the pituitary that stimulates the thyroid gland to grow and produce thyroid hormone (TH). The concentration of TH controls developmental changes that take place in a wide variety of organisms. Many use the metaphoric ch...

  16. Thyroid-stimulating Hormone (TSH): Measurement of Intracellular, Secreted, and Circulating Hormone in Xenopus laevis and Xenopus tropicalis.

    EPA Science Inventory

    Thyroid Stimulating Hormone (TSH) is a hormone produced in the pituitary that stimulates the thyroid gland to grow and produce thyroid hormone (TH). The concentration of TH controls developmental changes that take place in a wide variety of organisms. Many use the metaphoric ch...

  17. [Screening for congenital hypothyroidism with an immunoradiometric assay (IRMA) for thyroid stimulating hormone].

    PubMed

    Sander, J; Niehaus, C

    1986-01-01

    A commercial immunoradiometric assay (IRMA) for thyroid stimulating hormone (TSH) was modified to be used with dried blood on filter paper of our neonatal screening programme. Sensitivity and precision were as good as with the conventional radioimmunoassay (RIA), but the IRMA was faster. In addition the IRMA was extremely cheap, because all kit reagents could be prediluted 1:4. Our screening procedure for congenital hypothyroidism now combines a determination of TSH with the IRMA technic and a determination of free thyroxin (FT4) by radioimmunoassay. The kit for FT4 can be diluted 1:3, as described earlier. The combination of TSH-IRMA und FT4-RIA to our knowledge is not only much faster but also considerably cheaper than measuring one parameter with consecutive retesting of suspicious samples, which is the procedure in some countries. As the combination gives two independent results it is also of greater clinical value than measuring TSH in dublicates, which is still officially recommended in the Federal Republic of Germany.

  18. Can thyroid stimulating hormone levels by TSH (IRMA) predict relapse of thyrotoxicosis following carbimazole treatment?

    PubMed Central

    Wilson, R.; Semple, C. G.; Reid, A. M.; Glen, A. C.; McKillop, J. H.; Thomson, J. A.

    1987-01-01

    Serum thyrotrophin receptor antibody (TRAb) and thyroid stimulating hormone (TSH) (IRMA) levels were measured in 38 patients at one month after the end of a course of carbimazole/T3 therapy for Graves' disease. Despite the increased sensitivity of the IRMA assay a TSH measurement at this stage was found to be of no predictive value, in contrast to estimation of serum TRAb levels which correctly predicted relapse and remission in 90% of patients. PMID:3444799

  19. Novel Insights on Thyroid-Stimulating Hormone Receptor Signal Transduction

    PubMed Central

    Neumann, Susanne; Grüters, Annette; Krude, Heiko

    2013-01-01

    The TSH receptor (TSHR) is a member of the glycoprotein hormone receptors, a subfamily of family A G protein-coupled receptors. The TSHR is of great importance for the growth and function of the thyroid gland. The TSHR and its endogenous ligand TSH are pivotal proteins with respect to a variety of physiological functions and malfunctions. The molecular events of TSHR regulation can be summarized as a process of signal transduction, including signal reception, conversion, and amplification. The steps during signal transduction from the extra- to the intracellular sites of the cell are not yet comprehensively understood. However, essential new insights have been achieved in recent years on the interrelated mechanisms at the extracellular region, the transmembrane domain, and intracellular components. This review contains a critical summary of available knowledge of the molecular mechanisms of signal transduction at the TSHR, for example, the key amino acids involved in hormone binding or in the structural conformational changes that lead to G protein activation or signaling regulation. Aspects of TSHR oligomerization, signaling promiscuity, signaling selectivity, phenotypes of genetic variations, and potential extrathyroidal receptor activity are also considered, because these are relevant to an understanding of the overall function of the TSHR, including physiological, pathophysiological, and pharmacological perspectives. Directions for future research are discussed. PMID:23645907

  20. Control of pituitary thyroid-stimulating hormone synthesis and secretion by thyroid hormones during Xenopus metamorphosis.

    PubMed

    Sternberg, Robin M; Thoemke, Kara R; Korte, Joseph J; Moen, Scott M; Olson, Jessica M; Korte, Lisa; Tietge, Joseph E; Degitz, Sigmund J

    2011-09-15

    We used ex vivo and in vivo experiments with Xenopus laevis tadpoles to examine the hypothesis that the set-point for negative feedback on pituitary thyroid-stimulating hormone (TSH) synthesis and secretion by thyroid hormones (THs) increases as metamorphosis progresses to allow for the previously documented concomitant increase in serum TH concentrations and pituitary TSH mRNA expression during this transformative process. First, pituitaries from climactic tadpoles were cultured for up to 96 h to characterize the ability of pituitary explants to synthesize and secrete TSHβ in the absence of hypothalamic and circulating hormones. Next, pituitary explants from tadpoles NF stages 54-66 were exposed to physiologically-relevant concentrations of THs to determine whether stage-specific differences exist in pituitary sensitivity to negative feedback by THs. Finally, in vivo exposures of tadpoles to THs were conducted to confirm the results of the ex vivo experiments. When pituitaries from climactic tadpoles were removed from the influence of endogenous hormones, TSHβ mRNA expression increased late or not at all whereas the rate of TSHβ secreted into media increased dramatically, suggesting that TSH secretion, but not TSH mRNA expression, is under the negative regulation of an endogenous signal during the climactic stages of metamorphosis. Pituitaries from pre- and prometamorphic tadpoles were more sensitive to TH-induced inhibition of TSHβ mRNA expression and secretion than pituitaries from climactic tadpoles. The observed decrease in sensitivity of pituitary TSHβ mRNA expression to negative feedback by THs from premetamorphosis to metamorphic climax was confirmed by in vivo experiments in which tadpoles were reared in water containing THs. Based on the results of this study, a model is proposed to explain the seemingly paradoxical, concurrent rise in serum TH concentrations and pituitary TSH mRNA expression during metamorphosis in larval anurans.

  1. The relationships between thyroid hormones and thyroid-stimulating hormone with lipid profile in euthyroid men.

    PubMed

    Chin, Kok-Yong; Ima-Nirwana, Soelaiman; Mohamed, Isa Naina; Aminuddin, Amilia; Johari, Mohamad Hanapi; Ngah, Wan Zurinah Wan

    2014-01-01

    Alteration in lipid profile is a common observation in patients with thyroid dysfunction, but the current knowledge on the relationship between lipids and thyroid hormone levels in euthyroid state is insufficient. The current study aimed to determine the association between thyroid hormones and thyroid-stimulating hormone (TSH) with lipid profile in a euthyroid male population. A total of 708 Chinese and Malay men aged 20 years and above were recruited in this cross-sectional study. Their blood was collected for the determination of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), free thyroxine (FT4), free triiodothyronine (FT3) and TSH levels. The association was analyzed using multiple regression and logistic regression models with adjustment for age, ethnicity, body mass index and FT4/FT3/TSH levels. In multiple regression models, TSH was positively and significantly associated with TG (p<0.05). Free T4 was positively and significantly associated with TC, LDL-C and HDL-C (p<0.05). Free T3 was negatively and significantly associated with HDL-C (p<0.05). In binary logistic models, an increase in TSH was significantly associated with higher prevalence of elevated TG in the subjects (p<0.05), while an increase in FT4 was significantly associated with higher prevalence of elevated TC but a lower prevalence of subnormal HDL in the subjects (p<0.05). Free T3 was not associated with any lipid variables in the logistic regression (p>0.05). In euthyroid Malaysian men, there are positive and significant relationships between TSH level and TG level, and between FT4 level and cholesterol levels.

  2. Persistent Graves' hyperthyroidism despite rapid negative conversion of thyroid-stimulating hormone-binding inhibitory immunoglobulin assay results: a case report.

    PubMed

    Ohara, Nobumasa; Kaneko, Masanori; Kitazawa, Masaru; Uemura, Yasuyuki; Minagawa, Shinichi; Miyakoshi, Masashi; Kaneko, Kenzo; Kamoi, Kyuzi

    2017-02-06

    Graves' disease is an autoimmune thyroid disorder characterized by hyperthyroidism, and patients exhibit thyroid-stimulating hormone receptor antibody. The major methods of measuring circulating thyroid-stimulating hormone receptor antibody include the thyroid-stimulating hormone-binding inhibitory immunoglobulin assays. Although the diagnostic accuracy of these assays has been improved, a minority of patients with Graves' disease test negative even on second-generation and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulins. We report a rare case of a thyroid-stimulating hormone-binding inhibitory immunoglobulin-positive patient with Graves' disease who showed rapid lowering of thyroid-stimulating hormone-binding inhibitory immunoglobulin levels following administration of the anti-thyroid drug thiamazole, but still experienced Graves' hyperthyroidism. A 45-year-old Japanese man presented with severe hyperthyroidism (serum free triiodothyronine >25.0 pg/mL; reference range 1.7 to 3.7 pg/mL) and tested weakly positive for thyroid-stimulating hormone-binding inhibitory immunoglobulins on second-generation tests (2.1 IU/L; reference range <1.0 IU/L). Within 9 months of treatment with oral thiamazole (30 mg/day), his thyroid-stimulating hormone-binding inhibitory immunoglobulin titers had normalized, but he experienced sustained hyperthyroidism for more than 8 years, requiring 15 mg/day of thiamazole to correct. During that period, he tested negative on all first-generation, second-generation, and third-generation thyroid-stimulating hormone-binding inhibitory immunoglobulin assays, but thyroid scintigraphy revealed diffuse and increased uptake, and thyroid ultrasound and color flow Doppler imaging showed typical findings of Graves' hyperthyroidism. The possible explanations for serial changes in the thyroid-stimulating hormone-binding inhibitory immunoglobulin results in our patient include the presence of thyroid-stimulating

  3. Association of the thyroid stimulating hormone receptor gene (TSHR) with Graves' disease.

    PubMed

    Brand, Oliver J; Barrett, Jeffrey C; Simmonds, Matthew J; Newby, Paul R; McCabe, Christopher J; Bruce, Christopher K; Kysela, Boris; Carr-Smith, Jackie D; Brix, Thomas; Hunt, Penny J; Wiersinga, Wilmar M; Hegedüs, Laszlo; Connell, John; Wass, John A H; Franklyn, Jayne A; Weetman, Anthony P; Heward, Joanne M; Gough, Stephen C L

    2009-05-01

    Graves' disease (GD) is a common autoimmune disease (AID) that shares many of its susceptibility loci with other AIDs. The thyroid stimulating hormone receptor (TSHR) represents the primary autoantigen in GD, in which autoantibodies bind to the receptor and mimic its ligand, thyroid stimulating hormone, causing the characteristic clinical phenotype. Although early studies investigating the TSHR and GD proved inconclusive, more recently we provided convincing evidence for association of the TSHR region with disease. In the current study, we investigated a combined panel of 98 SNPs, including 70 tag SNPs, across an extended 800 kb region of the TSHR to refine association in a cohort of 768 GD subjects and 768 matched controls. In total, 28 SNPs revealed association with GD (P < 0.05), with strongest SNP associations at rs179247 (chi(2) = 32.45, P = 8.90 x 10(-8), OR = 1.53, 95% CI = 1.32-1.78) and rs12101255 (chi(2) = 30.91, P = 1.95 x 10(-7), OR = 1.55, 95% CI = 1.33-1.81), both located in intron 1 of the TSHR. Association of the most associated SNP, rs179247, was replicated in 303 GD families (P = 7.8 x 10(-4)). In addition, we provide preliminary evidence that the disease-associated genotypes of rs179247 (AA) and rs12101255 (TT) show reduced mRNA expression ratios of flTSHR relative to two alternate TSHR mRNA splice variants.

  4. Human longevity is characterised by high thyroid stimulating hormone secretion without altered energy metabolism

    PubMed Central

    Jansen, S. W.; Akintola, A. A.; Roelfsema, F.; van der Spoel, E.; Cobbaert, C. M.; Ballieux, B. E.; Egri, P.; Kvarta-Papp, Z.; Gereben, B.; Fekete, C.; Slagboom, P. E.; van der Grond, J.; Demeneix, B. A.; Pijl, H.; Westendorp, R. G. J.; van Heemst, D.

    2015-01-01

    Few studies have included subjects with the propensity to reach old age in good health, with the aim to disentangle mechanisms contributing to staying healthier for longer. The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating levels of thyroid stimulating hormone (TSH) and thyroid hormone (TH) in an inverse relationship. Greater longevity has been associated with higher TSH and lower TH levels, but mechanisms underlying TSH/TH differences and longevity remain unknown. The HPT axis plays a pivotal role in growth, development and energy metabolism. We report that offspring of nonagenarians with at least one nonagenarian sibling have increased TSH secretion but similar bioactivity of TSH and similar TH levels compared to controls. Healthy offspring and spousal controls had similar resting metabolic rate and core body temperature. We propose that pleiotropic effects of the HPT axis may favour longevity without altering energy metabolism. PMID:26089239

  5. Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies

    PubMed Central

    Davies, Terry F; Latif, Rauf

    2015-01-01

    Introduction The thyroid-stimulating hormone receptor (TSHR) is the essential molecule for thyroid growth and thyroid hormone production. Since it is also a key autoantigen in Graves’ disease and is involved in thyroid cancer pathophysiology, the targeting of the TSHR offers a logical model for disease control. Areas covered We review the structure and function of the TSHR and the progress in both small molecule ligands and TSHR antibodies for their therapeutic potential. Expert opinion Stabilization of a preferential conformation for the TSHR by allosteric ligands and TSHR antibodies with selective modulation of the signaling pathways is now possible. These tools may be the next generation of therapeutics for controlling the pathophysiological consequences mediated by the effects of the TSHR in the thyroid and other extrathyroidal tissues. PMID:25768836

  6. The Synthesis and Evaluation of Dihydroquinazolin-4-ones and Quinazolin-4-ones as Thyroid Stimulating Hormone Receptor Agonists

    PubMed Central

    Englund, Erika E.; Neumann, Susanne; Eliseeva, Elena; McCoy, Joshua G.; Titus, Steven; Zheng, Wei; Southall, Noel; Shin, Paul; Leister, William; Thomas, Craig J.; Inglese, James; Austin, Christopher P.; Gershengorn, Marvin C.

    2011-01-01

    We herein describe the rapid synthesis of a diverse set of dihydroquinazolin-4-ones and quinazolin-4-ones, their biological evaluation as thyroid stimulating hormone receptor (TSHR) agonists, and SAR analysis. Among the compounds screened, 8b was 60-fold more potent than the hit compound 1a, which was identified from a high throughput screen of over 73,000 compounds. PMID:22408719

  7. Serum thyroxine and thyroid-stimulating hormone concentration in hyperthyroid cats that develop azotaemia after radioiodine therapy.

    PubMed

    Peterson, M E; Nichols, R; Rishniw, M

    2017-09-01

    The objectives of this study were to determine which serum thyroid hormone test best identifies iatrogenic hypothyroidism in cats that develop azotaemia after radioiodine treatment and to determine which thyroid test best differentiates these azotaemic, hypothyroid cats from azotaemic, radioiodine-treated euthyroid cats, as well as from azotaemic cats with chronic kidney disease and no history of thyroid disease. A total of 42 hyperthyroid cats that developed azotaemia (serum creatinine ê220 µmol/L) after radioiodine treatment had serum concentrations of thyroxine and free thyroxine by dialysis and thyroid--stimulating hormone measured at 3, 6 and 12 months. Iatrogenic hypothyroidism was confirmed (n=28) or excluded (n=14) on the basis of thyroid scintigraphy. A total of 14 cats with chronic kidney disease and 166 clinically normal cats underwent similar serum thyroid testing and scintigraphy. Concentrations of thyroxine and free thyroxine were lower and thyroid-stimulating hormone higher in hypothyroid cats than in all three groups of euthyroid cats (P<0·0001). Of the hypothyroid cats, thyroxine and free thyroxine concentrations were low in 15 (53·6%) and seven (25%), respectively. Low serum thyroxine and free thyroxine concentrations were also detected in seven (50%) and two (14·3%) of the cats with chronic kidney disease. Thyroid-stimulating hormone concentrations were elevated in all hypothyroid cats but remained within the reference interval in all three groups of euthyroid cats. Serum thyroid--stimulating hormone had a higher test sensitivity and specificity than either thyroxine or free thyroxine concentration. The finding of high serum thyroid-stimulating hormone concentrations best identifies feline iatrogenic hypothyroidism and differentiates it from non-thyroidal illness syndrome in cats that develop azotaemia after treatment. © 2017 British Small Animal Veterinary Association.

  8. Capsaicin, arterial hypertensive crisis and acute myocardial infarction associated with high levels of thyroid stimulating hormone.

    PubMed

    Patanè, Salvatore; Marte, Filippo; Di Bella, Gianluca; Cerrito, Marco; Coglitore, Sebastiano

    2009-05-01

    Chili peppers are rich in capsaicin. The potent vasodilator calcitonin gene-related peptide (CGRP) is stored in a population of C-fiber afferents that are sensitive to capsaicin. CGRP and peptides released from cardiac C fibers have a beneficial effect in myocardial ischemia and reperfusion. It has been reported that capsaicin pretreatment deplete cardiac C-fiber peptide stores. Furthermore, it has also been reported that capsaicin-treated pigs significantly increase mean arterial blood pressure compared with controls and that the decrease in CGRP synthesis and release contributes to the elevated blood pressure. It has also been reported that sub-clinical hypothyroidism is associated with a significant risk of coronary heart disease (CHD). We present a case of arterial hypertensive crisis and acute myocardial infarction in a 59-year-old Italian man with high levels of thyroid stimulating hormone and with an abundant ingestion of peppers and of chili peppers which occurred the day before.

  9. Thyroid-stimulating Hormone and Insulin Resistance: Their Association with Polycystic Ovary Syndrome without Overt Hypothyroidism.

    PubMed

    Benetti-Pinto, Cristina Laguna; Piccolo, Vanessa Berini; Yela, Daniela Angerame; Garmes, Heraldo

    2017-04-11

    Objective This study analyzed the effectiveness of the thyroid-stimulating hormone (TSH) as a predictor of insulin resistance (IR) and its association with the clinical and metabolic parameters of women with polycystic ovary syndrome (PCOS) without overt hypothyroidism. Study Design A cross-sectional study was performed. Women with PCOS and without overt hypothyroidism (n = 168) were included. Methods Receiver operating characteristic (ROC) curve was used to determine the cut-off point for TSH that would maximize sensitivity and specificity for a diagnosis of IR using homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.71. Clinical and metabolic parameters were compared as a function of the TSH cut-off limit and the presence of IR. Results Thyroid-stimulating hormone ≥ 2.77 mIU/L was associated with a diagnosis of IR, with sensitivity of 47.9% and specificity of 65.3%. There were no differences in clinical, hormonal or metabolic parameters between TSH < 2.77 and TSH of 2.77 - 10 mIU/L. Conclusion In women with PCOS without overt hypothyroidism, TSH ≥ 2.77 mIU/L is associated with IR; however, with poor sensibility, showing TSH to be a poor predictor of IR in this population. No clinical or metabolic alterations were found that would justify a change in clinical management. Thus, the IR should be investigated in all women with PCOS irrespective of TSH level.

  10. Measurement of thyroid stimulating immunoglobulins using a novel thyroid stimulating hormone receptor-guanine nucleotide-binding protein, (GNAS) fusion bioassay.

    PubMed

    Pierce, M; Sandrock, R; Gillespie, G; Meikle, A W

    2012-11-01

    Hyperthyroidism, defined by overproduction of thyroid hormones, has a 2-3% prevalence in the population. The most common form of hyperthyroidism is Graves' disease. A diagnostic biomarker for Graves' disease is the presence of immunoglobulins which bind to, and stimulate, the thyroid stimulating hormone receptor (TSHR), a G-protein coupled receptor (GPCR). We hypothesized that the ectopically expressed TSHR gene in a thyroid stimulating immunoglobulin (TSI) assay could be engineered to increase the accumulation of the GPCR pathway second messenger, cyclic AMP (cAMP), the molecule measured in the assay as a marker for pathway activation. An ectopically expressing TSHR-mutant guanine nucleotide-binding protein, (GNAS) Chinese hamster ovary (CHO) cell clone was constructed using standard molecular biology techniques. After incubation of the new clone with sera containing various levels of TSI, GPCR pathway activation was then quantified by measuring cAMP accumulation in the clone. The clone, together with a NaCl-free cell assay buffer containing 5% polyethylene glycol (PEG)6000, was tested against 56 Graves' patients, 27 toxic thyroid nodule patients and 119 normal patients. Using receiver operating characteristic analysis, when comparing normal with Graves' sera, the assay yielded a sensitivity of 93%, a specificity of 99% and an efficiency of 98%. Total complex precision (within-run, across runs and across days), presented as a percentage coefficient of variation, was found to be 7·8, 8·7 and 7·6% for low, medium and high TSI responding serum, respectively. We conclude that the performance of the new TSI assay provides sensitive detection of TSI, allowing for accurate, early detection of Graves' disease.

  11. Impact of light exposure on thyroid-stimulating hormone results using the Siemens Advia Centaur TSH-3Ultra assay.

    PubMed

    Armer, Jane; Giles, Diane; Lancaster, Ian; Brownbill, Kathryn

    2017-09-01

    Background Thyroid-stimulating hormone (TSH) is used as the first-line test of thyroid function. Siemens Healthcare Diagnostics recommend that Siemens Centaur reagents must be protected from light in the assay information and on reagent packaging. We have compared the effect of light exposure on results using Siemens TSH-3Ultra and follicle-stimulating hormone reagents. The thyroid-stimulating hormone reagent includes fluoroscein thiocyanate whereas the follicle-stimulating hormone reagent does not. Methods Three levels of quality controls were analysed using SiemensTSH-3Ultra and follicle-stimulating hormone reagent packs that had been kept protected from light or exposed to light at 6-h intervals for 48 h and then at 96 h. Results Thyroid-stimulating hormone results were significantly lower after exposure of TSH-3Ultra reagent packs to light. Results were >15% lower at all three levels of quality control following 18 h of light exposure and continued to decrease until 96 h. There was no significant difference in follicle-stimulating hormone results whether reagents had been exposed to or protected from light. Conclusions Thyroid-stimulating hormone results but not follicle-stimulating hormone results are lowered after exposure of reagent packs to light. Laboratories must ensure that TSH-3Ultra reagents are not exposed to light and analyse quality control samples on every reagent pack to check that there has not been light exposure prior to delivery. The labelling on TSH-3Ultra reagent packs should reflect the significant effect of light exposure compared with the follicle-stimulating hormone reagent. We propose that the effect of light exposure on binding of fluoroscein thiocyanate to the solid phase antibody causes the falsely low results.

  12. Receptors for thyrotropin-releasing hormone, thyroid-stimulating hormone, and thyroid hormones in the macaque uterus: effects of long-term sex hormone treatment.

    PubMed

    Hulchiy, Mariana; Zhang, Hua; Cline, J Mark; Hirschberg, Angelica Lindén; Sahlin, Lena

    2012-11-01

    Thyroid gland dysfunction is associated with menstrual cycle disturbances, infertility, and increased risk of miscarriage, but the mechanisms are poorly understood. However, little is known about the regulation of these receptors in the uterus. The aim of this study was to determine the effects of long-term treatment with steroid hormones on the expression, distribution, and regulation of the receptors for thyrotropin-releasing hormone (TRHR) and thyroid-stimulating hormone (TSHR), thyroid hormone receptor α1/α2 (THRα1/α2), and THRβ1 in the uterus of surgically menopausal monkeys. Eighty-eight cynomolgus macaques were ovariectomized and treated orally with conjugated equine estrogens (CEE; n = 20), a combination of CEE and medroxyprogesterone acetate (MPA; n = 20), or tibolone (n = 28) for 2 years. The control group (OvxC; n = 20) received no treatment. Immunohistochemistry was used to evaluate the protein expression and distribution of the receptors in luminal epithelium, glands, stroma, and myometrium of the uterus. Immunostaining of TRHR, TSHR, and THRs was detected in all uterine compartments. Epithelial immunostaining of TRHR was down-regulated in the CEE + MPA group, whereas in stroma, both TRHR and TSHR were increased by CEE + MPA treatment as compared with OvxC. TRHR immunoreactivity was up-regulated, but THRα and THRβ were down-regulated, in the myometrium of the CEE and CEE + MPA groups. The thyroid-stimulating hormone level was higher in the CEE and tibolone groups as compared with OvxC, but the level of free thyroxin did not differ between groups. All receptors involved in thyroid hormone function are expressed in monkey uterus, and they are all regulated by long-term steroid hormone treatment. These findings suggest that there is a possibility of direct actions of thyroid hormones, thyroid-stimulating hormone and thyrotropin-releasing hormone on uterine function.

  13. A clinical and therapeutic approach to thyrotoxicosis with thyroid-stimulating hormone suppression only.

    PubMed

    Papi, Giampaolo; Papi, Giovanni; Pearce, Elizabeth N; Braverman, Lewis E; Betterle, Corrado; Roti, Elio

    2005-04-01

    Subclinical hyperthyroidism is defined as normal serum free thyroxine (T4) and triiodothyronine (T3) concentrations and persistently suppressed thyroid stimulating hormone (TSH) concentrations. The most common cause of subclinical hyperthyroidism is the use of suppressive doses of L-thyroxine for treatment of hypothyroidism or, less commonly, diffuse nontoxic goiter or thyroid carcinoma (exogenous subclinical hyperthyroidism). Endogenous subclinical hyperthyroidism may be caused by a variety of thyroid disorders that result in overproduction and release of thyroid hormones from the gland with normal/high 24-hour thyroid radioiodine uptake or by inflammation in the thyroid resulting in release of excess thyroid hormones and low 24-hour thyroid radioiodine uptake. Several groups have investigated whether persistent endogenous or exogenous subclinical hyperthyroidism, like overt hyperthyroidism, causes symptoms, adverse effects on the cardiovascular and the skeletal systems, and increased mortality, whether endogenous subclinical hyperthyroidism evolves to overt thyrotoxicosis, and whether or not it should be treated. The present report reviews the most important and recent studies of subclinical hyperthyroidism and attempts to draw conclusions based upon the literature and the authors' experience.

  14. Similar clinical performance of a novel chimeric thyroid-stimulating hormone receptor bioassay and an automated thyroid-stimulating hormone receptor binding assay in Graves' disease.

    PubMed

    Kamijo, Keiichi; Murayama, Hiroshi; Uzu, Takahiro; Togashi, Kazuyoshi; Olivo, Paul D; Kahaly, George J

    2011-12-01

    Graves' disease (GD) is caused by the continuous stimulation of the thyroid gland by autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR). Two frequent assays for the measurement of TSHR autoantibodies (TSHRAb) were compared, one measuring stimulation of cyclic adenosine monophosphate (cAMP) production and one measuring inhibition of TSH binding, with regard to diagnostic accuracy for GD as well as whether there was an existence of their discordant results in patients with GD and painless thyroiditis (PT). Using 106 sera from untreated GD and 80 sera from autoimmune PT, we compared the diagnostic performance of two TSHRAb assays that have been recently developed. The first one is a bioreporter assay using chimera TSHR (Mc-4), which detects a stimulation signal of cAMP level in cultured CHO cells (Mc4-TSAb assay). The second is a binding inhibition assay using the extracelluar domain of porcine TSHR and a monoclonal antibody (M22) closely mimicking the binding to TSH (M22-TRAb assay). In addition, we compared both assays by using eight sera from eight GD subjects becoming spontaneously hypothyroid due to appearance of thyroid blocking autoantibodies (TBAb) that were measured with inhibition rates of TSH-stimulated cAMP in porcine cells. The Mc4-TSAb assay and the M22-TRAb assay were positive in 94.3% and 92.5% of the GD patients, respectively, whereas they were negative in 95.0% and 98.8% of the PT subjects. However, 10 of 106 GD sera (9.4%) showed discordant results. Six of 106 cases with untreated GD (5.7%) were Mc4-TSAb positive and M22-TRAb negative. In contrast, 4 of 106 sera (3.8%) were Mc4-TSAb negative but M22-TRAb positive. Two cases of untreated GD were negative for both Mc4-TSAb and M22-TRAb. In eight GD subjects with TBAb and hypothyroidism, the binding assay was highly positive, although Mc4-TSAb was negative. Similar and excellent performance was noted for the Mc4-TSAb and M22-TRAb assays in a large group of patients with GD

  15. Persistent hypothyroid symptoms in a patient with a normal thyroid stimulating hormone level.

    PubMed

    Jonklaas, Jacqueline

    2017-10-01

    A subset of patients being treated for hypothyroidism do not feel well while taking levothyroxine (LT4) replacement therapy, despite having a normal serum thyroid stimulating hormone level. Pursuing a relative triiodothyronine deficiency as a potential explanation for patient dissatisfaction, has led to trials of combination therapy with liothyronine (LT3), with largely negative outcomes. This review attempts to reconcile these diverse findings, consider potential explanations, and identify areas for future research. Patients being treated with LT4 often have lower triiodothyronine levels than patients with endogenous thyroid function. Linking patient dissatisfaction with low triiodothyronine levels has fueled multiple combination therapy trials that have generally not shown improvement in patient quality of life, mood, or cognitive performance. Some trials, however, suggest patient preference for combination therapy. There continues, moreover, to be anecdotal evidence that patients have fewer unresolved symptoms while taking combination therapy. The 14 trials completed to date have suffered from employing doses of LT3 that do not result in steady triiodothyronine levels, and having insufficient power to analyze results based on baseline dissatisfaction with therapy and patient genotype. Future trials that are able to incorporate such features may provide insight into what thyroid hormone preparations will most improve patient satisfaction with therapy.

  16. Do Thyroxine and Thyroid-Stimulating Hormone Levels Reflect Urinary Iodine Concentrations?

    PubMed Central

    Soldin, Offie P.; Tractenberg, Rochelle E.; Pezzullo, John C.

    2013-01-01

    The toxicity of environmental chemicals such as nitrates, thiocynates, and perchlorates, some therapeutics, and dietary goitrogens can lower thyroidal iodine uptake and result in hypothyroidism and goiter. Iodine sufficiency, essential for normal thyroid hormone synthesis, is critical during gestation to assure that sufficient thyroxine (T4) and iodine reach the developing fetus. Spot urinary iodide (UI) measurements are used globally to indicate and monitor iodine sufficiency of populations. In individuals, however, UI are not routinely measured; instead, normal serum thyroid-stimulating hormone (TSH) and T4 concentrations serve as surrogate indicators of iodine sufficiency as well as thyroidal health. Our objective was to examine the relationship between UI concentrations and serum T4 and TSH concentrations in individuals in an ‘‘iodine-sufficient population.’’ Using a cross-sectional sample of the US population (n = 7628) from the National Health and Nutrition Examination Survey (NHANES III; 1988–1994) database, we examined the relationship among UI, T4, and TSH in pregnant and nonpregnant women and in men (15–44 years). There was a lack of relationship between UI (or UI/Cr) concentrations and serum T4 or TSH concentrations. Therefore, TSH and T4 are not appropriate markers of UI concentrations in this population. Monitoring the status of iodine nutrition of individuals in the United States may be important because serum TSH and T4 concentrations do not indicate low iodine status. PMID:15795649

  17. Sensitive and specific immunoradiometric assay (IRMA) for human thyroid stimulating hormone

    SciTech Connect

    Piaditis, G.P.; Hodgkinson, S.C.; McLean, C.; Lowry, P.J.

    1985-01-01

    A liquid phase ''two-site'' immunoradiometric assay (IRMA) specific for human thyroid stimulating hormone (hTSH) is described. The assay is based on the simultaneous addition of affinity purified sheep anti hTSH IgG- SVI and rabbit anti hTSH antiserum to standards and unknowns followed by 4h incubation at room temperature. The separation of free labelled sheep IgG- SVI from that bound to hTSH is achieved by the addition of sheep anti-rabbit IgG Fc fragment antiserum. The radiolabelled sheep anti-hTSH IgG- SVI was pretreated with solid phase urinary postmenopausal gonadotropins to remove cross reaction with FSH and LH. The assay is specific for hTSH and no cross reaction with the other anterior pituitary glycoproteins or protein hormones has been found. In addition it is characterized by a wide operating range, rapid equilibration of reactants and high sensitivity. The precision of dose estimates was less than 10% between 0.25-2.5 microU/ml and less than 2.5% over the range 2.5-60 microU/ml.

  18. Thyroid-stimulating hormone, anti-thyroid antibodies, and pregnancy outcomes.

    PubMed

    Plowden, Torie C; Schisterman, Enrique F; Sjaarda, Lindsey A; Perkins, Neil J; Silver, Robert; Radin, Rose; Kim, Keewan; Galai, Noya; DeCherney, Alan H; Mumford, Sunni L

    2017-09-14

    Overt thyroid dysfunction has been associated with adverse obstetric outcomes. However, less is known regarding subclinical hypothyroidism or thyroid autoimmunity and their relationship to pregnancy complications. The purpose of this study was to examine the association between prepregnancy anti-thyroid antibodies and subclinical hypothyroidism and preterm delivery, gestational diabetes mellitus, and preeclampsia. We conducted a secondary analysis of a prospective cohort of 18- to 40-year-old women with 1-2 previous pregnancy losses (n=1193) who participated in a multicenter randomized, placebo-controlled trial of low-dose aspirin. Prepregnancy levels of thyroid-stimulating hormone, free thyroxine, thyroglobulin antibody, and thyroid peroxidase antibody were measured. Relative risks and 95% confidence intervals were estimated with the use of generalized linear models with adjustment for age and body mass index. Among women with an ongoing pregnancy of >20 weeks estimated gestational age, there was no association between prepregnancy thyroid-stimulating hormone level (>2.5 vs ≤2.5 mIU/L) and preterm delivery (adjusted relative risk, 0.77; 95% confidence interval, 0.40-1.47), gestational diabetes mellitus (adjusted relative risk, 1.28; 95% confidence interval, 0.54-3.04), or preeclampsia (adjusted relative risk, 1.20; 95% confidence interval, 0.71-2.04). Similarly, among women with thyroid antibodies, there was no increase in the likelihood of preterm delivery (relative risk, 1.26; 95% confidence interval, 0.65-2.45), gestational diabetes mellitus (relative risk, 1.33; 95% confidence interval, 0.51-3.49), or preeclampsia (relative risk, 1.02; 95% confidence interval, 0.54-1.92), compared with women without these antibodies. Among women with 1-2 previous pregnancy losses, subclinical hypothyroidism and thyroid autoimmunity were not associated with an increased risk of preterm delivery, gestational diabetes mellitus, or preeclampsia. These data support current

  19. Circulating thyroxine, thyroid-stimulating hormone, and hypothyroid status and the risk of prostate cancer.

    PubMed

    Mondul, Alison M; Weinstein, Stephanie J; Bosworth, Tracey; Remaley, Alan T; Virtamo, Jarmo; Albanes, Demetrius

    2012-01-01

    Thyroid hormones may influence risk of cancer through their role in cell differentiation, growth, and metabolism. One study of circulating thyroid hormones supports this hypothesis with respect to prostate cancer. We undertook a prospective analysis of thyroid hormones and prostate cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Within the ATBC Study, a randomized controlled trial of α-tocopherol and β-carotene supplements and cancer incidence in male smokers, 402 prostate cancer cases were sampled. Controls were matched 2:1 to cases on age and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) of prostate cancer were estimated for quintiles of serum total and free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroid-binding globulin (TBG), and by categories of thyroid status. Men with serum higher TSH had a decreased risk of prostate cancer compared to men with lower TSH (Q5 vs. Q1-4: OR = 0.70, 95% CI: 0.51-0.97, p = 0.03). When the T4 and TSH measurements were combined to define men as hypothyroid, euthyroid or hyperthyroid, hypothyroid men had a lower risk of prostate cancer compared to euthyroid men (OR = 0.48, 95% CI = 0.28-0.81, p = 0.006). We observed no association between hyperthyroid status and risk, although the number of hyperthyroid men with prostate cancer was small (n = 9). In this prospective study of smokers, men with elevated TSH and those classified as being in a hypothyroid state were at decreased risk of prostate cancer. Future studies should examine the association in other populations, particularly non-smokers and other racial/ethnic groups.

  20. Circulating thyroid stimulating hormone receptor messenger RNA and differentiated thyroid cancer: A diagnostic meta-analysis

    PubMed Central

    Kong, Chao-Yue; Li, Zhan-Ming; Wang, Li-Shun

    2017-01-01

    Thyroid stimulating hormone receptor messenger RNA (TSHR-mRNA) is over-expressed in thyroid cancer patients, which indicates that TSHR-mRNA is a potential biomarker of thyroid cancer. However, system evaluation for TSHR-mRNA as a diagnostic biomarker of thyroid cancer is deficient. The performance of TSHR-mRNA for thyroid cancer diagnosis was evaluated in this study. Three common international databases as well as a Chinese database were applied for literature researching. Quality assessment of the included literatures was conducted by the QUADAS-2 tool. Totally, 1027 patients from nine studies eligible for the meta-analysis were included in this study. Global sensitivity and specificity for the positivity of TSHR-mRNA in the thyroid cancer diagnosis is 72% and 82%. The value of AUC for this test performance was 0.84. Our meta-analysis suggests that TSHR-mRNA might be a potential biomarker to complete present diagnostic methods for early and precision diagnosis of thyroid cancer. Notably, this findings need validation thorough large-scale clinical studies. PMID:28036261

  1. Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells.

    PubMed

    Tran, Neil; Valentín-Blasini, Liza; Blount, Benjamin C; McCuistion, Caroline Gibbs; Fenton, Mike S; Gin, Eric; Salem, Andrew; Hershman, Jerome M

    2008-04-01

    Perchlorate blocks thyroidal iodide transport in a dose-dependent manner. The human sodium/iodide symporter (NIS) has a 30-fold higher affinity for perchlorate than for iodide. However, active transport of perchlorate into thyroid cells has not previously been demonstrated by direct measurement techniques. To demonstrate intracellular perchlorate accumulation, we incubated NIS-expressing FRTL-5 rat thyroid cells in various concentrations of perchlorate, and we used a sensitive ion chromatography tandem mass spectrometry method to measure perchlorate accumulation in the cells. Perchlorate caused a dose-related inhibition of 125-iodide uptake at 1-10 microM. The perchlorate content from cell lysate was analyzed, showing a higher amount of perchlorate in cells that were incubated in medium with higher perchlorate concentration. Thyroid-stimulating hormone increased perchlorate uptake in a dose-related manner, thus supporting the hypothesis that perchlorate is actively transported into thyroid cells. Incubation with nonradiolabeled iodide led to a dose-related reduction of intracellular accumulation of perchlorate. To determine potential toxicity of perchlorate, the cells were incubated in 1 nM to 100 microM perchlorate and cell proliferation was measured. Even the highest concentration of perchlorate (100 microM) did not inhibit cell proliferation after 72 h of incubation. In conclusion, perchlorate is actively transported into thyroid cells and does not inhibit cell proliferation.

  2. Point prevalence of abnormal thyroid-stimulating hormone during the first trimester of pregnancy in Israel.

    PubMed

    Zornitzki, Taiba; Froimovici, Miron; Amster, Rubi; Lurie, Samuel

    2014-09-01

    The prevalence of thyroid dysfunction in early pregnancy in Israel is not known. To assess the rate of abnormal thyroid-stimulating hormone (TSH) tests in low risk pregnant women attending a community clinic in Israel. We conducted a retrospective analysis of the charts of low risk pregnant women (n = 303) who had undergone a TSH screening during the first trimester of pregnancy at Clalit Health Services Women's Health Centers in Ashkelon and Tel Aviv. TSH of 0.1-2.5 mIU/L during the first trimester was considered to be normal. The TSH levels ranged from 0.04 to 13.3 mIU/L (median 1.73 mIU/L, mean 1.88 mIU/L).The rate of abnormal TSH was 25.6%, with low TSH 2.3% and high TSH 23.4%. The prevalence of abnormal TSH was not influenced by gravidity (primigravidas versus multigravidas) or place of residence (Ashkelon or Tel Aviv). In view of the high prevalence of abnormal TSH (25.6%) in pregnant women in Israel during the first trimester, a universal country-wide screening should be considered.

  3. Serum thyroid-stimulating hormone and interleukin-8 levels in boys with autism spectrum disorder.

    PubMed

    Singh, Sarika; Yazdani, Umar; Gadad, Bharathi; Zaman, Sayed; Hynan, Linda S; Roatch, Nichole; Schutte, Claire; Marti, C Nathan; Hewitson, Laura; German, Dwight C

    2017-06-02

    Autism spectrum disorder (ASD) affects approximately 1 in 68 children in the USA. An ASD blood biomarker may enable early diagnosis and/or identification of new therapeutic targets. Serum samples from ASD and typically developing (TD) boys (n = 30/group) were screened for differences in 110 proteins using a multiplex immunoassay. Eleven proteins were found that together could confirm ASD with modest accuracy using multiple training and test sets. Two of the 11 proteins identified here were further tested using a different detection platform and with a larger sample of ASD and TD boys. The two proteins, thyroid-stimulating hormone (TSH) and interleukin-8 (IL-8), have been previously identified as putative biomarkers for ASD. TSH levels were significantly lower in ASD boys, whereas IL-8 levels were significantly elevated. The diagnostic accuracy for ASD based upon TSH or IL-8 levels alone varied from 74 to 76%, but using both proteins together, the diagnostic accuracy increased to 82%. In addition, TSH levels were negatively correlated with the Autism Diagnostic Observation Schedule subdomain scores. These data suggest that a panel of proteins may be useful as a putative blood biomarker for ASD.

  4. Thyroid-stimulating hormone, 5-HTTLPR genotype, and antidepressant response in depressed women.

    PubMed

    Gressier, Florence; Trabado, Séverine; Verstuyft, Céline; Bouaziz, Elodie; Hardy, Patrick; Fève, Bruno; Becquemont, Laurent; Corruble, Emmanuelle

    2011-10-01

    Basal serum thyroid-stimulating hormone (TSH) levels may predict antidepressant efficacy in patients with major depressive episodes (MDE), but data are inconsistent. As the SS genotype of the 5-HTTLPR polymorphism has been associated with a lower antidepressant efficacy in women with MDE, we aimed at assessing the relationship between normal basal TSH, 5-HTTLPR, and antidepressant efficacy in women. A total of 71 women and 28 men, with normal baseline TSH serum levels, hospitalized for a MDE, were assessed for 5-HTTLPR genotypes and prospectively followed for short-term antidepressant efficacy. Women with SS genotype had higher TSH levels (P=0.002) and a worse antidepressant response (P=0.046) than the women with LL/LS genotype, whereas no significant difference was shown in men. In multivariate analyses, antidepressant response in women was explained by TSH and 5-HTTLPR, but not by other variables. Further research is needed to understand the underlying mechanism explaining interactions between sex, TSH, and serotonergic function.

  5. First trimester thyroid stimulating hormone as an independent risk factor for adverse pregnancy outcome.

    PubMed

    Arbib, Nissim; Hadar, Eran; Sneh-Arbib, Orly; Chen, Rony; Wiznitzer, Arnon; Gabbay-Benziv, Rinat

    2017-09-01

    Maternal thyroid gland dysfunction may adversely affect pregnancy outcome. We aimed to examine the association between subclinical thyroid dysfunction, both hypothyroidism and hyperthyroidism, to adverse pregnancy outcome. Retrospective cohort study of all women with an available first trimester thyroid function testing and known pregnancy outcome, categorized to subclinical hypothyroidism, or hyperthyroidism and evaluated for complication during gestation and delivery. Four thousand five hundred and four women were included in the final analysis - 3231 were euthyroid, 73 (1.6%) were categorized as subclinical hyperthyroidism and 1200 (26.6%) had subclinical hypothyroidism. Low thyroid-stimulating hormone (TSH) levels, i.e. subclinical hyperthyroidism, correlates with higher rates of placental abruption and extremely low birth weight, below 1500 g. Also, the risk for preterm delivery prior to 34 gestational weeks is higher among women with subclinical hypothyroidism, with greater risk among those with a higher TSH level. (OR 1.81, 95% CI 1.0-3.28 for TSH 2.5-4.0 mIU/L and OR 2.33, 95% CI 1.11-4.42 for those with TSH > 4 4.0 mIU/L). Subclinical hypothyroidism is associated with an increased risk for preterm delivery prior to 34 gestational weeks. Additionally, subclinical hyperthyroidism may also have a role in adverse pregnancy outcome - low birth weight and placental abruption - although this needs to be further explored.

  6. Targeting the thyroid gland with thyroid-stimulating hormone (TSH)-nanoliposomes.

    PubMed

    Paolino, Donatella; Cosco, Donato; Gaspari, Marco; Celano, Marilena; Wolfram, Joy; Voce, Pasquale; Puxeddu, Efisio; Filetti, Sebastiano; Celia, Christian; Ferrari, Mauro; Russo, Diego; Fresta, Massimo

    2014-08-01

    Various tissue-specific antibodies have been attached to nanoparticles to obtain targeted delivery. In particular, nanodelivery systems with selectivity for breast, prostate and cancer tissue have been developed. Here, we have developed a nanodelivery system that targets the thyroid gland. Nanoliposomes have been conjugated to the thyroid-stimulating hormone (TSH), which binds to the TSH receptor (TSHr) on the surface of thyrocytes. The results indicate that the intracellular uptake of TSH-nanoliposomes is increased in cells expressing the TSHr. The accumulation of targeted nanoliposomes in the thyroid gland following intravenous injection was 3.5-fold higher in comparison to untargeted nanoliposomes. Furthermore, TSH-nanoliposomes encapsulated with gemcitabine showed improved anticancer efficacy in vitro and in a tumor model of follicular thyroid carcinoma. This drug delivery system could be used for the treatment of a broad spectrum of thyroid diseases to reduce side effects and improve therapeutic efficacy. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. The Genetics of the Thyroid Stimulating Hormone Receptor: History and Relevance

    PubMed Central

    Yin, Xiaoming; Latif, Rauf

    2010-01-01

    Background The thyroid stimulating hormone receptor (TSHR) is the key regulator of thyrocyte function. The gene for the TSHR on chromosome 14q31 has been implicated as coding for the major autoantigen in the autoimmune hyperthyroidism of Graves' disease (GD) to which T cells and autoantibodies are directed. Summary The TSHR is a seven-transmembrane domain receptor that undergoes complex posttranslational processing. In this brief review, we look at the genetics of this important autoantigen and its influence on a variety of tissue functions in addition to its role in the induction of GD. Conclusions There is convincing evidence that the TSH receptor gene confers increased susceptibility for GD, but not Hashimoto's thyroiditis. GD is associated with polymorphisms in the intron 1 gene region. How such noncoding nucleotide changes influence disease susceptibility remains uncertain, but is likely to involve TSHR splicing variants and/or microRNAs arising from this gene region. Whether such influences are confined to the thyroid gland or whether they influence cell function in the many extrathyroidal sites of TSHR expression remains unknown. PMID:20578897

  8. Thyroid-stimulating hormone maintains bone mass and strength by suppressing osteoclast differentiation.

    PubMed

    Zhang, Wenwen; Zhang, Yanling; Liu, Yuantao; Wang, Jie; Gao, Ling; Yu, Chunxiao; Yan, Huili; Zhao, Jiajun; Xu, Jin

    2014-04-11

    It has been suggested that pituitary hormone might be associated with bone metabolism. To investigate the role of thyroid-stimulating hormone (TSH) in bone metabolism, we designed the present study as follows. After weaning, TSH receptor (TSHR) null mice (Tshr(-/-)) were randomly divided into a thyroxine treatment group (n=10) or non-treatment group (n=10); the treatment group received a dose of desiccated thyroid extract at 100 ppm daily for 5 weeks. Age-matched wild-type (Tshr(+/+), n=10) and heterozygote mice (Tshr(+/-), n=10) served as controls. After 5 weeks, the animals were sacrificed, and the femurs were collected for histomorphometrical and biomechanical analyses. In addition, the effect of TSH on osteoclastogenesis was examined in the RAW264.7 osteoclast cell line. We found that compared with Tshr(+/+) mice, Tshr(-/-) and Tshr(+/-) mice had lower bone strength. The histomorphometric results showed that trabecular bone volume, osteoid surface, osteoid thickness and osteoblast surface were significantly decreased, whereas the osteoclast surface was significantly increased in both Tshr(-/-) and Tshr(+/-) mice compared with Tshr(+/+) mice. Bone resorption and formation in Tshr(-/-) mice were further enhanced by thyroxine replacement. bTSH inhibited osteoclast differentiation in vitro, as demonstrated by reduced development of TRAP-positive cells and down-regulation of differentiation markers, including tartrate-resistant acid phosphatase, matrix metallo-proteinase-9 and cathepsin K in RAW264.7 cells. Our results confirm that TSH increased bone volume and improved bone microarchitecture and strength at least partly by inhibiting osteoclastogenesis.

  9. Screening for thyroid disease in a primary care unit with a thyroid stimulating hormone assay with a low detection limit.

    PubMed Central

    Eggertsen, R.; Petersen, K.; Lundberg, P. A.; Nyström, E.; Lindstedt, G.

    1988-01-01

    In a study at a primary care centre in a predominantly rural area of Sweden the records of all patients with established thyroid disease were scrutinised and 2000 consecutive adult patients screened with an immunoenzymometric thyroid stimulating hormone assay. The aims of the study were fourfold: firstly, to assess the total burden of thyroid disease in primary care centres in Sweden; secondly, to assess the efficacy of clinical diagnosis of the disease in unselected populations of patients; thirdly, to assess the efficacy of clinical evaluation of treatment with thyroxine; and, lastly, to see whether a single analysis of the serum thyroid stimulating hormone concentration by recent methods would be enough to identify an abnormality of thyroid function. Of the roughly 17,400 adults in the study community, 111 women and 10 men were being treated for thyroid disease. Screening detected 68 patients (3.5%) not receiving thyroxine who had a serum thyroid stimulating hormone concentration of 0.20 mU/l or less, all of whom were followed up clinically. Fifty of these patients were also studied biochemically during follow up. Only nine of the 68 patients had thyroid disease (three with thyrotoxicosis requiring treatment), no evidence of the disease being found in the remainder. Sixteen patients had spontaneous hypothyroidism requiring treatment, and neither these nor three patients with thyrotoxicosis had been detected at the preceding clinical examination. Of 35 patients in whom thyroid disease was suspected clinically at screening, none had laboratory evidence of thyroid dysfunction. In this series 1.3% of all women in the study community (2.6% of all 50-59 year olds) and 0.1% of the men were being treated for thyroid disease at the primary care centre, roughly 1.0% of adults subjected to screening were found to have thyroid disease requiring treatment, and most patients with a thyroid stimulating hormone concentration of 0.20 mU/l or less did not have thyroid dysfunction

  10. Endogenous excitatory amino acid neurotransmission regulates thyroid-stimulating hormone and thyroid hormone secretion in conscious freely moving male rats.

    PubMed

    Arufe, M C; Durán, R; Perez-Vences, D; Alfonso, M

    2002-04-01

    The role of neurotransmission of endogenous excitatory amino acid (EAA) on serum thyroid hormones and thyroid-stimulating hormone (TSH) levels was examined in conscious and freely moving adult male Sprague-Dawley rats. The rats were cannulated at the third ventricle 2 d before the experiments. Several glutamate receptor agonists, such as kainic acid and domoic acid, and antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and dizocilpine (MK-801) were administered into the third ventricle. Serum TSH levels were assesed by radioimmunoassay, and serum thyroid hormone levels were assessed by enzyme immunoassay. The results showed that the administration of CNQX and MK-801 produced a decrease in serum levels of TSH and thyroid hormones. The administration of kainic acid and domoic acid increased TSH concentrations, whereas CNQX completely blocked the release of TSH induced by kainic acid and domoic acid. These results suggest the importance of endogenous EAA in the regulation of hormone secretion from the pituitary-thyroid axis, as well as the role of the N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the stimulatory effect of EAAs on the pituitary-thyroid axis.

  11. The application of NIR Raman spectroscopy in the assessment of serum thyroid-stimulating hormone in rats.

    PubMed

    Medina-Gutiérrez, C; Quintanar, J Luis; Frausto-Reyes, C; Sato-Berrú, R

    2005-01-01

    Serum blood samples of euthyroid and thyroidectomized rats treated with thyrotropin-releasing hormone (TRH) were analyzed on aluminum substrates using the near-infrared Raman spectroscopy (830 nm). Spectra of thyroid-stimulating hormone (TSH), TRH and prolactin standards were obtained. Differences between Raman spectra profiles of control and Tx + TRH samples groups were found. These differences were confirmed by the linear discriminant analysis (LDA), which presents a good classification between groups. It is supposed that these differences are produced by the increment of TSH in the thyroidectomized rats.

  12. The application of NIR Raman spectroscopy in the assessment of serum thyroid-stimulating hormone in rats

    NASA Astrophysics Data System (ADS)

    Medina-Gutiérrez, C.; Quintanar, J. Luis; Frausto-Reyes, C.; Sato-Berrú, R.

    2005-01-01

    Serum blood samples of euthyroid and thyroidectomized rats treated with thyrotropin-releasing hormone (TRH) were analyzed on aluminum substrates using the near-infrared Raman spectroscopy (830 nm). Spectra of thyroid-stimulating hormone (TSH), TRH and prolactin standards were obtained. Differences between Raman spectra profiles of control and Tx+TRH samples groups were found. These differences were confirmed by the linear discriminant analysis (LDA), which presents a good classification between groups. It is supposed that these differences are produced by the increment of TSH in the thyroidectomized rats.

  13. De novo triiodothyronine formation from thyrocytes activated by thyroid-stimulating hormone.

    PubMed

    Citterio, Cintia E; Veluswamy, Balaji; Morgan, Sarah J; Galton, Valerie A; Banga, J Paul; Atkins, Stephen; Morishita, Yoshiaki; Neumann, Susanne; Latif, Rauf; Gershengorn, Marvin C; Smith, Terry J; Arvan, Peter

    2017-09-15

    The thyroid gland secretes primarily tetraiodothyronine (T4), and some triiodothyronine (T3). Under normal physiological circumstances, only one-fifth of circulating T3 is directly released by the thyroid, but in states of hyperactivation of thyroid-stimulating hormone receptors (TSHRs), patients develop a syndrome of relative T3 toxicosis. Thyroidal T4 production results from iodination of thyroglobulin (TG) at residues Tyr(5) and Tyr(130), whereas thyroidal T3 production may originate in several different ways. In this study, the data demonstrate that within the carboxyl-terminal portion of mouse TG, T3 is formed de novo independently of deiodination from T4 We found that upon iodination in vitro, de novo T3 formation in TG was decreased in mice lacking TSHRs. Conversely, de novo T3 that can be formed upon iodination of TG secreted from PCCL3 (rat thyrocyte) cells was augmented from cells previously exposed to increased TSH, a TSHR agonist, a cAMP analog, or a TSHR-stimulating antibody. We present data suggesting that TSH-stimulated TG phosphorylation contributes to enhanced de novo T3 formation. These effects were reversed within a few days after removal of the hyperstimulating conditions. Indeed, direct exposure of PCCL3 cells to human serum from two patients with Graves' disease, but not control sera, led to secretion of TG with an increased intrinsic ability to form T3 upon in vitro iodination. Furthermore, TG secreted from human thyrocyte cultures hyperstimulated with TSH also showed an increased intrinsic ability to form T3 Our data support the hypothesis that TG processing in the secretory pathway of TSHR-hyperstimulated thyrocytes alters the structure of the iodination substrate in a way that enhances de novo T3 formation, contributing to the relative T3 toxicosis of Graves' disease.

  14. Newborn thyroid-stimulating hormone in children with optic nerve hypoplasia: associations with hypothyroidism and vision.

    PubMed

    Fink, Cassandra; Vedin, Amy M; Garcia-Filion, Pamela; Ma, Nina S; Geffner, Mitchell E; Borchert, Mark

    2012-10-01

    To assess in children with optic nerve hypoplasia (ONH) whether newborn screening (NBS) thyroid-stimulating hormone (TSH) measurements can detect central hypothyroidism and whether newborn TSH or subsequent thyroidal status is associated with visual function. From a registry of children with ONH at Children's Hospital Los Angeles, post-natal thyroidal status was retrospectively compared with NBS TSH levels in the subset of subjects born in California. The subset of subjects with outcome data at age 5 years was assessed for relationship of vision to NBS TSH levels and ultimate thyroidal status. A total of 135 subjects from the ONH registry were included in this study. Approximately 50% of subjects in each analysis were hypothyroid. Those diagnosed with hypothyroidism had lower median NBS TSH levels than did euthyroid subjects (3.2 vs 4.5 μIU/mL; P = 0.006) and significantly worse quantitative vision outcomes (median visual acuity, logMAR 3.0 vs 1.0; P = 0.039). Receiver operating characteristic analysis suggested an optimal NBS TSH cut-point of 3.3 μIU/mL. Serum TSH levels greater than this (30/43) were associated with relatively better vision outcomes (median visual acuity, logMAR 1.2 vs 3.3; P = 0.04). Children with ONH and lower NBS TSH levels are more likely to have central hypothyroidism and less likely to experience good vision than those with greater NBS TSH levels. Copyright © 2012 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  15. Graves disease in children: thyroid-stimulating hormone receptor antibodies as remission markers.

    PubMed

    Gastaldi, Roberto; Poggi, Elena; Mussa, Alessandro; Weber, Giovanna; Vigone, Maria Cristina; Salerno, Mariacarolina; Delvecchio, Maurizio; Peroni, Elena; Pistorio, Angela; Corrias, Andrea

    2014-05-01

    To evaluate clinical and biochemical features of 115 children (98 female, mean age 11.3 ± 3.5 years) with Graves disease to identify possible determinants of remission. We defined as positive outcome the improvement of clinical features and restoration of euthyroidism or induction of hypothyroidism after antithyroid drug (ATD) therapy and as negative outcome hyperthyroidism persistent over 2 years of ATD therapy or relapsed after ATD withdrawal. Thirty-eight children (33%) had remission after 2 years of ATD therapy. The absence of goiter at diagnosis was correlated with a better outcome. Median thyroid-stimulating hormone receptor antibody (TRAb) values at diagnosis were significantly lower in patients with a positive outcome (P = .031). We found a significant relationship between the time required for TRAb normalization and the patient outcome; TRAb normalization within 1 year from time of Graves disease diagnosis was significantly more common among patients with a positive outcome (P < .0001), and the mean time for TRAb normalization was significantly shorter in patients with a positive outcome (1.3 ± 0.8 years) compared with that observed in patients with a negative outcome (2.5 ± 2.7 years, P = .026). Although no clinical variable investigated is constantly associated with a definite outcome, the absence of goiter at the diagnosis may be associated with a better outcome. The most relevant predictor of Graves disease outcome was serum level; TRAb at time of Graves disease diagnosis less than 2.5 times the upper reference limit, TRAb normalization during ATD, and TRAb normalization timing each may predict positive outcomes. These results may have a role in the empiric clinical management of pediatric patients with Graves disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Serum Thyroid-Stimulating Hormone Levels and Frailty in the Elderly: The Progetto Veneto Anziani Study.

    PubMed

    Veronese, Nicola; Fernando-Watutantrige, Sara; Maggi, Stefania; Noale, Marianna; Stubbs, Brendon; Incalzi, Raffaele Antonelli; Zambon, Sabina; Corti, Maria Chiara; Perissinotto, Egle; Crepaldi, Gaetano; Manzato, Enzo; Sergi, Giuseppe

    2017-06-01

    High or low thyroid-stimulating hormone (TSH) levels seem to be associated with several negative outcomes in the elderly, but the literature about TSH and frailty is still limited. In this article, we investigated whether TSH is associated with prevalent and incident frailty in a cohort of older community-dwelling subjects. Among 3099 initially screened in the Progetto Veneto Anziani Study, 2571 men and women aged ≥65 years (for cross-sectional analyses) and 1732 (longitudinal, mean follow-up period of 4.4 years) were divided into sex-specific quintiles according to baseline serum TSH concentrations within normal range (0.3 and 4.2 mUI/L). Frailty was defined as the presence of three among five Fried's criteria. At baseline, taking those in the third quintile of serum TSH as reference (Q3) and adjusting for potential confounders, participants in the highest (Q5) quintile had an increased odds ratio (OR) of having frailty (OR = 1.55; 95% confidence interval [CI]: 1.03-2.33 for men; OR = 1.97; 95% CI: 1.59-2.45 for women). Men in Q1 had significant higher odds of having muscle weakness and exhaustion, while those in Q5 had muscle weakness and slow gait speed. Women in Q1 had significantly higher odds of having all the Fried's criteria (except for exhaustion), while those in Q5 reported a significantly higher presence of muscle weakness and slow gait speed. At follow-up, men in Q5 had an increased risk of frailty (OR = 1.37; 95% CI: 1.02-1.91) similar to women in Q1 (OR = 1.47; 95% CI: 1.21-1.78). In conclusion, men with higher and women with lower serum TSH levels are at increased risk of frailty.

  17. Screening for hypothyroidism in Down syndrome using the capillary thyroid stimulating hormone method.

    PubMed

    McGowan, Sheena; Jones, Jeremy; McMillan, Donald; McLaughlin, Kirsty; Smith, Sarah; Leyland, Kath; Charleton, Patricia; Donaldson, Malcolm

    2015-04-01

    To analyze data from the Scottish capillary thyroid stimulating hormone (TSH) screening program for hypothyroidism in Down syndrome to identify a threshold for capillary TSH elevation below which low venous free thyroxine (fT4) (<9 pmol/L) and/or frank venous TSH elevation (>10 mU/L) range is unlikely. Review of proformas prospectively submitted on all children with Down syndrome referred via the screening program between 2003 and 2013. Ninety-nine patients with Down syndrome (50 females, 49 males) were identified, 76 school-age (≥ 5 years) and 23 preschool (<5 years), mean (range) age at referral 9.4 (0.9-18.1) years. Pearson correlation between capillary TSH and venous TSH was 0.814; between capillary TSH and venous fT4 -0.522 (P = .01). Receiver operator curve analysis showed that capillary TSH values of 4 and 6 mU/L were 95.9% and 73.5% sensitive, 5.8% and 80.8% specific, respectively, in predicting venous TSH >10 mU/L. Fifty-three children had capillary TSH values of 4-5.9 mU/L of whom only one, a boy of 15.8 years, had subnormal venous fT4 (<9 pmol/L), and venous TSH >10 mU/L was found in 13 (4 preschool). Venous fT4 is normal in almost all patients with Down syndrome with capillary TSH 4-6 mU/L. We propose an algorithm incorporating rescreening by finger prick after 6 months, rather than venepuncture, in school-aged children with borderline capillary TSH elevation. Further data are needed before this approach can be recommended for preschool children. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Site-specific PEGylation of human thyroid stimulating hormone to prolong duration of action.

    PubMed

    Qiu, Huawei; Boudanova, Ekaterina; Park, Anna; Bird, Julie J; Honey, Denise M; Zarazinski, Christine; Greene, Ben; Kingsbury, Jonathan S; Boucher, Susan; Pollock, Julie; McPherson, John M; Pan, Clark Q

    2013-03-20

    Recombinant human thyroid stimulating hormone (rhTSH or Thyrogen) has been approved for thyroid cancer diagnostics and treatment under a multidose regimen due to its short circulating half-life. To reduce dosing frequency, PEGylation strategies were explored to increase the duration of action of rhTSH. Lysine and N-terminal PEGylation resulted in heterogeneous product profiles with 40% or lower reaction yields of monoPEGylated products. Eleven cysteine mutants were designed based on a structure model of the TSH-TSH receptor (TSHR) complex to create unique conjugation sites on both α and β subunits for site-specific conjugation. Sequential screening of mutant expression level, oligomerization tendency, and conjugation efficiency resulted in the identification of the αG22C rhTSH mutant for stable expression and scale-up PEGylation. The introduced cysteine in the αG22C rhTSH mutant was partially blocked when isolated from conditioned media and could only be effectively PEGylated after mild reduction with cysteine. This produced a higher reaction yield, ~85%, for the monoPEGylated product. Although the mutation had no effect on receptor binding, PEGylation of αG22C rhTSH led to a PEG size-dependent decrease in receptor binding. Nevertheless, the 40 kDa PEG αG22C rhTSH showed a prolonged duration of action compared to rhTSH in a rat pharmacodynamics model. Reverse-phase HPLC and N-terminal sequencing experiments confirmed site-specific modification at the engineered Cys 22 position on the α-subunit. This work is another demonstration of successful PEGylation of a cysteine-knot protein by an engineered cysteine mutation.

  19. Gastroparesis - a novel cause of persistent thyroid stimulating hormone elevation in hypothyroidism.

    PubMed

    O S, Khraisha; M M, Al-Madani; A N, Peiris; T K, Paul

    2015-01-01

    Hypothyroidism is easily treated by levothyroxine therapy which has an 80 percent absorption rate, mostly in the jejunum. The replacement dose of daily levothyroxine is usually calculated at 1.6 mcg/kg body weight per day. We report a 77-year-old man who required supraphysiologic thyroxine replacement (>2.7 mcg/ kg/day) to treat his hypothyroidism. The patient was referred for persistent thyroid stimulating hormone (TSH) elevation (40 mcIU/ml) while on 175 mcg of levothyroxine. Patient was compliant with medication. Medical history included diabetes mellitus type 2, cerebrovascular accident, depression, hypertension, hyperlipidemia, atherosclerotic cardiovascular disease, vitamin B12 deficiency, Addison’s disease, as well as a colostomy secondary to diverticulitis. He was taking aspirin, carvedilol, cholecalciferol, finasteride, fluoxetine, furosemide, ketoconazole, levothyroxine, prednisone, and albuterol/ipratropium inhaler. His height was 180.3 cm; weight, 107 kg. Thyroid was impalpable, and he was clinically euthyroid. Despite discontinuation of iron and statin which are known to interfere with thyroxine absorption and crushing of thyroxine tablets to enhance absorption, his TSH remained elevated. Celiac disease and Helicobacter pylori infection were ruled out with serological testing. There was no proteinuria and anti-parietal cell antibody was positive. Gastroparesis was confirmed by gastric emptying study. He continued to require increasing doses of thyroxine with increment to 300 mcg daily. To our knowledge, this is the first documented association between gastroparesis and thyroxine malabsorption. We recommend that gastroparesis be considered in any patient with persistent TSH elevation despite usual thyroxine doses.

  20. Prevalence and clinical relevance of thyroid stimulating hormone receptor-blocking antibodies in autoimmune thyroid disease.

    PubMed

    Diana, T; Krause, J; Olivo, P D; König, J; Kanitz, M; Decallonne, B; Kahaly, G J

    2017-09-01

    The prevalence and clinical relevance of thyroid stimulating hormone (TSH) receptor (TSHR) blocking antibodies (TBAb) in patients with autoimmune thyroid disease (AITD) was investigated. Serum TBAb were measured with a reporter gene bioassay using Chinese hamster ovary cells. Blocking activity was defined as percentage inhibition of luciferase expression relative to induction with bovine TSH alone (cut-off 40% inhibition). All samples were measured for TSHR stimulatory antibody (TSAb) and TSHR binding inhibiting immunoglobulins (TBII). A total of 1079 unselected, consecutive patients with AITD and 302 healthy controls were included. All unselected controls were negative for TBAb and TSAb. In contrast, the prevalence of TBAb-positive patients with Hashimoto's thyroiditis and Graves' disease was 67 of 722 (9·3%) and 15 of 357 (4·2%). Of the 82 TBAb-positive patients, thirty-nine (48%), 33 (40%) and 10 (12%) were hypothyroid, euthyroid and hyperthyroid, respectively. Ten patients were both TBAb- and TSAb-positive (four hypothyroid, two euthyroid and four hyperthyroid). Thyroid-associated orbitopathy was present in four of 82 (4·9%) TBAb-positive patients, with dual TSHR antibody positivity being observed in three. TBAb correlated positively with TBII (r = 0·67, P < 0·001) and negatively with TSAb (r = -0·86, P < 0·05). The percentage of TBII-positive patients was higher the higher the level of inhibition in the TBAb assay. Of the TBAb-positive samples with  > 70% inhibition, 87% were TBII-positive. Functional TSHR antibodies impact thyroid status. TBAb determination is helpful in the evaluation and management of patients with AITD. The TBAb assay is a relevant and important tool to identify potentially reversible hypothyroidism. © 2017 British Society for Immunology.

  1. Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation testing in euthyroid ferrets.

    PubMed

    Mayer, Jörg; Wagner, Robert; Mitchell, Mark A; Fecteau, Kellie

    2013-11-15

    To evaluate the effects of IM administration of recombinant human thyroid-stimulating hormone (rhTSH) on plasma total thyroxine (T4) concentrations in euthyroid ferrets. Evaluation study. 25 healthy neutered ferrets (14 female and 11 male) of various ages from 2 populations (laboratory ferrets from Georgia and pet ferrets from Pennsylvania). Each ferret underwent a physical examination and standard hematologic testing to ensure it was healthy and had clinically normal thyroid function. Once determined to be euthyroid, ferrets received a single IM injection of 100 μg of rhTSH. Blood samples were collected into plasma-separator tubes immediately before the rhTSH injection (time 0) and 4 hours after injection to measure T4 concentrations. Males did not differ from females in regard to prestimulation or poststimulation plasma T4 concentrations; however, prestimulation and poststimulation T4 concentrations were significantly different between the 2 groups of ferrets. A significant difference was also identified between prestimulation T4 concentration (mean ± SD, 21.3 ± 6.1 nmol/L) and poststimulation T4 concentration (29.9 ± 8.2 nmol/L). All 25 ferrets had high poststimulation T4 concentrations (median difference, 7. 5 nmol/L; 10% to 90% interval, 3.26 to 17.70 nmol/L [0.25 to 1.38 μg/dL]; range, 2.50 to 20.70 nmol/L [0.19 to 1.61 μg/dL]); this represented a median increase in T4 concentration of 35% (10% to 90% interval, 18% to 81%; range, 8% to 126%). Results suggested that rhTSH can be used for thyrotropin stimulation testing in ferrets when administered IM. According to the findings, a euthyroid ferret should have an increase of approximately 30% in plasma T4 concentration 4 hours after rhTSH injection.

  2. Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase.

    PubMed

    Perez-Ruiz, Fernando; Chinchilla, Sandra Pamela; Atxotegi, Joana; Urionagüena, Irati; Herrero-Beites, Ana Maria; Aniel-Quiroga, Maria Angeles

    2015-11-01

    Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels.

  3. High normal thyroid-stimulating hormone is associated with arterial stiffness in healthy postmenopausal women.

    PubMed

    Lambrinoudaki, Irene; Armeni, Eleni; Rizos, Demetrios; Georgiopoulos, Georgios; Kazani, Maria; Alexandrou, Andreas; Deligeoroglou, Efthymios; Livada, Alexandra; Psychas, Charalampos; Creatsa, Maria; Bouboulis, George; Alevizaki, Maria; Stamatelopoulos, Kimon

    2012-03-01

    Apart from the effects of a dysfunctional thyroid gland on the cardiovascular system, thyroid function within the reference range may have an impact on the vasculature. The present study aimed to evaluate the association between thyroid function and markers of arterial structure and function in euthyroid postmenopausal women. The present cross-sectional study recruited 106 healthy postmenopausal women with a mean age of 55.0 years and thyroid-stimulating hormone (TSH) levels within the laboratory reference range (0.4-4.5 μIU/ml). Anthropometric and biochemical measures as well as blood pressure were determined in each individual. Vascular structure and function were assessed by intima-media thickness, pulse wave velocity (PWV), augmentation index and flow-mediated dilation, respectively. We evaluated the associations between arterial markers and serum TSH, free triiodothyronine, free thyroxin, as well as serum thyroid peroxidase and thyroglobulin autoantibodies. Mean levels of PWV increased linearly across increasing TSH quartiles (P value = 0.014). Individuals with serum TSH greater than 2.5 μIU/ml had significantly higher values of PWV when compared with individuals with TSH levels below 2.5 μIU/ml (9.68 ± 1.97 vs. 8.54 ± 1.83 m/s; P = 0.030). In multivariate analysis, age, insulin resistance and TSH above 2.5 μIU/ml were the only significant predictors of PWV (TSH, β-coefficient = 0.222; P = 0.014). No associations were found between the remaining markers and levels of thyroid hormones, whereas thyroid antibodies were not associated with any of the arterial markers. Women with TSH levels in the upper reference range have increased arterial stiffness compared to women with lower TSH. The upper limit of normal TSH in postmenopausal women may need re-evaluation with respect to the effects on the vasculature.

  4. Serum Spot 14 concentration is negatively associated with thyroid-stimulating hormone level

    PubMed Central

    Chen, Yen-Ting; Tseng, Fen-Yu; Chen, Pei-Lung; Chi, Yu-Chao; Han, Der-Sheng; Yang, Wei-Shiung

    2016-01-01

    Abstract Spot 14 (S14) is a protein involved in fatty acid synthesis and was shown to be induced by thyroid hormone in rat liver. However, the presence of S14 in human serum and its relations with thyroid function status have not been investigated. The objectives of this study were to compare serum S14 concentrations in patients with hyperthyroidism or euthyroidism and to evaluate the associations between serum S14 and free thyroxine (fT4) or thyroid-stimulating hormone (TSH) levels. We set up an immunoassay for human serum S14 concentrations and compared its levels between hyperthyroid and euthyroid subjects. Twenty-six hyperthyroid patients and 29 euthyroid individuals were recruited. Data of all patients were pooled for the analysis of the associations between the levels of S14 and fT4, TSH, or quartile of TSH. The hyperthyroid patients had significantly higher serum S14 levels than the euthyroid subjects (median [Q1, Q3]: 975 [669, 1612] ng/mL vs 436 [347, 638] ng/mL, P < 0.001). In univariate linear regression, the log-transformed S14 level (logS14) was positively associated with fT4 but negatively associated with creatinine (Cre), total cholesterol (T-C), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and TSH. The positive associations between logS14 and fT4 and the negative associations between logS14 and Cre, TG, T-C, or TSH remained significant after adjustment with sex and age. These associations were prominent in females but not in males. The logS14 levels were negatively associated with the TSH levels grouped by quartile (ß = −0.3020, P < 0.001). The association between logS14 and TSH quartile persisted after adjustment with sex and age (ß = −0.2828, P = 0.001). In stepwise multivariate regression analysis, only TSH grouped by quartile remained significantly associated with logS14 level. We developed an ELISA to measure serum S14 levels in human. Female patients with hyperthyroidism had higher serum S14 levels

  5. Use of thyroid-stimulating hormone tests for identifying primary hypothyroidism in family medicine patients.

    PubMed

    Birk-Urovitz, Elizabeth; Elisabeth Del Giudice, M; Meaney, Christopher; Grewal, Karan

    2017-09-01

    To assess the use of thyroid-stimulating hormone (TSH) tests for identifying primary hypothyroidism in 2 academic family medicine settings. Descriptive study involving a retrospective electronic chart review of family medicine patients who underwent TSH testing. Two academic family practice sites: one site is within a tertiary hospital in Toronto, Ont, and the other is within a community hospital in Newmarket, Ont. A random sample of 205 adult family medicine patients who had 1 or more TSH tests for identifying potential primary hypothyroidism between July 1, 2009, and September 15, 2013. Exclusion criteria included a previous diagnosis of any thyroid condition or abnormality, as well as pregnancy or recent pregnancy within the year preceding the study period. The proportion of normal TSH test results and the proportion of TSH tests that did not conform to test-ordering guidelines. Of the 205 TSH test results, 200 (97.6%, 95% CI 94.4% to 99.2%) showed TSH levels within the normal range. All 5 patients with abnormal TSH test results had TSH levels above the upper reference limits. Nearly one-quarter (22.4%, 95% CI 16.9% to 28.8%) of tests did not conform to test-ordering guidelines. All TSH tests classified as not conforming to test-ordering guidelines showed TSH levels within normal limits. There was a significant difference (P < .001) between the proportions of nonconforming TSH tests at the tertiary site (14.3%, 95% CI 8.2% to 22.5%) and the community site (31.0%, 95% CI 22.1% to 41.0%). Preliminary analyses examining which variables might be associated with abnormal TSH levels showed that only muscle cramps or myalgia (P = .0286) and a history of an autoimmune disorder (P = .0623) met or approached statistical significance. In this study, the proportion of normal TSH test results in the context of primary hypothyroidism case finding and screening was high, and the overall proportion of TSH tests that did not conform to test-ordering guidelines was relatively

  6. Melatonin in the thyroid gland: regulation by thyroid-stimulating hormone and role in thyroglobulin gene expression.

    PubMed

    Garcia-Marin, R; Fernandez-Santos, J M; Morillo-Bernal, J; Gordillo-Martinez, F; Vazquez-Roman, V; Utrilla, J C; Carrillo-Vico, A; Guerrero, J M; Martin-Lacave, I

    2015-10-01

    Melatonin is an indoleamine with multiple functions in both plant and animal species. In addition to data in literature describing many other important roles for melatonin, such as antioxidant, circadian rhythm controlling, anti-aging, antiproliferative or immunomodulatory activities, our group recently reported that thyroid C-cells synthesize melatonin and suggested a paracrine role for this molecule in the regulation of thyroid activity. To discern the role played by melatonin at thyroid level and its involvement in the hypothalamic-pituitary-thyroid axis, in the present study we have analyzed the effect of thyrotropin in the regulation of the enzymatic machinery for melatonin biosynthesis in C cells as well as the effect of melatonin in the regulation of thyroid hormone biosynthesis in thyrocytes. Our results show that the key enzymes for melatonin biosynthesis (AANAT and ASMT) are regulated by thyroid-stimulating hormone. Furthermore, exogenous melatonin increases thyroglobulin expression at mRNA and protein levels on cultured thyrocytes and this effect is not strictly mediated by the upregulation of TTF1 or, noteworthy, PAX8 transcription factors. The present data show that thyroid C-cells synthesize melatonin under thyroid-stimulating hormone control and, consistently with previous data, support the hypothesis of a paracrine role for C-cell-synthesised melatonin within the thyroid gland. Additionally, in the present study we show evidence for the involvement of melatonin in thyroid function by directly-regulating thyroglobulin gene expression in follicular cells.

  7. Congenital Central Hypothyroidism Caused by a Novel Thyroid-Stimulating Hormone-Beta Subunit Gene Mutation in Two Siblings.

    PubMed

    Özhan, Bayram; Boz Anlaş, Özlem; Sarıkepe, Bilge; Albuz, Burcu; Semerci Gündüz, Nur

    2017-09-01

    Congenital central hypothyroidism (CCH) is a very rare disease. Alterations in pituitary development genes as well as mutations of immunoglobulin superfamily member 1 and transducin β-like protein 1 can result in CCH and multiple pituitary hormone deficiencies. However, mutations of the thyrotropin-releasing hormone receptor or thyroid-stimulating hormone-beta (TSHB) gene are responsible for isolated CCH. In this paper, we present the cases of two siblings with a novel mutation of TSHB. Direct sequencing of the coding regions and exon/intron boundaries of the TSHB gene revealed two homozygous nucleotides changes. One of them was c.40A>G (rs10776792) which is a very common variation that is also seen in healthy individuals, the other was c.94G>A at codon 32 of exon 2 which resulted in a change from glutamic acid to lysine (p.E32K). Both patients were homozygous and the parents were heterozygous.

  8. Intrathyroidal iodine metabolism in the rat. The influence of diet and the administration of thyroid-stimulating hormone

    PubMed Central

    Barnaby, C. F.; Davidson, Ailsa M.; Plaskett, L. G.

    1965-01-01

    1. Ratios of mono[131I]iodotyrosine and di[131I]iodotyrosine (R values) and the incorporation of 131I into iodothyronines have been estimated in rat thyroid glands from 30min. to 38hr. after the administration of [131I]iodide. 2. In rats receiving a powdered low-iodine diet the R values were close to unity and did not change with time after the administration of [131I]iodide. In rats receiving a commercial pellet diet the R values fell from a mean of 0·8 at 30min. after [131I]iodide administration to 0·49 at 38hr. 3. Administration of 0·5–2·0i.u. of thyroid-stimulating hormone before giving the injection of [131I]iodide caused a small diminution in the R value when the time between injecting [131I]iodide and killing the animal was 16hr. or more. 4. Iodothyronines represented a greater percentage of the total thyroid-gland radioactivity in the iodine-deficient animals than in animals fed on the pellet diet. Thyroid-stimulating hormone had little effect, if any, on the iodothyronine contents. PMID:14342520

  9. Routine serum thyroid-stimulating hormone testing-optimizing pre-conception health or generating toxic knowledge?

    PubMed

    Maheshwari, Abha; Bhide, Priya; Pundir, Jyotsna; Bhattacharya, Siladitya

    2017-09-01

    Monitoring subclinical hypothyroidism (SCH) in women is believed to be important in terms of preventing overt hypothyroidism and optimizing the health and cognitive development of their children. Current systematic reviews have suggested an association between maternal SCH and adverse obstetric and neonatal outcomes. However, initiating the administration of thyroxine during pregnancy has failed to demonstrate appreciable health benefits. Hence there are calls by professional endocrine societies for optimizing serum thyroid-stimulating hormone (TSH) levels pre-conception. The strategy of ensuring that serum TSH levels are below 2.5 mIU/l during the pre-conception period has generated considerable uncertainty partly because the recommended level of <2.5 mIU/l is lower than those previously used to define the condition and partly due to uncertainty about the best screening programme clinicians can use in this context. Recalibrating the expected normal peri-conceptional range of serum TSH (<2.5 mIU/l), will have a significant impact on clinical services due to an inevitable increase in numbers of women diagnosed with SCH who will need to be investigated, treated and monitored. Serum TSH fulfils the criteria for a screening test and oral thyroxine is an inexpensive drug. Therefore, there is no reason to believe that screening cannot be undertaken in all women planning to conceive. Yet this approach will miss women whose pregnancies are unplanned and generate anxiety, further tests and many more prescriptions for thyroxine, coupled with the need for lifelong monitoring in affected women. A number of existing and ongoing randomized trials have evaluated the use of thyroxine in women with infertility or miscarriage with detectable thyroid auto-antibodies. These are unlikely to answer the question whether routine pre-conception testing for SCH in asymptomatic women is beneficial. Routine screening of women at risk of pregnancy and optimization of their thyroid status could

  10. Near-lethal respiratory failure after recombinant human thyroid-stimulating hormone use in a patient with metastatic thyroid carcinoma.

    PubMed

    Goffman, Thomas; Ioffe, Vladimir; Tuttle, Michael; Bowers, John T; Mason, M Elizabeth

    2003-08-01

    A patient with widely metastatic differentiated thyroid cancer who had been heavily pretreated with (131)I was given recombinant human thyroid stimulating hormone (rhTSH) prior to (131)I treatment. Clinical and physical data from both this case and the literature suggest that the recombinant hormone, not the (131)I, may have caused a significant portion of the tumor swelling, which in turn was the most likely cause of the patient's symptoms. The potential effect of (131)I-induced tumor swelling and direct radiation effect on the lung is also analyzed. We review the potential hazards associated with rhTSH in patients with metastasis and propose means of minimizing this risk.

  11. Thyroid-stimulating hormone suppression therapy for differentiated thyroid cancer: The role for a combined T3/T4 approach.

    PubMed

    Fussey, Jonathan Mark; Khan, Habib; Ahsan, Farhan; Prashant, Ravi; Pettit, Laura

    2017-09-27

    In the management of differentiated thyroid carcinoma, surgery with or without postoperative radioiodine, and thyroid-stimulating hormone (TSH) suppression is the standard of care in most patients. Levothyroxine is recommended for long-term TSH suppression. For some patients, this may be difficult to tolerate due to adverse effects, such as impaired cognitive function. This article reviews the evidence for the role of combination treatment with triiodothyronine (T3) and levothyroxine (T4) in these patients. The evidence for combination T3 and T4 treatment comes mainly from studies on hypothyroidism, and research into its use for TSH suppression is limited. Although the evidence base is not strong, there is a small group of patients who may benefit from combination T3 and T4 treatment due to difficulty tolerating thyroxine. Until further evidence is available, a case-by-case approach is recommended. © 2017 Wiley Periodicals, Inc.

  12. Functional expression of thyroid-stimulating hormone receptor on nano-sized bacterial magnetic particles in Magnetospirillum magneticum AMB-1.

    PubMed

    Sugamata, Yasuhiro; Uchiyama, Ryo; Honda, Toru; Tanaka, Tsuyoshi; Matsunaga, Tadashi; Yoshino, Tomoko

    2013-07-11

    The measurement of autoantibodies to thyroid-stimulating hormone receptor (TSHR) is important for the diagnosis of autoimmune thyroid disease such as Graves' disease (GD). Although TSHR from porcine thyroid membrane is commonly used for the measurement of TSHR autoantibodies (TRAb), recombinant human TSHR (hTSHR) remains ideal in terms of stable supply and species identity. Here we set out to express recombinant hTSHR on the lipid-bilayer surface of magnetic nanoparticles from a magnetotactic bacterium, Magnetospirillum magneticum AMB-1. Using a tetracycline-inducible expression system, we successfully overexpressed functional hTSHR on bacterial magnetic particles (BacMPs) in AMB-1 via an anchor protein specific for BacMPs. The overexpressed hTSHR was membrane integrated and possessed both ligand and autoantibody binding activity. Our data suggest that hTSHR-displayed BacMPs have potential as novel tools for ligand-receptor interaction analysis or for TRAb immunoassay in GD patients.

  13. Thyroid-stimulating hormone levels in newborns and early life exposure to endocrine-disrupting chemicals: analysis of three European mother-child cohorts.

    PubMed

    de Cock, Marijke; de Boer, Michiel R; Govarts, Eva; Iszatt, Nina; Palkovicova, Lubica; Lamoree, Marja H; Schoeters, Greet; Eggesbø, Merete; Trnovec, Tomas; Legler, Juliette; van de Bor, Margot

    2017-09-01

    BackgroundVarious studies have reported interactions between thyroid hormones and early life chemical exposure. Our objective was to analyze the associations between markers of endocrine-disrupting chemical exposure and thyroid function in newborns, determined through heel prick blood spots.MethodsThree European mother-child cohorts (FLEHSI-Belgium, HUMIS-Norway, and the PCB cohort-Slovakia. Total n=1,784) were pooled for the purpose of this study. Data on thyroid-stimulating hormone (TSH) were obtained from national neonatal screening registries, and samples of cord plasma and/or breast milk were collected to determine exposure to various chemicals. Multiple regression models were composed with exposure and cohort as fixed factors, and adjustments were made for a priori defined covariates.ResultsMedian TSH concentrations were 1, 1.10, and 2.76 mU/l for the Belgian, Norwegian, and Slovak cohorts, respectively. For polychlorinated biphenyl (PCB)-153 and dichlorodiphenyldichloroethylene (p,p'-DDE), children in the third exposure quartile had a 12-15% lower TSH at birth. Results remained unchanged after additional adjustment for birth weight and gestational weight gain. No effect on TSH was observed for the other compounds.ConclusionEarly life exposure to PCB-153 and p,p'-DDE impacts newborn TSH levels. Higher exposure levels were associated with 12-15% lower TSH levels.

  14. Diagnosis and discrimination of autoimmune Graves' disease and Hashimoto's disease using thyroid-stimulating hormone receptor-containing recombinant proteoliposomes.

    PubMed

    Fukushima, Hidetaka; Matsuo, Hideaki; Imamura, Koji; Morino, Kazuhiko; Okumura, Katsuzumi; Tsumoto, Kanta; Yoshimura, Tetsuro

    2009-12-01

    Graves' disease (GD) is an autoimmune disease of the thyroid gland caused by autoantibodies against thyroid-stimulating hormone receptor (TSHR). Currently, the diagnostic test for TSHR autoantibodies is based on an indirect competitive binding assay that measures the ability of TSHR autoantibodies to inhibit the binding of thyroid-stimulating hormone (TSH) to TSHR. Here, we have developed a specific and direct diagnostic method for autoantibodies in GD that incorporates immobilized TSHR-containing recombinant proteoliposomes into an enzyme-linked immunosorbent assay (ELISA). To reduce non-specific binding of autoantibodies to recombinant proteoliposomes, we investigated the effect of polyethylene glycol (PEG)-lipid on the binding of commercially available anti-TSHR antibodies (aTSHRAb). The incorporation of PEG-lipids into liposomes decreased non-specific binding, as compared to liposomes that did not contain PEG-lipids, and the addition of blocking reagents further decreased non-specific reactivity. aTSHRAb exhibited higher reactivity towards PEG-modified TSHR recombinant proteoliposomes than PEG-modified liposomes without TSHR (bare liposomes). Importantly, serum autoantibodies from patients with GD, which is associated with hyperthyroidism, exhibited remarkably specific binding to TSHR recombinant proteoliposomes. Serum autoantibodies from patients with Hashimoto's disease (HD), which is associated with hypothyroidism, also reacted specifically with proteoliposomal TSHR. These results suggest that immobilized TSHR recombinant proteoliposomes can serve as a direct diagnostic test for GD and HD. Furthermore, given that there is no competition test currently available for detecting autoantibodies in HD, the combination of TSHR recombinant proteoliposome ELISA and indirect competitive TSHR binding assay might be an effective way to discriminate between GD and HD.

  15. Thyroid-Stimulating Hormone Suppression for Protection Against Hypothyroidism Due to Craniospinal Irradiation for Childhood Medulloblastoma/Primitive Neuroectodermal Tumor

    SciTech Connect

    Massimino, Maura Gandola, Lorenza; Collini, Paola; Seregni, Ettore; Marchiano, Alfonso; Serra, Annalisa; Pignoli, Emanuele Ph.D.; Spreafico, Filippo; Pallotti, Federica; Terenziani, Monica; Biassoni, Veronica; Bombardieri, Emilio; Fossati-Bellani, Franca

    2007-10-01

    Purpose: Hypothyroidism is one of the earliest endocrine effects of craniospinal irradiation (CSI). The effects of radiation also depend on circulating thyroid-stimulating hormone (TSH), which acts as an indicator of thyrocyte function and is the most sensitive marker of thyroid damage. Hence, our study was launched in 1998 to evaluate the protective effect of TSH suppression during CSI for medulloblastoma/primitive neuroectodermal tumor. Patients and Methods: From Jan 1998 to Feb 2001, a total of 37 euthyroid children scheduled for CSI for medulloblastoma/primitive neuroectodermal tumor underwent thyroid ultrasound and free triiodothyronine (FT3), free thyroxine (FT4), and TSH evaluation at the beginning and end of CSI. From 14 days before and up to the end of CSI, patients were administered L-thyroxine at suppressive doses; every 3 days, TSH suppression was checked to ensure a value <0.3 {mu}M/ml. During follow-up, blood tests and ultrasound were repeated after 1 year; primary hypothyroidism was considered an increased TSH level greater than normal range. CSI was done using a hyperfractionated accelerated technique with total doses ranging from 20.8-39 Gy; models were used to evaluate doses received by the thyroid bed. Results: Of 37 patients, 25 were alive a median 7 years after CSI. They were well matched for all clinical features, except that eight children underwent adequate TSH suppression during CSI, whereas 17 did not. Hypothyroidism-free survival rates were 70% for the 'adequately TSH-suppressed' group and 20% for the 'inadequately TSH-suppressed' group (p = 0.02). Conclusions: Thyroid-stimulating hormone suppression with L-thyroxine had a protective effect on thyroid function at long-term follow-up. This is the first demonstration that transient endocrine suppression of thyroid activity may protect against radiation-induced functional damage.

  16. [Congestive heart failure caused by the thyroid stimulating hormone(TSH) secreting pituitary adenoma: report of two cases].

    PubMed

    Fujita, K; Yanaka, K; Tomono, Y; Kamezaki, T; Kujiraoka, Y; Nose, T

    2001-08-01

    A 42-year-old man and a 31-year-old man with congestive heart failure caused by the thyroid stimulating hormone(TSH) secreting pituitary adenoma were reported. Heart failure was improved after transsphenoidal resection of the pituitary adenoma in each patient. The syndrome of inappropriate secretion of TSH causes hyperthyroidism. Thyroid hormone acts directly on cardiac muscle to increase the stroke volume. Hyperthyroidism itself reduces the peripheral vascular resistance and an elevated basal metabolism which is the basic physiologic change in hyperthyroidism dilates small vessels and reduces vascular resistance. The reduced vascular resistance contributes to increase stroke volume. Thyroid hormone also acts directly on the cardiac pacemakers to be apt to cause tachycardiac atrial fibrillation. These mechanical changes in hyperthyroidism increase not only the cardiac output but also the venous return. The increased blood volume and the shortened ventricular filling time due to tachycardia result in congestive heart failure. TSH secreting pituitary adenoma is a rare tumor, however heart failure is common disease. TSH secreting pituitary adenoma should be taken into consideration in patients with heart failure. The presented cases were very enlightening to understand the relation between brain tumor and heart disease.

  17. A novel thyroid stimulating hormone beta-subunit isoform in human pituitary, peripheral blood leukocytes, and thyroid.

    PubMed

    Schaefer, Jeremy S; Klein, John R

    2009-07-01

    Thyroid stimulating hormone (TSH) is produced by the anterior pituitary and is used to regulate thyroid hormone output, which in turn controls metabolic activity. Currently, the pituitary is believed to be the only source of TSH used by the thyroid. Recent studies in mice from our laboratory have identified a TSHbeta isoform that is expressed in the pituitary, in peripheral blood leukocytes (PBL), and in the thyroid. To determine whether a human TSHbeta splice variant exists that is analogous to the mouse TSHbeta splice variant, and whether the pattern of expression of the splice variant is similar to that observed in mice, PCR amplification of RNAs from pituitary, thyroid, PBL, and bone marrow was done by reverse-transcriptase PCR and quantitative realtime PCR. Human pituitary expressed a TSHbeta isoform that is analogous to the mouse TSHbeta splice variant, consisting of a 27 nucleotide portion of intron 2 and all of exon 3, coding for 71.2% of the native human TSHbeta polypeptide. Of particular interest, the TSHbeta splice variant was expressed at significantly higher levels than the native form or TSHbeta in PBL and the thyroid. The TSHalpha gene also was expressed in the pituitary, thyroid, and PBL, but not the BM, suggesting that the TSHbeta polypeptide in the thyroid and PBL may exist as a dimer with TSHalpha. These findings identify an unknown splice variant of human TSHbeta. They also have implications for immune-endocrine interactions in the thyroid and for understanding autoimmune thyroid disease from a new perspective.

  18. Immunodetection of luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid stimulating hormone (TSH) and prolactin (PRL) in Brachionus calyciflorus (Rotifera: Monogononta).

    PubMed

    Alvarado-Flores, Jesús; Montoya-Garcia, María Del Rosario; Juárez, Javier Ventura; Rico-Martínez, Roberto

    2009-12-01

    The endocrine system controls and coordinates behavioral, biochemical, and physiological processes through signal mechanisms using neuropeptides or products of neurosecretory cells. Among invertebrates, this system is poorly studied in rotifers, in which estrogens and androgens significantly affect sexual reproduction. This is the first report of the presence of the Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), Thyroid Stimulating Hormone (TSH) and Prolactin (PRL) in rotifers. Analyses included the avidin-biotin-peroxidase complex method with primary antibodies LH (Anti-Rat LH serum for RIA), PRL (Anti-Rat PRL serum for RIA), FSH (Anti-Rat FSH serum for RIA) and TSH (Anti-Rat TSH serum for RIA). These hormones were found in females, males and parthenogenetic and sexual eggs of the freshwater Brachionus calyciflorus. The immunoreactivity of FSH, LH, TSH and PRL in females was observed in: ovaries, cerebrum, mastax, stomach, lorica, and the stomach gland. However, in males LH was observed only at the trochal disk and cerebrum. The hormones FSH, TSH and PRL, were observed in testicles, contractil vesicles, and cementary gland of males. Regarding amictic or parthenogenetic eggs, the hormones LH, FSH, TSH, and PRL were located mainly in the micromeres, and the staining in the macromeres was weak. On the other hand, in the mictic or sexual eggs the inner shell is stained for the hormones PRL and LH, opposite to the staining of FSH and TSH, located mainly in the embryo. In general, immuno-reactivity was observed in areas important for the reproductive, excretory, digestive and developmental processes.

  19. Clinical Association of Thyroid Stimulating Hormone Receptor Antibody Levels with Disease Severity in the Chronic Inactive Stage of Graves' Orbitopathy.

    PubMed

    Woo, Young Jae; Jang, Sun Young; Lim, Tyler Hyung Taek; Yoon, Jin Sook

    2015-08-01

    To investigate associations between serum thyroid stimulating hormone (TSH) receptor antibody (TRAb) levels and Graves' orbitopathy (GO) activity/severity in chronic-stage GO and compare the performance of two newly-developed TRAb assays (third-generation TSH-binding inhibition immunoglobulin [TBII] assay versus Mc4 thyroid-stimulating immunoglobulin [TSI] bioassay). This study is a retrospective review of medical charts and blood tests from Korean GO patients who first visited the departments of ophthalmology and endocrinology, Yonsei University College of Medicine from January 2008 to December 2011, were diagnosed with GO and Graves' hyperthyroidism, and were followed up for ≥18 months. Third-generation M22-TBII and Mc4-TSI assays were performed in the chronic-inactive GO patients in whom euthyroidism status was restored. Patients' GO activity/severity clinical activity scores (CAS), and modified NOSPECS scores were examined for a correlation with TRAb assays. Fifty patients (mean age, 41.3 years; 41 females) were analyzed. The mean duration of Graves' hyperthyroidism symptom was 63 months (range, 18 to 401 months) and that of GO was 46 months (range, 18 to 240 months). All patients had been treated previously with anti-thyroid drugs for a median period of 52.3 months, and two patients underwent either radioiodine therapy or total thyroidectomy. Mean CAS and NOSPECS scores were 0.5 ± 0.9 (standard deviation) and 4.8 ± 3.1, respectively. Mean M22-TBII and Mc4-TSI values were 7.5 ± 10.2 IL/L and 325.9 ± 210.1 specimen-to-reference control ratio. TSI was significantly correlated with NOSPECS score (R = 0.479, p < 0.001); however, TBII was not associated with NOSPECS score (p = 0.097). Neither TSI nor TBII correlated with CAS (p > 0.05), because GO inflammatory activity subsided in the chronic stages of GO. In chronic-inactive GO after euthyroid restoration, GO activity score did not associate with serum levels of TRAb or TBII. However, levels of the functional

  20. Electron Capture Dissociation of Divalent Metal-adducted Sulfated N-Glycans Released from Bovine Thyroid Stimulating Hormone

    NASA Astrophysics Data System (ADS)

    Zhou, Wen; Håkansson, Kristina

    2013-11-01

    Sulfated N-glycans released from bovine thyroid stimulating hormone (bTSH) were ionized with the divalent metal cations Ca2+, Mg2+, and Co by electrospray ionization (ESI). These metal-adducted species were subjected to infrared multiphoton dissociation (IRMPD) and electron capture dissociation (ECD) and the corresponding fragmentation patterns were compared. IRMPD generated extensive glycosidic and cross-ring cleavages, but most product ions suffered from sulfonate loss. Internal fragments were also observed, which complicated the spectra. ECD provided complementary structural information compared with IRMPD, and all observed product ions retained the sulfonate group, allowing sulfonate localization. To our knowledge, this work represents the first application of ECD towards metal-adducted sulfated N-glycans released from a glycoprotein. Due to the ability of IRMPD and ECD to provide complementary structural information, the combination of the two strategies is a promising and valuable tool for glycan structural characterization. The influence of different metal ions was also examined. Calcium adducts appeared to be the most promising species because of high sensitivity and ability to provide extensive structural information.

  1. Wide-range quantification of human thyroid-stimulating hormone using gold-nanopatterned single-molecule sandwich immunoassay chip.

    PubMed

    Lee, Seungah; Kang, Seong Ho

    2012-09-15

    We performed wide-range quantification of human thyroid-stimulating hormone (hTSH) using a gold nano-patterned sandwich immunoassay chip. Objective-type total internal reflection fluorescence microscopy (TIRFM) was used to detect hTSH at the single-molecule level. A gold spot with a diameter of 100 nm on a 10-mm square glass substrate was fabricated by electron beam nanolithography. When hTSH bound to antibodies conjugated to each 100-nm gold spot, there was an increase in the relative fluorescent intensity (RFI). The detection limit of this "TSH-nanoarray chip" was 360 zM (equivalent to five molecules), which demonstrated that a TSH-nanoarray chip could be used for detection at the single-molecule level. A linear response was observed over a wide dynamic range (from 360 zM to 36 pM, R=0.9812) without a fluorescence quenching effect. A significant enhancement in the sensitivity (~12,000-fold) was achieved with the 100-nm gold nano-patterned chip compared with results obtained using a traditional chemiluminescence immunoassay for the evaluation of TSH in human serum.

  2. Association between Serum Thyroid-Stimulating Hormone Levels and Visceral Adipose Tissue: A Population-Based Study in Northeast Germany.

    PubMed

    Witte, Tilman; Völzke, Henry; Lerch, Markus M; Hegenscheid, Katrin; Friedrich, Nele; Ittermann, Till; Batsis, John A

    2017-02-01

    Abdominal obesity is a major driver for adverse medical conditions. While an interaction between adipose tissue and thyroid function is thought to exist, to our knowledge, no study has examined the effect of thyroid-stimulating hormone (TSH) on visceral adipose tissue (VAT) in a population-based context. We determined an association between serum TSH levels and VAT. A sample of 1,021 female and 956 male adults aged 20-79 years was drawn from registry offices in the cross-sectional, population-based Study of Health in Pomerania Trend (SHIP Trend) in Northeast Germany from 2008 to 2012. Our main exposure was serum TSH levels. Our main outcome was VAT measured using magnetic resonance imaging. The possibly mediating role of leptin on the TSH-VAT association was also assessed. A total of 1,719 participants (87.9%) had serum TSH levels within the reference range. The mean volume of VAT was 5.33 liters for men and 2.83 liters for women. No association between TSH and VAT (β = 0.06, 95% CI: -0.02, 0.14) was observed, and there were no differences detected between sexes. VAT was strongly associated with leptin with a greater effect in women than in men. Leptin was strongly associated with TSH. No association between TSH and VAT was observed. Other biomarkers such as leptin may play a role in the relationship between thyroid function and metabolic risk.

  3. Periostin silencing suppresses the aggressive phenotype of thyroid carcinoma cells by suppressing the Akt/thyroid stimulating hormone receptor axis.

    PubMed

    Wang, Min; Gui, Chunyi; Qiu, Shenglong; Tang, Jingdong; Peng, Zhihai

    2017-09-30

    Clinical evidence indicates that high periostin expression correlates with aggressive phenotype in thyroid carcinoma. However, the biological roles of periostin in thyroid carcinoma development and progression are still unclear. In this study, we explored the effects of periostin silencing on thyroid carcinoma cell growth, invasion, and tumorigenesis. We also studied the impact of periostin on the activation of phosphoinositide 3-kinase (PI3-K)/Akt signaling, which is involved in the pathogenesis of thyroid carcinoma. It was found that downregulation of periostin significantly inhibited the proliferation, colony formation, and invasion in both FTC-133 and BCPAP thyroid carcinoma cells. In vivo tumorigenic studies confirmed that periostin depletion retarded the growth of subcutaneous FTC-133 xenograft tumors, which was coupled with a significant decline in the percentage of Ki-67-positive proliferating cells. Western blot analysis demonstrated that periostin downregulation caused a marked inhibition of thyroid stimulating hormone receptor (TSHR) expression and Akt phosphorylation in FTC-133 and BCPAP cells. Co-expression of constitutively active Akt (CA-Akt) significantly reversed periostin-mediated downregulation of TSHR. Most importantly, overexpression of TSHR or CA-Akt rescued FTC-133 cells from periostin-induced growth and invasion suppression. Collectively, periostin regulates thyroid carcinoma growth and progression via the Akt/TSHR axis and represents a promising therapeutic target for this malignancy.

  4. Serum Thyroid Stimulating Hormone Levels Are Associated with the Presence of Coronary Atherosclerosis in Healthy Postmenopausal Women

    PubMed Central

    Chon, Seung Joo; Heo, Jin Young; Yun, Bo Hyon; Jung, Yeon Soo

    2016-01-01

    Objectives Menopause is a natural aging process causing estrogen deficiency, accelerating atherogenic processes including dyslipidemia. Prevalence of thyroid dysfunction is also high in postmenopausal women, and it is known to elevate the risk of cardiovascular disease (CVD). Therefore, we are to study on the associations in between serum thyroid stimulating hormone (TSH) and prevalence of CVD in postmenopausal women who have normal thyroid function. Methods We performed a retrospective review of 247 Korean postmenopausal women who visited the health promotion center from January, 2007 to December, 2009. Postmenopausal women with normal serum TSH were included in the study. Coronary atherosclerosis was assessed by 64-row multidetector computed tomography. Results In multiple linear regression analysis, serum TSH was associated with serum triglyceride (TG) (β = 0.146, P = 0.023). In multiple logistic regression analysis, increasing age and serum TSH were associated with an increased risk of coronary atherosclerosis in euthyroid postmenopausal women (odds ratio [OR] = 1.107 [1.024-1.197], P = 0.011 and OR = 1.303 [1.024-1.658], P = 0.031, respectively). Conclusions It revealed that significant predictor of serum TSH was serum TG, and increasing age and TSH were found to have associations with an increased risk of coronary atherosclerosis in euthyroid postmenopausal women. Screening and assessing risks for CVD in healthy postmenopausal women would be helpful before atherosclerosis develops. PMID:28119894

  5. Use of recombinant human thyroid-stimulating hormone for thyrotropin stimulation test in healthy, hypothyroid and euthyroid sick dogs

    PubMed Central

    Daminet, Sylvie; Fifle, Lyanne; Paradis, Manon; Duchateau, Luc; Moreau, Maxim

    2007-01-01

    Recombinant human thyroid-stimulating hormone (rhTSH) was evaluated for the diagnosis of canine hypothyroidism, using TSH response tests. Phase I stimulation tests were performed in 6 healthy dogs weighing over 20 kg, using 50 and then 100 μg of freshly reconstituted rhTSH administered intravenously. In phase II, the same dogs were stimulated by using 100 μg of rhTSH frozen for 3 months at −20°C. Phase III stimulation tests were performed by using 50 or 100 μg of freshly reconstituted or frozen rhTSH in healthy (n = 14), euthyroid sick (n = 11) and hypothyroid dogs (n = 9). A dose of 100 μg of rhTSH was judged more appropriate for dogs weighing more than 20 kg. Biological activity of rhTSH after freezing at −20°C for up to 12 weeks was maintained. When stimulated, significant (P < 0.05) increases in total thyroxine concentration were observed only in healthy and euthyroid sick dogs. Results of this study show that the rhTSH stimulation test is able to differentiate euthyroidism from hypothyroidism in dogs. PMID:18189051

  6. Functional Expression of Thyroid-Stimulating Hormone Receptor on Nano-Sized Bacterial Magnetic Particles in Magnetospirillum magneticum AMB-1

    PubMed Central

    Sugamata, Yasuhiro; Uchiyama, Ryo; Honda, Toru; Tanaka, Tsuyoshi; Matsunaga, Tadashi; Yoshino, Tomoko

    2013-01-01

    The measurement of autoantibodies to thyroid-stimulating hormone receptor (TSHR) is important for the diagnosis of autoimmune thyroid disease such as Graves’ disease (GD). Although TSHR from porcine thyroid membrane is commonly used for the measurement of TSHR autoantibodies (TRAb), recombinant human TSHR (hTSHR) remains ideal in terms of stable supply and species identity. Here we set out to express recombinant hTSHR on the lipid-bilayer surface of magnetic nanoparticles from a magnetotactic bacterium, Magnetospirillum magneticum AMB-1. Using a tetracycline-inducible expression system, we successfully overexpressed functional hTSHR on bacterial magnetic particles (BacMPs) in AMB-1 via an anchor protein specific for BacMPs. The overexpressed hTSHR was membrane integrated and possessed both ligand and autoantibody binding activity. Our data suggest that hTSHR-displayed BacMPs have potential as novel tools for ligand-receptor interaction analysis or for TRAb immunoassay in GD patients. PMID:23852019

  7. Serum thyroid-stimulating hormone level and relation with size of hippocampus in patients with mild cognitive disorders

    PubMed Central

    Daghighi, Mohammad-Hossein; Poureisa, Masoud; Ahmadi, Pegah; Reshadatjoo, Mahmoud; Golestani, Sahar; Naghavi-Behzad, Mohammad; Karkon-Shayan, Farid

    2016-01-01

    Background: Cognitive disorders and dementia are common problems, and Alzheimer's disease is one of the major leading causes of death worldwide. Thyroid hormone disorders as a common problem effect on hippocampus size which as a prognostic factor in dementia. The aim of the present study was to investigate the relationship between serum thyroid-stimulating hormone (TSH) level and the size of hippocampus in patients with mild cognitive disorders. Materials and Methods: In a descriptive-analytical study, 41 patients with symptoms of mild cognitive disorders whom referred to take the brain magnetic resonance image (MRI) in a radiology center under the direction of Tabriz University of Medical Sciences (Tabriz, Iran) were evaluated. The right and left hippocampal and brain volume was calculated by MRI at coronal T1-weighted. Serum TSH level was also measured in these patients. Correlation between serum TSH level and hippocampal volume size was evaluated. Results: Male to female ratio was 1.05:1 with mean age of 54.09 ± 3.11 years. Mean serum TSH level of patients was 1.55 ± 1.45 uU/ml. The right and left hippocampal volumes were 1.61 ± 0.42 and 1.62 ± 0.39 ml, respectively. There were slight negative correlations between the right and left hippocampal volumes with TSH level (r = −0.133 and r = −0.092, respectively). Correlations between the right and left hippocampal volumes with TSH level were not statistically significant (P = 0.406, P = 0.566, respectively). Conclusion: Based on findings of the present study, there was a weak negative correlation between serum level of TSH with the right and left hippocampal and brain volume ratio, but the correlation was not statistically significant. It seems that controlling of clinical or subclinical hypothyroidism may have a role in slowing of dementia progression and also have a preventive role. PMID:27942104

  8. How well does the capillary thyroid-stimulating hormone test for newborn thyroid screening predict the venous free thyroxine level?

    PubMed Central

    Pokrovska, Tzveta; Jones, Jeremy; Shaikh, M Guftar; Smith, Sarah; Donaldson, Malcolm D C

    2016-01-01

    Objectives To determine, in newborn infants referred with elevated capillary thyroid-stimulating hormone (TSH), a threshold below which a frankly subnormal venous free thyroxine (fT4) level of <10 pmol/L is unlikely, so that treatment with levo-thyroxine (L-T4) might be deferred until venous thyroid function tests (TFTs) become available. Subjects and methods All infants referred in Scotland since 1979 with capillary TSH elevation were studied, with particular focus on infants screened using the AutoDELFIA assay between 2002 and 2013. Results Of the 321 infants referred with capillary TSH elevation using AutoDELFIA, 35 were excluded (fT4/TSH unavailable (12), venous sample either preceding or >10 days after capillary sampling (13, 10)), leaving 286 eligible for analysis (208 definite/probable hypothyroidism, 61 transient TSH elevation, 17 of uncertain thyroid status). Capillary TSH and venous T4 were strongly correlated (Spearman's rank correlation coefficient −0.707355). The optimal capillary TSH threshold for predicting a venous fT4 of <10 pmol/L was found to be >40 mU/L (90.3% sensitivity and 65.9% specificity compared with 90.25% and 59.1% for >35 mU/L and 88.3% and 68.2% for >45 mU/L). 93 infants (32.5%) had capillary TSH ≤40 mU/L at referral of whom 15 (9.7%) had venous fT4 <10 pmol/L, comprising seven with true congenital hypothyroidism, five with transient TSH elevation and three with uncertain status, two of whom died. Conclusion For infants in whom capillary TSH is ≤40 mU/L, it is reasonable to defer L-T4 treatment until venous TFT results are known provided that the latter become available quickly. PMID:26966265

  9. Using Hashimoto thyroiditis as gold standard to determine the upper limit value of thyroid stimulating hormone in a Chinese cohort.

    PubMed

    Li, Yu; Chen, Dong-Ning; Cui, Jing; Xin, Zhong; Yang, Guang-Ran; Niu, Ming-Jia; Yang, Jin-Kui

    2016-11-06

    Subclinical hypothyroidism, commonly caused by Hashimoto thyroiditis (HT), is a risk factor for cardiovascular diseases. This disorder is defined as merely having elevated serum thyroid stimulating hormone (TSH) levels. However, the upper limit of reference range for TSH is debated recently. This study was to determine the cutoff value for the upper normal limit of TSH in a cohort using the prevalence of Hashimoto thyroiditis as "gold" calibration standard. The research population was medical staff of 2856 individuals who took part in health examination annually. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, thyroid peroxidase antibody (TPAb), thyroglobulin antibody (TGAb) and other biochemistry parameters were tested. Meanwhile, thyroid ultrasound examination was performed. The diagnosis of HT was based on presence of thyroid antibodies (TPAb and TGAb) and abnormalities of thyroid ultrasound examination. We used two different methods to estimate the cutoff point of TSH based on the prevalence of HT. Joinpoint regression showed the prevalence of HT increased significantly at the ninth decile of TSH value corresponding to 2.9 mU/L. ROC curve showed a TSH cutoff value of 2.6 mU/L with the maximized sensitivity and specificity in identifying HT. Using the newly defined cutoff value of TSH can detect patients with hyperlipidemia more efficiently, which may indicate our approach to define the upper limit of TSH can make more sense from the clinical point of view. A significant increase in the prevalence of HT occurred among individuals with a TSH of 2.6-2.9 mU/L made it possible to determine the cutoff value of normal upper limit of TSH.

  10. The association between soya consumption and serum thyroid-stimulating hormone concentrations in the Adventist Health Study-2.

    PubMed

    Tonstad, Serena; Jaceldo-Siegl, Karen; Messina, Mark; Haddad, Ella; Fraser, Gary E

    2016-06-01

    Consumers may choose soya foods as healthful alternatives to animal products, but concern has arisen that eating large amounts of soya may adversely affect thyroid function. The present study aimed to examine the association between soya food consumption and serum thyroid-stimulating hormone (TSH) concentrations in North American churchgoers belonging to the Seventh-day Adventist denomination that encourages vegetarianism. Participants completed six repeated 24 h dietary recalls within a 6-month period. Soya protein and soya isoflavone intakes were estimated, and their relationships to TSH concentrations measured at the end of 6 months were calculated using logistic regression analyses. Calibration sub-study of the Adventist Health Study-2. Women (n 548) and men (n 295) who were not taking thyroid medications. In men, age and urinary iodine concentrations were associated with high serum TSH concentrations (>5 mIU/l), while among women White ethnicity was associated with high TSH. In multivariate models adjusted for age, ethnicity and urinary iodine, soya isoflavone and protein intakes were not associated with high TSH in men. In women higher soya isoflavone consumption was associated with higher TSH, with an adjusted odds ratio (highest v. lowest quintile) of 4·17 (95 % CI 1·73, 10·06). Likewise, women with high consumption of soya protein (midpoint of highest quintile, 11 g/d) v. low consumption (midpoint of lowest quintile, 0 g/d) carried increased odds of high TSH (OR=2·69; 95 % CI 1·34, 5·30). In women high consumption of soya was associated with elevated TSH concentrations. No associations between soya intake and TSH were found in men.

  11. Genetic associations of the thyroid stimulating hormone receptor gene with Graves diseases and Graves ophthalmopathy: A meta-analysis

    PubMed Central

    Xiong, Haibo; Wu, Mingxing; Yi, Hong; Wang, Xiuqing; Wang, Qian; Nadirshina, Sophia; Zhou, Xiyuan; Liu, Xueqin

    2016-01-01

    Graves’ disease (GD) is a common thyroid disease, and Graves ophthalmopathy(GO) is the most common extra-thyroidal manifestation of GD. Genetic associations of the thyroid stimulating hormone receptor (TSHR) gene with GD and GO have been studied in different population groups for a long time. We aimed to obtain a more precise estimation of the effects of TSHR single nucleotide polymorphisms (SNPs) on GD/GO using a meta-analysis. Publications were searched on Pub Med and EMBASE up to December 30, 2015. Eight studies involving three SNPs (rs179247, rs12101255, and rs2268458), which included 4790 cases and 5350 controls, met the selection criteria. The pooled odds ratios (OR) and the 95% confidence intervals (CI) were estimated. SNPs rs179247 (dominant model [GG + GA vs. AA]: OR = 0.66, 95%CI: 0.61–0.73, P = 0.000, I2 = 0%) and rs12101255 (dominant model [TT + TC vs. CC]: OR = 1.67, 95%CI: 1.53–1.83, P = 0.000, I2 = 0%) were significantly associated with GD in all of the genetic models. TSHR rs12101255 and rs2268458 polymorphisms had no association between GO and GD (GD without GO). The results indicate that rs179247 and rs12101255 are likely to be genetic biomarkers for GD. Further studies with different population groups and larger sample sizes are needed to confirm the genetic associations of the TSHR gene with GD/GO. PMID:27456991

  12. Serum Lipid Transfer Proteins in Hypothyreotic Patients Are Inversely Correlated with Thyroid-Stimulating Hormone (TSH) Levels.

    PubMed

    Skoczyńska, Anna; Wojakowska, Anna; Turczyn, Barbara; Zatońska, Katarzyna; Wołyniec, Maria; Rogala, Natalia; Szuba, Andrzej; Bednarek-Tupikowska, Grażyna

    2016-11-30

    BACKGROUND Plasma cholesteryl ester transfer protein (CETP) activity is often decreased in patients with hypothyroidism, whereas less is known about the phospholipid transfer protein (PLTP). We aimed to evaluate simultaneously serum CETP and PLTP activity in patients diagnosed with hypothyroidism. MATERIAL AND METHODS The selection criteria for control group members (without thyroid dysfunction) in this case to case study were levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides similar to those in study group patients (101 patients diagnosed with hypothyroidism). Serum CETP and PLTP activities were measured by homogenous fluorometric assays using synthetic donor particle substrates. RESULTS Serum CETP and PLTP activities in hypothyreotic patients were lower (p<0.001) compared with those in healthy subjects. This lowering was associated with significant changes in HDL-C subclasses: decrease in HDL2- and increase in HDL3 cholesterol levels. Multiple linear regression analyses adjusted for age, sex, body mass index, smoking habits, and alcohol drinking showed a strong association between hypothyroidism and activity of lipid transfer proteins. A linear inverse relationship between thyroid-stimulating hormone (TSH) and CETP (r=-0.21; p<0.01) and between TSH and PLTP (r=-0.24; p<0.001) was shown. There also was a positive correlation (p<0.001) between CETP and HDL2 cholesterol (r=0.27) and between PLTP and HDL2 cholesterol (r=0.37). A negative correlation between CETP and HDL3 cholesterol (r=-0.22: p<0.01) and between PLTP and HDL3 cholesterol (r=-0.24; p<0.001) has been demonstrated as well. CONCLUSIONS The decreased HDL2 and increased HDL3 cholesterol levels in subjects with hypothyroidism are consequences of decreased activity of lipid transfer proteins. These changes are early symptoms of lipid disturbances in hypothyroidism.

  13. Thyroid Stimulating Hormone Receptor (TSHR) Intron 1 Variants Are Major Risk Factors for Graves' Disease in Three European Caucasian Cohorts

    PubMed Central

    Jurecka-Lubieniecka, Beata; Franaszczyk, Maria; Kula, Dorota; Krajewski, Paweł; Karamat, Muhammad A.; Simmonds, Matthew J.; Franklyn, Jayne A.; Gough, Stephen C. L.; Jarząb, Barbara; Bednarczuk, Tomasz

    2010-01-01

    Background The thyroid stimulating hormone receptor (TSHR) gene is an established susceptibility locus for Graves' disease (GD), with recent studies refining association to two single nucleotide polymorphisms (SNPs), rs179247 and rs12101255, within TSHR intron 1. Methodology and Principal Findings We aimed to validate association of rs179247 and rs12101255 in Polish and UK Caucasian GD case-control subjects, determine the mode of inheritance and to see if association correlates with specific GD clinical manifestations. We investigated three case-control populations; 558 GD patients and 520 controls from Warsaw, Poland, 196 GD patients and 198 controls from Gliwice, Poland and 2504 GD patients from the UK National collection and 2784 controls from the 1958 British Birth cohort. Both rs179247 (P = 1.2×10−2–6.2×10−15, OR = 1.38–1.45) and rs12101255 (P = 1.0×10−4–3.68×10−21, OR = 1.47–1.87) exhibited strong association with GD in all three cohorts. Logistic regression suggested association of rs179247 is secondary to rs12101255 in all cohorts. Inheritance modeling suggested a co-dominant mode of inheritance in all cohorts. Genotype-phenotype correlations provided no clear evidence of association with any specific clinical characteristics. Conclusions We have validated association of TSHR intron 1 SNPs with GD in three independent European cohorts and have demonstrated that the aetiological variant within the TSHR is likely to be in strong linkage disequilibrium with rs12101255. Fine mapping is now required to determine the exact location of the aetiological DNA variants within the TSHR. PMID:21124799

  14. Serum Lipid Transfer Proteins in Hypothyreotic Patients Are Inversely Correlated with Thyroid-Stimulating Hormone (TSH) Levels

    PubMed Central

    Skoczyńska, Anna; Wojakowska, Anna; Turczyn, Barbara; Zatońska, Katarzyna; Wołyniec, Maria; Rogala, Natalia; Szuba, Andrzej; Bednarek-Tupikowska, Grażyna

    2016-01-01

    Background Plasma cholesteryl ester transfer protein (CETP) activity is often decreased in patients with hypothyroidism, whereas less is known about the phospholipid transfer protein (PLTP). We aimed to evaluate simultaneously serum CETP and PLTP activity in patients diagnosed with hypothyroidism. Material/Methods The selection criteria for control group members (without thyroid dysfunction) in this case to case study were levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides similar to those in study group patients (101 patients diagnosed with hypothyroidism). Serum CETP and PLTP activities were measured by homogenous fluorometric assays using synthetic donor particle substrates. Results Serum CETP and PLTP activities in hypothyreotic patients were lower (p<0.001) compared with those in healthy subjects. This lowering was associated with significant changes in HDL-C subclasses: decrease in HDL2- and increase in HDL3 cholesterol levels. Multiple linear regression analyses adjusted for age, sex, body mass index, smoking habits, and alcohol drinking showed a strong association between hypothyroidism and activity of lipid transfer proteins. A linear inverse relationship between thyroid-stimulating hormone (TSH) and CETP (r=−0.21; p<0.01) and between TSH and PLTP (r=−0.24; p<0.001) was shown. There also was a positive correlation (p<0.001) between CETP and HDL2 cholesterol (r=0.27) and between PLTP and HDL2 cholesterol (r=0.37). A negative correlation between CETP and HDL3 cholesterol (r=−0.22: p<0.01) and between PLTP and HDL3 cholesterol (r=−0.24; p<0.001) has been demonstrated as well. Conclusions The decreased HDL2 and increased HDL3 cholesterol levels in subjects with hypothyroidism are consequences of decreased activity of lipid transfer proteins. These changes are early symptoms of lipid disturbances in hypothyroidism. PMID:27899788

  15. Glutamine and glutamic acid enhance thyroid-stimulating hormone β subunit mRNA expression in the rat pars tuberalis.

    PubMed

    Aizawa, Sayaka; Sakai, Takafumi; Sakata, Ichiro

    2012-03-01

    Thyroid-stimulating hormone (TSH)-producing cells of the pars tuberalis (PT) display distinct characteristics that differ from those of the pars distalis (PD). The mRNA expression of TSHβ and αGSU in PT has a circadian rhythm and is inhibited by melatonin via melatonin receptor type 1; however, the detailed regulatory mechanism for TSHβ expression in the PT remains unclear. To identify the factors that affect PT, a microarray analysis was performed on laser-captured PT tissue to screen for genes coding for receptors that are abundantly expressed in the PT. In the PT, we found high expression of the KA2, which is an ionotropic glutamic acid receptor (iGluR). In addition, the amino acid transporter A2 (ATA2), also known as the glutamine transporter, and glutaminase (GLS), as well as GLS2, were highly expressed in the PT compared to the PD. We examined the effects of glutamine and glutamic acid on TSHβ expression and αGSU expression in PT slice cultures. l-Glutamine and l-glutamic acid significantly stimulated TSHβ expression in PT slices after 2- and 4-h treatments, and the effect of l-glutamic acid was stronger than that of l-glutamine. In contrast, treatment with glutamine and glutamic acid did not affect αGSU expression in the PT or the expression of TSHβ or αGSU in the PD. These results strongly suggest that glutamine is taken up by PT cells through ATA2 and that glutamic acid locally converted from glutamine by Gls induces TSHβ expression via the KA2 in an autocrine and/or paracrine manner in the PT.

  16. A domestication related mutation in the thyroid stimulating hormone receptor gene (TSHR) modulates photoperiodic response and reproduction in chickens.

    PubMed

    Karlsson, Anna-Carin; Fallahshahroudi, Amir; Johnsen, Hanna; Hagenblad, Jenny; Wright, Dominic; Andersson, Leif; Jensen, Per

    2016-03-01

    The thyroid stimulating hormone receptor gene (TSHR) has been suggested to be a "domestication locus" in the chicken. A strong selective sweep over TSHR in domestic breeds together with significant effects of a mutation in the gene on several domestication related traits, indicate that the gene has been important for chicken domestication. TSHR plays a key role in the signal transduction of seasonal reproduction, which is characteristically less strict in domestic animals. We used birds from an advanced intercross line between ancestral Red Junglefowl (RJF) and domesticated White Leghorn (WL) to investigate effects of the mutation on reproductive traits as well as on TSHB, TSHR, DIO2 and DIO3 gene expression during altered day length (photoperiod). We bred chickens homozygous for either the mutation (d/d) or wild type allele (w/w), allowing assessment of the effect of genotype at this locus while also controlling for background variation in the rest of the genome. TSHR gene expression in brain was significantly lower in both d/d females and males and d/d females showed a faster onset of egg laying at sexual maturity than w/w. Furthermore, d/d males showed a reduced testicular size response to decreased day length, and lower levels of TSHB and DIO3 expression. Additionally, purebred White Leghorn females kept under natural short day length in Sweden during December had active ovaries and lower levels of TSHR and DIO3 expression compared to Red Junglefowl females kept under similar conditions. Our study indicates that the TSHR mutation affects photoperiodic response in chicken by reducing dependence of seasonal reproduction, a typical domestication feature, and may therefore have been important for chicken domestication. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Purification of bovine thyroid-stimulating hormone by a monoclonal antibody

    SciTech Connect

    Lock, A.J.; van Denderen, J.; Aarden, L.A.

    1988-01-01

    A monoclonal antibody directed against bovine TSH was obtained by hybridoma technology. This antibody was specific for TSH and did not react with bovine LH and FSH. Affinity chromatography of crude TSH was performed on anti-TSH Sepharose. Bovine TSH was purified in a single step to near homogeneity by this technique, as shown by cation exchange chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified TSH. The biological activity of the hormone was not affected during the purification, as determined by (/sup 3/H)thymidine incorporation of the TSH-dependent FRTL5 cell line. The results indicate that affinity purification of TSH by means of a monoclonal antibody is a simple one-step procedure for the production of biologically active, highly purified TSH.

  18. A genome-wide association study of thyroid stimulating hormone and free thyroxine in Danish children and adolescents

    PubMed Central

    Svendstrup, Mathilde; Ohrt, Johanne Dam; Dahl, Maria; Fonvig, Cilius Esmann; Hollensted, Mette; Have, Christian Theil; Kadarmideen, Haja N.; Pedersen, Oluf; Hansen, Torben; Holm, Jens-Christian; Grarup, Niels

    2017-01-01

    Background Hypothyroidism is associated with obesity, and thyroid hormones are involved in the regulation of body composition, including fat mass. Genome-wide association studies (GWAS) in adults have identified 19 and 6 loci associated with plasma concentrations of thyroid stimulating hormone (TSH) and free thyroxine (fT4), respectively. Objective This study aimed to identify and characterize genetic variants associated with circulating TSH and fT4 in Danish children and adolescents and to examine whether these variants associate with obesity. Methods Genome-wide association analyses of imputed genotype data with fasting plasma concentrations of TSH and fT4 from a population-based sample of Danish children, adolescents, and young adults, and a group of children, adolescents, and young adults with overweight and obesity were performed (N = 1,764, mean age = 12.0 years [range 2.5−24.7]). Replication was performed in additional comparable samples (N = 2,097, mean age = 11.8 years [1.2−22.8]). Meta-analyses, using linear additive fixed-effect models, were performed on the results of the discovery and replication analyses. Results No novel loci associated with TSH or fT4 were identified. Four loci previously associated with TSH in adults were confirmed in this study population (PDE10A (rs2983511: β = 0.112SD, p = 4.8 ∙ 10−16), FOXE1 (rs7847663: β = 0.223SD, p = 1.5 ∙ 10−20), NR3C2 (rs9968300: β = 0.194SD), p = 2.4 ∙ 10−11), VEGFA (rs2396083: β = 0.088SD, p = 2.2 ∙ 10−10)). Effect sizes of variants known to associate with TSH or fT4 in adults showed a similar direction of effect in our cohort of children and adolescents, 11 of which were associated with TSH or fT4 in our study (p<0.0002). None of the TSH or fT4 associated SNPs were associated with obesity in our cohort, indicating no pleiotropic effects of these variants on obesity. Conclusion In a group of Danish children and adolescents, four loci previously associated with plasma TSH

  19. Is Very High Thyroid Stimulating Hormone Level Required in Differentiated Thyroid Cancer for Ablation Success?

    PubMed

    Hasbek, Zekiye; Turgut, Bülent

    2016-06-05

    Amaç: Diferansiye tiroid kanser (DTK), hastalarında total tiroidektomi sonrası radyoaktif iyot (I-131) ile remnant ablasyon kalan rezidü doku ve/veya metastatik dokunun yok edilmesi amacıyla kullanılan başarılı bir tedavi yöntemidir. Başarılı ablasyon tedavisi için yüksek tiroid simüle edici hormon (TSH) (≥30 mIU/L) seviyesi önerilmektedir. Bu retrospektif çalışmada ablasyon sırasındaki TSH düzeyinin radyoaktif iyot remnant ablasyonun başarısı üzerine etkisinin araştırılması amaçlandı. Yöntem: Bu çalışmaya DTK tanısı olan, bilateral total/totale yakın tiroidektomi ile tedavi edilen ve I-131 ile remnant ablasyon için yönlendirilmiş hastalar dahil edildi. Detekte edilemeyen stimüle-TSH serum tiroglobulin düzeyi, normal fizik muayene, I-131 ile tüm vücut tarama sonuçları negatif ve ultrasonda boyun lenf nodu metastazı bulgusu olmayan hastalar hastalıksız olarak kabul edildi. Ablasyon başarısı ile ablasyon sırasındaki TSH düzeyi arasındaki ilişki değerlendirildi. Bulgular: Mevcut çalışmaya ardışık 261 hasta dahil edildi. I-131 ile remnant ablasyon sırasında TSH düzeyi <30 mIU/L olan 34 hastada ortalama TSH düzeyi 19,47±6 mIU/L, TSH düzeyi ≥30 mIU/L olan 227 hastada ortalama TSH düzeyi 73,65±27 mIU/L idi. TSH <30 mIU/L olan bu hastaların yalnızca birinde ablasyon başarısızdı ve bu hastada akciğer metastazı vardı. TSH düzeyi ≥30 mIU/L olan hastaların ise %5,1’inde ablasyon başarısızdı. TSH düzeyinin ablasyon başarısına etkisi anlamlı değildi (p=0,472). Sonuç: Sonuç olarak, biz ablasyon başarısı için yalnızca yüksek serum TSH seviyesinin yeterli bir faktör olmayacağını düşünüyoruz. Yaş, metastaz varlığı, rezidü tiroid dokusunun büyüklüğü de dikkate alınması gereken faktörlerdir. Özellikle metastatik doku varlığında TSH seviyesini yeterli derecede yükseltmek mümkün olmaz. Ablasyon başarısında hastalarda daha düşük düzeyde TSH y

  20. Thyroid stimulating hormone suppression post-therapy in patients with Graves' disease: a systematic review of pathophysiology and clinical data.

    PubMed

    Yu, Huan; Farahani, Pendar

    2015-04-08

    Post-treatment hypothyroidism is common in Graves' disease, and clinical guidelines recommend monitoring for it; however, thyroid stimulating hormone (TSH) can remain suppressed in these patients following treatment. The objectives of this study were to explore the proposed pathophysiology behind the phenomenon of post-therapy TSH suppression and to systematically review existing clinical data on post-therapy TSH suppression in patients with Graves' disease. A systematic literature search was performed using EMBASE and PubMed databases, with several combinations of MeSH terms. Bibliography mining was also done on relevant articles to be as inclusive as possible. A total of 18 articles described possible mechanisms for post-therapy TSH suppression. Several of the studies demonstrate evidence of thyrotroph atrophy and hypothesize that this contributes to the ongoing suppression. TSH receptors have been identified in folliculo-stellate cells of the pituitary as well as astroglial cells of the hypothalamus, mediating paracrine feedback. A few studies have demonstrated inverse correlation between autoantibody titres and TSH levels, suggestive of their role in mediating ongoing TSH suppression in patients with Graves' disease. In addition, five studies were identified that provided clinical data on the duration of TSH suppression. Combined data show that 45.5% of patients recover TSH by 3 months after treatment, increasing to 69.3% by 6 months, and plateauing to 73.8% by 12 months (p>0.0001). Sub-analysis also shows that for patients who are TBII negative, 80.7% recover their TSH by 6 months compared with only 58.7% in those who are TBII positive (p= 0.003). Clinical data suggests that TSH recovery is most likely to occur within the first 6 months after treatment, with recovery plateauing at approximately 70% of patients, suggesting that reliance on this assay for monitoring can be very misleading. Furthermore, TBII positivity is associated with lower likelihood of TSH

  1. Evidence for the presence of thyroid stimulating hormone, thyroglobulin and their receptors in Eisenia fetida: a multilevel hormonal interface between the nervous system and the peripheral tissues.

    PubMed

    Wilhelm, Márta; Koza, Anna; Engelmann, Péter; Németh, Péter; Csoknya, Mária

    2006-06-01

    The present study describes the localization and distribution of thyroid-stimulating hormone (TSH), thyroglobulin (TGB) and their receptors in Eisenia fetida (Annelida, Oligochaeta) as revealed by immunohistological methods. Immunopositive neuronal and non-neuronal cells are present in both the central nervous system and some peripheral organs (e.g. foregut and coelomocytes). TSH- and TGB-immunopositive neurons in the various ganglia of the central nervous system are differentially distributed. Most of the immunoreactive cells are found in the suboesophageal ganglion. The stained cells also differ in their shapes (round, oval, pear-shaped) and sizes (small, 12-25 microm; medium, 20-35 microm; large, 30-50 microm). In all ganglia of the central nervous system, TSH-positive neurons additionally show gamma aminobutyric acid (GABA) immunopositivity. Non-neuronal cells also take part in hormone secretion and transport. Elongated TSH-positive cells have been detected in the capsule of the central ganglia and bear granules or vacuoles in areas lacking neurons. Many of capillaries show immunoreactivity for all four tested antibodies in the entire central nervous system and foregut. Among the coelomocytes, granulocytes and eleocytes stain for TSH and its receptor and for TGB but not for thyroid hormone receptor. Most of the granulocytes are large (25-50 microm) but a population of small cells (10-25 microm) are also immunoreactive. None of the coelomocytes stain for GABA. We therefore suggest that the members of this hormone system can modify both metabolism and immune functions in Eisenia. Coelomocytes might be able to secrete, transport and eliminate hormones in this system.

  2. Serum levels of thyroid hormones and thyroid stimulating hormone in patients with biliogenic and hyperlipidaemic acute pancreatitis: Difference and value in predicting disease severity.

    PubMed

    Yang, Ning; Zhang, Dong-Lei; Hao, Jian-Yu; Wang, Guang

    2016-04-01

    To compare retrospectively serum levels of thyroid hormones (THs) and thyroid stimulating hormone (TSH) between patients with biliogenic acute pancreatitis (BAP) and those with hyperlipidaemic acute pancreatitis (HLAP), in order to assess their value for predicting the severity of acute pancreatitis (AP). Patients with AP were divided into BAP and HLAP groups, then further divided into either a mild AP (MAP) group or a moderately severe AP (MSAP) group. Routine blood parameters were measured. Free tri-iodothyronine (FT3), free thyroxine (FT4) and TSH levels were measured. Seventy-six patients with AP were enrolled in the study. FT3 and TSH levels were significantly higher in patients with MAP than in patients with MSAP. FT4 and TSH levels were significantly lower in the HLAP group than in the BAP group. TSH levels in both MAP and MSAP patients were significantly lower in the HLAP group than in the BAP group. TSH was inversely correlated with triglyceride levels in patients with HLAP. FT3 was a risk factor for MSAP in patients with AP and also demonstrated moderate accuracy in predicting AP severity. THs and TSH decrease with the severity of AP, especially in patients with HLAP. FT3 may be a useful biomarker for the early assessment of the severity of AP. © The Author(s) 2016.

  3. Somatostatin receptor subtype specificity in human fetal pituitary cultures. Differential role of SSTR2 and SSTR5 for growth hormone, thyroid-stimulating hormone, and prolactin regulation.

    PubMed

    Shimon, I; Taylor, J E; Dong, J Z; Bitonte, R A; Kim, S; Morgan, B; Coy, D H; Culler, M D; Melmed, S

    1997-02-15

    Somatostatin (SRIF), a hypothalamic inhibitor of pituitary growth hormone (GH) and thyroid-stimulating hormone (TSH) secretion, binds to five distinct receptor (SSTR) subtypes. We therefore tested SSTR subtype-specific SRIF analogs in primary human fetal pituitary cultures (23-25-wk gestation) to elucidate their role in regulating human pituitary function. Using reverse transcription-PCR, mRNA expression of SSTR2 and SSTR5 were detected in fetal pituitary by 25 wk. SRIF analog affinities were determined by membrane radioligand binding in cells stably expressing the human SSTR forms. GH secretion was suppressed equally (40-60%, P < 0.005) by analogs preferential for either SSTR2 (IC50 for receptor binding affinity, 0.19-0.42 nM) or SSTR5 (IC50, 0.37 nM), and compounds with enhanced affinity for SSTR2 were more potent (EC50 for GH suppression, 0.05-0.09 nM) than Lanreotide (EC50, 2.30 nM) and SRIF (EC50, 0.19 nM). Similarly, analogs with high affinity for SSTR2 or SSTR5 decreased TSH secretion (30-40%, P < 0.005). However, prolactin was effectively inhibited only by compounds preferentially bound to SSTR2 (20-30%, P < 0.05). Luteinizing hormone was modestly decreased (15-20%) by SSTR2- or SSTR5-specific analogs. An SSTR5-specific analog also exclusively inhibited GH in acromegalic tumor cells. Thus, SRIF regulation of GH and TSH in primary human fetal pituitary cells is mediated by both SSTR2 and SSTR5, both of which are abundantly expressed by 25 wk. In contrast, suppression of prolactin is mediated mainly by SSTR2. These results indicate that SSTR5 is critical for physiologic regulation of GH and TSH. SRIF analogs with selective affinity for this receptor may therefore be more effective in the treatment of hormone-secreting pituitary adenomas.

  4. Localization of the aromatase enzyme expression in the human pituitary gland and its effect on growth hormone, prolactin, and thyroid stimulating hormone axis.

    PubMed

    Caglar, Asli Sezgin; Kapucu, Aysegul; Dar, Kadriye Akgun; Ozkaya, Hande Mefkure; Caglar, Erkan; Ince, Haluk; Kadioglu, Pinar

    2015-08-01

    The aim of this study is to evaluate aromatase expression in prolactin (PRL), thyroid stimulating hormone (TSH), and growth hormone (GH) secreting cells. Nontumoral human pituitary specimens were obtained from autopsy samples. Aromatase co-expression was determined by double immunohistochemical staining and assessed using H scores. H scores for GH-aromatase co-expression (GH-aromatase), TSH-aromatase co-expression (TSH-aromatase), and PRL-aromatase co-expression (PRL-aromatase) were 83.1 ± 13.1, 95.6 ± 16.1, and 83.7 ± 14.5, respectively. TSH producing cells exhibited the highest H score for co-expression of aromatase (p < 0.001). There was no gender difference in terms of H scores for aromatase expression and double immunohistochemical staining results (p > 0.05 for all). There was a negative correlation between the H scores for aromatase and PRL-aromatase, GH-aromatase and TSH-aromatase, respectively (r = -0.592, p < 0.001; r = -0.593, p < 0.001; r = -0.650, p < 0.001, respectively). Also, H scores for aromatase co-expression of each hormone were negatively correlated with the H scores for the corresponding hormone (r = -0.503, p < 0.001 for PRL-aromatase and PRL; r = -0.470, p < 0.001 for GH-aromatase, and GH; r = -0.641, p < 0.001 for TSH-aromatase and TSH). H scores for mean aromatase, GH-aromatase, TSH-aromatase were invariant of age (p > 0.05 for all). Age was negatively correlated with PRL-aromatase H score (r = -0.373, p = 0.008). Our study demonstrated significant aromatase co-expression in PRL, GH, and TSH secreting cells of the human anterior pituitary gland. The mutual paracrinal regulation between aromatase and three adenohypophyseal hormones indicates that aromatase may have a regulatory role on the synthesis and secretion of these hormones.

  5. Economic Evaluation of Recombinant Human Thyroid Stimulating Hormone Stimulation vs. Thyroid Hormone Withdrawal Prior to Radioiodine Ablation for Thyroid Cancer: The Korean Perspective

    PubMed Central

    Sohn, Seo Young; Jang, Hye Won; Cho, Yoon Young; Kim, Sun Wook

    2015-01-01

    Background Previous studies have suggested that recombinant human thyroid stimulating hormone (rhTSH) stimulation is an acceptable alternative to thyroid hormone withdrawal (THW) when radioiodine remnant ablation is planned for thyroid cancer treatment, based on superior short-term quality of life with non-inferior remnant ablation efficacy. This study evaluated the cost-effectiveness of radioiodine remnant ablation using rhTSH, compared with the traditional preparation method which renders patients hypothyroid by THW, in Korean perspective. Methods This economic evaluation considered the costs and benefits to the Korean public healthcare system. Clinical experts were surveyed regarding the current practice of radioiodine ablation in Korea and their responses helped inform assumptions used in a cost effectiveness model. Markov modelling with 17 weekly cycles was used to assess the incremental costs per quality-adjusted life year (QALY) associated with rhTSH. Clinical inputs were based on a multi-center, randomized controlled trial comparing remnant ablation success after rhTSH preparation with THW. The additional costs associated with rhTSH were considered relative to the clinical benefits and cost offsets. Results The additional benefits of rhTSH (0.036 QALY) are achieved with an additional cost of Korean won ₩961,105, equating to cost per QALY of ₩26,697,361. Sensitivity analyses had only a modest impact upon cost-effectiveness, with one-way sensitivity results of approximately ₩33,000,000/QALY. Conclusion The use of rhTSH is a cost-effective alternative to endogenous hypothyroid stimulation prior to radioiodine ablation for patients who have undergone thyroidectomy in Korea. PMID:26394733

  6. Enhancing effect of human thyroid stimulating hormone (hTSH) monoclonal antibody in the hTSH immunoradiometric assay (IRMA) system.

    PubMed

    Mirapurkar, Shubhangi; Samuel, G; Borkute, S D; Sivaprasad, N

    2012-01-01

    Different monoclonal antibodies, both commercial and indigenously produced, were evaluated in various combinations to optimize an immunoradiometric assay (IRMA) system for human thyroid stimulating hormone (hTSH). During these studies, it was observed that mixing one of the indigenously produced hTSH monoclonal antibody (2B11) in the hTSH IRMA system using Immunotech (Beckman Coulter, Czech Republic) kit reagents, led to an overall increase in the assay binding and sensitivity (from 0.025 mIU/L to 0.015mIU/L) of this IRMA system. This is not a general property of all monoclonal antibodies against hTSH. The mechanism for this enhancement can be attributed to the formation of a multicomponent complex.

  7. Assignment of the gene for the. beta. subunit of thyroid-stimulating hormone to the short arm of human chromosome 1

    SciTech Connect

    Dracopoli, N.C.; Rettig, W.J.; Whitfield, G.K.; Darlington, G.J.; Spengler, B.A.; Biedler, J.L.; Old, L.J.; Kourides, I.A.

    1986-03-01

    The chromosomal locations of the genes for the ..beta.. subunit of human thyroid-stimulating hormone (TSH) and the glycoprotein hormone ..cap alpha.. subunit have been determined by restriction enzyme analysis of DNA extracted from rodent-human somatic cell hybrids. Human chorionic gonadotropin (CG) ..cap alpha..-subunit cDNA and a cloned 0.9-kilobase (kb) fragment of the human TSH ..beta..-subunit gene were used as hybridization probes in the analysis of Southern blots of DNA extracted from rodent-human hybrid clones. Analysis of the segregation of 5- and 10-kb EcoRI fragments hybridizing to CG ..cap alpha..-subunit cDNA confirmed the previous assignment of this gene to chromosome 6. Analysis of the patterns of segregation of a 2.3-kb EcoRI fragment containing human TSH ..beta..-subunit sequences permitted the assignment of the TSH ..beta..-subunit gene to human chromosome 1. The subregional assignment of TSH ..beta.. subunit to chromosome 1p22 was made possible by the additional analysis of a set of hybrids containing partially overlapping segments of this chromosome. Human TSH ..beta.. subunit is not syntenic with genes encoding the ..beta.. subunits of CG, luteinizing hormone, or follicle-stimulating hormone and is assigned to a conserved linkage group that also contains the structural genes for the ..beta.. subunit of nerve growth factor (NGFB) and the proto-oncogene N-ras (NRAS).

  8. The Effect of a Mutation in the Thyroid Stimulating Hormone Receptor (TSHR) on Development, Behaviour and TH Levels in Domesticated Chickens

    PubMed Central

    Karlsson, Anna-Carin; Svemer, Frida; Eriksson, Jonas; Darras, Veerle M.; Andersson, Leif; Jensen, Per

    2015-01-01

    The thyroid stimulating hormone receptor (TSHR) has been suggested to be a “domestication locus” in the chicken, due to a strong selective sweep over the gene found in domesticated chickens, differentiating them from their wild ancestor the Red Junglefowl (RJF). We investigated the effect of the mutation on development (incubation time), behaviour and thyroid hormone levels in intercross chickens homozygous for the mutation (d/d), wild type homozygotes (w/w) or heterozygotes (d/w). This allowed an assessment of the effect of genotype at this locus against a random mix of RJF and WL genotypes throughout the rest of the genome, controlling for family effects. The d/d genotype showed a longer incubation time, less fearful behaviours, lower number of aggressive behaviours and decreased levels of the thyroid hormone T4, in comparison to the w/w genotype. The difference between TSHR genotypes (d/d vs. w/w) in these respects mirrors the differences in development and behaviour between pure domesticated White Leghorns and pure RJF chickens. Higher individual T3 and T4 levels were associated with more aggression. Our study indicates that the TSHR mutation affects typical domestication traits, possibly through modifying plasma levels of thyroid hormones, and may therefore have been important during the evolution of the domestic chicken. PMID:26053744

  9. The Physiological Role of Thyrotropin-Releasing Hormone in the Regulation of Thyroid-Stimulating Hormone and Prolactin Secretion in the Rat

    PubMed Central

    Harris, Arthur R. C.; Christianson, Dana; Smith, M. Susan; Fang, Shih-Lieh; Braverman, Lewis E.; Vagenakis, Apostolos G.

    1978-01-01

    The physiological role of thyrotropin-releasing hormone (TRH) in the regulation of thyrotropin (thyroid-stimulating hormone, TSH) and prolactin (Prl) secretion has been assumed but not proven. Stimulation of their release requires pharmacologic doses of TRH. Lesions of the hypothalamus usually induce an inhibition of TSH secretion and an increase in Prl. To determine whether TRH is essential for TSH and Prl secretion in the rat, 0.1 ml of TRH antiserum (TRH-Ab) or normal rabbit serum was administered to normal, thyroidectomized, cold-exposed, and proestrus rats through indwelling atrial catheter. Serum samples were obtained before and at frequent intervals thereafter. Serum TSH concentrations in normal, thyroidectomized, cold-exposed, and proestrus rats were not depressed in specimens obtained up to 24 h after injection of normal rabbit serum. In contrast, serum TSH was significantly decreased after the administration of TRH-Ab in all normal (basal, 41±8 μU/ml [mean±SE]; 30 min, 6±2; 45 min, 8±3; 75 min, 4±2); thyroidectomized (basal, 642±32 μU/ml; 30 min, 418±32; 60 min, 426±36; 120 min, 516±146); coldstressed (basal, 68±19 μU/ml; 30 min, 4±3; 180 min, 16±8); and proestrus (basal, 11 a.m., 57±10 μU/ml; 1 p.m., 20±3; 3 p.m., 13±4; 5 p.m., 19±3) rats. However, 0.1 ml of TRH-Ab had no effect on basal Prl concentrations in normal or thyroidectomized rats and did not prevent the Prl rise in rats exposed to cold (basal, 68±7 ng/ml; 15 min, 387±121; 30 min, 212±132; 60 min, 154±114), or the Prl surge observed on the afternoon of proestrus (basal 11 a.m., 23±2 ng/ml; 1 p.m., 189±55; 3 p.m., 1,490±260; 5 p.m., 1,570±286). These studies demonstrate that TRH is required for TSH secretion in the normal, cold-exposed and proestrus rat and contributes, at least in part, to TSH secretion in the hypothyroid rat, but is not required for Prl secretion in these states. PMID:413840

  10. Effects of forced swimming stress on thyroid function, pituitary thyroid-stimulating hormone and hypothalamus thyrotropin releasing hormone expression in adrenalectomy Wistar rats

    PubMed Central

    Sun, Qiuyan; Liu, Aihua; Ma, Yanan; Wang, Anyi; Guo, Xinhong; Teng, Weiping; Jiang, Yaqiu

    2016-01-01

    In order to study the impact that is imposed on the hypothalamic-pituitary-thyroid (HPT) axis of adrenalectomy male Wistar rats by stress caused by swimming, the blood level of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH), the expression of TSHβ mRNA at the pituitary and thyrotropin releasing hormone (TRH) expression at the paraventricular nucleus (PVN) were measured. A total of 50 male Wistar rats of 6–8 weeks of age and with an average weight of 190–210 grams were randomly divided into the following two groups: The surgical (without adrenal glands) and non-surgical (adrenalectomy) group. These two groups were then divided into the following five groups, according to the time delay of sacrifice following forced swim (10 min, 2 h, 12 h and 24 h) and control (not subjected to swimming) groups. A bilateral adrenalectomy animal model was established. Serum TSH in the blood was measurement by chemiluminescent immunoassay, and cerebrum tissue were excised for the measurement of TRH expression using an immunohistochemistry assay. In addition, pituitaries were excised for the extraction of total RNA. Finally, reverse transcription-quantitative polymerase chain reaction was performed for quantitation of TSHβ. Following swimming, the serum T3, T4 and TSH, the TSHβ mRNA expression levels in the pituitary and the TRH expression in the PVN of the surgical group were gradually increased. In the non-surgical group, no significant differences were observed in the serum T3, T4 and TSH levels compared with the control group. The TSHβ mRNA expression at the pituitary showed a similar result. Furthermore, the TRH expression at PVN was gradually increased and stress from swimming could increase the blood T4, T3 and TSH levels, TSHβ mRNA expression at the pituitary and TRH expression at the PVN in adrenalectomy Wistar rats. Moreover, the index in the surgical group changed significantly compared with the non-surgical group. In conclusion, the

  11. Thyroid hormones and thyroid-stimulating hormone in Egyptian patients with systemic lupus erythematosus: correlation between secondary hypothyroidism and neuropsychiatric systemic lupus erythematosus syndromes.

    PubMed

    Shahin, A A; Mostafa, H; Mahmoud, S

    2002-12-01

    Abstract The purpose of this study was to determine the serum levels of thyroid hormones and thyroid-stimulating hormone (TSH), in addition to antithyroglobulin and antimicrosomal antibodies and to investigate the correlation between these hormones and various disease manifestations among Egyptian patients with systemic lupus erythematosus (SLE). A group of 45 patients with SLE (43 women and 2 men with a mean age of 27.57 ± 9.89 years) underment assessment of their thyroid hormones. Antithyroglobulin and antimicrosomal antibodies were assessed in 27 patients. Various disease manifestations were evaluated. A group of 20 normal female volunteers were involved as controls. The mean serum free triiodothyronine (FT3) levels in all patients were significantly lower than in controls (1.89 ± 1.14 vs. 3.15 ± 0.93 pg/ml; P < 0.05). Patients with a history of intravenous pulsed cyclophosphamide therapy showed significantly decreased levels of FT3 compared to those in other patients (1.17 ± 0.5 vs. 2.05 ± 0.95 pg/ml; P = 0.04). The mean serum free thyroxine (FT4) levels in all patients were significantly less than in the control group (1.24 ± 1.22 vs. 1.4 ± 0.3 mg/dl; P < 0.001). Of the 45 patients, 2 (4.4%) were considered to have primary hypothyroidism. Five of six patients (83.3%) with decreased FT4 levels developed fibromyalgia compared to 7 of 39 (17.9%) patients with normal T4 (P = 0.003). The mean serum TSH levels in all patients were significantly higher than in the controls (4.82 ± 22.2 vs. 2.65 ± 1.18 μIU/ml; P < 0.001). Six patients with decreased TSH levels were considered to have secondary hypothyroidism (13.3%); one of them showed decreased T3 and T4, two had decreased T4 only, and the other three were euthyroid. Comparing patients with and without secondary hypothyroidism, showed acute confusion in four (66.7%) in the former group versus four (10.3%) in the latter group (P = 0.006), anxiety in four (66.7%) in the former group versus six (15

  12. Antenatal management of recurrent fetal goitrous hyperthyroidism associated with fetal cardiac failure in a pregnant woman with persistent high levels of thyroid-stimulating hormone receptor antibody after ablative therapy.

    PubMed

    Matsumoto, Tadashi; Miyakoshi, Kei; Saisho, Yoshifumi; Ishii, Tomohiro; Ikenoue, Satoru; Kasuga, Yoshifumi; Kadohira, Ikuko; Sato, Seiji; Momotani, Naoko; Minegishi, Kazuhiro; Yoshimura, Yasunori

    2013-01-01

    High titer of maternal thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease could cause fetal hyperthyroidism during pregnancy. Clinical features of fetal hyperthyroidism include tachycardia, goiter, growth restriction, advanced bone maturation, cardiomegaly, and fetal death. The recognition and treatment of fetal hyperthyroidism are believed to be important to optimize growth and intellectual development in affected fetuses. We herein report a case of fetal treatment in two successive siblings showing in utero hyperthyroid status in a woman with a history of ablative treatment for Graves' disease. The fetuses were considered in hyperthyroid status based on high levels of maternal TRAb, a goiter, and persistent tachycardia. In particular, cardiac failure was observed in the second fetus. With intrauterine treatment using potassium iodine and propylthiouracil, fetal cardiac function improved. A high level of TRAb was detected in the both neonates. To the best of our knowledge, this is the first report on the changes of fetal cardiac function in response to fetal treatment in two siblings showing in utero hyperthyroid status. This case report illustrates the impact of prenatal medication via the maternal circulation for fetal hyperthyroidism and cardiac failure.

  13. Enhanced response to mouse thyroid-stimulating hormone (TSH) receptor immunization in TSH receptor-knockout mice.

    PubMed

    Nakahara, Mami; Mitsutake, Norisato; Sakamoto, Hikaru; Chen, Chun-Rong; Rapoport, Basil; McLachlan, Sandra M; Nagayama, Yuji

    2010-08-01

    Graves-like hyperthyroidism is induced in BALB/c mice by immunization with adenovirus expressing the human TSH receptor (TSHR) A-subunit (amino acids 1-289). However, because of nonidentity between the human and mouse TSHR ( approximately 87% amino acid homology), we compared the responses of mice immunized with adenoviruses expressing either the mouse or the human TSHR A-subunit. Wild-type (wt) BALB/c mice immunized with the mouse A-subunit developed neither TSHR antibodies (measured by flow cytometry) nor thyroid lymphocytic infiltration. However, wt C57BL/6 mice developed sparse intrathyroidal lymphocyte infiltration without antibody production. Depletion of naturally occurring regulatory CD4(+)CD25(+) T cells had little effect. These results indicate the inability to break tolerance to the mouse TSHR in wt mice. In contrast, TSHR knockout (KO) BALB/c mice generated mouse TSHR antibodies in response to mouse A-subunit immunization and augmented human TSHR antibody response to human A-subunit immunization. Thyroid-stimulating antibody titers measured in a functional bioassay were comparable in human A-subunit immunized wt mice and in TSHR KO mice immunized with either the mouse or human A-subunit. In conclusion, immune response to the mouse TSHR is readily induced in TSHR KO but not in wt mice. Only in the former does immunization with adenovirus expressing the mouse A-subunit generate antibodies capable of activating the mouse TSHR. TSHR KO mice are, therefore, of value for future studies dissecting the autoimmune response to the mouse TSHR.

  14. Thyroid-stimulating hormone stimulates increases in inositol phosphates as well as cyclic AMP in the FRTL-5 rat thyroid cell line.

    PubMed Central

    Field, J B; Ealey, P A; Marshall, N J; Cockcroft, S

    1987-01-01

    Studies were conducted to determine whether thyroid-stimulating hormone (TSH; thyrotropin), a hormone known to increase cytosol concentrations of cyclic AMP, also stimulates the formation of inositol phosphates in thyroid cells. TSH and noradrenaline both stimulated [3H]inositol phosphate formation in a concentration-dependent manner in the rat thyroid cell line, FRTL-5 cells, which had been prelabelled with [3H]inositol. The threshold concentration of TSH required to stimulate inositol phosphate formation was more than 20 munits/ml, which is approx. 10(3)-fold greater than that required for cyclic AMP accumulation and growth in these cells. We also demonstrate that membranes prepared from FRTL-5 cells possess a guanine nucleotide-activatable polyphosphoinositide phosphodiesterase, which suggests that activation of inositide metabolism in these cells may be coupled to receptors by the G-protein, Gp. Our findings suggest that two second-messenger systems exist to mediate the action of TSH in the thyroid. PMID:2827631

  15. Effect of subcutaneous injection of a long-acting analogue of somatostatin (SMS 201-995) on plasma thyroid-stimulating hormone in normal human subjects

    SciTech Connect

    Itoh, S.; Tanaka, K.; Kumagae, M.; Takeda, F.; Morio, K.; Kogure, M.; Hasegawa, M.; Horiuchi, T.; Watabe, T.; Miyabe, S.

    1988-01-01

    SMS 201-995 (SMS), a synthetic analogue of somatostatin (SRIF) has been shown to be effective in the treatment of the hypersecretion of hormones such as in acromegaly. However, little is known about the effects of SMS on the secretion of thyroid-stimulating hormone (TSH) in normal subjects. In this study, plasma TSH was determined with a highly sensitive immunoradiometric assay, in addition to the concentration of SMS in plasma and urine with a radioimmunoassay, following subcutaneous injection of 25, 50, 100 ..mu..g of SMS or a placebo to normal male subjects, at 0900 h after an overnight fast. The plasma concentrations of SMS were dose-responsive and the peak levels were 1.61 +/- 0.09, 4.91 +/- 0.30 and 8.52 +/- 1.18 ng/ml, which were observed at 30, 15 and 45 min after the injection of 25, 50, and 100 ..mu..g of SMS, respectively. Mean plasma disappearance half-time of SMS was estimated to be 110 +/- 3 min. Plasma TSH was suppressed in a dose dependent manner and the suppression lasted for at least 8 hours. At 8 hours after the injection of 25, 50, and 100 ..mu..g of SMS, the plasma TSH levels were 43.8 +/- 19.4, 33.9 +/- 9.4 and 24.9 +/- 3.2%, respectively, of the basal values.

  16. Radioactive body burden measurements in (131)iodine therapy for differentiated thyroid cancer: effect of recombinant thyroid stimulating hormone in whole body (131)iodine clearance.

    PubMed

    Ravichandran, Ramamoorthy; Al Saadi, Amal; Al Balushi, Naima

    2014-01-01

    Protocols in the management of differentiated thyroid cancer, recommend adequate thyroid stimulating hormone (TSH) stimulation for radioactive (131)I administrations, both for imaging and subsequent ablations. Commonly followed method is to achieve this by endogenous TSH stimulation by withdrawal of thyroxine. Numerous studies worldwide have reported comparable results with recombinant human thyroid stimulating hormone (rhTSH) intervention as conventional thyroxine hormone withdrawal. Radiation safety applications call for the need to understand radioactive (131)I (RA(131)I) clearance pattern to estimate whole body doses when this new methodology is used in our institution. A study of radiation body burden estimation was undertaken in two groups of patients treated with RA(131)I; (a) one group of patients having thyroxine medication suspended for 5 weeks prior to therapy and (b) in the other group retaining thyroxine support with two rhTSH injections prior to therapy with RA(131)I. Sequential exposure rates at 1 m in the air were measured in these patients using a digital auto-ranging beta gamma survey instrument calibrated for measurement of exposure rates. The mean measured exposure rates at 1 m in μSv/h immediately after administration and at 24 h intervals until 3 days are used for calculating of effective ½ time of clearance of administered activity in both groups of patients, 81 patients in conventionally treated group (stop thyroxine) and 22 patients with rhTSH administration. The (131)I activities ranged from 2.6 to 7.9 GBq. The mean administered (131)I activities were 4.24 ± 0.95 GBq (n = 81) in "stop hormone" group and 5.11 ± 1.40 GBq (n = 22) in rhTSH group. The fall of radioactive body burden showed two clearance patterns within observed 72 h. Calculated T½eff values were 16.45 h (stop hormone group) 12.35 h (rhTSH group) for elapsed period of 48 h. Beyond 48 h post administration, clearance of RA(131)I takes place with T½eff> 20 h in both groups

  17. An electrochemiluminescence immunosensor for thyroid stimulating hormone based on polyamidoamine-norfloxacin functionalized Pd-Au core-shell hexoctahedrons as signal enhancers.

    PubMed

    Liu, Yuting; Zhang, Qiqi; Wang, Haijun; Yuan, Yali; Chai, Yaqin; Yuan, Ruo

    2015-09-15

    In this work, a novel polyamidoamine-norfloxacin (PAMAM-NFLX) complex and core-shell Pd-Au hexoctahedrons (Pd@Au HOHs) as enhancers are employed for development of a sensitive sandwich-type electrochemiluminescence (ECL) immunosensor to detect thyroid stimulating hormone (TSH). Here, norfloxacin (NFLX) is decorated abundantly on the surface of polyamidoamine (PAMAM) dendrimer via amide linkage to form PAMAM-NFLX complex. Thus, the resultant PAMAM-NFLX can serve as a novel co-reactant to efficiently amplify the ECL signal of peroxydisulfate-oxygen (S2O8(2-)-O2) system. Pd@Au HOHs were used as nano-carriers to assemble detection antibody (Ab2) and the PAMAM-NFLX complex. Besides, it can further enhance the ECL signal by promoting the generation of intermediate free radical HO(•) during the ECL reaction of S2O8(2-)-O2 system. The proposed immunosensor shows high sensitivity and specificity, and responds linearly to the concentration of TSH from 0.05 to 20 μIU mL(-1) with a low detection limit of 0.02 μIU mL(-1) (S/N=3). Moreover, the immunosensor successfully achieves the detection of TSH in practical human blood serum with desirable results. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. The upper limit of the reference range for thyroid-stimulating hormone should not be confused with a cut-off to define subclinical hypothyroidism.

    PubMed

    Waise, Ahmed; Price, Hermione C

    2009-03-01

    The upper limit of the reference range for serum thyroid-stimulating hormone (TSH) is used to assist in identifying individuals with hypothyroidism. Improvements in TSH assays have led to better definition of the lower limit of the reference range, but the upper limit of the range for a healthy population is currently a topic of some debate. Population studies have improved our understanding of the clinical implications of elevated serum TSH concentrations in terms of future progression to hypothyroidism, but have not yet fully elucidated the correlation of modestly elevated TSH levels with long-term morbidity. This paper will review the current debate including the arguments for and against reducing the upper limit of the TSH range, whether such a level should be based on evidence from epidemiological studies, and the implications of categorizing large numbers of people with subclinical hypothyroidism. The impact of using different methodologies for the measurement of TSH and the inherent variability of results on reference ranges is also discussed. We argue that the reference range for TSH should be assay-specific and be determined by standard techniques in normal populations as recommended by the National Academy of Clinical Biochemistry. In contrast, we suggest that a decision level be determined separately from epidemiological studies to identify a population with subclinical hypothyroidism. Serial monitoring of TSH in this population deserves further study as a means of identifying those at risk of progressing to frank hypothyroidism and meriting treatment.

  19. An innovative sample-to-answer polymer lab-on-a-chip with on-chip reservoirs for the POCT of thyroid stimulating hormone (TSH).

    PubMed

    Jung, Wooseok; Han, Jungyoup; Kai, Junhai; Lim, Ji-Youn; Sul, Donggeun; Ahn, Chong H

    2013-12-07

    A new sample-to-answer polymer lab-on-a-chip, which can perform immunoassay with minimum user intervention through on-chip reservoirs for reagents and single-channel assay system, has been designed, developed and successfully characterized as a point-of-care testing (POCT) cartridge for the detection of thyroid stimulating hormone (TSH). Test results were obtained within 30 minutes after a sample was dropped into the POCT cartridge. The analyzed results of TSH showed a linear range of up to 55 μIU mL(-1) with the limit of detection (LOD) of 1.9 μIU mL(-1) at the signal-to-noise ratio (SNR) of 3. The reagents stored in the on-chip reservoirs maintained more than 97% of their initial volume for 120 days of storage time while the detection antibody retained its activity above 98% for 120 days. The sample-to-answer polymer lab-on-a-chip developed in this work using the mass-producible and low-cost polymer is well suited for the point-of-care testing of rapid in vitro diagnostics (IVD) of TSH.

  20. Stimulation of Cultured H9 Human Embryonic Stem Cells with Thyroid Stimulating Hormone Does Not Lead to Formation of Thyroid-Like Cells

    PubMed Central

    Onyshchenko, Mykola I.; Panyutin, Igor G.; Panyutin, Irina V.; Neumann, Ronald D.

    2012-01-01

    The sodium-iodine symporter (NIS) is expressed on the cell membrane of many thyroid cancer cells, and is responsible for the radioactive iodine accumulation. However, treatment of anaplastic thyroid cancer is ineffective due to the low expression of NIS on cell membranes of these tumor cells. Human embryonic stem cells (ESCs) provide a potential vehicle to study the mechanisms of NIS expression regulation during differentiation. Human ESCs were maintained on feeder-independent culture conditions. RT-qPCR and immunocytochemistry were used to study differentiation marker expression, 125I uptake to study NIS function. We designed a two-step protocol for human ESC differentiation into thyroid-like cells, as was previously done for mouse embryonic stem cells. First, we obtained definitive endoderm from human ESCs. Second, we directed differentiation of definitive endoderm cells into thyroid-like cells using various factors, with thyroid stimulating hormone (TSH) as the main differentiating factor. Expression of pluripotency, endoderm and thyroid markers and 125I uptake were monitored throughout the differentiation steps. These approaches did not result in efficient induction of thyroid-like cells. We conclude that differentiation of human ESCs into thyroid cells cannot be induced by TSH media supplementation alone and most likely involves complicated developmental patterns that are yet to be understood. PMID:22619683

  1. Induction of T(4) UDP-GT activity, serum thyroid stimulating hormone, and thyroid follicular cell proliferation in mice treated with microsomal enzyme inducers.

    PubMed

    Hood, Alan; Allen, Marcia L; Liu, YaPing; Liu, Jie; Klaassen, Curtis D

    2003-04-01

    The microsomal enzyme inducers phenobarbital (PB), pregnenolone-16 alpha-carbonitrile (PCN), 3-methylcholanthrene (3MC), and Aroclor 1254 (PCB) are known to induce thyroxine (T(4)) glucuronidation and reduce serum T(4) concentrations in rats. Also, microsomal enzyme inducers that increase serum TSH (i.e., PB and PCN) also increase thyroid follicular cell proliferation in rats. Little is known about the effects of these microsomal enzyme inducers on T(4) glucuronidation, serum thyroid hormone concentrations, serum TSH, and thyroid gland growth in mice. Therefore, we tested the hypothesis that microsomal enzyme inducers induce T(4) UDP-GT activity, resulting in reduced serum T(4) concentrations, as well as increased serum TSH and thyroid follicular cell proliferation in mice. B6C3F male mice were fed a control diet or a diet containing PB (600, 1200, 1800, or 2400 ppm), PCN (250, 500, 1000, or 2000 ppm), 3MC (62.5, 125, 250, or 500 ppm), or PCB (10, 30, 100, or 300 ppm) for 21 days. All four inducers increased liver weight and hepatic microsomal UDP-GT activity toward chloramphenicol, alpha-naphthol, and T(4). PB and PCB decreased serum total T(4), but PCN and 3MC did not. Serum thyroid stimulating hormone was markedly increased by PCN and 3MC treatments, and slightly increased by PB and PCB treatments. All four microsomal enzyme inducers dramatically increased thyroid follicular cell proliferation in mice. The findings suggest that PB, PCN, 3MC, and PCB disrupt thyroid hormone homeostasis in mice.

  2. The Direct Cooling of the Preoptic-Hypothalamic Area Elicits the Release of Thyroid Stimulating Hormone during Wakefulness but Not during REM Sleep

    PubMed Central

    Cerri, Matteo; Tupone, Domenico; Mastrotto, Marco; Perez, Emanuele; Zamboni, Giovanni; Amici, Roberto

    2014-01-01

    Thermoregulatory responses to temperature changes are not operant during REM sleep (REMS), but fully operant in non-REM sleep and wakefulness. The specificity of the relationship between REMS and the impairment of thermoregulation was tested by eliciting the reflex release of Thyrotropin Releasing Hormone (TRH), which is integrated at hypothalamic level. By inducing the sequential secretion of Thyroid Stimulating Hormone (TSH) and Thyroid Hormone, TRH intervenes in the regulation of obligatory and non-shivering thermogenesis. Experiments were performed on male albino rats implanted with epidural electrodes for EEG recording and 2 silver-copper wire thermodes, bilaterally placed in the preoptic-hypothalamic area (POA) and connected to small thermoelectric heat pumps driven by a low-voltage high current DC power supply. In preliminary experiments, a thermistor was added in order to measure hypothalamic temperature. The activation of TRH hypophysiotropic neurons by the thermode cooling of POA was indirectly assessed, in conditions in which thermoregulation was either fully operant (wakefulness) or not operant (REMS), by a radioimmunoassay determination of plasmatic levels of TSH. Different POA cooling were performed for 120 s or 40 s at current intensities of 80 mA and 125 mA, respectively. At both current intensities, POA cooling elicited, with respect to control values (no cooling current), a significant increase in plasmatic TSH levels in wakefulness, but not during REMS. These results confirm the inactivation of POA thermal sensitivity during REMS and show, for the first time, that this inactivation concerns also the fundamental endocrine control of non-shivering thermogenesis. PMID:24498374

  3. Serum leptin, thyroxine and thyroid-stimulating hormone levels interact to affect cognitive function among US adults: evidence from a large representative survey.

    PubMed

    Beydoun, May A; Beydoun, Hind A; Shroff, Monal R; Kitner-Triolo, Melissa H; Zonderman, Alan B

    2012-08-01

    Neuroanatomical connections point to possible interactions between areas influencing energy homeostasis and those influencing cognition. We assessed whether serum leptin, thyroxine, and thyroid stimulating hormone (TSH) levels are associated with and interact to influence cognitive performance among US adults. Data from the National Health and Nutrition Examination Survey III (1988-1994) were used. Measures included a battery of neuropsychological tests and serum leptin, thyroxine, and TSH levels (20-59-year-old: n = 1114-2665; 60-90-year-old: n = 1365-5519). Among those 20-59-year-old, the middle tertile of leptin (vs. first tertile) was inversely related to the number of errors on the symbol digits substitution test. Increased thyroxine level was associated with a poorer performance on the serial digits test in the 20-59-year-old, but a better performance on the math test in 60-90-year-old group. TSH was associated with poor performance on various tests in the 20-59-year-old, but better performance in the 60-90-year-old group. Significant antagonistic interactions were found in both age groups between thyroxine, TSH, and leptin for a number of tests, including between leptin and thyroxine in the 60-90-year-old group in their association with word recall-correct score. We found significant associations of our main exposures with cognitive function among US adults, going in opposite directions between age groups in the cases of thyroid hormonal levels, as well as some interactive effects between exposures. It is important to conduct prospective cohort studies to provide further insight into potential interventions that would assess interactive effects of various hormonal replacement regimens.

  4. Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer treatment in Spanish hospitals.

    PubMed

    Vallejo, J A; Muros, M A

    2017-05-20

    In thyroid cancer treatment, the thyroid-stimulating hormone (TSH) must be elevated before radioiodine ablation, either by exogenous (with recombinant human thyrotropin [rhTSH]) or endogenous stimulation by thyroid hormone withdrawal (THW). The use of rhTSH avoids hypothyroidism and favours the subsequent elimination of radioiodine, but involves the cost of the product. For this reason, a cost-effectiveness analysis was performed, taking into account all costs involved and the benefits associated with the use of this therapy. Using a Markov modelling with two analysis arms (rhTSH and THW), stratified into high (100mCi/3700 MBq) and low (30mCi/1110 MBq) radioiodine doses, and using 17 weekly cycles, the incremental cost per quality-adjusted life-year (QALY) related to the use of rhTSH was determined. The clinical inputs included in the model were based on published studies and in a treatment survey conducted in Spain. Radioablation preparation with rhTSH is superior to THW, showing additional benefits (0.048 AVAC), as well as cost savings (-€614.16), with an incremental cost-effectiveness rate (ICER) of -€12,795/QALY. The univariate and multivariate sensitivity analyses showed the result to be robust. The use of rhTSH previous to radioablation in Spain has cost savings, as well as a series of health benefits for the patient, making it highly cost-effective. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  5. Adequate thyroid-stimulating hormone levels after levothyroxine discontinuation in the follow-up of patients with well-differentiated thyroid carcinoma.

    PubMed

    Sánchez, Reyna; Espinosa-de-los-Monteros, Ana Laura; Mendoza, Victoria; Brea, Eduardo; Hernández, Irma; Sosa, Ernesto; Mercado, Moisés

    2002-01-01

    In the follow-up of patients with well-differentiated thyroid carcinomas (WTC), a thyroid-stimulating hormone (TSH) >or=30 micro U/mL is generally accepted as adequate to perform whole body scans (WBS), determine thyroglobulin (Tg), and administer radioiodine therapeutically. These patients, inevitably rendered hypothyroid, are traditionally switched to T3 for 3-4 weeks prior to withdrawing all thyroid hormones for an additional 2-3 weeks. Neither TSH and Tg elevation dynamics nor WBS characteristics after simply interrupting L-T4 treatment without T3 administration have been evaluated. TSH, total T4 and T3, as well as FT4 were measured weekly after discontinuing L-T4 in 21 subjects (group I) and after thyroidectomy in 10 subjects (group II). WBS and Tg determination was performed upon achievement of TSH >or=30 micro U/mL. By the second week, 42% of group I patients and 70% of group II patients had TSH >or=30 micro U/mL. By the third week, 90% in group I and 100% in group II had achieved this target. Group I patients who needed 4 weeks to increase TSH received a greater cumulative radioiodine dose and had higher Tg levels. Positive WBS were found in eight cases and the incidence of a negative WBS with elevated Tg was significantly higher when evaluation occurred at the second week of L-T4 withdrawal compared to the fourth week. L-T4 interruption is a reasonable alternative to temporary T3 in preparation for radioiodine scanning and treatment.

  6. Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), are located less than 310 kb apart in both human and mouse genomes.

    PubMed

    Dracopoli, N C; Rose, E; Whitfield, G K; Guidon, P T; Bale, S J; Chance, P A; Kourides, I A; Housman, D E

    1988-08-01

    Two thyroid hormone regulated genes, the beta-subunits of nerve growth factor (NGFB) and thyroid stimulating hormone (TSHB), have been assigned to mouse chromosome 3 and human chromosome 1p22. We have used the techniques of linkage analysis and pulsed field gel electrophoresis to determine the proximity of these two antithetically regulated genes in this conserved linkage group. Four novel restriction fragment length polymorphisms were identified at the human TSHB gene. Two-point linkage analysis between TSHB and NGFB in 46 families, including the Centre d'Etude du Polymorphisme Humain (CEPH) reference panel, demonstrated no recombination (theta = 0.00, Z = 42.8). Analysis of this region by pulsed field gel electrophoresis showed that the genes for TSHB and NGFB are located less than 310 kb apart in man and 220 kb in the mouse.

  7. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure

    PubMed Central

    Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K.; Bechmann, Lars P.; Gerken, Guido; Moeller, Lars C.; Canbay, Ali

    2015-01-01

    Introduction Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. Methods 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. Results More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. Conclusions In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity. PMID:26147961

  8. Higher Thyroid-Stimulating Hormone, Triiodothyronine and Thyroxine Values Are Associated with Better Outcome in Acute Liver Failure.

    PubMed

    Anastasiou, Olympia; Sydor, Svenja; Sowa, Jan-Peter; Manka, Paul; Katsounas, Antonios; Syn, Wing-Kin; Führer, Dagmar; Gieseler, Robert K; Bechmann, Lars P; Gerken, Guido; Moeller, Lars C; Canbay, Ali

    2015-01-01

    Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF. 84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined. More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression. In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.

  9. Effect of metformin on thyroid stimulating hormone and thyroid volume in patients with prediabetes: A randomized placebo-controlled clinical trial

    PubMed Central

    Karimifar, Mozhgan; Aminorroaya, Ashraf; Amini, Masoud; Mirfendereski, Taghi; Iraj, Bijan; Feizi, Awat; Norozi, Atsa

    2014-01-01

    Background: The people with prediabetes have insulin resistance (IR). IR may affect thyroid function, size and nodules. We investigated the effects of metformin on the thyroid gland in prediabetic people. Materials and Methods: In a randomized, double-blind placebo-control clinical trial, 89 people with prediabetes, aged 18-65 years were studied for 3 months. They were divided into two, metformin (n = 43) and placebo (n = 46) treated groups. Serum thyroid stimulating hormone (TSH) was measured and thyroid nodules and volume was studied by ultrasonography. The data were compared between and within groups, before and after the study. Results: Mean of the baseline characteristics in metformin and placebo-treated groups had no statistically significant difference. At the end of the study, serum TSH was not significantly different between the two groups. However, if the TSH range was divided into two low normal (0.3-2.5 μU/ml) and high-normal (2.6-5.5 μU/ml) ranges, significant decrease was observed in metformin-treated group with a high-normal basal serum TSH (P = 0.01). Thyroid volume did not change in metformin-treated group. However, in placebo-treated group, the thyroid was enlarged (P = 0.03). In 53.9% of participants, thyroid nodule was observed. There was just a decrease in the volume of small solid (not mixed) nodules from median of 0.07 ml to 0.04 ml in metformin-treated group (P = 0.01). Conclusion: In prediabetic people, metformin decreases serum TSH, only, in those people with TSH >2.5 μU/ml and reduces the size of small solid thyroid nodules. It also prevents an increase in the thyroid volume. PMID:25657744

  10. Long noncoding RNA PVT1 modulates thyroid cancer cell proliferation by recruiting EZH2 and regulating thyroid-stimulating hormone receptor (TSHR).

    PubMed

    Zhou, Qinyi; Chen, Jun; Feng, Jialin; Wang, Jiadong

    2016-03-01

    The purposes of this study were to investigate the potential roles of long noncoding RNA (lncRNA) PVT1 in thyroid cancer cell proliferation and to explore their possible mechanisms. A total of 84 patients who were diagnosed as having thyroid cancer (papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), and anaplastic thyroid carcinoma (ATC)) in Renji Hospital were enrolled in this study. Expressions of lncRNA PVT1 in thyroid cancer tissues and cell lines (IHH-4, FTC-133, and 8505C) were analyzed using RT-polymerase chain reaction (PCR) and western blotting analysis. The effects of lncRNA PVT1 expression on thyroid cancer cell proliferation and cell cycle were analyzed using flow cytometry. Furthermore, the effects of lncRNA expression on thyroid-stimulating hormone receptor (TSHR) expression and polycomb enhancer of zeste homolog 2 (EZH2) were also analyzed using RNA immunoprecipitation (RIP) assay and chromatin immunoprecipitation (ChIP) assay, respectively. Compared to the controls, lncRNA PVT1 was significantly up-regulated in thyroid tissues, as well as in three kinds of tumor cell lines (P < 0.05). Silenced PVT1 significantly inhibited thyroid cell line IHH-4, FTC-133, and 8505C cell proliferation and arrested cell cycle at G0/G1 stage and significantly decreased cyclin D1 and TSHR expressions (P < 0.05). Moreover, lncRNA PVT1 could be enriched by EZH2, and silencing PVT1 resulted in the decreased recruitment of EZH2. This study suggested that lncRNA PVT1 may contribute to tumorigenesis of thyroid cancer through recruiting EZH2 and regulating TSHR expression.

  11. Temporal trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (ATPO) testing across two phases of iodine fortification in Tasmania (1995-2013).

    PubMed

    Hong, A; Stokes, B; Otahal, P; Owens, D; Burgess, J R

    2017-10-01

    Tasmania is an island state of the Australian Commonwealth with a well-documented history of mild iodine deficiency. Between 2001 and 2009, Tasmania experienced two incremental phases of iodine fortification. To examine trends in thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (ATPO) testing and their relationship to different phases of iodine nutrition in the Tasmanian population between 1995 and 2013. Retrospective longitudinal study. The major primary care and largest public hospital pathology providers in Tasmania submitted data for all TSH and ATPO tests performed between 1995 and 2013. Data linkage methodology was used to determine trends in TSH and ATPO testing. A total of 1.66 million TSH assessments, involving 389,910 individual patients, were performed in Tasmania between 1995 and 2013. There was approximately a fourfold increase in the overall rate of TSH testing during this period with the rate of incident TSH assessment remaining relatively stable over the study period. The incidence of overt suppression and elevation of TSH (TSH≤0.1 mIU/L and ≥10 mIU/L) declined 62.3% and 59.7%, respectively, with a trend for increased incidence of borderline TSH elevation ≥4.0 mIU/L. The incidence of thyroid autoimmunity as determined by the proportion of abnormal ATPO results remained stable, with the absolute number of positive test results increasing during the study period. Iodine supplementation of this mildly iodine-deficient population was not associated with an obvious increase in incidence of overt thyroid dysfunction or autoimmunity. Whilst the volume of TSH testing increased over the study period, the increase was driven by patients undergoing follow-up TSH assessments. © 2017 John Wiley & Sons Ltd.

  12. Serum thyroid-stimulating hormone levels are not associated with exercise capacity and lung function parameters in two population-based studies

    PubMed Central

    2014-01-01

    Background Thyroid dysfunction has been described to be linked to a variety of cardiovascular morbidities. Through this pathway thyroid function might also be associated with cardiorespiratory function and exercise capacity. So far only few patient-studies with small study populations investigated the association between thyroid dysfunction and exercise capacity. Thus, the aim of our study was to investigate the association of serum thyroid-stimulating hormone (TSH) levels with lung function and cardiopulmonary exercise testing (CPET) in the general population. Methods Data from the two independent cross-sectional population-based studies (Study of Health in Pomerania [SHIP] and SHIP-Trend-0) were pooled. SHIP was conducted between 2002 and 2006 and SHIP-Trend-0 between 2008 and 2012. Participants were randomly selected from population registries. In total, 4206 individuals with complete data were available for the present analysis. Thyroid function was defined based on serum TSH levels. Lung function was evaluated by forced expiratory volume in 1 s and forced vital capacity. CPET was based on symptom limited exercise tests on a bicycle in a sitting position according to a modified Jones protocol. Associations of serum TSH levels with lung function and CPET parameters were analysed by multivariable quantile regression adjusted for age, sex, height, weight, use of beta blockers, smoking status, and physical activity. Results Serum TSH levels, used as continuously distributed variable and categorized according to the clinical cut-offs 0.3 and 3.0 mIU/L or according to quintiles, were not consistently associated with parameters of lung function or CPET. Conclusions Our results suggest that thyroid dysfunction is not associated with lung function and cardiopulmonary exercise capacity in the general population. PMID:25182209

  13. Thyroid Stimulating Hormone Reference Range and Prevalence of Thyroid Dysfunction in the Korean Population: Korea National Health and Nutrition Examination Survey 2013 to 2015

    PubMed Central

    2017-01-01

    Background No nationwide epidemiological study evaluating the prevalence of subclinical and overt forms of hypothyroidism and hyperthyroidism has yet been conducted in Korea. This study aimed to evaluate the reference range of serum thyroid stimulating hormone (TSH) and the national prevalence of thyroid dysfunctions in Korea. Methods Nation-wide cross-sectional data were analyzed from a representative sample of the civilian, non-institutionalized Korean population (n=6,564) who underwent blood testing for thyroid function and anti-thyroid peroxidase antibody (TPOAb) as part of the Korea National Health and Nutrition Examination Survey VI (2013 to 2015). Results The reference interval of serum TSH in the Korean reference population was 0.62 to 6.68 mIU/L. Based on this reference interval, the prevalence of overt and subclinical hypothyroidism was 0.73% (males 0.40%, females 1.10%) and 3.10% (males 2.26%, females 4.04%), respectively. The prevalence of hypothyroidism increased with age until the age group between 50 to 59 years. Positive TPOAb were found in 7.30% of subjects (males 4.33%, females 10.62%). The prevalence of overt and subclinical hypothyroidism TPOAb-positive subjects was 5.16% and 10.88%, respectively. The prevalence of overt and subclinical hyperthyroidism was 0.54% (males 0.30%, females 0.81%) and 2.98% (males 2.43%, females, 3.59%), respectively. Conclusion The Serum TSH reference levels in the Korean population were higher than the corresponding levels in Western countries. Differences were found in the prevalence of hypothyroidism and hyperthyroidism according to age, sex, and TPOAb positivity. This study provides important baseline information for understanding patterns of thyroid dysfunction and diseases in Korea. PMID:28116874

  14. Clinical Evaluation of the Immune Colloidal Gold Method for Rapid Qualitative and Quantitative Measurement of Thyroid-Stimulating Hormone as an Assay for Hypothyroidism.

    PubMed

    Wang, Tingting; Sheng, Shiwei; Ruan, Meifang; Yan, Jing; Gu, Jianying; Jiang, Yumin; Gao, Yunchao; Lu, Hankui

    2016-11-01

    The immune colloidal gold (ICG) method of measuring thyroid-stimulating hormone (TSH) is a rapid and easy-to-perform test, allowing off-site measurements. This study compared the clinical utility of the first ICG-based qualitative and quantitative TSH test methods in China with the third-generation serum TSH assay used worldwide. Fingertip and venous blood was collected within 30 min from 283 patients initially suspected of hypothyroidism. TSH was measured in fingertip blood using ICG-based qualitative quantitative tests. Serum TSH in venous blood was tested using the third-generation serum TSH assay. Correlations between systems were tested by kappa or Spearman correlation coefficients. Compared with the third-generation serum TSH assay, the ICG-qualitative TSH test kit had a kappa coefficient of 0.86, a sensitivity of 85.00%, and a specificity of 99.38% in screening for hypothyroidism. The percentages of false negatives and false positives among all subjects were 6.38% and 0.35% respectively; the total consistency rate of the two methods was 93.26%. When compared with the third-generation serum TSH assay, the ICG-quantitative TSH analysis system had a Spearman correlation coefficient of 0.91, a sensitivity of 88.43%, and a specificity of 98.77%. The percentages of false negatives and false positives among all subjects were 4.95% and 0.71%, respectively; the total consistency rate of the two methods was 94.35%. Both ICG-based assays are easier and faster to perform than the third-generation, laboratory-based serum TSH assay method. The ICG-based methods showed acceptable performance in the simplified screening for hypothyroidism. ClinicalTrials.gov identifier, NCT01921452. Merck Serono Co., Ltd.

  15. Differential expression of thyroid-stimulating hormone beta subunit in gonads during sex reversal of orange-spotted and red-spotted groupers.

    PubMed

    Wang, Yang; Zhou, Li; Yao, Bo; Li, Chuang-Ju; Gui, Jian-Fang

    2004-05-31

    We have cloned and characterized the full-length cDNA encoding thyroid-stimulating hormone beta-subunit (TSHbeta) from orange-spotted grouper Epinephelus coioides. It contains 913 nucleotides with an open reading frame encoding 146 amino acids with a 20 amino acid signal peptide. The grouper mature TSHbeta has 75, 70, 61, 59, 41, 42 and 40% identities to that of rainbow trout, Atlantic salmon, zebrafish, European eel, chicken, mouse and human, respectively. RT-PCR analysis indicated that the TSHbeta mRNA was expressed abundantly not only in pituitary but also in gonads. A more interesting finding is to reveal the differential TSHbeta expressions between the ovaries and the transitional gonads or testes in natural individuals of orange-spotted grouper and red-spotted grouper Epinephelus akaara, and in artificial sex reversal individuals of red-spotted grouper induced by MT feeding. In situ hybridization localization provided direct evidence that the TSHbeta was transcribed in the germ cells. In the growing oocytes, the TSHbeta transcripts were concentrated on the ooplasm periphery. In testicular tissues, the intensively expressed TSHbeta cells were found to be spermatogonia and spermatocytes in the spermatogenic cysts. This is the first report of a TSHbeta expressed in the gonads of any vertebrates in addition to the expected expression in the pituitary, and it expresses more transcripts in the gonads during sex reversal or testis than in the ovaries both in E. coioides and E. akaara. Importantly, the TSHbeta identification in germ cells allows us to further investigate the functional roles and the molecular mechanisms in gametogenesis of groupers, especially in sex reversal and in spermatogenesis.

  16. Dominant negative effect of mutated thyroid stimulating hormone receptor (P556L) causes hypothyroidism in C.RF-Tshr(hyt/wild) mice.

    PubMed

    Endo, Toyoshi; Kobayashi, Tetsuro

    2012-01-01

    C.RF-Tshr(hyt/hyt) mice have a mutated thyroid stimulating hormone receptor (P556L-TSHR) and these mice develop severe hypothyroidism. We found that C.RF-Tshr(hyt/wild) heterozygous mice are also in a hypothyroid state. Thyroid glands from C.RF-Tshr(hyt/wild) mice are smaller than those from wild-type mice, and (125)I uptake activities of the former are significantly lower than those in the latter. When TSHR (TSHR(W)) and P556L-TSHR (TSHR(M)) cDNAs were cloned and co-transfected into HEK 293 cells, the cells retained (125)I-TSH binding activity, but cAMP response to TSH was decreased to about 20% of HEK 293 cells transfected with TSHR(W) cDNA. When TSHR(W) and TSHR(M) were tagged with eCFP or eYFP, we observed fluorescence resonance energy transfer (FRET) in HEK 293 cells expressing TSHR(W)-eCFP and TSHR(W)-eYFP in the absence of TSH, but not in the presence of TSH. In contrast, we obtained FRET in HEK 293 cells expressing TSHR(W)-eCFP and TSHR (M)-eYFP, regardless of the presence or absence of TSH. These results suggest that P556L TSHR has a dominant negative effect on TSHR(W) by impairing polymer to monomer dissociation, which decreases TSH responsiveness and induces hypothyroidism in C.RF-Tshr(hyt/wild) mice.

  17. Characterization of recombinant human and bovine thyroid-stimulating hormone preparations by mass spectrometry and determination of their endotoxin content

    PubMed Central

    2013-01-01

    Background The TSH stimulation test to confirm canine hypothyroidism is commonly performed using a recombinant human TSH (rhTSH), as up to date, canine TSH is not yet commercially available. Limiting factors for the use of rhTSH are its high costs and occasional difficulties in product availability. Less expensive bovine TSH preparations (bTSH) purified from bovine pituitary glands are readily commercially available. The aim of this study was to evaluate two different bTSH products as alternative to rhTSH using mass spectrometry. Results More than 50 proteins, including other pituitary hormones, bovine albumin, hemoglobin, and tissue proteins were identified in the bTSH preparations. In contrast, rhTSH proved to be a highly pure product. Significantly higher endotoxin levels could be detected in all bTSH products compared to the rhTSH. Conclusions Both bTSH products are crude mixtures and therefore not an acceptable alternative to rhTSH. Their use should be discouraged to prevent unintended side effects. PMID:23870652

  18. Characterization of recombinant human and bovine thyroid-stimulating hormone preparations by mass spectrometry and determination of their endotoxin content.

    PubMed

    Schaefer, Sandra; Hassa, Paul O; Sieber-Ruckstuhl, Nadja S; Piechotta, Marion; Reusch, Claudia E; Roschitzki, Bernd; Boretti, Felicitas S

    2013-07-16

    The TSH stimulation test to confirm canine hypothyroidism is commonly performed using a recombinant human TSH (rhTSH), as up to date, canine TSH is not yet commercially available. Limiting factors for the use of rhTSH are its high costs and occasional difficulties in product availability. Less expensive bovine TSH preparations (bTSH) purified from bovine pituitary glands are readily commercially available. The aim of this study was to evaluate two different bTSH products as alternative to rhTSH using mass spectrometry. More than 50 proteins, including other pituitary hormones, bovine albumin, hemoglobin, and tissue proteins were identified in the bTSH preparations. In contrast, rhTSH proved to be a highly pure product. Significantly higher endotoxin levels could be detected in all bTSH products compared to the rhTSH. Both bTSH products are crude mixtures and therefore not an acceptable alternative to rhTSH. Their use should be discouraged to prevent unintended side effects.

  19. Genetic Variants Associated with Serum Thyroid Stimulating Hormone (TSH) Levels in European Americans and African Americans from the eMERGE Network

    PubMed Central

    Malinowski, Jennifer R.; Denny, Joshua C.; Bielinski, Suzette J.; Basford, Melissa A.; Bradford, Yuki; Peissig, Peggy L.; Carrell, David; Crosslin, David R.; Pathak, Jyotishman; Rasmussen, Luke; Pacheco, Jennifer; Kho, Abel; Newton, Katherine M.; Li, Rongling; Kullo, Iftikhar J.; Chute, Christopher G.; Chisholm, Rex L.; Jarvik, Gail P.; Larson, Eric B.; McCarty, Catherine A.; Masys, Daniel R.; Roden, Dan M.; de Andrade, Mariza; Ritchie, Marylyn D.; Crawford, Dana C.

    2014-01-01

    Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10−17, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10−6, β = −0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = −0.09), VEGFA (rs11755845 p = 0.01, β = −0.13), and NFIA (rs334699 p = 1.50×10−3, β = −0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic

  20. Day-night variations in thyroid stimulating hormone and its relation with clinical status and metabolic parameters in patients with cirrhosis of the liver.

    PubMed

    Atalay, Roni; Ersoy, Reyhan; Demirezer, Aylin Bolat; Akın, Fatma Ebru; Polat, Sefika Burcak; Cakir, Bekir; Ersoy, Osman

    2015-04-01

    To investigate day-night variations in thyroid stimulating hormone (TSH) and its relation with clinical status and metabolic parameters in patients with cirrhosis. Forty-one patients with negative thyroid antibodies and normal thyroid function tests who were diagnosed with cirrhosis were included. Thirty-five age- and gender-matched healthy subjects were included in control group.TSH, fT3, and fT4 levels, which were measured both in the morning and late evening. The difference between nocturnal TSH and morning TSH (ΔTSH) were compared between groups. Relation between Child-Turcotte-Pugh, model for End-Stage Liver Disease (MELD) and MELD-Na scores and levels of thyroid hormones, ΔTSH and serum sodium (Na) levels was investigated. Relation between ΔTSH and clinical status and metabolic parameters was also evaluated. The mean morning fT3, nocturnal fT3, nocturnal TSH, and ΔTSH levels were significantly lower, morning and nocturnal fT4 levels were higher in patients with cirrhosis (p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001). As the ROC analysis, day-night variation was detected to be impaired in the event that difference between nocturnal TSH level and morning TSH level was lower than 1 uIU/mL in patients with cirrhosis with a sensitivity of 92.7% and specificity of 71.4% (p<0.001).A significant positive correlation was found between serum Na levels and fT3 in patients with cirrhosis (r=0.479, p=0.001), and a significant negative correlation was found between the severity of clinical status and low levels of fT3 in patients with cirrhosis (p<0.001).Nocturnal TSH increase does not occur in cases of cirrhosis without known thyroid disease and with normal thyroid function tests, which may be an early finding of impaired thyroid functions in patients with cirrhosis.

  1. Genetic variants associated with serum thyroid stimulating hormone (TSH) levels in European Americans and African Americans from the eMERGE Network.

    PubMed

    Malinowski, Jennifer R; Denny, Joshua C; Bielinski, Suzette J; Basford, Melissa A; Bradford, Yuki; Peissig, Peggy L; Carrell, David; Crosslin, David R; Pathak, Jyotishman; Rasmussen, Luke; Pacheco, Jennifer; Kho, Abel; Newton, Katherine M; Li, Rongling; Kullo, Iftikhar J; Chute, Christopher G; Chisholm, Rex L; Jarvik, Gail P; Larson, Eric B; McCarty, Catherine A; Masys, Daniel R; Roden, Dan M; de Andrade, Mariza; Ritchie, Marylyn D; Crawford, Dana C

    2014-01-01

    Thyroid stimulating hormone (TSH) hormone levels are normally tightly regulated within an individual; thus, relatively small variations may indicate thyroid disease. Genome-wide association studies (GWAS) have identified variants in PDE8B and FOXE1 that are associated with TSH levels. However, prior studies lacked racial/ethnic diversity, limiting the generalization of these findings to individuals of non-European ethnicities. The Electronic Medical Records and Genomics (eMERGE) Network is a collaboration across institutions with biobanks linked to electronic medical records (EMRs). The eMERGE Network uses EMR-derived phenotypes to perform GWAS in diverse populations for a variety of phenotypes. In this report, we identified serum TSH levels from 4,501 European American and 351 African American euthyroid individuals in the eMERGE Network with existing GWAS data. Tests of association were performed using linear regression and adjusted for age, sex, body mass index (BMI), and principal components, assuming an additive genetic model. Our results replicate the known association of PDE8B with serum TSH levels in European Americans (rs2046045 p = 1.85×10-17, β = 0.09). FOXE1 variants, associated with hypothyroidism, were not genome-wide significant (rs10759944: p = 1.08×10-6, β = -0.05). No SNPs reached genome-wide significance in African Americans. However, multiple known associations with TSH levels in European ancestry were nominally significant in African Americans, including PDE8B (rs2046045 p = 0.03, β = -0.09), VEGFA (rs11755845 p = 0.01, β = -0.13), and NFIA (rs334699 p = 1.50×10-3, β = -0.17). We found little evidence that SNPs previously associated with other thyroid-related disorders were associated with serum TSH levels in this study. These results support the previously reported association between PDE8B and serum TSH levels in European Americans and emphasize the need for additional genetic studies in more

  2. The effect of thyroid stimulating hormone suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma.

    PubMed

    Moon, Jae Hoon; Jung, Kyong Yeun; Kim, Kyoung Min; Choi, Sung Hee; Lim, Soo; Park, Young Joo; Park, Do Joon; Jang, Hak Chul

    2016-02-01

    Subclinical hyperthyroidism has been reported to increase the fracture risk. However, the effect of thyroid stimulating hormone (TSH) suppressive therapy on bone geometry in the hip area of patients with differentiated thyroid carcinoma (DTC) is still unclear. The aim of this study was to investigate the effect of TSH suppression on bone geometry in the hip area of pre- and postmenopausal women with DTC. We conducted a retrospective cohort study including 99 women with DTC (25 pre- and 74 postmenopausal) who had received TSH suppressive therapy for at least 3years and 297 control subjects (75 and 222, respectively) matched for sex and age. Bone mineral density (BMD) in the spine and hip area and bone geometry at the femoral neck measured by dual energy X-ray absorptiometry (DXA) were compared between patients and controls. The association between thyroid hormone and bone parameters was investigated. All analyses of bone parameters were adjusted for age, body mass index, and serum calcium levels. In premenopausal subjects, TSH suppressive therapy was not associated with poor bone parameters. In postmenopausal subjects, patients with DTC undergoing TSH suppression showed lower cross-sectional moment of inertia (CSMI), cross-sectional area, and section modulus and thinner cortical thickness at the femoral neck than those of control subjects, whereas their femoral neck BMD was comparable with controls. Total hip BMD was lower in postmenopausal patients than in controls. CSMI and section modulus at the femoral neck were independently associated with serum free T4 levels in postmenopausal patients. The difference in femoral neck bone geometry between patients and controls was only apparent in postmenopausal DTC patients with free T4 >1.79ng/dL (23.04pmol/l), and not in those with free T4 levels ≤1.79ng/dL (23.04pmol/l). TSH suppression in postmenopausal DTC patients was associated with decreased bone strength by altering bone geometry rather than BMD in the hip area

  3. Serum Thyroid-Stimulating Hormone and Anti-Thyroglobulin Antibody Are Independently Associated with Lesions in Spinal Cord in Central Nervous System Demyelinating Diseases

    PubMed Central

    Long, Youming; Zheng, Yangbo; Chen, Mengyu; Zhang, Bin; Gao, Cong; Shan, Fulan; Yang, Ning; Fan, Yongxiang

    2014-01-01

    Transverse myelitis (TM) is associated with neuromyelitis optica (NMO) and multiple sclerosis (MS). Early recognition of useful parameters may be helpful to distinguish their difference. This retrospective study analyzed thyroid parameters from 243 serum samples (relapse = 128; remission = 115) of 178 patients with demyelinating diseases (NMO, n = 25; TM, n = 48; MS, n = 105). The relationship between thyroid and clinical parameters was analyzed. Patients with NMO and TM had a higher frequency of abnormal thyroid-stimulating hormone (TSH), anti-thyroglobulin antibodies (TG-Ab), and antithyroid peroxidase antibody (TPO-Ab) than MS patients (p<0.05). The level of TSH and TG-Ab returned to normal levels after administration of high-dose intravenous methylprednisolone (p<0.05). In 96 patients (NMO, n = 19; TM, n = 25; MS, n = 52) without treatment, serum levels of TSH, TG-Ab and TPO-Ab were significantly different between patients with and without myelitis (p<0.01). Patients positive for aquaporin-4 (AQP4) antibodies showed higher abnormalities of TSH (p = 0.001), TG-Ab (p = 0.004) and TPO-Ab (p<0.0001) levels than AQP4 antibodies negative patients. Logistic regression analyses revealed independent relationships between TSH (odds ratio [OR]  = 33.994; p<0.0001), TG-Ab (OR = 7.703; p = 0.017) and myelitis occurrence in 96 patients at the active stage. In 52 MS patients experiencing their first attack, MS patients with myelitis were associated with TSH abnormalities (OR = 42.778; p<0.0001). This study showed increased abnormalities of thyroid parameters in patients with NMO and TM than in MS patients. MS patients with myelitis also had greater TSH abnormality than in MS patients without myelitis. Abnormal TSH and TG-Ab were independently associated with myelitis occurrence in central nervous system demyelinating disorders. PMID:25093326

  4. Association of polymorphisms of rs179247 and rs12101255 in thyroid stimulating hormone receptor intron 1 with an increased risk of Graves' disease: A meta-analysis.

    PubMed

    Gong, Jing; Jiang, Shu-Jun; Wang, Ding-Kun; Dong, Hui; Chen, Guang; Fang, Ke; Cui, Jin-Rui; Lu, Fu-Er

    2016-08-01

    The polymorphisms of thyroid stimulating hormone receptor (TSHR) intron 1 rs179247 and rs12101255 have been found to be associated with Graves' disease (GD) in genetic studies. In the present study, we conducted a meta-analysis to examine this association. Two reviewers systematically searched eligible studies in PubMed, Web of Science, Embase and China Biomedical Literature Database (CBM). A meta-analysis on the association between GD and TSHR intron 1 rs179247 or rs12101255 was performed. The odd ratios (OR) were estimated with 95% confidence interval (CI). Meta package in R was used for the analyses. Seven articles (13 studies) published between 2009 and 2014, involving 5754 GD patients and 5768 controls, were analyzed. The polymorphism of rs179247 was found to be associated with an increased GD risk in the allele analysis (A vs. G: OR=1.40, 95% CI=1.33-1.48) and all genetic models (AA vs. GG: OR=1.94, 95% CI=1.73-2.19; AA+AG vs. GG: OR=1.57, 95% CI=1.41-1.74; AA vs. AG+GG: OR=1.54, 95% CI=1.43-1.66). The site rs12101255 also conferred a risk of GD in the allele analysis (T vs. C: OR=1.50, 95% CI=1.40-1.60) and all genetic models (TT vs. CC: OR=2.22, 95% CI=1.92-2.57; TT+TC vs. CC: OR=1.66, 95% CI=1.50-1.83; TT vs. TC+CC: OR=1.74, 95% CI=1.53-1.98). Analysis of the relationship between rs179247 and Graves' ophthalmopathy (GO) showed no statistically significant correlation (A vs. G: OR=1.02, 95% CI=0.97-1.07). Publication bias was not significant. In conclusion, GD is associated with polymorphisms of TSHR intron 1 rs179247 and rs12101255. There is no association between rs179247 SNPs and GO.

  5. Thyroid-Stimulating Hormone and Free Thyroxine Levels in Persons with HFE C282Y Homozygosity, a Common Hemochromatosis Genotype: The HEIRS Study

    PubMed Central

    Leiendecker-Foster, Catherine; Reboussin, David M.; Adams, Paul C.; Acton, Ronald T.; Eckfeldt, John H.

    2008-01-01

    Background Relationships of thyroid and iron measures in large cohorts are unreported. We evaluated thyroid-stimulating hormone (TSH) and free thyroxine (T4) in white participants of the primary care–based Hemochromatosis and Iron Overload Screening (HEIRS) Study. Methods We measured serum TSH and free T4 in 176 HFE C282Y homozygotes without previous hemochromatosis diagnoses and in 312 controls without HFE C282Y or H63D who had normal serum iron measures and were matched to C282Y homozygotes for Field Center, age group, and initial screening date. We defined hypothyroidism as having TSH >5.00 mIU/L and free T4 <0.70 ng/dL, and hyperthyroidism as having TSH <0.400 mIU/L and free T4 >1.85 ng/dL. Multivariate analyses were performed using age, sex, Field Center, log10 serum ferritin (SF), HFE genotype, log10 TSH, and log10 free T4. Results Prevalences of hypothyroidism in C282Y homozygotes and controls were 1.7% and 1.3%, respectively, and of hyperthyroidism 0% and 1.0%, respectively. Corresponding prevalences did not differ significantly. Correlations of log10 SF with log10 free T4 were positive (p = 0.2368, C282Y homozygotes; p = 0.0492, controls). Independent predictors of log10 free T4 were log10 TSH (negative association) and age (positive association); positive predictors of log10 SF were age, male sex, and C282Y homozygosity. Proportions of C282Y homozygotes and controls who took medications to supplement or suppress thyroid function did not differ significantly. Conclusions Prevalences of hypothyroidism and hyperthyroidism are similar in C282Y homozygotes without previous hemochromatosis diagnoses and controls. In controls, there is a significant positive association of SF with free T4. We conclude that there is no rationale for routine measurement of TSH or free T4 levels in hemochromatosis or iron overload screening programs. PMID:18651828

  6. Out-of-Reference Range Thyroid-Stimulating Hormone Levels in Levothyroxine-Treated Primary Hypothyroid Patients: A Multicenter Observational Study.

    PubMed

    Yavuz, Dilek Gogas; Yazıcı, Dilek; Keskin, Lezzan; Atmaca, Ayşegül; Sancak, Seda; Saraç, Fulden; Şahin, İbrahim; Dikbaş, Oğuz; Hekimsoy, Zeliha; Yalın, Serap; Uygur, Melin; Yılmaz, Murat; Yirmibeşcik, Sibel; Asmaz, Özlem

    2017-01-01

    Although levothyroxine (LT4) replacement therapy for hypothyroidism has been established as safe, inexpensive and effective, many studies from different countries reported out-of-reference range thyroid-stimulating hormone (TSH) values for the hypothyroid patients under LT4 treatment. The aim of this study was to determine TSH levels of primary hypothyroid patients under LT4 treatment and to assess self-reported compliance with daily LT4 intake in tertiary care centers in Turkey. In this cross-sectional, observational study, adult patients with primary hypothyroidism, receiving LT4 treatment for at least 6 months, were included. The patients were from 12 tertiary care centers in 9 cities of Turkey. TSH and free T4 levels were recorded from patient files and self-reported compliance with daily LT4 intake was assessed by interviewing the subjects at the last visit. A total of 1,755 subjects (46 ± 13 years; F/M: 89.9/10.1%) with primary hypothyroidism were enrolled. Of the hypothyroid subjects, 44.8% had out-of-reference range serum TSH levels. TSH values were over the reference range (TSH > 4 mIU/L) in 26.2% and were under the reference range (TSH < 0.5 mIU/L) in 18.6% of the patients. Total duration of LT4 treatment was 5.9 ± 4.7 years and mean dose was 1.2 ± 0.6 μg/kg/day. Non-compliant patients (31.1%) had higher TSH levels (6.9 ± 16 vs 3.8 ± 0.9 mIU/L, P = 0.01) compared to compliant patients. The results of this study revealed that nearly half of the hypothyroid patients had out-of-reference range serum TSH values, despite under LT4 treatment. Compliance with LT4 treatment seems to be one of the major determinants to reach the target TSH levels in hypothyroid patients.

  7. Ovine thyroid stimulating hormone (TSH) heterologously stimulates production of thyroid hormones from Chinese soft-shell turtle (Pelodiscus sinensis) and bullfrog (Rana catesbeiana and Rana rugulosa) thyroids in vitro.

    PubMed

    Huang, Wei-Tung; Chien, Jung-Tsun; Weng, Ching-Feng; Jeng, Yung-Yue; Lu, Li-Chia; Yu, John Yuh-Lin

    2009-06-01

    Thyroid hormones are important for regulating a variety of developmental processes in vertebrates, including growth, differentiation, metamorphosis, and oxidative metabolism. In particular, this study focused on the in vitro production of thyroxine (T(4)) and triiodothyronine (T(3)) from thyroids in American bullfrogs (Rana catesbeiana), Chinese bullfrogs (Rana rugulosa Wiegmann), and Chinese soft-shell turtles (Pelodiscus sinensis) treated with ovine thyroid stimulating hormone (TSH) at different culture intervals (2, 4, 8, and 12 h) and dosages (1, 10, 50 or 100 ng). The levels of T(4) and T(3) in the tested animals were elevated upon stimulation in a time- and dose-dependent manner, indicating de novo synthesis of T(4) and T(3). Significantly higher hormone levels were observed in the Chinese bullfrog compared to the other two species, for both the time-course and dose-response experiments. Although the bullfrog secreted significantly higher levels of T(4) and T(3), a higher T(4)-conversion capacity was found in the Chinese soft-shell turtle. The highest ratios of T(3) to T(4) were observed in the American bullfrog and Chinese soft-shell turtle for the time-course and dose-response experiments, respectively. These findings suggest that the Chinese soft-shell turtle and bullfrog thyroids can accept ovine TSH for T(4)- and T(3)-formation in a time- and dose-dependent manner, supporting the hypothesis that the binding interactions between TSHs and thyroidal receptors are conserved in vertebrates.

  8. Changes in plasma melanocyte-stimulating hormone, ACTH, prolactin, GH, LH, FSH, and thyroid-stimulating hormone in response to injection of sulpiride, thyrotropin-releasing hormone, or vehicle in insulin-sensitive and -insensitive mares.

    PubMed

    Valencia, N Arana; Thompson, D L; Mitcham, P B

    2013-05-01

    Six insulin-sensitive and 6 insulin-insensitive mares were used in a replicated 3 by 3 Latin square design to determine the pituitary hormonal responses (compared with vehicle) to sulpiride and thyrotropin-releasing hormone (TRH), 2 compounds commonly used to diagnose pituitary pars intermedia dysfunction (PPID) in horses. Mares were classified as insulin sensitive or insensitive by their previous glucose responses to direct injection of human recombinant insulin. Treatment days were February 25, 2012, and March 10 and 24, 2012. Treatments were sulpiride (racemic mixture, 0.01 mg/kg BW), TRH (0.002 mg/kg BW), and vehicle (saline, 0.01 mL/kg BW) administered intravenously. Blood samples were collected via jugular catheters at -10, 0, 5, 10, 20, 30, 45, 60, 90, and 120 min relative to treatment injection. Plasma ACTH concentrations were variable and were not affected by treatment or insulin sensitivity category. Plasma melanocyte-stimulating hormone (MSH) concentrations responded (P < 0.01) to both sulpiride and TRH injection and were greater (P < 0.05) in insulin-insensitive mares than in sensitive mares. Plasma prolactin concentrations responded (P < 0.01) to both sulpiride and TRH injection, and the response was greater (P < 0.05) for sulpiride; no effect of insulin sensitivity was observed. Plasma thyroid-stimulating hormone (TSH) concentrations responded (P < 0.01) to TRH injection only and were higher (P < 0.05) in insulin-sensitive mares in almost all time periods. Plasma LH and FSH concentrations varied with time (P < 0.05), particularly in the first week of the experiment, but were not affected by treatment or insulin sensitivity category. Plasma GH concentrations were affected (P < 0.05) only by day of treatment. The greater MSH responses to sulpiride and TRH in insulin-insensitive mares were similar to, but not as exaggerated as, those observed by others for PPID horses. In addition, the reduced TSH concentrations in insulin-insensitive mares are

  9. A novel hypothesis for the etiology of Graves' disease: TSAb may be thyroid stimulating animal IgG-like hormone and TBAb may be the precursor of TSAb.

    PubMed

    Ochi, Yukio; Kajita, Yoshihiro; Hachiya, Takashi; Hamaoki, Masaru

    2012-06-01

    spite of no antibody function). There are many reports for co-existence of TSAb and TBAb-IgG in sera of GD. We reported conversion from TBAb (non-thyroid stimulating type IgG) to TSAb by co-incubation of anti-hIgG Ab (containing anti-animal IgG Ab as a cross-reaction) with TBAb-bound porcine thyroid cells. Thus, we suggest that TBAb may be the precursor form of TSAb.

  10. Differential expression of thrombospondin, collagen, and thyroglobulin by thyroid-stimulating hormone and tumor-promoting phorbol ester in cultured porcine thyroid cells.

    PubMed

    Bellon, G; Chaqour, B; Antonicelli, F; Wegrowski, J; Claisse, D; Haye, B; Borel, J P

    1994-07-01

    In the present study, we have investigated the potential regulation of thyroglobulin (Tg) and extracellular matrix components synthesis by thyroid-stimulating hormone (TSH) and tetradecanoyl phorbol-13-acetate (TPA) on thyroid cells. Porcine thyroid cells isolated by trypsin-EGTA digestion of thyroid glands were maintained in serum containing medium on poly (L-lysine)-coated dishes. Cells differentiated into follicular or vesicular-like structures were distinguished by their ability to organify Na[125I] and to respond to TSH stimulation. After an incubation of the cells with radiolabeled proline or methionine, two major proteins were identified, p450-480 and p290 (so named because of their molecular masses). Tg (p290) synthesis was demonstrated by the synthesis of [131I]-labeled polypeptides with electrophoretic properties identical to those of authentic Tg molecules. P450-480 resolved to M(r) 190,000 under reducing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) conditions. It was identified as thrombospondin by its reactivity with a monoclonal anti-human thrombospondin and by peptide sequencing of some of its tryptic fragments that displayed identity to thrombospondin I. Collagen synthesis was demonstrated by the formation of radioactive hydroxyproline and by the synthesis of pepsin-resistant polypeptides ranging from M(rs) 120,000 to 200,000. When the cells were cultured in the presence of 100 nM TPA, the culture medium contents of thrombospondin and collagen were increased by 2.7 and 1.6-fold, respectively, whereas Tg content was decreased by a factor 3.9. In contrast, the acute treatment of control cells with TPA induced a decrease in both Tg and collagen content by factors 3.0 and 1.5, respectively, and an increase in thrombospondin content by a factor 2.5. In the presence of 100 nM TPA, TSH (1 mU/ml) did not counteract the stimulating effect of TPA on extracellular matrix components synthesis. In contrast, when cells were cultured in the

  11. Relation of Thyroid Hormone Levels with Fluid-Resistant Shock among Preterm Septicemic Neonates.

    PubMed

    Dutta, Sourabh; Singh, Sarvendra; Bhattacharya, Anish; Venkataseshan, Sundaram; Kumar, Praveen

    2017-02-15

    To compare thyroid hormone levels between septicemic preterm neonates with and without shock. Preterm septicemic infants with shock constituted Group A (n=36) and those without shock constituted Group B, with groups matched (1:1) for gestation and postnatal age. Those with maternal thyroid disorders, thyrotropic medication and life expectancy <12 hours were excluded. We compared serum tri-iodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) between the groups by univariate and multivariate (adjusting for SNAPPE-II) analysis. Median (IQR) TSH was significantly lower in Group A [1.39 (0.83,3.48)] vs Group B [5.1 (2.32,7.19)] mmol/dL (P<0.001). Serum T3 and T4 were also lower in Group A (P<0.001). On multivariate analysis, none of these measures were independently associated with septic shock. Thyroid hormone levels do not independently predict presence of shock among septic preterms.

  12. Effects of sub-lethal heroin administration on thyroid stimulating hormone (TSH), thyroid hormones (T3, T4) and thyroid gland of Mus norvegicus.

    PubMed

    Bhoir, Kaminidevi K; Suryawanshi, S A; Pandey, A K

    2009-11-01

    Serum TSH level of control Mus norvegicus fluctuated between 498.20 +/- 21.92 and 506.80 +/- 22.35 ng ml(-1), thyroxine (T4) between 68.17 +/- 3.46 and 69.03 +/- 4.12 microg dl(-1) and triiodothyronine (T3) between 4.76 +/- 0.52 and 5.00 +/- 0.66 microg dl(-1). Sub-lethal heroin administration induced a significant decline in the levels of all the three hormones at 24 hr and 15 days post-administration. Decline in the levels of these hormones registered the lowest values (p<0.001) by day 30 of the treatment. Thyroid gland of control rat consisted of spherical, round follicles lined with low cuboidal and columnar epithelial cells and lumina filled with eosinophilic colloid. Ultrastructurally, the thyroid follicular cells showed the presence of round nuclei, polymorphic mitochondria, Golgi complex as well as lysosomes located on the apical side of the nucleus and cytoplasm with different sizes of lipid droplets and smooth along with rough endoplasmic reticulum. Basal lamina of the follicular cells was often in association with the endothelium of the capillaries. Sub-lethal heroin administration for 30 days elicited degenerative changes in the follicular epithelial cells as evident by the vacuolization of cytoplasm, pycnotic nuclei and reduced colloidal content. Ultrastructurally, the thyroid follicular cells showed indented nuclei with heavy deposition of chromatin material on the inner membrane of nucleus and dilated rough endoplasmic reticulum. Along with RBC infiltration, vesiculated mitochondria owing to the loss of cristae were also seen. Diffused electron-dense material was seen at the periphery of the cell body. Heroin treatment caused cellular necrosis as revealed by the fragmentation of cytoplasmic materials in follicular epithelial cells of the gland.

  13. Changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation.

    PubMed

    Leeuwen, L; van Heijst, A F J; van Rosmalen, J; de Rijke, Y B; Beurskens, L W J E; Tibboel, D; van den Akker, E L T; IJsselstijn, H

    2017-08-01

    Thyroid hormone concentrations can be disturbed during critical illness. Our aim was to determine changes in thyroid hormone concentrations during neonatal extracorporeal membrane oxygenation (ECMO). We included 21 ECMO-treated neonates. Age-specific s.d. scores (SDS) of free and total thyroxine (FT4; TT4), reverse and total triiodothyronine (rT3; TT3), thyroid-stimulating hormone (TSH) and thyroxine-binding globulin (TBG) were determined at six fixed time-points. Data were analyzed using general linear models. At baseline, mean SDS FT4 (-0.78, 95% CI: -1.37 to -0.19), TT4 (-1.97, 95% CI: -2.76 to -1.18), TT3 (-0.88, 95% CI: -1.13 to -0.63), TSH (-2.14, 95% CI: -2.93 to -1.35) and TBG (-3.52, 95% CI: -4.55 to -2.50) were low with high mean SDS rT3 (0.53, 95% CI: 0.28 to 0.78). One hour after start ECMO, TT4, TSH and TBG had further declined; 12 h after start ECMO TT3 had declined (all P<0.05). After this decline, mean SDS TSH increased to the baseline level 12 h after start ECMO (-2.50, 95% CI: -3.22 to -1.79), and was higher than baseline 48 h after start ECMO (-0.56, 95% CI: -1.29 to 0.17). This TSH increase was followed by increases in TT4 and TT3. FT4 remained constant within the normal range during ECMO. Thyroid hormone concentrations before ECMO were suggestive of non-thyroidal illness syndrome (NTIS). During ECMO, increases in TSH, TT4 and TT3 after an initial decline possibly reflect spontaneous restoration of the hypothalamic-pituitary-thyroid axis. FT4 remained constant within the normal range. This suggests that thyroxine therapy is not required during ECMO.

  14. Molecular cloning and sequence analysis of a cDNA encoding pituitary thyroid stimulating hormone beta-subunit of the Chinese soft-shell turtle Pelodiscus sinensis and regulation of its gene expression.

    PubMed

    Chien, Jung-Tsun; Chowdhury, Indrajit; Lin, Yao-Sung; Liao, Ching-Fong; Shen, San-Tai; Yu, John Yuh-Lin

    2006-04-01

    A cDNA encoding thyroid stimulating hormone beta-subunit (TSHbeta) was cloned from pituitary of the Chinese soft-shell turtle, Pelodiscus sinensis, and its regulation of mRNA expression was investigated for the first time in reptile. The Chinese soft-shell turtle TSHbeta cDNA was cloned from pituitary RNA by reverse transcription and polymerase chain reaction (RT-PCR), and rapid amplification cDNA end (RACE) methods. The Chinese soft-shell turtle TSHbeta cDNA consists of 580-bp nucleotides, including 67-bp nucleotides of 5'-untranslated region (UTR), 402-bp of the open reading frame, and 97-bp of 3'-UTR followed by a 14 poly (A) trait. It encodes a precursor protein molecule of 133 amino acids with a putative signal peptide of 19 amino acids and a putative mature protein of 114 amino acids. The number and position of 12 cysteine residues, presumably forming six disulfide bonds, one putative asparagine-linked glycosylation site, and six proline residues that are found at positions for changing the backbone direction of the protein have been conserved in the turtle as in other vertebrate groups. The deduced amino acid sequence of the Chinese soft-shell turtle TSHbeta mature protein shares identities of 82-83% with birds, 71-72% with mammals, 49-57% with amphibians, and 44-61% with fish. The Chinese soft-shell turtle pituitaries were incubated in vitro with synthetic TRH (TSH-releasing hormone), thyroxine and triiodothyronine at doses of 10(-10) and 10(-8)M. TRH stimulated, while thyroid hormones suppressed, TSHbeta mRNA levels in dose-related manner. The sequences of cDNA and its deduced peptide of TSHbeta as well as the regulation of its mRNA level were reported for the first time in reptile.

  15. Analytical Bias Exceeding Desirable Quality Goal in 4 out of 5 Common Immunoassays: Results of a Native Single Serum Sample External Quality Assessment Program for Cobalamin, Folate, Ferritin, Thyroid-Stimulating Hormone, and Free T4 Analyses.

    PubMed

    Kristensen, Gunn B B; Rustad, Pål; Berg, Jens P; Aakre, Kristin M

    2016-09-01

    We undertook this study to evaluate method differences for 5 components analyzed by immunoassays, to explore whether the use of method-dependent reference intervals may compensate for method differences, and to investigate commutability of external quality assessment (EQA) materials. Twenty fresh native single serum samples, a fresh native serum pool, Nordic Federation of Clinical Chemistry Reference Serum X (serum X) (serum pool), and 2 EQA materials were sent to 38 laboratories for measurement of cobalamin, folate, ferritin, free T4, and thyroid-stimulating hormone (TSH) by 5 different measurement procedures [Roche Cobas (n = 15), Roche Modular (n = 4), Abbott Architect (n = 8), Beckman Coulter Unicel (n = 2), and Siemens ADVIA Centaur (n = 9)]. The target value for each component was calculated based on the mean of method means or measured by a reference measurement procedure (free T4). Quality specifications were based on biological variation. Local reference intervals were reported from all laboratories. Method differences that exceeded acceptable bias were found for all components except folate. Free T4 differences from the uncommonly used reference measurement procedure were large. Reference intervals differed between measurement procedures but also within 1 measurement procedure. The serum X material was commutable for all components and measurement procedures, whereas the EQA materials were noncommutable in 13 of 50 occasions (5 components, 5 methods, 2 EQA materials). The bias between the measurement procedures was unacceptably large in 4/5 tested components. Traceability to reference materials as claimed by the manufacturers did not lead to acceptable harmonization. Adjustment of reference intervals in accordance with method differences and use of commutable EQA samples are not implemented commonly. © 2016 American Association for Clinical Chemistry.

  16. Thyroid-stimulating hormone (TSH)-directed induction of the CREM gene in the thyroid gland participates in the long-term desensitization of the TSH receptor.

    PubMed Central

    Lalli, E; Sassone-Corsi, P

    1995-01-01

    Thyroid gland function is regulated by the hypothalamic-pituitary axis via the secretion of TSH, according to environmental, developmental, and circadian stimuli. TSH modulates both the secretion of thyroid hormone and gland trophism through interaction with a specific guanine nucleotide-binding protein-coupled receptor (TSH receptor; TSH-R), which elicits the activation of the cAMP-dependent signaling pathway. After TSH stimulation, the levels of TSH-R RNA are known to decrease dramatically within a few hours. This phenomenon ultimately leads to homologous long-term desensitization of the TSH-R. Here we show that TSH drives the induction of the inducible cAMP early repressor (ICER) isoform of the cAMP response element (CRE) modulator gene both in rat thyroid gland and in the differentiated thyroid cell line FRTL-5. The kinetics of ICER protein induction mirrors the down-regulation of TSH-R mRNA. ICER binds to a CRE-like sequence in the TSH-R promoter and represses its expression. Thus, ICER induction by TSH in the thyroid gland represents a paradigm of the molecular mechanism by which pituitary hormones elicit homologous long-term desensitization. Images Fig. 1 Fig. 2 Fig. 3 PMID:7568187

  17. Fast determination of thyroid stimulating hormone in human blood serum without chemical preprocessing by using infrared spectroscopy and least squares support vector machines.

    PubMed

    Mello, Cesar; Marangoni, Antônio; Poppi, Ronei; Noda, Isao

    2011-06-24

    The least squares support vector machines (LS-SVM) was used to model infrared spectral data for TSH hormone secreted by thyroid, which regulates the basal metabolic rate. This model was used for direct estimation of the content of TSH in blood serum samples, and the results were comparable with those obtained with the conventional analytical method based on chemoluminescence methodology. Excellent agreement was observed between the conventional method and the newly developed calibration model based in analysis of spectral data with LS-SVM. The latter has clear advantages, because it is fast and requires no reagent once the measurements were done directly in the serum by using a simple mid-infrared spectrometer in the ATR mode. An important advantage observed in this calibration method based on LS-SVM is the remarkable capacity to avoid overfitting in the model-building step, that is, the developed method is highly robust.

  18. Short-term effects of lithium on white blood cell counts and on levels of serum thyroid-stimulating hormone and creatinine in adolescent inpatients: a retrospective naturalistic study.

    PubMed

    Amitai, Maya; Zivony, Amir; Kronenberg, Sefi; Nagar, Liron; Saar, Sivan; Sever, Jonathan; Apter, Alan; Shoval, Gal; Golubchik, Pavel; Hermesh, Haggai; Weizman, Abraham; Zalsman, Gil

    2014-11-01

    The purpose of this study was to determine if the known side effects of lithium in adults may be generalized to younger patients with psychiatric disorders. A retrospective naturalistic study design was used. Data were collected from the database of a tertiary pediatric medical center covering the years 1994-2010. Included were patients hospitalized for bipolar and non-bipolar disorders and treated with lithium, alone or in combination with other medications. The electronic medical files were reviewed for changes in thyroid and kidney function and for hematological parameters during the course of treatment. Sixty-one patients 12.5-20.4 years of age (mean 16.94±1.66) met the study criteria: 33 with bipolar disorder and 28 with a non-bipolar disorder. Mean duration of lithium treatment (mean lithium blood level, 0.73±0.24 mEq/L) was 193.68±254.35 days. Mean levels of thyroid-stimulating hormones (TSH) rose significantly from baseline to last measurement (3.16±2.68 vs. 1.52±0.92 mU/L; paired t=-5.19, df=50, p<0.001); in 25% of patients, TSH levels at the last measurement were above normal (≥4 mU/L). Only one patient developed TSH values >10 mU/L (the threshold considered clinically significant). Positive correlation was found between pre- and posttreatment TSH levels (Pearson's r=0.60; n=51, p<0.05). White blood cell count (WBC) also increased significantly following lithium treatment (7195±2151 vs. 7944±2096 cells/mm(3); t=2.83, df=60, p=0.006). No significant changes were noted in serum creatinine levels. There was no difference in these parameters between patients treated with lithium alone or in combination with other medications. Lithium treatment in adolescents with bipolar or non-bipolar disorders is associated with a significant increase in blood TSH levels and WBC count. Lithium-treated adolescent inpatients with a high basal TSH level may be at risk of developing pituitary-thyroid axis dysregulation. Therefore, baseline measurement of

  19. TSH (Thyroid-Stimulating Hormone) Test

    MedlinePlus

    ... symptoms of a thyroid disorder , including hyperthyroidism or hypothyroidism . TSH is produced by the pituitary gland , a ... thyroid Monitor thyroid replacement therapy in people with hypothyroidism Monitor anti-thyroid treatment in people with hyperthyroidism ...

  20. Assays of thyroid-stimulating antibody

    SciTech Connect

    McKenzie, J.M.; Zakarija, M.

    1985-01-01

    A comparison is presented of the two major assay methods of thyroid-stimulating antibody (TSAb) of Graves' disease. The basic procedures involve: (1) some index of thyroid stimulation, usually in vitro, using TSAb to indicate its activity; and (2) indirect recognition by assessment of the inhibition of binding of radioiodinated thyrotropin (TSH) to a preparation of its receptor, i.e., TSH-binding inhibition or TBI. There is potential for misinterpretation of data acquired by testing patients' sera by one or the other basic procedure.

  1. Neonatal thyroid function: influence of perinatal factors.

    PubMed Central

    Franklin, R C; Carpenter, L M; O'Grady, C M

    1985-01-01

    Indices of thyroid function were measured in 229 healthy term neonates at birth and at 5, 10, and 15 days of age. Results were analysed to assess whether maternal diabetes mellitus, toxaemia of pregnancy, intrapartum fetal distress, duration of labour, method of delivery, asphyxia at birth, race, sex, birthweight, birth length, head circumference, or method of feeding influenced any index. Thyroxine, the free thyroxine index, and free thyroxine concentrations at birth correlated with birthweight. Method of delivery influenced mean thyroxine and free thyroxine index values at birth and at age 5 days. Mean values of triiodothyronine, reverse triiodothyronine, thyroxine binding globulin, and thyroid stimulating hormone were not affected by any of the perinatal factors studied. Birthweight and perhaps method of delivery should be taken into account when interpreting neonatal thyroxine parameters but determination of thyroid stimulating hormone as a screen for congenital hypothyroidism in healthy term neonates circumvents these considerations. PMID:3977386

  2. Neonatal Endocrine Labomas - Pitfalls and Challenges in Reporting Neonatal Hormonal Reports.

    PubMed

    Chittawar, Sachin; Dutta, Deep; Khandelwal, Deepak; Singla, Rajiv

    2017-09-15

    This review highlights pitfalls and challenges in interpreting neonatal hormone reports. Pre-analytical errors contribute to nearly 50% of all errors. Modern chemiluminescence assay are more accurate, have lower risk of Hook's effect, but continue to have problems of assay interference. Liquid chromatography mass spectroscopy is gold standard for most hormone assays. Neonatal hypoglycemia diagnostic cut-offs are lower than adults. Random growth hormone testing is of value in diagnosing growth hormone deficiency in neonates. 17-hydroxy-progesterone testing in first three days of life for congenital adrenal hyperplasia (CAH) remains a challenge due to cross-reactivity with maternal circulating steroids, prematurity and lack of adrenal maturation. Both T4 and TSH testing is encouraged after 48 hours of delivery for diagnosing neonatal hypothyroidism; repeat testing should be done immediately for confirmation of diagnosis. There is an urgent need to develop age- sex- and ethnicity-based normative data for different hormone parameters in neonates. Laboratory should develop their own neonatal references and avoid using ranges from manufacturers. In neonatal endocrinopathies, the clinical scenario should primarily dictate the treatment formulation with hormonal assay to supplement treatment.

  3. Neonatal thyrotoxicosis caused by maternal autoimmune hyperthyroidism

    PubMed Central

    Correia, Miguel Fragata; Maria, Ana Teresa; Prado, Sara; Limbert, Catarina

    2015-01-01

    Neonatal immune hyperthyroidism is a rare but potentially fatal condition. It occurs in 1–5% of infants born to women with Graves’ disease (GD). In most of the cases it is due to maternal antibodies transferred from the mother into the fetal compartment, stimulating the fetal thyroid by binding thyrotropin (thyroid-stimulating hormone, TSH) receptor. We present a case of neonatal thyrotoxicosis due to maternal GD detected at 25 days of age and discuss the potential pitfalls in the diagnosis. PMID:25750228

  4. The Presence of Thyroid-Stimulation Blocking Antibody Prevents High Bone Turnover in Untreated Premenopausal Patients with Graves’ Disease

    PubMed Central

    Cho, Sun Wook; Bae, Jae Hyun; Noh, Gyeong Woon; Kim, Ye An; Moon, Min Kyong; Park, Kyoung Un; Song, Junghan; Yi, Ka Hee; Park, Do Joon; Chung, June-Key; Cho, Bo Youn; Park, Young Joo

    2015-01-01

    Osteoporosis-related fractures are one of the complications of Graves’ disease. This study hypothesized that the different actions of thyroid-stimulating hormone receptor (TSHR) antibodies, both stimulating and blocking activities in Graves’ disease patients might oppositely impact bone turnover. Newly diagnosed premenopausal Graves’ disease patients were enrolled (n = 93) and divided into two groups: patients with TSHR antibodies with thyroid-stimulating activity (stimulating activity group, n = 83) and patients with TSHR antibodies with thyroid-stimulating activity combined with blocking activity (blocking activity group, n = 10). From the stimulating activity group, patients who had matched values for free T4 and TSH binding inhibitor immunoglobulin (TBII) to the blocking activity group were further classified as stimulating activity-matched control (n = 11). Bone turnover markers BS-ALP, Osteocalcin, and C-telopeptide were significantly lower in the blocking activity group than in the stimulating activity or stimulating activity-matched control groups. The TBII level showed positive correlations with BS-ALP and osteocalcin levels in the stimulating activity group, while it had a negative correlation with the osteocalcin level in the blocking activity group. In conclusion, the activation of TSHR antibody-activated TSH signaling contributes to high bone turnover, independent of the actions of thyroid hormone, and thyroid-stimulation blocking antibody has protective effects against bone metabolism in Graves’ disease. PMID:26650844

  5. Neonatal detection of generalized resistance to thyroid hormone

    SciTech Connect

    Weiss, R.E.; Balzano, S.; Scherberg, N.H.; Refetoff, S. )

    1990-11-07

    Generalized resistance to thyroid hormone (GRTH) is an inherited disease that is usually suspected when elevated serum thyroid hormone levels are associated with nonsuppressed thyrotropin. Often these test results are obtained because of short stature, decreased intelligence, and/or hyperactivity with learning disability noted in childhood and adolescence, or because of goiter in adulthood. The authors detected GRTH at birth by analysis of blood obtained during routine neonatal screening. The proposita, born to a mother with GRTH, had a thyrotropin level of 26 mU/L and a corresponding thyroxine concentration of 656 nmol/L. Administration of thyroid hormone in doses eightfold to 10-fold above replacement levels were required to reduce serum thyrotropin to normal levels without induction of hypermetabolism. This case, and the retrospective finding of high thyroxine levels in five newborns subsequently diagnosed as having GRTH, suggest that measurement of thyroxine at birth, in conjunction with thyrotropin, could allow the early detection of GRTH.

  6. Maternal iron deficiency alters circulating thyroid hormone levels in developing neonatal rats

    EPA Science Inventory

    Thyroid hormone insufficiency and iron deficiency (FeD) during fetal and neonatal life are both similarly deleterious to mammalian development suggesting a possible linkage between iron and thyroid hormone insufficiencies. Recent published data from our laboratory demonstrate a r...

  7. Maternal iron deficiency alters circulating thyroid hormone levels in developing neonatal rats

    EPA Science Inventory

    Thyroid hormone insufficiency and iron deficiency (FeD) during fetal and neonatal life are both similarly deleterious to mammalian development suggesting a possible linkage between iron and thyroid hormone insufficiencies. Recent published data from our laboratory demonstrate a r...

  8. Thyroid stimulating antibody: an index of thyroid stimulation in Graves' disease?

    PubMed

    Baldet, L; Madec, A M; Papachristou, C; Stefanutti, A; Orgiazzi, J; Jaffiol, C

    1987-09-01

    Early (20 min) thyroid radio-iodine uptake (ERU) and thyroid-stimulating antibodies (TSab) were determined in 27 untreated unselected patients with Graves' disease at the time of diagnosis. In 21 subjects the same tests were further performed in parallel during combined carbimazole-L-T3 therapy (mean duration of follow-up: 10.8 +/- 5.8 months; mean +/- SD). TSab was determined by a cAMP-human thyrocyte culture stimulation assay and expressed in microliter-equivalent of a TSab standard/ml (microliter-eq/ml). Before treatment, ERU, ranging from 15 to 54% of the injected dose (normal less than or equal to 8% dose) correlated with serum T3 (r: 0.54; P less than 0.01); TSab, ranging from 6 to 85 microliter-eq/ml was detected in 21/27 patients. There was a significant correlation between ERU and TSab (Spearman rank test: r: 0.57; P less than 0.01). During the first months of treatment, 5 of the 21 patients sequentially studied had undetectable TSab levels throughout the study and in these patients ERU decreased by 57% of its initial value; the remaining 16 subjects were divided into two groups according to ERU changes: in group A (9 patients), initial ERU decreased by 50% or more or the absolute value became less than 20% of the dose and TSab decreased from 10.9 +/- 4.8 microliter-eq/ml to 5.3 +/- 1.6 microliter-eq/ml (P less than 0.01); in group B (7 patients), the fall of ERU was less than 50% or the absolute value remained greater than 20% of the dose and TSab values remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. A patient with Graves’ disease showing only psychiatric symptoms and negativity for both TSH receptor autoantibody and thyroid stimulating antibody

    PubMed Central

    2012-01-01

    Background Both thyroid stimulating hormone (TSH) and thyroid stimulating antibody (TSAb) negative Graves’s disease (GD) is extremely rare. Here we present such a patient. Case presentation The patient was a 76-year-old woman who was diagnosed as having schizophrenia forty years ago. She did not show characteristic symptoms for hyperthyroidism, such as swelling of thyroid, exophthalmos, tachycardia and tremor, however, she showed only psychomotor agitation. Serum free triiodothyronine and free thyroxine levels were elevated and TSH level was suppressed, suggesting the existence of hyperthyroidism. However, both the first generation TSH receptor autoantibody (TRAb1) and the thyroid stimulating autoantibody (TSAb) were negative. Slightly increased blood flow and swelling was detected by thyroid echography. Thyroid scintigraphy demonstrated diffuse and remarkably elevated uptake of 123I uptake. Finally, we diagnosed her as having GD. She was treated by using methimazole, and hyperthyroidism and her psychiatric symptoms were promptly ameliorated. Discussion We experienced a patient with GD who did not show characteristic symptoms except for psychiatric symptoms, and also showed negativity for both TRAb1 and TSAb. Thyroid autoantibody-negative GD is extremely rare. Thyroid scintigraphy was useful to diagnose such a patient. PMID:23206540

  10. Validation of cytochemical section bioassay for thyroid-stimulating immunoglobulins in treated and untreated Graves' disease.

    PubMed

    Prentice, M G; Alaghband-Zadeh, J; Wise, P H

    1984-01-01

    The cytochemical section-bioassay of thyroid stimulating activity is described. Plasma of thyrotoxic patients as well as those on block-replace treatment with carbimazole and thyroid hormones was used. Linear parallel responses were obtained over the range 1.5 X 10(-7) to 1.5 X 10(-5) mU/1 MRC LATS-B standard. The index of precision was 0.19 +/- 0.028. The fiducial limits (p=0.95) of a sample tested on ten separate occasions were 52-192%. Specificity was investigated using time course studies, and the effect of anti-TSH or anti-IgG antisera. No effect of methimazole or a variety of other drugs was detected. The assay is accordingly validated for measurement of TSI in patients both untreated and on block-replace therapy.

  11. Hormonal regulation of glycogen metabolism in neonatal rat liver

    PubMed Central

    Schwartz, Alan L.; Rall, Theodore W.

    1973-01-01

    1. The development of active and inactive phosphorylase was determined in rat liver during the perinatal period. No inactive form could be found in tissues from animals less than 19 days gestation or older than the fifth postnatal day. 2. The regulation of phosphorylase in organ cultures of foetal rat liver was examined. None of the agents examined [glucagon, insulin or dibutyryl cyclic AMP (6-N,2′-O-dibutyryladenosine 3′:5′-cyclic monophosphate)] changed the amount of phosphorylase activity. 3. Glycogen concentration in these explants were nevertheless decreased more than twofold by 4h of incubation with glucagon or dibutyryl cyclic AMP. Incubation with insulin for 4h increased the glycogen content twofold. 4. Glycogen synthetase activity was examined in these explants. I-form activity (without glucose 6-phosphate) was found to decrease by a factor of two after 4h of incubation with dibutyryl cyclic AMP, whereas I+D activity (with glucose 6-phosphate) remained nearly constant. Incubation for 4h with insulin increased I-form activity threefold, with only a slight increase in I+D activity. 5. When explants were incubated with insulin followed by addition of dibutyryl cyclic AMP, the effects of insulin on glycogen concentration and glycogen synthetase activity were reversed. 6. These results indicate that the regulation of glycogen synthesis may be the major factor in the hormonal control of glycogen metabolism in neonatal rat liver. PMID:4357717

  12. Molecular impact of juvenile hormone agonists on neonatal Daphnia magna.

    PubMed

    Toyota, Kenji; Kato, Yasuhiko; Miyakawa, Hitoshi; Yatsu, Ryohei; Mizutani, Takeshi; Ogino, Yukiko; Miyagawa, Shinichi; Watanabe, Hajime; Nishide, Hiroyo; Uchiyama, Ikuo; Tatarazako, Norihisa; Iguchi, Taisen

    2014-05-01

    Daphnia magna has been used extensively to evaluate organism- and population-level responses to pollutants in acute toxicity and reproductive toxicity tests. We have previously reported that exposure to juvenile hormone (JH) agonists results in a reduction of reproductive function and production of male offspring in a cyclic parthenogenesis, D. magna. Recent advances in molecular techniques have provided tools to understand better the responses to pollutants in aquatic organisms, including D. magna. DNA microarray was used to evaluate gene expression profiles of neonatal daphnids exposed to JH agonists: methoprene (125, 250 and 500 ppb), fenoxycarb (0.5, 1 and 2 ppb) and epofenonane (50, 100 and 200 ppb). Exposure to these JH analogs resulted in chemical-specific patterns of gene expression. The heat map analyses based on hierarchical clustering revealed a similar pattern between treatments with a high dose of methoprene and with epofenonane. In contrast, treatment with low to middle doses of methoprene resulted in similar profiles to fenoxycarb treatments. Hemoglobin and JH epoxide hydrolase genes were clustered as JH-responsive genes. These data suggest that fenoxycarb has high activity as a JH agonist, methoprene shows high toxicity and epofenonane works through a different mechanism compared with other JH analogs, agreeing with data of previously reported toxicity tests. In conclusion, D. magna DNA microarray is useful for the classification of JH analogs and identification of JH-responsive genes.

  13. Genetic differences in the production of male neonates in Daphnia magna exposed to juvenile hormone analogs.

    PubMed

    Oda, Shigeto; Tatarazako, Norihisa; Watanabe, Hajime; Morita, Masatoshi; Iguchi, Taisen

    2006-06-01

    We studied the susceptibility of three genetically different strains of the cyclical parthenogen Daphnia magna (Cladocera, Crustacea) in producing male neonates following exposure to juvenile hormone analogs. In experiment 1, NIES, Clone A, and Belgium A strains were exposed to the insect growth regulators (IGRs) fenoxycarb or epofenonane in a 21-day reproduction experiment. Fenoxycarb exposure decreased the total number of neonates and increased production of male neonates in a concentration-dependent manner in the NIES strain. The decrease in the total number of neonates was so great in Clone A following fenoxycarb exposure that male neonates were not observed, even at the highest concentration, where the total number of neonates was only 2% of the control. In the Belgium A strain, male neonates were observed at a rate of about 20% following exposure to the highest fenoxycarb concentration, but the total number observed was small. Epofenonane did not decrease reproduction in the NIES and Belgium A strains as dramatically as did fenoxycarb, but the neonatal sex ratio changed in a concentration-dependent manner. Although the ratio of males was as low as about 10%, induction of male neonates was also observed in Clone A following epofenonane exposure. In experiment 2, gravid females were exposed to high concentrations (5 or 10 microg/l) of fenoxycarb or pyriproxyfen for 12h. These treatments induced the production of male neonates in all strains, with a small decrease in the total number of neonates. Although induction of male neonates by juvenile hormones and their analogs was universal among genetically different strains, care is needed in interpreting the results of the 21-day reproduction tests, because decreased numbers of neonates at higher concentrations could obscure the presence of male neonates.

  14. Production of male neonates in Daphnia magna (Cladocera, Crustacea) exposed to juvenile hormones and their analogs.

    PubMed

    Oda, Shigeto; Tatarazako, Norihisa; Watanabe, Hajime; Morita, Masatoshi; Iguchi, Taisen

    2005-12-01

    We exposed the water flea Daphnia magna (Cladocera, Crustacea) to either juvenile hormone I (JH I), juvenile hormone II (JH II), or the juvenile hormone-mimicking insecticides kinoprene, hydroprene, epofenonane, or fenoxycarb. By 21-day reproduction tests, we investigated the effects on the number of neonates born per female and the offspring sex ratio. All six chemicals induced D. magna to produce male neonates; the male sex ratio of the offspring increased as the chemical concentration increased. EC50 values for production of male neonates were estimated as 400 (JH I), 410 (JH II), 190 (kinoprene), 2.9 (hydroprene), 64 (epofenonane), and 0.92 (fenoxycarb) microg/l. The number of neonates produced was reduced with all chemicals at the concentrations investigated. At the EC50 for male production, five of the six chemicals reduced the reproductive rate to less than 50%; the exception was epofenonane, which caused only a slight reduction in reproductive rate. These results were similar to those obtained for five juvenoids studied previously, one of which was studied here again. There are now 10 chemical substances--all juvenile hormones or their analogs-that are known to induce D. magna to produce male neonates. This suggests that juvenile hormone is involved in initiating male production followed by sexual reproduction in D. magna, and probably in most cladocerans that exhibit cyclic parthenogenesis.

  15. Stimulation of thyroid hormone secretion by thyrotropin in beluga whales, Delphinapterus leucas.

    PubMed

    St Aubin, D J

    1987-07-01

    Bovine thyroid stimulating hormone administered to three beluga whales, Delphinapterus leucas, was effective in producing an increase in circulating levels of triiodothyronine and thyroxine. A single dose of 10 I.U. of thyroid stimulating hormone resulted in a 145% increase in triiodothyronine and a 35% increase in thyroxine after nine hours in a whale tested within two hours after capture. The response was less pronounced in an animal tested with the same does on two occasions after four and eight weeks in captivity. In the third whale, 10 I.U. of thyroid stimulating hormone given on each of three consecutive days produced a marked increase in triiodothyronine and thyroxine. The elevation of thyroxine concentration persisted for at least two days after the last injection of thyroid stimulating hormone. A subsequent decrease in thyroxine to levels below baseline signalled the suppression of endogenous thyroid stimulating hormone. This preliminary study helps to establish a protocol for testing thyroid function in cetaceans.

  16. Stimulation of thyroid hormone secretion by thyrotropin in beluga whales, Delphinapterus leucas.

    PubMed Central

    St Aubin, D J

    1987-01-01

    Bovine thyroid stimulating hormone administered to three beluga whales, Delphinapterus leucas, was effective in producing an increase in circulating levels of triiodothyronine and thyroxine. A single dose of 10 I.U. of thyroid stimulating hormone resulted in a 145% increase in triiodothyronine and a 35% increase in thyroxine after nine hours in a whale tested within two hours after capture. The response was less pronounced in an animal tested with the same does on two occasions after four and eight weeks in captivity. In the third whale, 10 I.U. of thyroid stimulating hormone given on each of three consecutive days produced a marked increase in triiodothyronine and thyroxine. The elevation of thyroxine concentration persisted for at least two days after the last injection of thyroid stimulating hormone. A subsequent decrease in thyroxine to levels below baseline signalled the suppression of endogenous thyroid stimulating hormone. This preliminary study helps to establish a protocol for testing thyroid function in cetaceans. PMID:3651900

  17. Production of male neonates in four cladoceran species exposed to a juvenile hormone analog, fenoxycarb.

    PubMed

    Oda, Shigeto; Tatarazako, Norihisa; Watanabe, Hajime; Morita, Masatoshi; Iguchi, Taisen

    2005-06-01

    Previous studies have found that exposure of a cyclic parthenogen, the water flea Daphnia magna (Cladocera, Crustacea), to juvenile hormones and their analogs results in the production of neonates of male sex at concentration-dependent rates. We conducted reproduction experiments in four different species (Moina macrocopa, M. micrura, Ceriodaphnia dubia and C. reticulata) of cladoceran to test for the first time whether the occurrence of this phenomenon after exposure of the parent to such hormones is a generalized phenomenon. In the presence of a juvenile hormone analog, fenoxycarb, all four species produced male neonates and showed reduced rates of reproduction. The estimated median effective concentration (EC50) for the production of male neonates varied with species, ranging from 0.60 x 10(3) to 9.3 x 10(3) ng/l. Although there was a wide range of sensitivity to fenoxycarb, the production of male neonates in all four species demonstrates that this phenomenon is a common response to juvenile hormone analogs and further suggests that these hormones are capable of initiating sexual reproduction in cladocerans, most of which exhibit cyclic parthenogenesis.

  18. EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS

    EPA Science Inventory

    EFFECTS OF PERFLUOROOCTANE SULFONATE (PFOS) ON THYROID HORMONE STATUS IN ADULT AND NEONATAL RATS. M.N. Logan1, J.R. Thibodeaux2, R.G. Hanson2, C. Lau2. 1North Carolina Central University, Durham, NC, 2Reprod. Tox. Div. NHEERL, US EPA, Research Triangle Park, NC.

    Perfluor...

  19. Hormone levels in neonatal hair reflect prior maternal stress exposure during pregnancy.

    PubMed

    Kapoor, Amita; Lubach, Gabriele R; Ziegler, Toni E; Coe, Christopher L

    2016-04-01

    Hormones present in hair provide summative information about endocrine activity while the hair was growing. Therefore, it can be collected from an infant after birth and still provide retrospective information about hormone exposure during prenatal development. We employed this approach to determine whether a delimited period of maternal stress during pregnancy affected the concentrations of glucocorticoids and gonadal hormones in the hair of neonatal rhesus monkeys. Hair from 22 infant monkeys exposed to 5 weeks of gestational disturbance was compared to specimens from 13 infants from undisturbed control pregnancies. Using an LC/MS/MS based technique, which permitted seven steroid hormones to be quantified simultaneously, we found 2 hormones were significantly different in infants from disturbed pregnancies. Cortisol and testosterone levels were lower in the hair of both male and female neonates. Maternal hair hormone levels collected on the same day after delivery no longer showed effects of the disturbance earlier during pregnancy. This study documents that a period of acute stress, lasting for 20% of gestation, has sustained effects on the hormones to which a developing fetus is exposed.

  20. Hormone levels in neonatal hair reflect prior maternal stress exposure during pregnancy

    PubMed Central

    Kapoor, Amita; Lubach, Gabriele R.; Ziegler, Toni E.; Coe, Christopher L.

    2016-01-01

    Hormones present in hair provide summative information about endocrine activity while the hair was growing. Therefore, it can be collected from an infant after birth and still provide retrospective information about hormone exposure during prenatal development. We employed this approach to determine whether a delimited period of maternal stress during pregnancy affected the concentrations of glucocorticoids and gonadal hormones in the hair of neonatal rhesus monkeys. Hair from 22 infant monkeys exposed to 5 weeks of gestational disturbance was compared to specimens from 13 infants from undisturbed control pregnancies. Using an LC/MS/MS based technique, which permitted seven steroid hormones to be quantified simultaneously, we found 2 hormones were significantly different in infants from disturbed pregnancies. Cortisol and testosterone levels were lower in the hair of both male and female neonates. Maternal hair hormone levels collected on the same day after delivery no longer showed effects of the disturbance earlier during pregnancy. This study documents that a period of acute stress, lasting for 20% of gestation, has sustained effects on the hormones to which a developing fetus is exposed. PMID:26802598

  1. Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

    PubMed Central

    Misra, Madhusmita; Levitsky, Lynne L.

    2015-01-01

    Background: Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with 123I or 99Tc (99mTc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with 99mTc uptake for diagnosis of pediatric hyperthyroidism. Methods: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and 99mTc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. 99mTc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Results: Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI–. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. Conclusion: 99mTc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of 99mTc (two and a half times as much as TSI), it is reasonable to reserve 99mTc uptake assessment for hyperthyroidism of unclear etiology and negative TSI. PMID:25257665

  2. [Influence of growth hormone (GH) and nutrition on neonatal growth].

    PubMed

    Díaz-Gómez, N M; Doménech Martínez, E; Barroso Guerrero, F; Cortabarria Bayona, C; Rico Sevillano, J

    1997-01-01

    At present, growth regulating factors in the transition from fetal to postnatal life remain unknown. The purpose of this study was to analyze the influence of GH and nutrition on neonatal growth. Serum and 24-hour urine GH levels, various anthopometric variables and daily energy and nutrient intake were measured in appropriate (AGA), large (LGA) and small for gestational age (SGA) newborn infants. These variables were measured at 1 (n = 98), 3 (n = 41) and 5 weeks of postnatal age (n = 8). The highest GH levels at the 1st week of postnatal life were obtained in preterm SGA infants (GHs: 61.4 +/- 20.0 microUI/m; GHu: 18.6 +/- 10.3 ng/kg/24 h). GH levels decreased in preterm infants, so that differences between groups failed to be significant at the third and fifth weeks of postnatal life. Urinary GH excretion did not show significant variations in the control group during the study (1st wk 3.0 +/- 3.5; 3rd wk 2.3 +/- 2.7; 5th wk 3.2 +/- 4.7 ng/kg/24 h). Daily protein intake had a direct relationship with both triceps skinfold and weight and head perimeter increase. SGA preterm infants showed a higher fat increase compared to AGA preterm infants. Serum and urinary GH levels were not related to the anthopometric variables studied. There are differences in GH secretion and body composition between SGA and AGA preterm infants. GH probably does not contribute to neonatal growth.

  3. [Thyroid stimulating immunoglobulin bioassay using cultured normal human thyroid cells].

    PubMed

    Ando, M; Yamauchi, K; Tanaka, H; Mori, Y; Takatsuki, K; Yamamoto, M; Matsui, N; Tomita, A

    1985-08-20

    It is currently believed that the thyroid stimulating immunoglobulin (TSI) of Graves' disease is involved in the pathogenesis of hyperthyroidism through the stimulation of the adenylate cyclase-cyclic AMP system. To evaluate this mechanism, TSI in the serum of patients with Graves' disease was determined by its ability to generate cyclic AMP (cAMP) in monolayer cells prepared from a normal thyroid gland. The thyroid tissue was digested with collagenase, and the liberated follicles were collected from the supernatant and cultured for 7 days. One gram of thyroid tissue yielded more than 1 X 10(7) monolayer cells which were stored in aliquots at -80C. Cells (1 approximately 2 X 10(4)/0.28 cm2 microtiter well) were incubated for 4 hours in 0.2 ml Hanks solution poor in NaCl, with various amounts of bovine TSH (bTSH) or 1.5 mg/ml Graves' serum IgG extracted by polyethylene glycol. cAMP accumulated in medium and cells was measured by RIA. Total cAMP (both medium and cells) was about 4 times higher when NaCl was deleted from Hanks solution. Moreover, as more than 90% of the cAMP was released into the medium, it was possible to omit the measurement of cellular cAMP, which requires extraction. The increase in medium cAMP concentration was dependent upon the number of cells, incubation time, and dose of bTSH. Time course and dose response curves in medium cAMP stimulated by IgG from 3 Graves' patients paralleled those of bTSH equivalent units. Accordingly, TSI activity could be expressed in bTSH equivalent units (bTSH microUeq). The assay could detect 1.0 or 3.3 microU/ml of bTSH and was highly reproducible. TSI activity in all of 16 IgGs from normal subjects was under 3.3 bTSH microUeq/ml, while it was greater than 3.3 bTSH microUeq/ml in IgGs from 33 of 37 (89%) untreated patients with Graves disease. Of the 13 patients followed for 2 to 7 months while on antithyroid drugs, 12 had greater than 3.3 bTSH microUeq/ml and, with the exception of one, all showed a decrease in

  4. Neonatal imprinting predetermines the sexually dimorphic, estrogen-dependent expression of galanin in luteinizing hormone-releasing hormone neurons.

    PubMed Central

    Merchenthaler, I; Lennard, D E; López, F J; Negro-Vilar, A

    1993-01-01

    The incidence of colocalization of galanin (GAL) in luteinizing hormone-releasing hormone (LHRH) neurons is 4- to 5-fold higher in female than male rats. This fact and the finding that the degree of colocalization parallels estradiol levels during the estrous cycle suggest that GAL is an estrogen-inducible product in a subset of LHRH neurons. To analyze further this paradigm we evaluated the effects of gonadectomy and steroid replacement therapy in male and female rats. Ovariectomy resulted in a significant decrease in the number of cells colocalizing LHRH and GAL, whereas estradiol replacement to such animals restored the incidence of colocalization to that observed in controls. In males, however, estradiol treatment failed to enhance the incidence of colocalization of GAL and LHRH, indicating, therefore, that the colocalization of these peptides is gender-determined. This possibility--i.e., gender-specific determination of LHRH neurons coexpressing GAL--was evaluated by neonatal manipulation of hypothalamic steroid imprinting. As mentioned above, male rats did not respond to estrogen or testosterone by increasing GAL/LHRH colocalization as females did. Neonatally orchidectomized rats, whose hypothalami have not been exposed to testosterone during the critical period, when treated with estrogen in adulthood showed an increase in colocalization of GAL and LHRH similar to that seen in female animals. These observations indicate that the colocalization of LHRH/GAL is neonatally determined by an epigenetic mechanism that involves the testis. In summary, this sex difference in the incidence of colocalization of GAL and LHRH represents a unique aspect of sexual differentiation in that only certain phenotypic characteristics of a certain cellular lineage are dimorphic. The subpopulation of LHRH neurons that also produces GAL represents a portion of the LHRH neuronal system that is sexually differentiated and programed to integrate, under steroidal control, a network of

  5. Roles of thyroid hormones in follicular development in the ovary of neonatal and immature rats.

    PubMed

    Fedail, Jaafar Sulieman; Zheng, Kaizhi; Wei, Quanwei; Kong, Lingfa; Shi, Fangxiong

    2014-08-01

    Thyroid hormones (TH) play a critical role in ovarian follicular development, maturation and the maintenance of various endocrine functions. However, whether TH can affect ovarian follicular development in neonatal and immature rats remains unclear. Therefore, the aim of the present study was to elucidate the effect of TH on ovarian follicular development in neonatal and immature rats. Thirty female post-lactation mothers of Sprague-Dawley rat pups were randomly divided into three groups: control, hyperthyroid (hyper), and hypothyroid (hypo). On postnatal days (PND) 10 and 21, body weights, serum hormones, ovarian histologic changes, and immunohistochemistry of thyroid hormone receptor alpha 1 (TRα1) and nitric oxide synthase types (NOS), and NOS activities, were determined. The data showed that body weights significantly decreased in both hyper and hypo groups compared with the control group (P < 0.05). In addition, the hyper group had increased serum concentrations of T3, T4, and E2; whereas the hypo group manifested reduced serum concentrations of T3, T4, and E2 on PND 10 and 21. The hyper and hypo groups showed significantly reduced total number of primordial, primary and secondary follicles on PND 10 and 21 compared with the control group (P < 0.05). Similarly, antral follicle numbers in the hyper and hypo groups were significantly decreased on PND 21 compared with the control group (P < 0.05). Immunostaining indicated that TRα1 and NOS were expressed in ovarian surface epithelium and oocytes of growing and antral follicles, with strong staining of the granulosa and theca cells of follicles. NOS activities were significantly augmented in the hyper, but diminished in the hypo groups on PND 10 and 21. In summary, our findings suggest that TH play important roles in ovarian functions and in the regulation of NOS activity. Our results also indicate that a relationship exists between the TH and NO signaling pathways during the process of ovarian follicular

  6. Growth hormone release induced by growth hormone-releasing hexapeptide is not mediated by thyrotropin-releasing hormone in neonatal rats.

    PubMed

    Kacsóh, B; Kacsóh, G; Guzzardo, M B; Black, A C; Bisat, T

    1997-02-01

    GH-releasing hexapeptide (GHRP-6) and nursing stimulate GH secretion in rat pups via GH-releasing factors (GRFs: distinct from GH-releasing hormone (GHRH). It was determined whether GH secretion induced by GHRP-6 or nursing was mediated by TSH-releasing hormone (TRH) in 2-d-old rats. In vitro. GHRP-6 and TRH stimulated GH secretion of neonatal pituitary glands. At their maximally effective doses, GHRP-6 and TRH evoked approximately equal GH responses. Treatment with a combination of the maximally effective doses of GHRP-6 and TRH resulted in a GH response comparable to that evoked by either treatment alone. GHRP-6 in vivo induced a greater GH response than did TRH. Treatment in vivo with a combination of the maximally effective doses of GHRP-6 and TRH synergistically increased serum GH levels. Unlike GHRP-6 TRH was an effective stimulus of prolactin secretion either in vitro or in vivo. Nursing was an effective stimulus for GH secretion, but only marginally increased serum prolactin levels. The effects of either of the peptides and nursing on GH secretion were additive. These results suggest that GHRP-6 stimulates GH secretion both by acting directly on the pituitary gland and indirectly via a hypothalamic GRF. The indirect effect appears to be greater. The alternative GRFs released by GHRP-6 or nursing are distinct from each other and from TRH. These findings suggest that alternative GRFs play a significant role in the regulation of GH secretion in neonatal rats.

  7. Differences in neonatal exposure to estradiol or testosterone on ovarian function and hormonal levels.

    PubMed

    Marcondes, Rodrigo R; Carvalho, Kátia C; Duarte, Daniele C; Garcia, Natália; Amaral, Vinícius C; Simões, Manuel J; Lo Turco, Edson G; Soares, José M; Baracat, Edmund C; Maciel, Gustavo A R

    2015-02-01

    Exposure to an excess of androgen or estrogen can induce changes in reproductive function in adult animals that resemble polycystic ovary syndrome in humans. However, considerable differences exist among several types of animal models. Little is known about the molecular features of steroidogenesis and folliculogenesis in the ovaries of rats exposed to different sex steroids as neonates. Here, we evaluated the impact of androgen and estrogen exposure on the ovaries of adult female rats during their neonatal period in the gene expression of Lhr and Cyp17a1, two key players of steroidogenesis. We also assessed hormone levels, folliculogenesis and the theca-interstitial cell population. The study was performed on the second postnatal day in thirty female Wistar rats that were sorted into the following three intervention groups: testosterone, estradiol and vehicle (control group). The animals were euthanized 90 days after birth. The main outcomes were hormone serum levels, ovary histomorphometry and gene expression of Lhr and Cyp17a1 as analyzed via quantitative real-time PCR. We found that exposure to excess testosterone in early life increased the LH and testosterone serum levels, the LH/FSH ratio, ovarian theca-interstitial area and gene expression of Lhr and Cyp17a1 in adult rats. Estrogen induced an increase in the ovarian theca-interstitial area, the secondary follicle population and gene expression of Lhr and Cyp17a1. All animals exposed to the sex steroids presented with closed vaginas. Our data suggest that testosterone resulted in more pronounced reproductive changes than did estrogen exposure. Our results might provide some insight into the role of different hormones on reproductive development and on the heterogeneity of clinical manifestations of conditions such as polycystic ovary syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. [Hypothyroidism Associated to TSH Hormone-Receptor Autoantibodies with Blocking Activity Assessed In Vitro].

    PubMed

    Marques, Pedro; Chikh, Karim; Charrié, Anne; Pina, Rosa; Bugalho, Maria João; Lopes, Lurdes

    2015-01-01

    Thyroid-stimulating hormone-receptor autoantibodies normally causes hyperthyroidism. However, they might have blocking activity causing hypothyroidism. A 11-year-old girl followed due to type 1 diabetes mellitus, celiac disease and euthyroid lymphocytic thyroiditis at diagnosis. Two years after the initial evaluation, thyroid-stimulating hormone was suppressed with normal free T4; nine months later, a biochemical evolution to hypothyroidism with thyroid-stimulating hormone-receptor autoantibodies elevation was seen; the patient remained always asymptomatic. Chinese hamster ovary cells were transfected with the recombinant human thyroid-stimulating hormone -receptor, and then exposed to the patient's serum; it was estimated a 'moderate' blocking activity of these thyroid-stimulating hormone-receptor autoantibodies, and concomitantly excluded stimulating action. In this case, the acknowledgment of the blocking activity of the serum thyroid-stimulating hormone-receptor autoantibodies, supported the hypothesis of a multifactorial aetiology of the hypothyroidism, which in the absence of the in vitro tests, we would consider only as a consequence of the destructive process associated to lymphocytic thyroiditis.

  9. Risk factors for neonatal thyroid dysfunction in pregnancies complicated by Graves' disease.

    PubMed

    Uenaka, Mizuki; Tanimura, Kenji; Tairaku, Shinya; Morioka, Ichiro; Ebina, Yasuhiko; Yamada, Hideto

    2014-06-01

    To determine the factors related to adverse pregnancy outcomes and neonatal thyroid dysfunction in pregnancies complicated by Graves' disease. Thirty-five pregnancies complicated by Graves' disease were divided into two groups: adverse pregnancy outcome (n=15) and no adverse pregnancy outcome (n=20). Adverse pregnancy outcomes included spontaneous abortion, stillbirth, premature delivery, fetal growth restriction, and pregnancy-induced hypertension. The 31 pregnancies resulting in live births were also divided into two groups: neonatal thyroid dysfunction (n=9) and normal neonatal thyroid function (n=22). Serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4), TSH-receptor antibody (TRAb), the duration of hyperthyroidism in pregnancy, doses of antithyroid medication, and the duration of maternal antithyroid medication throughout pregnancy were compared. There were no significant differences in these factors between pregnancies with an adverse pregnancy outcome and those with no adverse pregnancy outcome. However, serum levels of FT4, TRAb, the duration of hyperthyroidism in pregnancy, the maximum daily dose of antithyroid medication, and the total dose of antithyroid medication were significantly different between pregnancies with neonatal thyroid dysfunction and those with normal neonatal thyroid function. Multivariate logistic regression analysis showed that the FT4 level in mothers was a significant factor related to the development of neonatal thyroid dysfunction (odds ratio 28.84, 95% confidence interval 1.65-503.62, p<0.05). Graves' disease activity in women of childbearing age should be well controlled prior to conception. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Release of Multiple Hormones by a Direct Action of Interleukin-1 on Pituitary Cells

    DTIC Science & Technology

    1987-10-23

    monolayer culture was investigated. Recombinant human IL-I beta stimulated the secretion of adrenocorticotropic hormone, luteinizing hormone, growth ... hormone , and thyroid-stimulating hormone. Prolactin secretion by the monolayers was inhibited by similar doses. These concentrations of IL-I are within

  11. Neonatal thyroid function: prematurity, prenatal steroids, and respiratory distress syndrome.

    PubMed Central

    Franklin, R C; Purdie, G L; O'Grady, C M

    1986-01-01

    Indices of thyroid function were measured in 97 preterm infants at birth and at 5, 10, and 15 days of age. Triiodothyronine uptake, free thyroxine index, thyroxine, free thyroxine, triiodothyronine, reverse triiodothyronine, and thyroxine binding globulin values at birth correlated with gestational age, whereas thyroid stimulating hormone values did not. Treatment with steroids prenatally had no apparent effect on thyroid function at birth or postnatally. Infants developing respiratory distress syndrome had normal values for all indices at birth. These infants had significantly lower thyroxine, free thyroxine index, free thyroxine, and triiodothyronine values at 5 days of age, while thyroid stimulating hormone values remained normal. This alteration in thyroid function was interpreted as being secondary to respiratory distress syndrome. Gestational maturity and respiratory distress syndrome, if present, must be taken into account when evaluating thyroxine variables in preterm infants, whereas measurement of thyroid stimulating hormone as the screen for congenital hypothyroidism circumvents these considerations. PMID:3729529

  12. Thyroid Stimulating Hormone Is Increased in Hypertensive Patients with Obstructive Sleep Apnea

    PubMed Central

    Heizhati, Mulalibieke; Sun, Chao; Abulikemu, Suofeiya; Shao, Liang; Yao, Xiaoguang; Wang, Yingchun; Hong, Jing; Zhou, Ling; Wang, Lei; Zhang, Yu; Zhang, Weiwei

    2016-01-01

    Purpose. To evaluate alteration in serum TSH in hypertensives with OSA and its relation with cardiometabolic risk factors. Methods. 517 hypertensives were cross-sectionally studied. OSA was determined by polysomnography and thyroid function by standard methods. Results. OSA was diagnosed in 373 hypertensives (72.15%). Prevalence of subclinical hypothyroidism was significantly higher in OSA hypertensives than in non-OSA ones (15.0% versus 6.9%, P = 0.014). Serum LnTSH in hypertensives with severe OSA was significantly higher (0.99 ± 0.81 versus 0.74 ± 0.77 μIU/mL, P < 0.05) than in those without OSA. AHI, LSaO2, ODI3, and ODI4 were independently associated with serum TSH for those aged 30–65 years. Dividing subjects into four groups as TSH < 1.0 μIU/mL, 1.0 ≤ THS ≤ 1.9 μIU/mL, 1.91 ≤ TSH < 4.5 μIU/mL, and TSH ≥ 4.5 μIU/mL, only 26.3% of OSA subjects exhibited TSH between 1.0 and 1.9 μIU/mL, significantly less than non-OSA subjects (26.3% versus 38.2%, P = 0.01). DBP and serum LDL-c elevated with TSH increasing and were only significantly higher in TSH ≥ 4.5 μIU/mL group than in 1.0 ≤ TSH ≤ 1.9 μIU/mL group (96.32 ± 14.19 versus 92.31 ± 12.86 mmHg; P = 0.040; 0.99 ± 0.60 versus 0.87 ± 0.34 mmol/L, P = 0.023). Conclusion. OSA might be a risk factor for increased TSH even within reference range in hypertensive population. PMID:27882050

  13. High Thyroid-stimulating Hormone Levels Increase Proinflammatory and Cardiovascular Markers in Patients with Extreme Obesity.

    PubMed

    Gómez-Zamudio, Jaime Héctor; Mendoza-Zubieta, Victoria; Ferreira-Hermosillo, Aldo; Molina-Ayala, Marío Antonio; Valladares-Sálgado, Adán; Suárez-Sánchez, Fernando; de Jesús Peralta-Romero, Jose; Cruz, Miguel

    2016-08-01

    Obesity is an important health problem worldwide and many studies have suggested a relationship between obesity and thyroid function, with controversial results. Interestingly, high TSH levels have been involved with the presence of inflammatory state and risk for developing cardiovascular diseases in hypothyroid and obese patients. The aim in this work was to determine the prevalence of hypothyroidism in patients with extreme obesity and to determine whether their TSH levels were related to increased serum levels of inflammatory and cardiovascular markers. A cross-sectional study in 101 patients with extreme obesity (BMI ≥40) was performed. Anthropometric (weight, height and waist circumference) and biochemical (fasting glucose, glycosylated hemoglobin, triglycerides, total cholesterol, LDL-C, HDL-C and insulin) parameters were measured. TSH and FT4 levels as well as clinical exploration for diagnosis of hypothyroidism were carried out. Serum concentration of IL-10, IL-6, adiponectin, resistin, leptin, ICAM-1, VCAM-1 and E-selectin were determined. A high prevalence for diabetes (37.6%), prediabetes (50.5%), dyslipidemia (74.3%), hypertension (61.4%) and hypothyroidism (48.5%) was observed in patients with extreme obesity. The presence of hypothyroidism increased serum concentration of proinflammatory cytokines IL-6 and leptin and decreased the antiinflammatory cytokine adiponectin. In addition, serum TSH levels showed a correlation for waist circumference, weight, BMI, A1c, insulin, IL-6, leptin, ICAM-1 and E-selectin. There is a high prevalence for hypothyroidism in patients with extreme obesity. High levels of TSH contribute to elevate proinflammatory and cardiovascular risk markers, increasing the risk for development of cardiovascular diseases. Copyright © 2016 IMSS. Published by Elsevier Inc. All rights reserved.

  14. Harmonization protocols for thyroid stimulating hormone (TSH) immunoassays: different approaches based on the consensus mean value.

    PubMed

    Clerico, Aldo; Ripoli, Andrea; Zucchelli, Gian Carlo; Plebani, Mario

    2015-02-01

    The lack of interchangeable laboratory results and consensus in current practices has underpinned greater attention to standardization and harmonization projects. In the area of method standardization and harmonization, there is considerable debate about how best to achieve comparability of measurement for immunoassays, and in particular heterogeneous proteins. The term standardization should be used only when comparable results among measurement procedures are based on calibration traceability to the International System of Units (SI unit) using a reference measurement procedure (RMP). Recently, it has been promoted the harmonization of methods for many immunoassays, and in particular for thyreotropin (TSH), as accepted RMPs are not available. In a recent paper published in this journal, a group of well-recognized authors used a complex statistical approach in order to reduce variability between the results observed with the 14 TSH immunoassay methods tested in their study. Here we provide data demonstrating that data from an external quality assessment (EQA) study allow similar results to those obtained using the reported statistical approach.

  15. Localization of cells producting thyroid stimulating hormone in the pituitary gland of the domestic drake.

    PubMed

    Sharp, P J; Chiasson, R B; El Tounsy, M M; Klandorf, H; Radke, W J

    1979-04-30

    Cells binding anti-bovine TASH beta serum were found exclusively in the rostral lobe of the adenohypophysis of the drake using the peroxidase-antiperoxidase complex unlabelled antibody method. The specificity of the binding of the anti-serum to TSH cells was established by relating the morphology and relative abundance of immunochemically stained cells to the TSH content of the adenohypophysis after experimentally altering the activity of the pituitary-thyroid axis. The TSH activity of the adenohypophysis was assessed indirectly, by the weight of the thyroid glands, and directly, by bioassay. As determined by bioassay, the TSH content of the rostral lobe of the adenohypophysis was much greater than that of the caudal lobe. Compared with control drakes, immunochemically stained cells in birds fed a goitrogen, methimazole, seemed to be enlarged and were closer together, while the stained cells in drakes injected with thyroxine were shrunken and less intensely stained. The TSH content of the adenohypophysis was increased in drakes fed methimazole. Castration did not alter the TSH content of the adenohypophysis or change the morphology of immunochemically stained cells. These observations suggest that in the drake: 1) anti-bovine TSH beta serum binds specifically to TSH cells; 2) the TSH cells occur in the rostral and not in the caudal lobe of the adenohypophysis; and 3) the activity of TSH cells is not inhibited by the feedback effects of gonadal steroids.

  16. Neonatal exposure to 17α-ethynyl estradiol (EE) disrupts follicle development and reproductive hormone profiles in female rats.

    PubMed

    Zhang, Haolin; Taya, Kazuyoshi; Nagaoka, Kentaro; Yoshida, Midori; Watanabe, Gen

    2017-07-05

    Toxic effects induced by exposure to endocrine-disrupting chemicals during fetal and neonatal periods can be irreversible and exert effects throughout an animal's entire life. Our previous study showed that neonatal exposure to 17α-ethynyl estradiol (EE) induced irregular estrous cycle in adults. To uncover the reason for the delayed effect after neonatal exposure to EE, reproductive parameters including ovarian weight, ovarian steroidogenesis, and hormonal profiles were investigated in developing female rats. Ovarian weight decreased at postnatal days (PND) 14 and 21 after neonatal exposure to EE. Ovarian histology at PND21 showed that the ratio of follicles with a diameter >300μm decreased and the ratio of follicles with a diameter of 100-150μm increased in EE-treated ovaries, indicating that neonatal exposure to EE retarded follicular development. Moreover, the expression of P450arom increased at PND14 and the expressions of inhibin/activin subunits βA and βB decreased at PND21 in EE-treated ovaries. Consistent with the expression of P450arom, circulating levels of 17β-estradiol increased at PND14 in EE-treated animals. Furthermore, the circulating levels of luteinizing hormone (LH) also increased at PND14 in the treated animals. Although the expression of Kiss1 did not change in the anteroventral periventricular nucleus (AVPV) of the hypothalamus between controls and EE-treated rats, the expression of Kiss1 was reduced in the arcuate nucleus (ARC) of the hypothalamus at PND14. Based upon those results, we suggest that neonatal exposure to EE disrupted the system regulating the interactions between the reproductive hormones and follicle development in pre-pubertal rats, which may result in reproduction dysfunction in adulthood. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Usefulness of Measuring Thyroid Stimulating Antibody at the Time of Antithyroid Drug Withdrawal for Predicting Relapse of Graves Disease.

    PubMed

    Kwon, Hyemi; Kim, Won Gu; Jang, Eun Kyung; Kim, Mijin; Park, Suyeon; Jeon, Min Ji; Kim, Tae Yong; Ryu, Jin Sook; Shong, Young Kee; Kim, Won Bae

    2016-06-01

    Hyperthyroidism relapse in Graves disease after antithyroid drug (ATD) withdrawal is common; however, measuring the thyrotropin receptor antibody (TRAb) at ATD withdrawal in order to predict outcomes is controversial. This study compared measurement of thyroid stimulatory antibody (TSAb) and thyrotropin-binding inhibitory immunoglobulin (TBII) at ATD withdrawal to predict relapse. This retrospective study enrolled patients with Graves disease who were treated with ATDs and whose serum thyroid-stimulating hormone levels were normal after receiving low-dose ATDs. ATD therapy was stopped irrespective of TRAb positivity after an additional 6 months of receiving the minimum dose of ATD therapy. Patients were followed using thyroid function tests and TSAb (TSAb group; n=35) or TBII (TBII group; n=39) every 3 to 6 months for 2 years after ATD withdrawal. Twenty-eight patients (38%) relapsed for a median follow-up of 21 months, and there were no differences in baseline clinical characteristics between groups. In the TSAb group, relapse was more common in patients with positive TSAb at ATD withdrawal (67%) than patients with negative TSAb (17%; P=0.007). Relapse-free survival was shorter in TSAb-positive patients. In the TBII group, there were no differences in the relapse rate and relapse-free survivals according to TBII positivity. For predicting Graves disease relapse, the sensitivity and specificity of TSAb were 63% and 83%, respectively, whereas those of TBII were 28% and 65%. TSAb at ATD withdrawal can predict the relapse of Graves hyperthyroidism, but TBII cannot. Measuring TSAb at ATD withdrawal can assist with clinical decisions making for patients with Graves disease.

  18. Analysis of serum Calcium, Magnesium, and Parathyroid Hormone in neonates delivered following preeclampsia treatment.

    PubMed

    Vahabi, S; Zaman, M; Farzan, B

    2016-12-30

    Due to the approximate clinical and biochemical manifestations of calcium and magnesium disturbances, with regard to the regulatory effects of parathyroid hormone (PTH), this present study is designed to analyze serum calcium (Ca), magnesium (Mg), and (PTH) at the time of birth, 24 hours afterwards in newborns after the mother has been treated with Mg-sulfate. We registered 86 term and preterm neonates (43 in each group) using simple census method delivered through vagina to preeclampsia pregnant women treated with Mg-sulfate immediately before birth in Khoramabad Asali Hospital, Iran. The first specimen was obtained from umbilical cord blood at birth, followed by the second sample of 2cc peripherally obtained from blood 24 hours after birth. The mean serum Mg level was higher than normal for both specimens in both term and preterm groups with no significant difference. The mean serum Ca level was higher in term group at both occasions, which turned out to be statistically significant (P<0.000) and (P=0.001) for the first and second specimens respectively. The mean PTH level was also in normal range for both groups at both times with no statistical significance. On the other hand, magnesium level showed a significant decline at 24 hours (P = 0.005) while PTH increased significantly (p<0.000) and (p=0.005) for term and preterm groups respectively. In contrast, Ca changes were not significantly different between the two specimens. Treatment with Mg-sulfate immediately before vaginal delivery increases Mg in both term and preterm neonates with no effect on Ca and PTH levels.

  19. Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone

    NASA Technical Reports Server (NTRS)

    Sajdel-Sulkowska, E. M.; Li, G. H.; Ronca, A. E.; Baer, L. A.; Sulkowski, G. M.; Koibuchi, N.; Wade, C. E.

    2001-01-01

    The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.

  20. Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone

    NASA Technical Reports Server (NTRS)

    Sajdel-Sulkowska, E. M.; Li, G. H.; Ronca, A. E.; Baer, L. A.; Sulkowski, G. M.; Koibuchi, N.; Wade, C. E.

    2001-01-01

    The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.

  1. Variability of Hormonal Stress Markers and Stress Responses in a Large Cross-Sectional Sample of Elephant Seals

    DTIC Science & Technology

    2012-09-30

    adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH) challenges and characterize the activation of the hypothalamic-pituitary-adrenal...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. Variability of Hormonal Stress Markers and Stress...number. 1. REPORT DATE 2012 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Variability of Hormonal Stress Markers and Stress

  2. Hormone replacement with 17β-estradiol plus dihydrotestosterone restores male sexual behavior in rats treated neonatally with clomipramine.

    PubMed

    Limón-Morales, Ofelia; Soria-Fregozo, Cesar; Arteaga-Silva, Marcela; González, Marisela Hernández; Vázquez-Palacios, Gonzalo; Bonilla-Jaime, Herlinda

    2014-11-01

    Male sexual behavior (MSB) in rodents, in both its consummatory and motivational components, is regulated by hormones such as testosterone, 17β-estradiol and 5-α-dihydrotestosterone. In experiments, neonatal treatment with clomipramine (CMI; a serotonin reuptake inhibitor) reproduces some of the signs of depression in adult age, including reduced sexual behavior manifested in a lower percentage of subjects that mount, intromit and ejaculate, although their testosterone levels were not altered. However, the effect of this treatment on estrogen levels and the consequences of hormone substitution using 17β-estradiol and 5-α-dihydrotestosterone on the expression of male sexual behavior are still unknown. Therefore, the objective of the present study was to analyze the effect of neonatal treatment with CMI on plasma testosterone and 17β-estradiol levels, and the role of testosterone, 17β-estradiol and 5-α-dihydrotestosterone in altering the consummatory and motivational components of sexual behavior in male rats. To this end, it analyzed the copulatory parameters and sexual incentive motivation (SIM) of rats treated with CMI under two conditions: basal and post-hormone replacements. Neonatal treatment with CMI did not affect plasma testosterone or 17β-estradiol concentrations, but did decrease both the consummatory component and sexual motivation according to the results of the SIM test. These aspects were recovered after administering 17β-estradiol +5-α-dihydrotestosterone, but not testosterone. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Developmental thyroid hormone insufficiency reduces expression of brain-derived neurotrophic factor (BDNF) in adults but not in neonates.

    PubMed

    Lasley, S M; Gilbert, M E

    2011-01-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expression of BDNF in a number of brain regions. The present study examined the impact of modest levels of developmental thyroid hormone insufficiency on BDNF protein expression in the hippocampus, cortex and cerebellum in the neonatal and adult offspring of rat dams treated throughout pregnancy and lactation. Graded levels of hormone insufficiency were induced by adding propylthiouracil (PTU, 0, 1, 2, 3 and 10 ppm) to the drinking water of pregnant dams from early gestation (gestational day 6) until weaning of the pups. Pups were sacrificed on postnatal days (PN) 14 and 21, and -PN100, and trunk blood collected for thyroid hormone analysis. Hippocampus, cortex, and cerebellum were separated from dissected brains and assessed for BDNF protein. Dose-dependent reductions in serum hormones in dams and pups were produced by PTU. Consistent with previous findings, age and regional differences in BDNF concentrations were observed. However, no differences in BDNF expression were detected in the preweanling animals as a function of PTU exposure; yet dose-dependent alterations emerged in adulthood despite the return of thyroid hormone levels to control values. Males were more affected by PTU than females, BDNF levels in hippocampus and cortex were altered but not those in cerebellum, and biphasic dose-response functions were detected in both sexes. These findings indicate that BDNF may mediate some of the adverse effects accompanying developmental thyroid hormone insufficiency, and reflect the potential for delayed impact of modest reductions in thyroid hormones during critical periods of brain development on a protein important for normal synaptic function.

  4. Thyroxine-Based Screening for Congenital Hypothyroidism in Neonates with Down Syndrome.

    PubMed

    Erlichman, Ira; Mimouni, Francis B; Erlichman, Matityahu; Schimmel, Michael S

    2016-06-01

    To ascertain whether thyroxine (T4)-based screening programs for congenital hypothyroidism (initial measurement of total T4 [tT4] followed by thyroid stimulating hormone [TSH] measurement in patients with tT4 <10th percentile) identifies congenital hypothyroidism in all neonates with Down syndrome. Retrospective cohort study of 159 neonates with Down syndrome, born during the period 1998-2007 were included. Screening test results were compared with those of the general population. All primary care physicians of these infants were contacted and infants' thyroid status verified. tT4 concentrations in children with Down syndrome were significantly lower, and TSH higher than those in the general population; tT4 concentrations did not correlate with screening TSH concentrations. Twenty children with Down syndrome were treated with L-thyroxin within the first month of life although only 10 babies had been identified by the routine screening test. T4-based screening does not identify many cases of congenital hypothyroidism in neonates with Down syndrome. We recommend that neonates with Down syndrome be screened by simultaneous measurements of both tT4 and TSH. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. The Relationship between Perchlorate in Drinking Water and Cord Blood Thyroid Hormones: First Experience from Iran.

    PubMed

    Javidi, Ashraf; Rafiei, Nasim; Amin, Mohammad Mehdi; Hovsepian, Silva; Hashemipour, Mahin; Kelishadi, Roya; Taghian, Zahra; Mofateh, Samaneh; Poursafa, Parinaz

    2015-01-01

    Considering the controversial information regarding the effects of perchlorate on thyroid function of high risk population as neonates, and given the high prevalence rate of thyroid disorders specially congenital hypothyroidism in our region, this study aims to investigate for the first time in Iran, the relationship between drinking groundwater perchlorate and cord blood thyroid hormones level in an industrial region. In this cross-sectional study, drinking groundwater perchlorate level of rural areas of Zarinshahr, Isfahan was measured. Simultaneously, cord blood level of thyroid hormones of neonates born in the studied region was measured. Thyroid function test of neonates in regions with low and high perchlorate level were compared. In this study, 25 tap water samples were obtained for perchlorate measurement. Level of cord blood thyroid stimulating hormone (TSH), T4 and T3 of 25 neonates were measured. Mean (standard deviation) of perchlorate, TSH, T4 and T3 was 3.59 (5.10) μg/l, 7.81 (4.14) mIU/m, 6.06 (0.85) mg/dl, and 63.46 (17.53) mg/dl, respectively. Mean levels of thyroid function tests were not different in low (<5 μg/l) and high level of drinking ground water perchlorate (P > 0.05). Perchlorate did not appear to be related to thyroid function of neonates in the studied industrial region. It seems that iodine status of the regions, as well as other environmental contaminants and genetic background, could impact on its relation with thyroid function of neonates.

  6. The Relationship between Perchlorate in Drinking Water and Cord Blood Thyroid Hormones: First Experience from Iran

    PubMed Central

    Javidi, Ashraf; Rafiei, Nasim; Amin, Mohammad Mehdi; Hovsepian, Silva; Hashemipour, Mahin; Kelishadi, Roya; Taghian, Zahra; Mofateh, Samaneh; Poursafa, Parinaz

    2015-01-01

    Background: Considering the controversial information regarding the effects of perchlorate on thyroid function of high risk population as neonates, and given the high prevalence rate of thyroid disorders specially congenital hypothyroidism in our region, this study aims to investigate for the first time in Iran, the relationship between drinking groundwater perchlorate and cord blood thyroid hormones level in an industrial region. Methods: In this cross-sectional study, drinking groundwater perchlorate level of rural areas of Zarinshahr, Isfahan was measured. Simultaneously, cord blood level of thyroid hormones of neonates born in the studied region was measured. Thyroid function test of neonates in regions with low and high perchlorate level were compared. Results: In this study, 25 tap water samples were obtained for perchlorate measurement. Level of cord blood thyroid stimulating hormone (TSH), T4 and T3 of 25 neonates were measured. Mean (standard deviation) of perchlorate, TSH, T4 and T3 was 3.59 (5.10) μg/l, 7.81 (4.14) mIU/m, 6.06 (0.85) mg/dl, and 63.46 (17.53) mg/dl, respectively. Mean levels of thyroid function tests were not different in low (<5 μg/l) and high level of drinking ground water perchlorate (P > 0.05). Conclusions: Perchlorate did not appear to be related to thyroid function of neonates in the studied industrial region. It seems that iodine status of the regions, as well as other environmental contaminants and genetic background, could impact on its relation with thyroid function of neonates. PMID:25789149

  7. Polyethylene glycol method is superior to ammonium sulfate and protein-A sepharose-4B method in fractionating thyroid stimulating immunoglobulin in Graves' disease.

    PubMed

    Jap, T S; Jenq, S F; Wong, M C; Chiang, H

    1995-03-01

    The purpose of this study is to compare the performance of three methods, i.e., ammonium sulfate, polyethylene glycol (PEG) and protein A sepharose 4B in fractionation of thyroid stimulating immunoglobulin. Twelve patients with Graves' disease and twelve age-, sex-matched normal controls were recruited. 0.9 ml of saturated ammonium sulfate was added slowly to 1.1 ml of sera of all subjects and was stirred until reaching 45% saturation. The precipitation was allowed to form at 4 degrees C overnight. The solution was centrifuged at 10,000 x g for 5 minutes. The precipitate was washed twice with 45% ammonium sulfate, dissolved in 0.55 ml of distilled water equal to half of the initial volume of the serum and dialyzed against 200 volumes of phosphate-buffered saline (PBS) for 48 hours. Another 0.5 ml of serum sample from the same patients was mixed with 1.5 ml of 20% polyethylene, followed by centrifugation at 2,800 g for 20 minutes. The pellet was dissolved in 0.6 ml of Hanks' medium without NaCl containing 1.5% bovine serum albumin, 20mM HEPES: 1 ml of sera was applied to 0.75 g of protein A sepharose-4B in PBS buffer and eluted with glycine, pH 2.3. By adding immunoglobulin (Ig) from the different methods to the FRTL-5 tissue culture, we determined the cAMP generation. Patients with Graves' disease were found to have higher serum thyroxine and triiodothyronine concentrations (p < 0.001) and significantly higher free thyroxine concentration than normal subjects. Ig elicited stronger response in cyclic AMP generation when prepared with PEG method, as compared with the other two methods (p < 0.001). With sepharose-4B Ig preparation, 10 out 12 patients (83.33%) showed positive thyroid stimulating immunoglobulin (TSI) while with ammonium sulfate precipitation, nine out 12 patients (75%) showed positive TSI. On the other hand, all patients showed positive TSI with PEG precipitation. When the degree of thyrotoxicosis was classified in terms of thyroid hormone

  8. Foetal and neonatal thyroid disorders.

    PubMed

    Radetti, G; Zavallone, A; Gentili, L; Beck-Peccoz, P; Bona, G

    2002-10-01

    recently identified are represented by TSH receptor mutations leading to constitutively activated TSH receptor. Infants born to mothers with Graves' history may develop neonatal thyrotoxicosis. Foetal/neonatal disease is due to transplacental thyrotrophin receptor stimulating antibodies (TRAb) passage. It's extremely important recognizing and treating Graves' disease in mothers as soon as possible, because a thyrotoxic state may have adverse effects on the outcome of pregnancy and both on the foetus and newborn. Thyrotoxic foetuses may develop goitre, tachycardia, hydrops associated with heart failure, growth retardation, craniosynostosis, increased foetal motility and accelerated bone maturation. Neonatal Graves' disease tends to resolve spontaneously within 3-12 weeks as maternal thyroid stimulating immunoglobulins are cleared from the circulation but subsequent development may be impaired by perceptual motor difficulties. Hashimoto's thyroiditis is a very common autoimmune thyroid disease. In presence of maternal Hashimoto's thyroiditis, there are usually no consequences on foetal thyroid, even if antiTPO and antiTg antibodies can be found in the newborn due to transplacental passage. However there are some literature reports describing foetal and neonatal hyperthyroidism in the affected mothers' offspring.

  9. Sexual differentiation of oxytocin stress responsiveness: effect of neonatal androgenization, castration and a luteinizing hormone-releasing hormone antagonist.

    PubMed

    Carter, D A; Saridaki, E; Lightman, S L

    1988-04-01

    The plasma OT increment following stress in rats is sexually dimorphic, females exhibiting greater responses than males. We have investigated the role of neonatal androgen secretion in determining the sex-typical level of response. Castration of male pups either surgically or functionally (GnRH antagonist treatment) within either 2 h or 5 days of birth did not elevate the OT responses of adult males. In contrast, androgenization of female pups (testosterone, 1.25 mg/pup) within 5 days of birth markedly reduced the OT stress responses of adults to a level insignificantly different to males. The results show that neonatal androgens can exert organizational effects on OT regulatory mechanisms. Since neonatal castration was ineffective it would appear that a prenatal defeminization or masculinization event determines OT stress responsiveness in males.

  10. Association between Maternal Serum Perfluoroalkyl Substances during Pregnancy and Maternal and Cord Thyroid Hormones: Taiwan Maternal and Infant Cohort Study

    PubMed Central

    Rogan, Walter J.; Chen, Pau-Chung; Lien, Guang-Wen; Chen, Hsiao-Yen; Tseng, Ying-Chih; Longnecker, Matthew P.

    2014-01-01

    Background: Perfluoroalkyl substances (PFASs) are synthetic compounds that are widely used in industry and are often detectable in humans. In pregnant rats and their pups, PFASs can interfere with thyroid hormone homeostasis. In humans, maternal thyroid hormones supply the fetus throughout pregnancy, and thyroid hormones play a critical role in fetal growth and neurodevelopment. Objectives: We investigated the association between maternal PFAS exposure and thyroid hormone status in pregnant women and neonates. Methods: In a study of environmental exposure and health in Taiwan, we measured serum concentrations of nine PFASs and four thyroid hormones for 285 pregnant women in their third trimester, and also measured cord serum thyroid hormones for 116 neonates. Associations between maternal PFASs and maternal and cord thyroid hormones were examined in multiple linear regression models. Results: Perfluorohexanesulfonic acid concentrations were positively associated with maternal thyroid-stimulating hormone (TSH) levels. Pregnant women with higher levels of perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUnDA), and perfluorododecanoic acid (PFDoDA) had lower free thyroxine (T4) and total T4 levels. For example, we estimated that maternal free T4 levels decreased 0.019 ng/dL (95% CI: –0.028, –0.009) with each nanogram per milliliter increase in maternal PFNA. Finally, maternal PFNA, PFUnDA, and PFDoDA levels were associated with lower cord total triiodothyronine (T3) and total T4 levels, and maternal perfluorodecanoic acid (PFDeA) was associated with lower cord total T3. Conclusions: Our results suggest that exposure to some PFASs during pregnancy may interfere with thyroid hormone homeostasis in pregnant women and fetuses. Citation: Wang Y, Rogan WJ, Chen PC, Lien GW, Chen HY, Tseng YC, Longnecker MP, Wang SL. 2014. Association between maternal serum perfluoroalkyl substances during pregnancy and maternal and cord thyroid hormones: Taiwan Maternal and

  11. Negative Feedback Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Metamorphosis in Xenopus laevis

    EPA Science Inventory

    A basic understanding of the endocrinology of the hypothalamic-pituitary-thyroid (HPT) axis of anuran larvae is necessary for predicting the consequences of HPT perturbation by thyroid-disrupting chemicals (TDCs) on the whole organism. This project examined negative feedback con...

  12. Negative Feedback Control of Pituitary Thyroid-stimulating Hormone Synthesis and Secretion by Thyroid Hormones during Metamorphosis in Xenopus laevis

    EPA Science Inventory

    A basic understanding of the endocrinology of the hypothalamic-pituitary-thyroid (HPT) axis of anuran larvae is necessary for predicting the consequences of HPT perturbation by thyroid-disrupting chemicals (TDCs) on the whole organism. This project examined negative feedback con...

  13. A bioassay for thyroid stimulating immunoglobulins of patients with Graves' disease using porcine thyroid monolayer cells.

    PubMed

    Fukue, Y; Uchimura, H; Kuzuya, N; Okano, S; Kanaji, Y; Takaku, F

    1986-06-01

    A bioassay for thyroid stimulating immunoglobulins (TSI) of patients with Graves' disease was developed by porcine thyroid monolayer cells. Thyroid cells were prepared by dispersion using collagenase and trypsin. Aliquots of the cell suspension (2 X 10(6) cells/1.5 ml/dish) in Ham's F-12 medium (pH 7.2) containing 10% calf serum and 1.5 mM Hepes were seeded and cultured in air at 36 C. On day 6 of culture, cells were incubated with test samples (IgG or bTSH) in 1 ml of serum-free, 0.5 mM IMX-included fresh medium for an additional time, and cAMP in the cells was measured by radioimmunoassay. Intracellular cAMP was increased within 5 minutes after the addition of bTSH and the maximal increase was observed after 30 min. Responses of cAMP were in a dose-related manner up to 10 mU/ml of bTSH. With the addition of IgG from untreated Graves' patients, dose-related increases in cAMP were also observed up to 10 mg/ml IgG and the maximal response was seen at 2 hours incubation. Thyroid stimulating activity in IgG's from normal subjects and patients with Graves' disease was tested with a dose of 10 mg/ml and 2 hours incubation and the activity was expressed as a percent of the control (incubated in the same experiment without IgG). One hundred forty one of 145 untreated patients showed higher activity (228 +/- 51.8%, mean +/- SD; 127-393%, range) than normal subjects (103 +/- 13.3%, mean +/- SD, n = 24; 80-129%, range). Sequential changes in TSI activity in 27 patients after initiating thionamide drugs were studied for 24 months. Initially all 27 patients showed positive TSI and 6 months later 15 remained positive. At 6 months after that, 10 of 23, 4 of 16, and 2 of 6 followed patients showed positive TSI. These results indicate that this bioassay is clinically useful for detecting TSI.

  14. Thyrotropin-Releasing Hormone is not Required for Thyrotropin Secretion in the Perinatal Rat

    PubMed Central

    Theodoropoulos, Theodor; Braverman, Lewis E.; Vagenakis, Apostolos G.

    1979-01-01

    To determine the role of thyrotropin-releasing hormone (TRH) in the regulation of thyroid-stimulating hormone (TSH) secretion in the perinatal period, a physiological approach of neutralizing circulating TRH in the fetal and early neonatal rat was employed. TRH-antiserum (TRH-AS) raised in rabbits and administered daily to low iodine-propylthiouracil (LID-PTU)-fed pregnant rats from days 12 to 19 of gestation markedly impaired the rise in serum TSH to LID-PTU when compared with normal rabbit serum-treated controls. In contrast, fetal serum TSH was unaffected by TRH-AS. The binding capacity of TRH-AS in the fetal serum (111 ng/ml) far exceeded circulating TRH in the fetus. Similarly, acute TRH-AS administration to the pregnant rat fed LID-PTU markedly decreased the serum TSH concentration in the mother, but not in the fetus, 60 min after TRH-AS administration. Chronic TRH-AS administration to neonatal rats whose nursing mothers were fed LID-PTU was in-effective in decreasing the elevated serum TSH in the neonate through day 8 of life, whereas a slight but significant decrease in serum TSH was observed on day 10. Chronic daily TRH-AS administration to neonatal rats through day 10 of life had no effect on the later development of the hypothalamic-pituitary-thyroid axis. These findings suggest that TRH does not participate in TSH regulation during the perinatal life in the rat and that thyroid hormones are probably the main regulators of TSH secretion during this period. Placental TRH is not important in regulating TSH secretion in the fetal rat. Furthermore, TRH “deprivation” during neonatal life does not prevent normal later development of the hypothalamic-pituitary-thyroid axis. PMID:108290

  15. Thyrotoxicosis in a neonate of a mother with no history of thyroid disease.

    PubMed

    Brookfield, D S; McCandless, A E; Smith, C S

    1976-04-01

    A newborn infant had rectal prolapse, congenital lactase deficiency, and temporary neonatal thyrotoxicosis. The thyrotoxicosis was associated with a raised long-acting thyroid stimulator index in a mother with no personal or family history of thyroid or related autoimmune disease. The parents were first cousins.

  16. Neonatal hormone changes and growth in lambs born to dams receiving differing nutritional intakes and selenium supplementation during gestation.

    PubMed

    Camacho, Leticia E; Meyer, Allison M; Neville, Tammi L; Hammer, Carolyn J; Redmer, Dale A; Reynolds, Lawrence P; Caton, Joel S; Vonnahme, Kimberly A

    2012-07-01

    To investigate the effects of maternal selenium (Se) supplementation and nutritional intake during gestation on hormone changes, percentage body weight (BW) change, and organ mass in neonatal lambs, ewes were allocated to differing Se levels (adequate Se (ASe, 11.5 μg/kg BW) or high Se (HSe, 77.0 μg/kg BW)) initiated at breeding and nutritional intake (60% (RES), 100% (CON), or 140% (HIGH) of NRC requirements) initiated at day 40 of gestation. At parturition, all lambs were removed from dams, fed common diets, and BW and blood samples were collected until day 19. There was a Se × nutritional intake × day interaction for percentage BW change from birth. Lambs born to ASe-HIGH ewes tended to have decreased BW change compared with ASe-CON and ASe-RES groups on day 7. Lambs from HSe-HIGH ewes tended to have increased BW change compared with HSe-RES and HSe-CON groups from days 7 to 19. At birth, there was a Se × sex of offspring interaction, in which male lambs from HSe ewes had decreased cortisol concentrations compared with all other lambs. By 24 h, lambs from RES ewes had decreased cortisol compared with those from HIGH ewes, with lambs from CON ewes being intermediate. Lambs from RES- and CON-fed ewes had greater thyroxine than HIGH ewes at 24 h. Organ masses on day 19 were mainly impacted by maternal nutritional intake and sex of the offspring. Birth weight alone did not predict growth performance during neonatal life. Moreover, despite a similar postnatal diet, maternal nutritional plane and Se status did impact neonatal endocrine profiles. Exact mechanisms of how neonatal endocrine status can influence later growth and development need to be determined.

  17. Effect of neonatal hypothyroidism on prepubertal mouse testis in relation to thyroid hormone receptor alpha 1 (THRα1).

    PubMed

    Sarkar, Debarshi; Singh, Shio Kumar

    2017-09-15

    Thyroid hormones (THs) are important for growth and development of many tissues, and altered thyroid status affects various organs and systems. Testis also is considered as a thyroid hormone responsive organ. Though THs play an important role in regulation of testicular steroidogenesis and spermatogenesis, the exact mechanism of this regulation remains poorly understood. The present study, therefore, is designed to examine the effect of neonatal hypothyroidism on prepubertal Parkes (P) strain mice testis in relation to thyroid hormone receptor alpha 1 (THRα1). Hypothyroidism was induced by administration of 6-propyl-2-thiouracil (PTU) in mother's drinking water from birth to day 28; on postnatal day (PND) 21 only pups, and on PND 28, both pups and lactating dams were euthanized. Serum T3 and T4 were markedly reduced in pups at PND 28 and in lactating mothers, while serum and intra-testicular testosterone levels were considerably decreased in pups of both age groups. Further, serum and intra-testicular levels of estrogen were significantly increased in hypothyroid mice at PND 28 with concomitant increase in CYP19 expression. Histologically, marked changes were noticed in testes of PTU-treated mice; immunohistochemical and western blot analyses of testes in treated mice also revealed marked decrease in the expression of THRα1 at both age groups. Semiquantitative RT-PCR and western blot analyses also showed reductions in both testicular mRNA and protein levels of SF-1, StAR, CYP11A1 and 3β-HSD in these mice. In conclusion, our results suggest that neonatal hypothyroidism alters localization and expression of THRα1 and impairs testicular steroidogenesis by down-regulating the expression SF-1, thereby affecting spermatogenesis in prepubertal mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Value of thyroid stimulating antibody in the diagnosis of thyroid associated ophthalmopathy of euthyroid patients

    PubMed Central

    Kazuo, K.; Fujikado, T.; Ohmi, G.; Hosohata, J.; Tano, Y.

    1997-01-01

    AIMS/BACKGROUND—Thyroid associated ophthalmopathy (TAO) of euthyroid patients is difficult to diagnose because clinical findings overlap with other conditions, and no confirmatory diagnostic tests are available. Recently, it was reported that TSH binding inhibitor immunoglobulin (TBII) and thyroid stimulating antibody (TSAb) are sensitive markers of TAO. The sensitivity of these antibodies in the detection of TAO were therefore studied to determine if they could be a useful criterion in the diagnosis of TAO of euthyroid patients.
METHODS—Serum values of TBII and TSAb of 35 patients with euthyroid TAO (group A) were compared with those of 27 patients with Graves' disease and TAO (group B). The relation between the serum value of TSAb and the eye symptoms of patients with euthyroid TAO were also examined by multiple linear regression analysis.
RESULTS—In group A, TBII was positive in 10 cases (28.6%) and TSAb was positive in 29 cases (82.9%). In group B, both TBII and TSAb were positive in all cases (100%). The titre of serum TBII in group A (15.6% (SD 18.0%)) was significantly lower (p<0.0001) than in group B (57.9% (21.5%)). The titre of serum TSAb in group A (1400.9% (2163.9%)) was significantly lower (p=0.0026) than in group B (2243.9% (1472.8%)). Among the eye findings of patients with euthyroid TAO, keratopathy was significantly (p=0.034) related to the value of TSAb.
CONCLUSION—These results suggest that the activity of TSAb is a more sensitive marker of euthyroid TAO than is TBII, and could be a useful criterion in the diagnosis of TAO of euthyroid patients.

 PMID:9497469

  19. The "TSH Receptor Glo Assay" - A High-Throughput Detection System for Thyroid Stimulation.

    PubMed

    Latif, Rauf; Lau, Zerlina; Cheung, Pamela; Felsenfeld, Dan P; Davies, Terry F

    2016-01-01

    To identify novel small molecules against the TSH receptor, we developed a sensitive transcription-based luciferase high-throughput screening (HTS) system named the TSHR-Glo Assay (TSHR-Glo). This assay uses double-transfected Chinese hamster ovary cells stably expressing the human TSHR and a cAMP-response element (CRE) construct fused to an improved luciferase reporter gene. The assay was highly responsive toward TSH in a dose-dependent manner with a TSH sensitivity of 10(-10)M (10 ± 1.12 μU/ml) and thyroid-stimulating antibodies, a hallmark of Graves' disease, could also be detected. The assay was validated against the standard indicator of HTS performance - the Z-factor (Z') - producing a score of 0.895. Using the TSHR-Glo assay, we screened 48,224 compounds from a diverse chemical library in duplicate plates at a fixed dose of 17 μM. Twenty molecules with the greatest activity out of 62 molecules that were identified by this technique were subsequently screened against the parent luciferase stable cell line in order to eliminate false positive stimulators. Using this approach, we were able to identify specific agonists against the TSH receptor leading to the characterization of several TSH agonist molecules. Hence, the TSHR-Glo assay was a one-step cell-based HTS assay, which was successful in the discovery of novel small molecular agonists and for the detection of stimulating antibodies to the TSH receptor.

  20. Value of thyroid stimulating antibody in the diagnosis of thyroid associated ophthalmopathy of euthyroid patients.

    PubMed

    Kazuo, K; Fujikado, T; Ohmi, G; Hosohata, J; Tano, Y

    1997-12-01

    Thyroid associated ophthalmopathy (TAO) of euthyroid patients is difficult to diagnose because clinical findings overlap with other conditions, and no confirmatory diagnostic tests are available. Recently, it was reported that TSH binding inhibitor immunoglobulin (TBII) and thyroid stimulating antibody (TSAb) are sensitive markers of TAO. The sensitivity of these antibodies in the detection of TAO were therefore studied to determine if they could be a useful criterion in the diagnosis of TAO of euthyroid patients. Serum values of TBII and TSAb of 35 patients with euthyroid TAO (group A) were compared with those of 27 patients with Graves' disease and TAO (group B). The relation between the serum value of TSAb and the eye symptoms of patients with euthyroid TAO were also examined by multiple linear regression analysis. In group A, TBII was positive in 10 cases (28.6%) and TSAb was positive in 29 cases (82.9%). In group B, both TBII and TSAb were positive in all cases (100%). The titre of serum TBII in group A (15.6% (SD 18.0%)) was significantly lower (p < 0.0001) than in group B (57.9% (21.5%)). The titre of serum TSAb in group A (1400.9% (2163.9%)) was significantly lower (p = 0.0026) than in group B (2243.9% (1472.8%)). Among the eye findings of patients with euthyroid TAO, keratopathy was significantly (p = 0.034) related to the value of TSAb. These results suggest that the activity of TSAb is a more sensitive marker of euthyroid TAO than is TBII, and could be a useful criterion in the diagnosis of TAO of euthyroid patients.

  1. Hormones

    MedlinePlus

    Hormones are your body's chemical messengers. They travel in your bloodstream to tissues or organs. They work ... glands, which are special groups of cells, make hormones. The major endocrine glands are the pituitary, pineal, ...

  2. Osteoclast Responses to Lipopolysaccharide, Parathyroid Hormone and Bisphosphonates in Neonatal Murine Calvaria Analyzed by Laser Scanning Confocal Microscopy

    PubMed Central

    Suzuki, Keiko; Takeyama, Sadaaki; Kikuchi, Takashi; Yamada, Shoji; Sodek, Jaro; Shinoda, Hisashi

    2005-01-01

    Because the development and activity of osteoclasts in bone remodeling is critically dependent on cell-cell and cell-matrix interactions, we used laser confocal microscopy to study the response of osteoclasts to lipopolysaccharide (LPS; 10 μg/ml), parathyroid hormone (PTH; 10−8 M), and bisphosphonates (BPs; 1–25 μM clodronate or 0.1–2.5 μM risedronate) in cultured neonatal calvaria. Following treatment with LPS or PTH (<48 hr), osteopontin (OPN) and the αvβ3 integrin were found colocalized with the actin ring in the sealing zone of actively resorbing osteoclasts. In contrast, non-resorbing osteoclasts in BP-treated cultures showed morphological abnormalities, including retraction of pseudopods and vacuolization of cytoplasm. In the combined presence of LPS and BP, bone-resorbing osteoclasts were smaller and the sealing zone diffuse, reflecting reduced actin, OPN, and β3 integrin staining. Depth analyses of calvaria showed that the area of resorbed bone was filled with proliferating osteoblastic cells that stained for alkaline phosphatase, collagen type I, and bone sialoprotein, regardless of the presence of BPs. These studies show that confocal microscopy of neonatal calvaria in culture can be used to assess the cytological relationships between osteoclasts and osteoblastic cells in response to agents that regulate bone remodeling in situ, avoiding systemic effects that can compromise in vivo studies and artifacts associated with studies of isolated osteoclasts. PMID:16087705

  3. [Oxytocin and syndrome of inappropriate secretion of antidiuretic neonatal hormone. Case report of early severe hyponatremia and literature review].

    PubMed

    Aldana-Valenzuela, Carlos; Prieto-Pantoja, José Alfredo; Hernández-Acevedo, Angélica

    2010-12-01

    This is a clinical case presentation of a full term newborn infant who suffered severe hyponatremia and early seizures, associated with maternal fluid overload with electrolyte free solutions and high doses of oxytocin for labor augmentation. Although this condition has been recognized since the 1960's with isolated reports, this particular case has features that needs further investigation, not only for the unsually severe hyponatremia, but most importantly we think, for the prominent signs of fluid retention, the infant had, that suggest excessive antidiuretic activity probably due to oxytocin. These findings are consistent with syndrome of inappropriate secretion of antidiuretic hormone. Although until now there is no proof that oxytocin by itself produces this syndrome. We think the association is possible in certain clinical circumstances, such as those found in this case. We also, briefly discussed the pathophysiology of perinatal hyponatremia, the neonatal treatment of this condition and the current guidelines for the women in labor. Hyponatremia should not be considered a benign condition, since in the neonate, it may affect brain function.

  4. Thyroid-stimulating antibody (TSAb) detected in sera of Graves' patients using human thyroid cell cultures

    PubMed Central

    Toccafondi, R. S.; Aterini, S.; Medici, Maria Alice; Rotella, C. M.; Tanini, Annalisa; Zonefrati, R.

    1980-01-01

    As a homologous system is required to evaluate the effect of thyroid-stimulating antibody (TSAb) present in the serum of Graves' patients, primary cultures obtained from normal human thyroid gland have been used and the stimulatory effect measured as an increase of cAMP intracellular levels. Monolayer cell cultures were stimulated by IgG purified from sera of Graves' patients or control subjects and compared to the effect of bovine TSH. Bovine TSH produced a dose-dependent increase in cAMP intracellular levels between 0·05 mU and 2·5 mU/ml, reaching a maximal value after 30 min with higher doses. While normal IgG had no effect, IgG prepared from untreated patients with frank Graves' disease elicited a significant increase in cAMP accumulation at a concentration between 0·05 and 0·5 mg/ml within 60 min in thirteen out of fourteen patients. A longer incubation period showed no further increase in cAMP values, even if in one case a higher concentration (5·0 mg/ml) of Graves' IgG had a delayed response. When the cAMP intracellular level modifications produced by Graves' IgG preparations in thyroid cell cultures were compared to those evoked in thyroid slices, an identical percentage (93%) of positive cases was obtained, without a coincidence of negative cases. Using thyroid slices the cAMP intracellular increase above basal levels was higher, if considered as a percentage, but in cultured cells a very low IgG concentration was sufficient to detect the presence of TSAb. No correlation between the two assays was found. In conclusion, normal human cultured thyroid cells appeared to be a more suitable substrate when compared to human thyroid slices for detecting the presence of TSAb in Graves' disease and for studying its effect on thyroid cells. However, a 100% TSAb positivity was present in our Graves' patient series only when both assays were used. PMID:6251989

  5. Thyroxine binding globulin excess detected by neonatal screening

    PubMed Central

    2016-01-01

    Inherited thyroxine binding globulin (TBG) disorder can be identified incidentally or through neonatal screening test. TBG excess is characterized by high levels of thyroxine (T4) but normal level of free T4 (fT4), while TBG deficiency presents with low T4 levels and normal fT4 levels. A 27-day-old newborn was brought to the hospital because of hyperthyroxinemia detected by neonatal screening. His T4 level was 18.83 µg/dL (normal range, 5.9–16.0 µg/dL). His mother had no history of any thyroid disease. His fT4 and thyroid stimulating hormone (TSH) levels were 1.99 ng/dL (normal range, 0.8–2.1 ng/dL) and 4.54 mIU/L (normal range, 0.5–6.5 mIU/L), respectively. His serum total triiodothyronine (T3) level was 322.5 ng/dL (normal range, 105.0–245.0 ng/dL). His TBG level was 68.27 mg/L (normal range, 16.0–36.0 mg/L) at the age of 3 months. At 6 months and 12 months of age, his TBG levels were 48.77 mg/L (normal range, 16.0–36.0 mg/L) and 50.20 mg/L (normal range, 14.0–28.0 mg/L), respectively, which were 2 to 3 times higher than normal values. Hormonal studies showed consistently elevated T3 and T4 levels and upper normal levels of fT4 and free T3 with normal TSH levels. His growth and development were normal. TBG excess should be considered as a potential differential diagnosis for hyperthyroxinemia and especially high T3 levels with normal TSH concentration. PMID:27462589

  6. Hyperemesis gravidarum affects maternal sanity, thyroid hormones and fetal health: a prospective case control study.

    PubMed

    Buyukkayaci Duman, Nuriye; Ozcan, Oguzhan; Bostanci, M Ömer

    2015-08-01

    Hyperemesis gravidarum (HG) is a condition of severe nausea or vomiting accompanied by various complications during pregnancy. In the present study, we aimed to demonstrate the effects of HG on mother and fetus health. Control and case group were arranged from 50 healthy pregnant women and 50 pregnant women with HG. Information about the participant women was gathered with data collection form and Beck's Depression Inventory (BDI) and State Anxiety Inventory (SAI) were administered to the women. Following an abortion or delivery, the data about birth complications and neonatal health were collected. All laboratory results (blood count, thyroid hormones, electrolyte values and biochemical parameters) were gathered from the laboratory information system used in the hospital. It was found that in the case group, mean postpartum weight, serum hemoglobin, hematocrit and thyroid stimulant hormone levels were lower than control group (p < 0.01). Conversely, case group women have higher T3 and T4 levels than control group (p < 0.01). There was no significant difference between the two groups in terms of intrauterine growth retardation, low birth weight and abortion but it was observed that women with HG had often delivered prematurely. The mean scores of BDI and SAI in the case group were higher than those of control group. These results suggested that HG may have adverse effects on both mother and baby's health. Pregnant women with HG should be provided with training and consultancy services and be closely monitored in terms of anemia and thyroid hormones.

  7. The effect of neonatal maternal stress on plasma levels of adrenocorticotropic hormone, corticosterone, leptin, and ghrelin in adult male rats exposed to acute heterotypic stressor.

    PubMed

    Holubová, A; Štofková, A; Jurčovičová, J; Šlamberová, R

    2016-12-22

    Activation of the hypothalamic-pituitary-adrenal (HPA) axis is important for maintenance of homeostasis during stress. Recent studies have shown a connection between the HPA axis and adipose tissue. The present study investigated the effect of acute heterotypic stress on plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), leptin, and ghrelin in adult male rats with respect to neonatal maternal social and physical stressors. Thirty rat mothers and sixty of their male progeny were used. Pups were divided into three groups: unstressed control (C), stressed by maternal social stressor (S), stressed by maternal social and physical stressors (SW). Levels of hormones were measured in adult male progeny following an acute swimming stress (10 min) or no stress. ELISA immunoassay was used to measured hormones. The ACTH and CORT levels were significantly increased in all groups of adult progeny after acute stress; however, CORT levels were significantly lower in both neonatally stressed groups compared to controls. After acute stress, plasma leptin levels were decreased in the C and SW groups but increased in the S group. The data suggest that long-term neonatal stressors lead to lower sensitivity of ACTH receptors in the adrenal cortex, which could be a sign of stress adaptation in adulthood. Acute stress in adult male rats changes plasma levels of leptin differently relative to social or physical neonatal stressors.

  8. Racial variation in umbilical cord blood sex steroid hormones and the insulin-like growth factor axis in African-American and white female neonates

    PubMed Central

    Agurs-Collins, Tanya; Rohrmann, Sabine; Sutcliffe, Catherine; Bienstock, Jessica L.; Monsegue, Deborah; Akereyeni, Folasade; Bradwin, Gary; Rifai, Nader; Pollak, Michael N.; Platz, Elizabeth A.

    2012-01-01

    Purpose To evaluate whether there is racial variation in venous umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF)-axis between female African-American and white neonates. Methods Maternal and birth characteristics and venous umbilical cord blood samples were collected from 77 African-American and 41 white full-term uncomplicated births at two urban hospitals in 2004 and 2005. Cord blood was measured for testosterone, dehydroespiandrosterone-sulfate (DHEAS), estradiol, sex-steroid hormone binding globulin (SHBG) by immunoassay. IGF-1, IGF-2, and IGF binding protein-3 (IGFBP-3) were measured by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed for the hormones. Results African-American neonates weighed less at birth (3,228 vs. 3,424 grams, p<0.004) than whites. Birth weight was positively correlated with IGF-1, IGFBP-3 and the molar ratio of IGF1 to IGFBP-3, but inversely correlated with the molar ratio of IGF-2 to IGFBP-3. Adjusted models showed higher testosterone (1.82 vs. 1.47 ng/mL, p=0.006) and the molar ratio of testosterone to SHBG (0.42 vs. 0.30, p=0.03) in African-American compared to white female neonates. IGF-1, IGF-2, and IGFBP-3 were lower in African-American compared to white female neonates, but only the difference for IGF-2 remained significant (496.5 vs. 539.2 ng/mL, p=0.04). Conclusion We provide evidence of racial variation in cord blood testosterone and testosterone to SHBG in African-American compared to white female neonates, and higher IGF-2 in white compared to African-American female neonates. Findings suggest plausible explanations for a prenatal influence on subsequent breast cancer risk and mortality. Further work is needed to confirm these observations. PMID:22252677

  9. Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children's Health.

    PubMed

    Minatoya, Machiko; Naka Jima, Sonomi; Sasaki, Seiko; Araki, Atsuko; Miyashita, Chihiro; Ikeno, Tamiko; Nakajima, Tamie; Goto, Yuko; Kishi, Reiko

    2016-09-15

    Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study. Maternal blood samples collected between 23 and 41weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18month of age. For the final analysis, 328 participants were included. The median levels of maternal MEHP was 10.6ng/ml, neonatal TSH and FT4 was 2.20 μU/ml and 2.03ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18month. In this study, prenatal DEHP exposure did not show adverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary.

  10. Neonatal thyrotoxicosis treated with exchange transfusion and Lugol's iodine.

    PubMed

    Wit, J M; Gerards, L J; Vermeulen-Meiners, C; Bruinse, H W

    1985-03-01

    An infant with neonatal thyrotoxicosis was born to a mother who had become euthyroid after subtotal thyroidectomy for Graves' disease. Exchange transfusion resulted in a 50% decrease of serum thyroxine levels and thyroid stimulating immunoglobulins. After 10 days mild thyrotoxic signs reappeared with high serum thyroxine levels, which were treated successfully with Lugol's iodine for 4 weeks. TSI was undetectable at 7 weeks of age. TSI was present in breast milk.

  11. Unusually high-pitched neonate distress calls of the open-habitat Mongolian gazelle ( Procapra gutturosa) and their anatomical and hormonal predictors

    NASA Astrophysics Data System (ADS)

    Volodin, Ilya A.; Volodina, Elena V.; Frey, Roland; Kirilyuk, Vadim E.; Naidenko, Sergey V.

    2017-06-01

    In neonate ruminants, the acoustic structure of vocalizations may depend on sex, vocal anatomy, hormonal profiles and body mass and on environmental factors. In neonate wild-living Mongolian gazelles Procapra gutturosa, hand-captured during biomedical monitoring in the Daurian steppes at the Russian-Mongolian border, we spectrographically analysed distress calls and measured body mass of 22 individuals (6 males, 16 females). For 20 (5 male, 15 female) of these individuals, serum testosterone levels were also analysed. In addition, we measured relevant dimensions of the vocal apparatus (larynx, vocal folds, vocal tract) in one stillborn male Mongolian gazelle specimen. Neonate distress calls of either sex were high in maximum fundamental frequency (800-900 Hz), but the beginning and minimum fundamental frequencies were significantly lower in males than in females. Body mass was larger in males than in females. The levels of serum testosterone were marginally higher in males. No correlations were found between either body mass or serum testosterone values and any acoustic variable for males and females analysed together or separately. We discuss that the high-frequency calls of neonate Mongolian gazelles are more typical for closed-habitat neonate ruminants, whereas other open-habitat neonate ruminants (goitred gazelle Gazella subgutturosa, saiga antelope Saiga tatarica and reindeer Rangifer tarandus) produce low-frequency (<200 Hz) distress calls. Proximate cause for the high fundamental frequency of distress calls of neonate Mongolian gazelles is their very short, atypical vocal folds (4 mm) compared to the 7-mm vocal folds of neonate goitred gazelles, producing distress calls as low as 120 Hz.

  12. Unusually high-pitched neonate distress calls of the open-habitat Mongolian gazelle (Procapra gutturosa) and their anatomical and hormonal predictors.

    PubMed

    Volodin, Ilya A; Volodina, Elena V; Frey, Roland; Kirilyuk, Vadim E; Naidenko, Sergey V

    2017-06-01

    In neonate ruminants, the acoustic structure of vocalizations may depend on sex, vocal anatomy, hormonal profiles and body mass and on environmental factors. In neonate wild-living Mongolian gazelles Procapra gutturosa, hand-captured during biomedical monitoring in the Daurian steppes at the Russian-Mongolian border, we spectrographically analysed distress calls and measured body mass of 22 individuals (6 males, 16 females). For 20 (5 male, 15 female) of these individuals, serum testosterone levels were also analysed. In addition, we measured relevant dimensions of the vocal apparatus (larynx, vocal folds, vocal tract) in one stillborn male Mongolian gazelle specimen. Neonate distress calls of either sex were high in maximum fundamental frequency (800-900 Hz), but the beginning and minimum fundamental frequencies were significantly lower in males than in females. Body mass was larger in males than in females. The levels of serum testosterone were marginally higher in males. No correlations were found between either body mass or serum testosterone values and any acoustic variable for males and females analysed together or separately. We discuss that the high-frequency calls of neonate Mongolian gazelles are more typical for closed-habitat neonate ruminants, whereas other open-habitat neonate ruminants (goitred gazelle Gazella subgutturosa, saiga antelope Saiga tatarica and reindeer Rangifer tarandus) produce low-frequency (<200 Hz) distress calls. Proximate cause for the high fundamental frequency of distress calls of neonate Mongolian gazelles is their very short, atypical vocal folds (4 mm) compared to the 7-mm vocal folds of neonate goitred gazelles, producing distress calls as low as 120 Hz.

  13. Evaluation of thyroid hormones in children receiving carbamazepine or valproate: a prospective study.

    PubMed

    Kafadar, İhsan; Kılıç, Betül Aydın; Arapoglu, Mujde; Yalçın, Koray; Dalgıç, Nazan

    2015-01-01

    The aim of this study was to determine the alterations in thyroid function during carbamazepine or valproate monotherapy in a prospective study. Forty patients treated with valproate, 33 patients treated with carbamazepine, and 36 control patients, all aged between 2 and 18 years, were enrolled in our study. Serum levels of thyroid hormones were measured before the beginning of the antiepileptic therapy and at 6 and 12 months of treatment. Carbamazepine-treated patients showed mean serum thyroid hormone levels significantly lower than baseline evaluation and the control group. Thyroid-stimulating hormone levels at 6 and 12 months were not significantly different in carbamazepine treated patients. Serum hormone levels did not change during valproate treatment. Thyroid-stimulating hormone levels were significantly higher at the 12th month of valproate treatment. Our data suggest that although carbamazepine causes significant alterations in thyroid hormone levels, these changes do not lead to clinical symptoms at the follow-up period of 12 months.

  14. Regulation of Thyroid-stimulating Hormone Release from the Pituitary by Thyroxine during Metamorphosis in Xenopus laevis

    EPA Science Inventory

    Environmentally-relevant chemicals such as perchlorate have the ability to disrupt the hypothalamo-pituitary-thyroid (HPT) axis of exposed individuals. Larval anurans are a particularly suitable model species for studying the effects of thyroid-disrupting chemicals (TDCs) becaus...

  15. Regulation of Thyroid-stimulating Hormone Release from the Pituitary by Thyroxine during Metamorphosis in Xenopus laevis

    EPA Science Inventory

    Environmentally-relevant chemicals such as perchlorate have the ability to disrupt the hypothalamo-pituitary-thyroid (HPT) axis of exposed individuals. Larval anurans are a particularly suitable model species for studying the effects of thyroid-disrupting chemicals (TDCs) becaus...

  16. Sialadenitis following low dose I-131 diagnostic thyroid scan with Thyrogen® (recombinant human thyroid stimulating hormone - thyrotropin alfa)

    PubMed Central

    Gonzalez, Marta E; Muttikkal, Thomas Jose Eluvathingal; Rehm, Patrice K

    2015-01-01

    Salivary dysfunction and sialadenitis are well known complications of radioiodine treatment for thyroid cancer. The parotid gland is more frequently affected and the salivary gland injury is dose related. The symptoms may develop shortly after therapeutic Iodine 131(I-131) administration or months later and progress with time. The development of unilateral parotiditis following a low dose, diagnostic I-131 scan performed following Thyrogen stimulation in a patient without prior history of sialadenitis is rare in our experience, and has not been reported in the medical literature. PMID:26622936

  17. Partial prediction of postpartum Graves' thyrotoxicosis by sensitive bioassay for thyroid-stimulating antibody measured in early pregnancy.

    PubMed

    Ide, Akane; Amino, Nobuyuki; Nishihara, Eijun; Kudo, Takumi; Ito, Mitsuru; Kimura, Yukiko; Tatsumi, Nobuya; Yamazaki, Mineo; Miyauchi, Akira

    2016-10-29

    Graves' disease often occurs after delivery. However, it has been difficult to predict who will develop Graves' hyperthyroidism. We attempted to predict postpartum onset of Graves' disease by measuring anti-TSH receptor antibodies (TRAb) and thyroid-stimulating antibodies (TSAb) in early pregnancy. TRAb was measured by a third generation assay and TSAb was measured by a newly developed sensitive bioassay. In 690 early pregnant women, 2 showed borderline TRAb positive reactions. However, none of them developed Graves' disease after delivery. Thirty-eight of 690 pregnant women were positive for anti-thyroid peroxidase antibodies (TPOAb) and 4 were positive for TSAb. Two of these 4 women developed postpartum Graves' hyperthyroidism. These findings indicate that the third generation TRAb assay was not useful, but that the sensitive TSAb bioassay was moderately useful for predicting the postpartum onset of Graves' hyperthyroidism.

  18. Possible effects of neonatal vitamin B12 status on TSH-screening program: a cross-sectional study from Turkey.

    PubMed

    Onal, Zerrin; Balkaya, Seda; Ersen, Atilla; Mutlu, Neval; Onal, Hasan; Adal, Erdal

    2017-05-01

    In this study we evaluated whether vitamin B12 deficiency affects neonatal screening (NS) for congenital hypothyroidism (CH). A cross-sectional study conducted from 2010 to 2011. A total of 10,740 infants were born in our hospital in this period. Thyroid-stimulating hormone (TSH) was tested for NS and neonates with abnormal screening results (TSH>20 mIU/L) were re-examined. Two hundred and twenty-nine re-called subjects (re-call rate 2.3%) were compared to 77 randomly selected newborns with normal TSH screening among these term newborns in terms of serum TSH, free T4, vitamin B12 and homocysteine status. Of the 229 re-called subjects, 11 infants with CH and 21 infants with transient TSH elevation were detected. In the normal TSH screening group, only two infants were diagnosed with transient TSH elevation. Mean serum B12 levels were 126.4±48.7 pg/mL and 211.9±127.9 pg/mL in the positive TSH-screening group and the control group, respectively. There was a significant difference between positive and normal TSH-screening groups in regard to serum TSH, free T4, serum B12 and homocysteine levels. We found a significant vitamin B12 deficiency in positive TSH-screening infants. Beside the crucial role of vitamin B12 in newborns, deficiency seems to increase the recall rates of infants in an NS program for CH.

  19. Illness-induced changes in thyroid hormone metabolism: focus on the tissue level.

    PubMed

    Kwakkel, J; Fliers, E; Boelen, A

    2011-05-01

    During illness changes in thyroid hormone metabolism occur, collectively known as the non-thyroidal illness syndrome (NTIS). NTIS is characterised by low serum thyroid hormone levels without the expected rise in serum thyroid-stimulating hormone, indicating a major change in thyroid hormone feedback regulation. Recent studies have made clear that during NTIS differential changes in thyroid hormone metabolism occur in various tissues, the net effect of which may be either activation or inhibition of thyroid hormone action. In this review we discuss systemic and local changes in thyroid hormone metabolism during illness, highlighting their physiological implications in terms of disease course.

  20. Corticotropin-Releasing Hormone As the Homeostatic Rheostat of Feto-Maternal Symbiosis and Developmental Programming In Utero and Neonatal Life

    PubMed Central

    Alcántara-Alonso, Viridiana; Panetta, Pamela; de Gortari, Patricia; Grammatopoulos, Dimitris K.

    2017-01-01

    A balanced interaction between the homeostatic mechanisms of mother and the developing organism during pregnancy and in early neonatal life is essential in order to ensure optimal fetal development, ability to respond to various external and internal challenges, protection from adverse programming, and safeguard maternal care availability after parturition. In the majority of pregnancies, this relationship is highly effective resulting in successful outcomes. However, in a number of pathological settings, perturbations of the maternal homeostasis disrupt this symbiosis and initiate adaptive responses with unpredictable outcomes for the fetus or even the neonate. This may lead to development of pathological phenotypes arising from developmental reprogramming involving interaction of genetic, epigenetic, and environmental-driven pathways, sometimes with acute consequences (e.g., growth impairment) and sometimes delayed (e.g., enhanced susceptibility to disease) that last well into adulthood. Most of these adaptive mechanisms are activated and controlled by hormones of the hypothalamo-pituitary adrenal axis under the influence of placental steroid and peptide hormones. In particular, the hypothalamic peptide corticotropin-releasing hormone (CRH) plays a key role in feto-maternal communication by orchestrating and integrating a series of neuroendocrine, immune, metabolic, and behavioral responses. CRH also regulates neural networks involved in maternal behavior and this determines efficiency of maternal care and neonate interactions. This review will summarize our current understanding of CRH actions during the perinatal period, focusing on the physiological roles for both mother and offspring and also how external challenges can alter CRH actions and potentially impact on fetus/neonate health. PMID:28744256

  1. The organizational and aromatization hypotheses apply to rapid, nonclassical hormone action: neonatal masculinization eliminates rapid estradiol action in female hippocampal neurons.

    PubMed

    Meitzen, John; Grove, Danielle D; Mermelstein, Paul G

    2012-10-01

    Early exposure to the steroid sex hormone testosterone and its estrogen metabolite estradiol masculinize neural tissue during a developmental critical period. Many aspects of neuron anatomy and physiology are permanently altered, including later sensitivity to estradiol. Although it is well established that early hormone exposure alters neuronal responsiveness regarding classical estradiol actions (i.e. acting via nuclear estrogen receptors), it has not yet been determined whether it also alters neuronal processing of nonclassical estrogen receptor signaling, including the actions of membrane-associated estrogen receptors. Hence, we tested whether membrane estrogen receptor regulation of cAMP response element binding protein (CREB) phosphorylation observed in female (but not male) hippocampal pyramidal neurons is due to the lack of androgen and/or estrogen exposure in females during this critical period. Female rat neonates on postnatal d 0 and 1 were systemically injected with one of four compounds: vehicle, testosterone, the nonaromatizable androgen dihydrotestosterone, or estradiol. On postnatal d 2, primary hippocampal neuron cultures were generated from these animals. After 8-9 d in culture, we assessed whether estradiol affected CREB phosphorylation. Neurons from female neonates exposed to testosterone lacked estradiol signaling to CREB. In contrast, dihydrotestosterone injections of female neonates did not disrupt estradiol regulation of CREB. Estradiol injections of female neonates, however, eliminated estradiol signaling to CREB. These findings indicate that testosterone aromatization to estradiol leads to a masculinization/defeminization process whereby hippocampal neurons fail to exhibit rapid estradiol signaling to CREB. Broadly, these findings extend the organizational and aromatization hypotheses to rapid, nonclassical hormone action.

  2. The Organizational and Aromatization Hypotheses Apply to Rapid, Nonclassical Hormone Action: Neonatal Masculinization Eliminates Rapid Estradiol Action in Female Hippocampal Neurons

    PubMed Central

    Grove, Danielle D.; Mermelstein, Paul G.

    2012-01-01

    Early exposure to the steroid sex hormone testosterone and its estrogen metabolite estradiol masculinize neural tissue during a developmental critical period. Many aspects of neuron anatomy and physiology are permanently altered, including later sensitivity to estradiol. Although it is well established that early hormone exposure alters neuronal responsiveness regarding classical estradiol actions (i.e. acting via nuclear estrogen receptors), it has not yet been determined whether it also alters neuronal processing of nonclassical estrogen receptor signaling, including the actions of membrane-associated estrogen receptors. Hence, we tested whether membrane estrogen receptor regulation of cAMP response element binding protein (CREB) phosphorylation observed in female (but not male) hippocampal pyramidal neurons is due to the lack of androgen and/or estrogen exposure in females during this critical period. Female rat neonates on postnatal d 0 and 1 were systemically injected with one of four compounds: vehicle, testosterone, the nonaromatizable androgen dihydrotestosterone, or estradiol. On postnatal d 2, primary hippocampal neuron cultures were generated from these animals. After 8–9 d in culture, we assessed whether estradiol affected CREB phosphorylation. Neurons from female neonates exposed to testosterone lacked estradiol signaling to CREB. In contrast, dihydrotestosterone injections of female neonates did not disrupt estradiol regulation of CREB. Estradiol injections of female neonates, however, eliminated estradiol signaling to CREB. These findings indicate that testosterone aromatization to estradiol leads to a masculinization/defeminization process whereby hippocampal neurons fail to exhibit rapid estradiol signaling to CREB. Broadly, these findings extend the organizational and aromatization hypotheses to rapid, nonclassical hormone action. PMID:22865367

  3. Corticotropin-Releasing Hormone As the Homeostatic Rheostat of Feto-Maternal Symbiosis and Developmental Programming In Utero and Neonatal Life.

    PubMed

    Alcántara-Alonso, Viridiana; Panetta, Pamela; de Gortari, Patricia; Grammatopoulos, Dimitris K

    2017-01-01

    A balanced interaction between the homeostatic mechanisms of mother and the developing organism during pregnancy and in early neonatal life is essential in order to ensure optimal fetal development, ability to respond to various external and internal challenges, protection from adverse programming, and safeguard maternal care availability after parturition. In the majority of pregnancies, this relationship is highly effective resulting in successful outcomes. However, in a number of pathological settings, perturbations of the maternal homeostasis disrupt this symbiosis and initiate adaptive responses with unpredictable outcomes for the fetus or even the neonate. This may lead to development of pathological phenotypes arising from developmental reprogramming involving interaction of genetic, epigenetic, and environmental-driven pathways, sometimes with acute consequences (e.g., growth impairment) and sometimes delayed (e.g., enhanced susceptibility to disease) that last well into adulthood. Most of these adaptive mechanisms are activated and controlled by hormones of the hypothalamo-pituitary adrenal axis under the influence of placental steroid and peptide hormones. In particular, the hypothalamic peptide corticotropin-releasing hormone (CRH) plays a key role in feto-maternal communication by orchestrating and integrating a series of neuroendocrine, immune, metabolic, and behavioral responses. CRH also regulates neural networks involved in maternal behavior and this determines efficiency of maternal care and neonate interactions. This review will summarize our current understanding of CRH actions during the perinatal period, focusing on the physiological roles for both mother and offspring and also how external challenges can alter CRH actions and potentially impact on fetus/neonate health.

  4. The Calcium-Sensing Receptor Mediates Bone Turnover Induced by Dietary Calcium and Parathyroid Hormone in Neonates

    PubMed Central

    Shu, Lei; Ji, Ji; Zhu, Qi; Cao, Guofan; Karaplis, Andrew; Pollak, Martin R; Brown, Edward; Goltzman, David; Miao, Dengshun

    2011-01-01

    We have investigated, in neonates, whether the calcium-sensing receptor (CaR) mediates the effects of dietary calcium on bone turnover and/or modulates parathyroid hormone (PTH)–induced bone turnover. Wild-type (WT) pups and pups with targeted deletion of the Pth (Pth–/–) gene or of both Pth and CaR (Pth–/–CaR–/–) genes were nursed by dams on a normal or high-calcium diet. Pups nursed by dams on a normal diet received daily injections of vehicle or of PTH(1–34) (80 µg/kg) for 2 weeks starting from 1 week of age. In pups receiving vehicle and fed by dams on a normal diet, trabecular bone volume, osteoblast number, type 1 collagen–positive area, and mineral apposition rate, as well as the expression of bone-formation-related genes, all were reduced significantly in Pth–/– pups compared with WT pups and were decreased even more dramatically in Pth–/–CaR–/– pups. These parameters were increased in WT and Pth–/– pups but not in Pth–/–CaR–/– pups fed by dams on a high-calcium diet compared with pups fed by dams on a normal diet. These parameters also were increased in WT, Pth–/–, and Pth–/–CaR–/– pups following exogenous PTH treatment; however, the percentage increase was less in Pth–/–CaR–/– pups than in WT and Pth–/– pups. In vehicle-treated pups fed by dams on either the normal or high-calcium diet and in PTH-treated pups fed by dams on a normal diet, the number and surfaces of osteoclasts and the ratio of RANKL/OPG were reduced significantly in Pth–/– pups and less significantly in Pth–/–CaR–/– pups compared with WT pups. These parameters were further reduced significantly in WT and Pth–/– pups from dams fed a high-calcium diet but did not decrease significantly in similarly treated Pth–/–CaR–/– pups, and they increased significantly in PTH-treated pups compared with vehicle-treated, genotype-matched pups fed by dams on the normal diet. These results indicate that in neonates

  5. Neonatal thyroid function born to mothers living with long-term excessive iodine intake from drinking water.

    PubMed

    Chen, Wen; Sang, Zhongna; Tan, Long; Zhang, Shufen; Dong, Feng; Chu, Zanjun; Wei, Wei; Zhao, Na; Zhang, Guiqin; Yao, Zhaixiao; Shen, Jun; Zhang, Wanqi

    2015-09-01

    The effects of long-term excessive maternal iodine intake on neonatal thyroid function are less known. This study aimed to assess the effects of maternal excessive iodine intake from drinking water on thyroid functions of both mothers and their neonates. This observational study was performed in high iodine (HI) areas and adequate iodine (AI) intake areas, including 384 healthy pregnant women in late gestation (mean week 39·3 ± 1·6 weeks) and their newborns. Blood and urine samples were obtained from pregnant women, while cord blood samples were obtained from neonates. Urinary iodine concentration (UIC) and thyroid function were evaluated. The median maternal UIC was 1241 and 217 μg/l in HI and AI areas, respectively (P < 0·001). The concentrations of serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) in neonates in HI areas were 7·33 mIU/l (range 5·47, 11·06 mIU/l), 2·93 ± 0·59 and 15·03 ± 1·92 pmol/l, respectively, while that were 4·71 mIU/l (range 3·96, 6·04 mIU/l), 2·31 ± 0·28 and 16·50 ± 1·35 pmol/l in AI neonates (P < 0·05). Similar changes were also observed in neonates in HI areas when excluding the effect of maternal thyroid autoimmunity. Cord blood TSH concentration (r = 0·31, P = 0·001) and FT3 concentration (r = 0·43, P = 0·001) were positively correlated with maternal UIC. Cord blood FT4 concentration was negatively correlated with maternal UIC (r = -0·25, P = 0·001). Mothers living in HI areas (β = 0·296, 95% CI: 0·163, 0·255) and with subclinical hypothyroidism (β = 0·360, 95% CI: 0·034, 0·175) contributed to elevated cord blood TSH concentration in neonates, while male neonates were more likely to present with higher TSH concentration compared with female infants (β = -0·760, 95% CI: -0·119, -0·033). Excessive iodine intake during pregnancy was associated with an increased rate of hyperthyrotropinaemia in neonates and their mothers, especially in male neonates.

  6. Artificial feeding synchronizes behavioral, hormonal, metabolic and neural parameters in mother-deprived neonatal rabbit pups

    PubMed Central

    Morgado, Elvira; Juárez, Claudia; Melo, Angel I.; Domínguez, Belisario; Lehman, Michael N.; Escobar, Carolina; Meza, Enrique; Caba, Mario

    2011-01-01

    Nursing in the rabbit is under circadian control, and pups have a daily anticipatory behavioral arousal synchronized to this unique event, but it is not known which signal is the main entraining cue. In the present study we hypothesized that food is the main entraining signal. Using mother-deprived pups we tested the effects of artificial feeding on the synchronization of locomotor behavior, plasma glucose, corticosterone, FOS and PER1 protein rhythms in suprachiasmatic, supraoptic, paraventricular and tuberomammillary nuclei. At postnatal day 1 an intragastric tube was placed by gastrostomy. The next day and for the rest of the experiment pups were fed with a milk formula through the cannula at either 02:00 or 10:00 h (feeding time = zeitgeber time (ZT) 0). At postnatal days 5–7 pups exhibited behavioral arousal with a significant increase in locomotor behavior 60 min before feeding. Glucose levels increased after feeding, peaking at ZT4–ZT12 and then declining. Corticosterone was highest around the time of feeding then decreased to trough concentrations at ZT12–ZT16, increasing again in anticipation of next feeding bout. In the brain, the suprachiasmatic nucleus had a rhythm of FOS and PER1 that was not significantly affected by the feeding schedule. Conversely, the supraoptic, paraventricular and tuberomammillary nuclei had rhythms of both FOS and PER1 induced by the time of scheduled feeding. We conclude that the nursing rabbit pup is a natural model of food entrainment, since food, in this case milk formula, is a strong synchronizing signal for behavioral, hormonal, metabolic and neural parameters. PMID:22098455

  7. Artificial feeding synchronizes behavioral, hormonal, metabolic and neural parameters in mother-deprived neonatal rabbit pups.

    PubMed

    Morgado, Elvira; Juárez, Claudia; Melo, Angel I; Domínguez, Belisario; Lehman, Michael N; Escobar, Carolina; Meza, Enrique; Caba, Mario

    2011-12-01

    Nursing in the rabbit is under circadian control, and pups have a daily anticipatory behavioral arousal synchronized to this unique event, but it is not known which signal is the main entraining cue. In the present study, we hypothesized that food is the main entraining signal. Using mother-deprived pups, we tested the effects of artificial feeding on the synchronization of locomotor behavior, plasma glucose, corticosterone, c-Fos (FOS) and PERIOD1 (PER1) rhythms in suprachiasmatic, supraoptic, paraventricular and tuberomammillary nuclei. At postnatal day 1, an intragastric tube was placed by gastrostomy. The next day and for the rest of the experiment, pups were fed with a milk formula through the cannula at either 02:00 h or 10:00 h [feeding time = zeitgeber time (ZT)0]. At postnatal days 5-7, pups exhibited behavioral arousal, with a significant increase in locomotor behavior 60 min before feeding. Glucose levels increased after feeding, peaking at ZT4-ZT12 and then declining. Corticosterone levels were highest around the time of feeding, and then decreased to trough concentrations at ZT12-ZT16, increasing again in anticipation of the next feeding bout. In the brain, the suprachiasmatic nucleus had a rhythm of FOS and PER1 that was not significantly affected by the feeding schedule. Conversely, the supraoptic, paraventricular and tuberomammillary nuclei had rhythms of both FOS and PER1 induced by the time of scheduled feeding. We conclude that the nursing rabbit pup is a natural model of food entrainment, as food, in this case milk formula, is a strong synchronizing signal for behavioral, hormonal, metabolic and neural parameters. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Neonatal low-protein diet changes deiodinase activities and pituitary TSH response to TRH in adult rats.

    PubMed

    Lisboa, P C; Fagundes, A T S; Denolato, A T A; Oliveira, E; Bonomo, I T; Alves, S B; Curty, F H; Passos, M C F; Moura, E G

    2008-01-01

    Protein malnutrition during neonatal programs for a lower body weight and hyperthyroidism in the adult offspring were analyzed. Liver deiodinase is increased in such animals, contributing to the high serum triiodothyronine (T3) levels. The level of deiodinase activities in other tissues is unknown. We analyzed the effect of maternal protein restriction during lactation on thyroid, skeletal muscle, and pituitary deiodinase activities in the adult offspring. For pituitary evaluation, we studied the in vitro, thyrotropin-releasing hormone (TRH)-stimulated thyroid-stimulating hormone (TSH) secretion. Lactating Wistar rats and their pups were divided into a control (C) group, fed a normal diet (23% protein), and a protein-restricted (PR) group, fed a diet containing 8% protein. At weaning, pups in both groups were fed a normal diet until 180 days old. The pituitary gland was incubated before and after TRH stimulation, and released TSH was measured by radioimmunoassay. Deiodinase activities (D1 and D2) were determined by release of (125)I from [(125)I]reverse triiodothyronine (rT3). Maternal protein malnutrition during lactation programs the adult offspring for lower muscle D2 (-43%, P<0.05) and higher muscle D1 (+83%, P<0.05) activities without changes in thyroidal deiodinase activities, higher pituitary D2 activity (1.5 times, P<0.05), and lower TSH response to in vitro TRH (-56%, P<0.05). The evaluations showed that the lower in vivo TSH detected in adult PR hyperthyroid offspring, programmed by neonatal undernutrition, may be caused by an increment of pituitary deiodination. As described for liver, higher skeletal muscle D1 activity suggests a hyperthyroid status. Our data broaden the knowledge about the adaptive changes to malnutrition during lactation and reinforce the concept of neonatal programming of the thyroid function.

  9. Bone development and mineral homeostasis in the fetus and neonate: roles of the calciotropic and phosphotropic hormones.

    PubMed

    Kovacs, Christopher S

    2014-10-01

    Mineral and bone metabolism are regulated differently in utero compared with the adult. The fetal kidneys, intestines, and skeleton are not dominant sources of mineral supply for the fetus. Instead, the placenta meets the fetal need for mineral by actively transporting calcium, phosphorus, and magnesium from the maternal circulation. These minerals are maintained in the fetal circulation at higher concentrations than in the mother and normal adult, and such high levels appear necessary for the developing skeleton to accrete a normal amount of mineral by term. Parathyroid hormone (PTH) and calcitriol circulate at low concentrations in the fetal circulation. Fetal bone development and the regulation of serum minerals are critically dependent on PTH and PTH-related protein, but not vitamin D/calcitriol, fibroblast growth factor-23, calcitonin, or the sex steroids. After birth, the serum calcium falls and phosphorus rises before gradually reaching adult values over the subsequent 24-48 h. The intestines are the main source of mineral for the neonate, while the kidneys reabsorb mineral, and bone turnover contributes mineral to the circulation. This switch in the regulation of mineral homeostasis is triggered by loss of the placenta and a postnatal fall in serum calcium, and is followed in sequence by a rise in PTH and then an increase in calcitriol. Intestinal calcium absorption is initially a passive process facilitated by lactose, but later becomes active and calcitriol-dependent. However, calcitriol's role can be bypassed by increasing the calcium content of the diet, or by parenteral administration of calcium. Copyright © 2014 the American Physiological Society.

  10. Vasoactive intestinal peptide enhanced aromatase activity in the neonatal rat ovary before development of primary follicles or responsiveness to follicle-stimulating hormone

    SciTech Connect

    George, F.W.; Ojeda, S.R.

    1987-08-01

    The authors have investigated the factors that regulate aromatase activity in fetal-neonatal rat ovaries. Ovarian aromatase activity (assessed by measuring the amount of /sup 3/H/sub 2/O formed from (1..beta..-/sup 3/H)testosterone) is low prior to birth and increases to values greater than 30 pmol/hr per mg of protein between days 8 and 12 after birth. The appearance of ovarian aromatase coincides with the development of primordial follicles. Fetal-neonatal ovaries maintained in serum-free organ culture do not develop aromatase activity at the expected time. Ovine follicle-stimulating hormone, ovine luteinizing hormone, or their combination failed to induce the enzyme activity in cultured fetal ovaries, whereas follicle-stimulating hormone is effective in preventing the decline in aromatase activity when postnatal day 8 ovaries are placed in culture. In contrast to follicle-stimulating hormone, dibutyryl-cAMP markedly enhances ovarian aromatase in cultured fetal ovaries. Likewise, enhancement of endogenouse cAMP formation with forskolin or cholera toxin caused an increase in enzyme activity within 24 hr. Vasoactive intestinal peptide, a peptide known to occur in ovarian nerves, caused a dose-dependent increase in aromatase activity in fetal ovaries prior to folliculogenesis. Of related peptides tested, only the peptide having N-terminal histidine and C-terminal isoleucine amide was capable of inducing aromatase activity in fetal ovaries. The fact that VIP can induce aromatase activity in fetal rat ovaries prior to follicle formation and prior to responsiveness to follicle-stimulating hormone suggests that this neuropeptide may play a critical role in ovarian differentiation.

  11. Vasoactive intestinal peptide enhances aromatase activity in the neonatal rat ovary before development of primary follicles or responsiveness to follicle-stimulating hormone.

    PubMed Central

    George, F W; Ojeda, S R

    1987-01-01

    We have investigated the factors that regulate aromatase activity in fetal-neonatal rat ovaries. Ovarian aromatase activity (assessed by measuring the amount of 3H2O) formed from [1 beta-3H]testosterone) is low prior to birth (less than 0.5 pmol/hr per mg of protein) and increases to values greater than 30 pmol/hr per mg of protein between days 8 and 12 after birth. The appearance of ovarian aromatase (postnatal days 2-4) coincides with the development of primordial follicles. Fetal-neonatal ovaries maintained in serum-free organ culture do not develop aromatase activity at the expected time. Ovine follicle-stimulating hormone (0.1-1 microgram/ml), ovine luteinizing hormone (0.1 microgram/ml), or their combination failed to induce the enzyme activity in cultured fetal ovaries, whereas follicle-stimulating hormone is effective in preventing the decline in aromatase activity when postnatal day 8 ovaries are placed in culture. In contrast to follicle-stimulating hormone, dibutyryl-cAMP markedly enhances ovarian aromatase in cultured fetal ovaries. Likewise, enhancement of endogenous cAMP formation with forskolin or cholera toxin caused an increase in enzyme activity within 24 hr. Vasoactive intestinal peptide, a peptide known to occur in ovarian nerves, caused a dose-dependent increase in aromatase activity in fetal ovaries prior to folliculogenesis. Of related peptides tested, only the peptide having N-terminal histidine and C-terminal isoleucine amide was capable of inducing aromatase activity in fetal ovaries. The fact that VIP can induce aromatase activity in fetal rat ovaries prior to follicle formation and prior to responsiveness to follicle-stimulating hormone suggests that this neuropeptide may play a critical role in ovarian differentiation. Images PMID:3039508

  12. [Study on the iodine status of pregnant women and thyroid function of neonate in high iodine area].

    PubMed

    Zhang, Gui-Qin; Sang, Zhong-Na; Liu, Hua; Zhang, Shu-Fen; Wei, Wei; Zhao, Na; Tan, Long; Zhang, Wan-Qi

    2012-03-01

    To reveal the iodine status of pregnant women and its impact on thyroid function of neonates in high iodine area. A total of 210 pregnant women were chosen from a hospital in Haixing county, Hebei province. Pregnant women's random urinary and neonates' cord blood were collected. The urinary iodine concentration (UIC) was examined by arsenic-cerium catalytic spectrophotometry. The levels of free triiodothyronine (FT3), free thyroxine (FT4) and sensitive thyroid-stimulating hormone (sTSH) in serum were measured by chemiluminescence. The age of 210 pregnant women was (27.69 +/- 4.73) years old, whose urinary iodine median (inter-quartile range ) was 1240.70 (1292.68) microg/L. 84.3% (177/210) of the pregnant women had excessive iodine intake (UIC > or = 500 microg/L), 13.8% (29/210) had more than adequate iodine intake( UIC within 250 - 499 microg/L), 0.5% (1/210) had adequate iodine intake (UIC within 150 - 249 microg/L) and 1.4% (3/210) had insufficient iodine intake (UIC < 150 microg/L). The average serum level of FT3, FT4 in neonates were (2.93 +/- 0.59), (15.03 +/- 1.92) pmol/L, respectively. The median (inter-quartile range) of serum sTSH in neonates were 7.33 (5.59) mU/L 78.1% (164/210) of the neonates' serum TSH were beyond 5 mU/L. There were no correlation between pregnant women's urinary iodine level and neonates' serum FT3 and sTSH level (P > 0.05), but there was a positive correlation between pregnant women's urinary iodine level and neonates' serum FT4 level (P < 0.01). Serum FT4 level of the neonates with whose mothers had insufficient iodine intake ((12.99 +/- 1.10) pmol/L) were statistically lower than those with their mothers had excessive iodine intake (15.16 +/- 1.83) pmol/L) (P < 0.05). Most of the pregnant women in high iodine area were excessive for iodine nutrition, but still a few pregnant women had insufficient iodine nutrition. The level of neonates' serum sTSH were relatively high and monitoring of risk of hypothyroidism and subclinical

  13. Neonatal Graves' Disease with Maternal Hypothyroidism.

    PubMed

    Akangire, Gangaram; Cuna, Alain; Lachica, Charisse; Fischer, Ryan; Raman, Sripriya; Sampath, Venkatesh

    2017-07-01

    Neonatal Graves' disease presenting as conjugated hyperbilirubinemia is a diagnostic challenge because the differential includes a gamut of liver and systemic diseases. We present a unique case of neonatal Graves' disease in a premature infant with conjugated hyperbilirubinemia born to a mother with hypothyroidism during pregnancy and remote history of Graves' disease. Infant was treated with a combination of methimazole, propranolol, and potassium iodide for 4 weeks. Thyroid function improved after 8 weeks of treatment with full recovery of thyroid function, disappearance of thyroid-stimulating antibodies, and resolution of failure to thrive and conjugated hyperbilirubinemia. This case provides several clinical vignettes as it is a rare, severe, presentation of an uncommon neonatal disease, signs, symptoms, and clinical history presented a diagnostic challenge for neonatologists and endocrinologists, normal newborn screen was misleading, and yet timely treatment led to a full recovery.

  14. Effects of prenatal exposure to organochlorines on thyroid hormone status in newborns from two remote coastal regions in Quebec, Canada

    SciTech Connect

    Dallaire, Renee; Dewailly, Eric Ayotte, Pierre; Muckle, Gina; Laliberte, Claire; Bruneau, Suzanne

    2008-11-15

    Background: Several prospective studies have revealed that prenatal exposure to polychlorinated biphenyls (PCBs) and other organochlorine compounds (OCs) affect neurodevelopment during infancy. One of the mechanisms by which PCBs might interfere with neurodevelopment is a deficit in thyroid hormone (TH) concentrations. Objectives: We investigated the potential impact of transplacental exposure to PCBs and hexachlorobenzene (HCB) on TH concentrations in neonates from two remote coastal populations exposed to OCs through the consumption of seafood products. Methods: Blood samples were collected at birth from the umbilical cord of neonates from Nunavik (n=410) and the Lower North Shore of the St. Lawrence River (n=260) (Quebec, Canada) for thyroid parameters [thyroid-stimulating hormone (TSH), free T{sub 4} (fT{sub 4}), total T{sub 3} (tT{sub 3}), and thyroxine-binding globuline (TBG)] and contaminants analyses. Results: In multivariate models, umbilical cord plasma concentrations of PCB 153, the predominant PCB congener, were not associated with TH and TSH levels in both populations. Prenatal exposure to HCB was positively associated with fT{sub 4} levels at birth in both populations (Nunavik, {beta}=0.12, p=0.04; St. Lawrence, {beta}=0.19, p<0.01), whereas TBG concentrations were negatively associated with PCB 153 concentrations ({beta}=-0.13, p=0.05) in the St. Lawrence cohort. Conclusion: OCs levels were not associated to a reduction in THs in neonates from our two populations. Essential nutrients derived from seafood such as iodine may have prevented the negative effects of OCs on the thyroid economy during fetal development.

  15. Thyroid hormone resistance and its management

    PubMed Central

    Lado-Abeal, Joaquin

    2016-01-01

    The syndrome of impaired sensitivity to thyroid hormone, also known as syndrome of thyroid hormone resistance, is an inherited condition that occurs in 1 of 40,000 live births characterized by a reduced responsiveness of target tissues to thyroid hormone due to mutations on the thyroid hormone receptor. Patients can present with symptoms of hyperthyroidism or hypothyroidism. They usually have elevated thyroid hormones and a normal or elevated thyroid-stimulating hormone level. Due to their nonspecific symptomatic presentation, these patients can be misdiagnosed if the primary care physician is not familiar with the condition. This can result in frustration for the patient and sometimes unnecessary invasive treatment such as radioactive iodine ablation, as in the case presented herein. PMID:27034574

  16. Thyroid hormone resistance: a novel mutation in thyroid hormone receptor beta (THRB) gene - case report.

    PubMed

    Işık, Emregül; Beck Peccoz, Paolo; Campi, Irene; Özön, Alev; Alikaşifoğlu, Ayfer; Gönç, Nazlı; Kandemir, Nurgün

    2013-01-01

    Thyroid hormone resistance (THR) is a dominantly inherited syndrome characterized by reduced sensitivity to thyroid hormones. It is usually caused by mutations in the thyroid hormone receptor beta (THRB) gene. In the present report, we describe the clinical and laboratory characteristics and genetic analysis of patients with a novel THRB gene mutation. The index patient had been misdiagnosed as hyperthyroidism and treated with antithyroid drugs since eight days of age. Thyroid hormone results showed that thyrotropin (thyroid-stimulating hormone, TSH) was never suppressed despite elevated thyroid hormone levels, and there was no symptom suggesting hyperthyroidism. A heterozygous mutation at codon 350 located in exon 9 of the THRB gene was detected in all the affected members of the family. It is important to consider thyroid hormone levels in association with TSH levels to prevent inappropriate treatment and the potential complications, such as clinical hypothyroidism or an increase in goiter size.

  17. Thyroid function testing in neonates born to women with hypothyroidism.

    PubMed

    McGovern, Matthew; Reyani, Zahra; O'Connor, Pamela; White, Martin; Miletin, Jan

    2016-12-01

    Our aim was to assess the utility of serum thyroxine and thyroid stimulating hormone performed at 10-14 days of life in diagnosing congenital hypothyroidism (CH) in babies born to mothers with hypothyroidism. This was a retrospective study of all babies born in a tertiary referral centre for neonatology over a 12-month period. Infants who had thyroid function testing (TFT) checked at 10-14 days of life because of maternal hypothyroidism during the period of study were included. The results of the newborn bloodspot and day 10-14 TFT were recorded along with whether or not patients were subsequently treated. Of the 319 patients included in the study, only two patients were found to have CH and in both cases the newborn blood spot had been abnormal. No extra cases of CH were detected from the thyroid test at 10-14 days and this practice should be discontinued due to the robust nature of existing newborn screening programmes. What is Known: • Congenital hypothyroidism(CH) is the commonest preventable cause of childhood intellectual impairment. • Family history of hypothyroidism has been implicated as a risk factor for CH. • CH has formed part of newborn screening since the 1970s. What is New: • There is no research recommending thyroid function testing at 10-14 days of life to detect CH in neonates born to mothers with hypothyroidism. • Thyroid function testing at 10-14 days of life does not improve diagnostic yield for CH in babies born to mothers with hypothyroidism. • Newborn blood spot remains the mainstay for accurate and timely diagnosis of CH.

  18. Screening of congenital hypothyroidism in preterm, low birth weight and very low birth weight neonates: A systematic review.

    PubMed

    Hashemipour, Mahin; Hovsepian, Silva; Ansari, Arman; Keikha, Mojtaba; Khalighinejad, Pooyan; Niknam, Negar

    2017-07-22

    Evidence from different screening programs indicated that the rate of congenital hypothyroidism (CH) was higher in pre-term and low-birth-weight (LBW) newborns than normal ones. Incomplete development of hypothalamic-pituitary axis in this group of neonates results in the delayed rise of TSH and missing cases with CH. Hence, there is a great need for a practicable systematic screening method for proper diagnosis of CH in this group of neonates. In this review, we systematically reviewed papers with the following key words ([Congenital Hypothyroidism AND Screening AND Thyroxine AND Thyroid Stimulating Hormone AND Low Birth Weight AND Premature]) in international electronic databases including PubMed, Scopus, and Google Scholar. After quality assessment of selected documents, data of finally included papers were extracted. In this review, 1452 papers (PubMed: 617; Scopus: 714; Google scholar: 121) were identified through electronic database search. One hundred and ninety four articles were assessed for eligibility, from which 36 qualified articles were selected for final evaluation. From the reviewed articles, 38.9%, 11.11% and 8.3% recommended rescreening in this group of neonates, lowering the screening cutoff of TSH and using cutoffs according to the gestational age, respectively. Some of them (13.9%) recommended using both TSH and T4 for screening of preterm infants. After reviewing available data, we recommend repeating the screening test in pre-term, LBW and very-low- birth-weight (VLBW) infants at age of two, six and ten weeks by measuring TSH and FT4 levels simultaneously and considering TSH = 10 mU/L as the cutoff level for positive and suspicious cases. Copyright © 2017. Published by Elsevier B.V.

  19. The role of thyroid hormone in sleep deprivation.

    PubMed

    Pereira, José Carlos; Andersen, Mônica Levy

    2014-03-01

    Sleep deprivation is a stressful condition, as the subject experiences feelings of inadequate well-being and exhibits impairments in his/her functioning. However, in some circumstances sleep deprivation may be crucial for survival of the individual. Most likely, complex neural circuits and hormones play a role in allowing sleep deprivation to occur. For instance, thyroid hormone activity sharply increases when an individual is in a state of sleep deprivation. We believe that this increase is central to sleep deprivation physiology. During sleep deprivation, the hypothalamic-pituitary-thyroid axis initially increases as a consequence of increased release of thyroid stimulating hormone from the pituitary. Subsequently, as sleep deprivation continues, the sympathetic nervous system is recruited through its anatomical connection with the thyroid gland. While thyroid stimulating hormone levels markedly increase during sleep deprivation, it has been suggested that these increases are secondary to sleep deprivation. However, there is little evidence to support this assumption. We believe that the physiology of the thyroid axis during sleep deprivation and the actions of the effector hormone thyroid hormone suggest that thyroid hormone inhibits sleep and not the contrary. To our knowledge, few studies have addressed the possible neural functions that enable sleep deprivation. In this article, we discuss the hypothesis that an augmentation in the thyroid hormone axis is central to a subject's ability to curtail sleep.

  20. Response of newborn foals with thyroid musculoskeletal disease to adrenocorticotrophic hormone (ACTH).

    PubMed

    Card, C E; Manning, S T

    2000-01-01

    Fetal maturation and equine parturition are not understood fully, although the adrenal and thyroid glands are thought to have regulatory roles. Thyroidectomized equine fetuses undergo prolonged gestation, and spontaneous diseases such as thyroid musculoskeletal disease and gestational fescue endophyte exposure are also associated with delayed parturition. Thyroid musculoskeletal disease is characterized by: histologically hyperplastic thyroid glands, chondro-osseous dysplasia and dysgenesis, angular limb deformity, low resting thyroxine and triiodothyronine concentrations, and lack of response to thyroid stimulating hormone. There are also similarities between foals born to mares grazing fescue grass infected with endophytes and foals with thyroid musculoskeletal disease (TH-MSD foals). It is thought that there may be an endocrine basis for the prolonged gestation observed in these disease states. The aim of the present study was to determine the endocrine competence of the adrenal gland in TH-MSD foals. Adrenocorticotrophic hormone (ACTH) response tests were used to compare the functional ability of the neonatal adrenal gland in healthy foals and TH-MSD foals. Basal thyroxine concentrations were significantly different between groups (P < 0.02): the thyroxine concentrations were lower in TH-MSD foals. After ACTH administration there was a significant effect of time (P < or = 0.001), but not treatment, on cortisol concentrations in foals. Thyroid hormone deficiency in TH-MSD foals did not significantly affect adrenal cortical secretion after ACTH administration. This finding indicates that thyroid function may play a major role in the timing of parturition either directly or indirectly via a mechanism other than by influencing adrenal responsiveness to ACTH.

  1. Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults But Not in Neonates

    EPA Science Inventory

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...

  2. Developmental Thyroid Hormone Insufficiency Reduces Expression of Brain-Derived Neurotrophic Factor (BDNF) in Adults But Not in Neonates

    EPA Science Inventory

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin critical for many developmental and physiological aspects of CNS function. Severe hypothyroidism in the early neonatal period results in developmental and cognitive impairments and reductions in mRNA and protein expressio...

  3. Thyroid hormone disorders and sepsis.

    PubMed

    Luo, Bin; Yu, Zhui; Li, Yinping

    2017-01-01

    Sepsis is a systemic inflammatory response syndrome with high mortality, which results from severe infection and can lead to secondary organ dysfunction. It is one of the most common cause of death in intensive care unit. Clinical reports have shown that sepsis was often accompanied by thyroid dysfunction, which is called "low triiodothyronine (T3)" syndrome and characterized by decreased blood total T3 and free T3, and by normal or decreased thyroxine (T4) and thyroid stimulating hormone (TSH). This syndrome may greatly affect the prognosis of patients with sepsis. The main purpose of this review is to illustrate the role of thyroid hormone disorder in the development and prognosis of sepsis.

  4. Leptin serum concentrations in healthy neonates within the first week of life: relation to insulin and growth hormone levels, skinfold thickness, body mass index and weight.

    PubMed

    Schubring, C; Siebler, T; Kratzsch, J; Englaro, P; Blum, W F; Triep, K; Kiess, W

    1999-08-01

    Leptin, the ob gene product, plays a key role in the regulation of body fat mass and weight in adult life. The mechanisms by which maternal and fetal/neonatal weight are regulated during human pregnancy and in early postnatal life are poorly understood. High leptin levels are observed in women during gestation and in cord blood at term. We have hypothesized that high leptin levels at term could represent an important feed-back indicator of nutrient supply. Subsequently, leptin could signal adipose tissue status during late gestation and during early neonatal life. 51 healthy newborns were studied. Clinical and auxological data (birth length, weight, and iliac, subscapular, biceps and triceps skinfold thickness) were recorded using a standardized data sheet. Venous cord blood was obtained immediately after birth in all neonates. Subsequently, capillary blood was obtained from the heel from some of the newborns when blood had to be obtained because of signs or symptoms of particular problems such as hypoglycaemia or hyperbilirubinaemia, at the following time points: two to four hours after birth in 51 infants, 56-79 h after birth in 47 infants and 99-128 h after birth in 23 of the newborns. The ratio between the sexes (girls/boys) was similar at all time points. The infants that were included in the study were subsequently found to be normal and healthy after analysis of the clinical and biochemical data. A specific ultrasensitive radioimmunoassay was used to measure leptin, while growth hormone and insulin were measured using commercially available immunoassays. Gestational age was 38-42 weeks, maternal age was 21-42 years. Birth weights ranged from 2480 to 4400 g. All newborns and mothers were subsequently found to be healthy. Leptin levels in venous cord blood was 0.16-6.80 microg/l, median 3. 47 microg/l and in capillary blood shortly after birth 0.26-7.03 microg/l, median 3.89 microg/l. 56-79 h after birth leptin levels had fallen dramatically, range 0

  5. Resistance to growth hormone releasing hormone and gonadotropins in Albright's hereditary osteodystrophy.

    PubMed

    Mantovani, Giovanna; Spada, Anna

    2006-05-01

    Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteo-dystrophy (AHO). Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action (pseudohypoparathyroidism type Ia [PHP-Ia), recent studies have provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad and pituitary. Accordingly, patients with PHP-Ia display variable degrees of resistance to parathyroid hormone (PTH), thyroid stimulating hormone (TSH), gonadotropins and growth hormone (GH) releasing hormone (GHRH). Although the incidence and the clinical and biochemical characteristics of PTH and TSH resistance have been widely investigated and described, the cause and significance of the reproductive dysfunction in AHO is still poorly understood. The clinical finding of alterations of GH secretion in these patients was described for the first time only 2 years ago. The present report briefly reviews the literature focusing on the actual knowledge about these last two subjects.

  6. Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats.

    PubMed

    Espinosa, Pedro; Silva, Roxana A; Sanguinetti, Nicole K; Venegas, Francisca C; Riquelme, Raul; González, Luis F; Cruz, Gonzalo; Renard, Georgina M; Moya, Pablo R; Sotomayor-Zárate, Ramón

    2016-01-01

    We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.

  7. Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats

    PubMed Central

    Espinosa, Pedro; Silva, Roxana A.; Sanguinetti, Nicole K.; Venegas, Francisca C.; Riquelme, Raul; González, Luis F.; Cruz, Gonzalo; Renard, Georgina M.; Moya, Pablo R.; Sotomayor-Zárate, Ramón

    2016-01-01

    We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area. PMID:26904299

  8. Resistance to Thyroid Hormone Complicated with Type 2 Diabetes and Cardiomyopathy in a Patient with a TRβ Mutation

    PubMed Central

    Wakasaki, Hisao; Matsumoto, Miyuki; Tamaki, Shinya; Miyata, Kaori; Yamamoto, Shohei; Minaga, Takamasa; Hayashi, Yoshitaka; Komukai, Kenichi; Imanishi, Toshio; Yamaoka, Hiroyuki; Matsuno, Shohei; Nishi, Masahiro; Akamizu, Takashi

    2016-01-01

    Resistance to thyroid hormone (RTH) is a genetic disorder characterized by reduced tissue responsiveness to thyroid hormone. We herein describe a 60-year old man who presented with the clinical features of cardiomyopathy, diabetes mellitus and elevated thyroid hormones with unsuppressed thyroid stimulating hormone. A genetic analysis of thyroid hormone receptor (TR) revealed a missense mutation (A268D) in the TRβ gene. Clinical manifestations of RTH may be variable due to different tissue distributions of TR subtypes and different actions of mutant receptors. The current case demonstrates that patients with a TRβ mutation may have impaired his glucose metabolism and a reduced cardiac function, although patients appear clinically euthyroid. PMID:27853072

  9. Protein Hormones and Immunity‡

    PubMed Central

    Kelley, Keith W.; Weigent, Douglas A.; Kooijman, Ron

    2007-01-01

    A number of observations and discoveries over the past 20 years support the concept of important physiological interactions between the endocrine and immune systems. The best known pathway for transmission of information from the immune system to the neuroendocrine system is humoral in the form of cytokines, although neural transmission via the afferent vagus is well documented also. In the other direction, efferent signals from the nervous system to the immune system are conveyed by both the neuroendocrine and autonomic nervous systems. Communication is possible because the nervous and immune systems share a common biochemical language involving shared ligands and receptors, including neurotransmitters, neuropeptides, growth factors, neuroendocrine hormones and cytokines. This means that the brain functions as an immune-regulating organ participating in immune responses. A great deal of evidence has accumulated and confirmed that hormones secreted by the neuroendocrine system play an important role in communication and regulation of the cells of the immune system. Among protein hormones, this has been most clearly documented for prolactin (PRL), growth hormone (GH), and insulin-like growth factor-1 (IGF-I), but significant influences on immunity by thyroid stimulating hormone (TSH) have also been demonstrated. Here we review evidence obtained during the past 20 years to clearly demonstrate that neuroendocrine protein hormones influence immunity and that immune processes affect the neuroendocrine system. New findings highlight a previously undiscovered route of communication between the immune and endocrine systems that is now known to occur at the cellular level. This communication system is activated when inflammatory processes induced by proinflammatory cytokines antagonize the function of a variety of hormones, which then causes endocrine resistance in both the periphery and brain. Homeostasis during inflammation is achieved by a balance between cytokines and

  10. Prolonged weightlessness effect on postflight plasma thyroid hormones

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Johnson, P. C.; Driscoll, T. B.

    1977-01-01

    Blood drawn before and after spaceflight from the nine Skylab astronauts showed a statistically significant increase in mean plasma thyroxine (T-4) of 1.4 micro g/dl and in thyroid-stimulating hormone (TSH) of 4 microunits ml. Concurrent triiodothyronine (T-3) levels decreased 27 ng/dl indicating inhibited conversion of T-4 to T-3. The T-3 decrease is postulated to be a result of the increased cortisol levels noted during and following each mission. These results confirm the thyroidal changes noted after the shorter Apollo flights and show that thyroid hormone levels change during spaceflight.

  11. Prolonged weightlessness effect on postflight plasma thyroid hormones

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Johnson, P. C.; Driscoll, T. B.

    1977-01-01

    Blood drawn before and after spaceflight from the nine Skylab astronauts showed a statistically significant increase in mean plasma thyroxine (T-4) of 1.4 micro g/dl and in thyroid-stimulating hormone (TSH) of 4 microunits ml. Concurrent triiodothyronine (T-3) levels decreased 27 ng/dl indicating inhibited conversion of T-4 to T-3. The T-3 decrease is postulated to be a result of the increased cortisol levels noted during and following each mission. These results confirm the thyroidal changes noted after the shorter Apollo flights and show that thyroid hormone levels change during spaceflight.

  12. Potential influence of hormones in the development of slipped capital femoral epiphysis: a preliminary study.

    PubMed

    Papavasiliou, Kyriakos A; Kirkos, John M; Kapetanos, George A; Pournaras, John

    2007-01-01

    The potential influence of hormonal imbalance on the development of slipped capital femoral epiphysis was assessed through a prospective clinical study. The serum levels of T3, T4, thyroid-stimulating hormone, testosterone, estradiol, dehydroepiandrosterone-sulfate, follicle-stimulating hormone, luteinizing hormone, human growth hormone, adrenal cortex hormone and cortisol were evaluated in seven boys and seven girls. Forty-three out of 154 hormonal determinations (27.9%) were abnormal. The results showed increased incidence of pathological values mainly in the levels of follicle-stimulating-hormone, luteinizing-hormone and testosterone. No patient had clinical findings of endocrinopathy. A (possibly) temporary hormonal disorder may play a potentially significant role in the development of slipped capital femoral epiphysis.

  13. The Role of Interleukin-6 and C-Reactive Protein in Non-Thyroidal Illness in Premature Infants Followed in Neonatal Intensive Care Unit

    PubMed Central

    Dilmen, Uğur

    2012-01-01

    Objective: To investigate the role of interleukin-6 (IL-6) and C-reactive protein (CRP) in non-thyroidal illness (NTI) in premature infants. Methods: Serum levels of IL-6 and CRP, thyroid-stimulating hormone (TSH), total thyroxine (T4), free T4 (fT4), total triiodothyronine (T3), and free T3 (fT3) were determined at the 1st, 2nd and 4th weeks of postnatal life in 148 premature infants born before 33 weeks of gestation. Results: At the 1st week, serum T3 was negatively correlated with IL-6(r= -0.33, p= 0.001) and CRP (r= -0.17, p= 0.03). Serum T3 was negatively and more strongly correlated with IL-6 (r= -0.49, p= 0.001) and CRP (r=- 0.33,p= 0.03) at the 2nd week, at which time sepsis frequency and low T3 rates were the highest. At the 4th week, mortality rate was higher among infants with lower T3 levels. Conclusions: High IL-6 and CRP values related to neonatal sepsis might have a significant role in the pathogenesis of NTI in premature infants. Conflict of interest:None declared. PMID:22672862

  14. Pituitary resistance to thyroid hormones: pathophysiology and therapeutic options.

    PubMed

    Suzuki, Satoru; Shigematsu, Satoshi; Inaba, Hidefumi; Takei, Masahiro; Takeda, Teiji; Komatsu, Mitsuhisa

    2011-12-01

    Thyroid hormone secretion suppresses the expression of thyroid stimulating hormone (TSH), both of which are strictly controlled by a negative feedback loop between the hypothalamus-pituitary and thyroid. Pituitary resistance to thyroid hormone (PRTH) is defined as resistance to the action of thyroid hormone that is more severe in the pituitary than at the peripheral tissue level. Although the molecular basis of PRTH is not well understood, the clinical issue mainly involves imbalance between the hypothalamus-pituitary and peripheral thyroid hormone responsivity, which may induce peripheral thyrotoxic phenomena. Here, we review the pathogenesis and molecular aspects of PRTH, present a single case with inappropriate TSH secretion suffering from thyrotoxicosis treated with PTU, and discuss the possible choice of therapeutic options to correct the imbalance of thyroid hormone responsivity in both the hypothalamus-pituitary and peripheral tissues.

  15. Biochemical Hyperthyroidism in a Newborn Baby Caused by Assay Interaction from Biotin Intake

    PubMed Central

    Bülow Pedersen, Inge; Laurberg, Peter

    2016-01-01

    We describe a case of biochemical neonatal thyrotoxicosis caused by biotin supplementation. Biotin may interact with thyroid function testing to imitate thyrotoxicosis with low thyroid-stimulating hormone and elevated triiodothyronine and thyroxine levels. PMID:27843813

  16. Biochemical Hyperthyroidism in a Newborn Baby Caused by Assay Interaction from Biotin Intake.

    PubMed

    Bülow Pedersen, Inge; Laurberg, Peter

    2016-09-01

    We describe a case of biochemical neonatal thyrotoxicosis caused by biotin supplementation. Biotin may interact with thyroid function testing to imitate thyrotoxicosis with low thyroid-stimulating hormone and elevated triiodothyronine and thyroxine levels.

  17. Thyroid hormone regulates Ca(2+)-ATPase mRNA levels of sarcoplasmic reticulum during neonatal development of fast skeletal muscle.

    PubMed

    van der Linden, G C; Simonides, W S; van Hardeveld, C

    1992-12-01

    In gastrocnemius muscle from newborn rats the mRNA for the fast sarcoplasmic reticulum (SR) Ca(2+)-ATPase isoform (SERCA1) comprised over 90% of total SR Ca(2+)-ATPase mRNA content and increased 5-fold between day 5 and 20 after birth, whereas in hypothyroid muscle the SERCA1 message level remained constant. Triiodothyronine (T3) treatment of 2-day-old euthyroid rats induced a precocious stimulation of SERCA1 mRNA levels, indicating that T3 is the determining factor in the stimulation of SERCA1 message levels and that this stimulation underlies the previously reported effect of the thyroid status on the neonatal development of SR Ca(2+)-ATPase activity. The low mRNA level for the slow SR Ca(2+)-ATPase isoform (SERCA2) was constant in both euthyroid and hypothyroid muscle development. Nevertheless, T3 treatment of hypothyroid neonates induced a transient stimulation of SERCA2 message levels, indicating that SERCA2 is responsive to higher levels of T3.

  18. Neonatal immunisation against a novel gonadotrophin-releasing hormone construct delays the onset of gonadal growth and puberty in bull calves.

    PubMed

    Hernandez-Medrano, J H; Williams, R W; Peters, A R; Hannant, D; Campbell, B K; Webb, R

    2012-01-01

    The aim of the present study was to investigate the effect of the neonatal immunisation of bull calves against a novel gonadotrophin-releasing hormone (GnRH) construct, comprised of GnRH coupled to the glycoprotein D subunit of the bovine herpes virus-1 (GnRH-BHV1 gD), on endocrine status, reproductive organ development and carcass quality. Eighteen bull calves received either GnRH construct (n=9) or saline (control; n=9) at 2, 6 and 13.5 weeks of age. Blood samples were taken to determine antibody titres against GnRH, FSH and testosterone (T) concentrations and LH pulse characteristics, with testicular circumference monitored monthly. Immunisation reduced LH pulse amplitude (P<0.05) and T concentrations (P<0.05), particularly at the peak in anti-GnRH titres after the second booster at 16 weeks of age (P<0.001), but not when titres fell. Despite antibody titres decreasing after 16 weeks, immunisation reduced testicular size between 16 to 57 weeks of age (P<0.05), provoking an 8-week delay in puberty onset, defined as testicular circumference ≥14 cm. In conclusion, neonatal immunisation induced a significant immune response against GnRH, provoking a temporary endocrine disturbance that had a long-term effect on testicular development, delaying the onset of puberty. These results support the hypothesis that a developmental window exists during testicular development, such that disturbance of the endocrine drive to the gonads during this period results in a longer-term impairment of gonadal function.

  19. Neonatal age and point of careTSH testing in the monitoring of iodine deficiency disorders: findings from western Uganda.

    PubMed

    Ehrenkranz, Joel; Fualal, Jane; Ndizihiwe, Assay; Clarke, Ian; Alder, Stephen

    2011-02-01

    Iodine deficiency is a major public health problem throughout Africa. Although salt for human consumption is said to contain adequate amounts of iodine in Uganda, iodine intake may not be optimal. We undertook a field study to assess the adequacy of iodine nutrition in western Uganda using on-site measurement methods of neonatal thyroid stimulating hormone (TSH) levels as recommended by the World Health Organization (WHO) for monitoring the degree of iodine deficiency during pregnancy. The study design consisted of a prevalence study using the percentage of newborns between the ages of 3 and 7 days with TSH >5 mIU/L, measured with a point-of-care immunochromatographic TSH assay, as a surrogate marker of iodine deficiency. Five districts in western Uganda were selected for study on the basis of a past history of iodine deficiency. One thousand seventy-eight newborns from the five districts were sequentially enrolled in each separate district and tested between July 2007 and January 2008. The prevalence of TSH levels >5 mlU/L ranged from 20% to 32%. Neonates tested on or before the age of 3 days were more likely to have a TSH level >5 mlU/L than those tested beyond the age of three days (28.2% vs. 18.7%, p < 0.001). Assessing neonatal TSH levels in developing countries with a TSH assay method suitable for field use can be successfully used to screen for congenital hypothyroidism and to indirectly assess a population's iodine status. Based on the percentage of neonates with TSH values >5 mIU/L, presumptive iodine deficiency persists in western Uganda. This finding suggests that continued monitoring of iodine nutrition in the area surrounding the Rwenzori Mountains in Uganda and Congo is needed. Due to the progressive fall in the percent of TSH values >5 mIU/L from day three to day five of life, we conclude that TSH measurement earlier than day five of life in newborns at risk for iodine deficiency may be misleading. Guidelines for the use of neonatal TSH

  20. MicroRNA-27a Regulates Beta Cardiac Myosin Heavy Chain Gene Expression by Targeting Thyroid Hormone Receptor β1 in Neonatal Rat Ventricular Myocytes▿

    PubMed Central

    Nishi, Hitoo; Ono, Koh; Horie, Takahiro; Nagao, Kazuya; Kinoshita, Minako; Kuwabara, Yasuhide; Watanabe, Shin; Takaya, Tomohide; Tamaki, Yodo; Takanabe-Mori, Rieko; Wada, Hiromichi; Hasegawa, Koji; Iwanaga, Yoshitaka; Kawamura, Teruhisa; Kita, Toru; Kimura, Takeshi

    2011-01-01

    MicroRNAs (miRNAs), small noncoding RNAs, are negative regulators of gene expression and play important roles in gene regulation in the heart. To examine the role of miRNAs in the expression of the two isoforms of the cardiac myosin heavy chain (MHC) gene, α- and β-MHC, which regulate cardiac contractility, endogenous miRNAs were downregulated in neonatal rat ventricular myocytes (NRVMs) using lentivirus-mediated small interfering RNA (siRNA) against Dicer, an essential enzyme for miRNA biosynthesis, and MHC expression levels were examined. As a result, Dicer siRNA could downregulate endogenous miRNAs simultaneously and the β-MHC gene but not α-MHC, which implied that specific miRNAs could upregulate the β-MHC gene. Among 19 selected miRNAs, miR-27a was found to most strongly upregulate the β-MHC gene but not α-MHC. Moreover, β-MHC protein was downregulated by silencing of endogenous miR-27a. Through a bioinformatics screening using TargetScan, we identified thyroid hormone receptor β1 (TRβ1), which negatively regulates β-MHC transcription, as a target of miR-27a. Moreover, miR-27a was demonstrated to modulate β-MHC gene regulation via thyroid hormone signaling and to be upregulated during the differentiation of mouse embryonic stem (ES) cells or in hypertrophic hearts in association with β-MHC gene upregulation. These findings suggested that miR-27a regulates β-MHC gene expression by targeting TRβ1 in cardiomyocytes. PMID:21149577

  1. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice

    PubMed Central

    Busby, Ellen R.; Sherwood, Nancy M.

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15–28 may account for the altered metabolism in the prepubertal female pups. PMID:28346489

  2. Gonadotropin-releasing hormone receptor (Gnrhr) gene knock out: Normal growth and development of sensory, motor and spatial orientation behavior but altered metabolism in neonatal and prepubertal mice.

    PubMed

    Busby, Ellen R; Sherwood, Nancy M

    2017-01-01

    Gonadotropin-releasing hormone (GnRH) is important in the control of reproduction, but its actions in non-reproductive processes are less well known. In this study we examined the effect of disrupting the GnRH receptor in mice to determine if growth, metabolism or behaviors that are not associated with reproduction were affected. To minimize the effects of other hormones such as FSH, LH and sex steroids, the neonatal-prepubertal period of 2 to 28 days of age was selected. The study shows that regardless of sex or phenotype in the Gnrhr gene knockout line, there was no significant difference in the daily development of motor control, sensory detection or spatial orientation among the wildtype, heterozygous or null mice. This included a series of behavioral tests for touch, vision, hearing, spatial orientation, locomotory behavior and muscle strength. Neither the daily body weight nor the final weight on day 28 of the kidney, liver and thymus relative to body weight varied significantly in any group. However by day 28, metabolic changes in the GnRH null females compared with wildtype females showed a significant reduction in inguinal fat pad weight normalized to body weight; this was accompanied by an increase in glucose compared with wildtype females shown by Student-Newman-Keuls Multiple Comparison test and Student's unpaired t tests. Our studies show that the GnRH-GnRHR system is not essential for growth or motor/sensory/orientation behavior during the first month of life prior to puberty onset. The lack of the GnRH-GnRHR axis, however, did affect females resulting in reduced subcutaneous inguinal fat pad weight and increased glucose with possible insulin resistance; the loss of the normal rise of estradiol at postnatal days 15-28 may account for the altered metabolism in the prepubertal female pups.

  3. Racial variation in sex steroid hormones and the insulin-like growth factor axis in umbilical cord blood of male neonates

    PubMed Central

    Rohrmann, Sabine; Sutcliffe, Catherine G.; Bienstock, Jessica L.; Monsegue, Deborah; Akereyeni, Folasade; Bradwin, Gary; Rifai, Nader; Pollak, Michael N.; Agurs-Collins, Tanya; Platz, Elizabeth A.

    2010-01-01

    Aim To address whether umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF)-axis differ between African-American and white male neonates. Methods In 2004/2005, venous cord blood samples were collected from 75 African-American and 38 white male full-term uncomplicated births along with birth weight, placental weight, mother’s age and parity, and time of birth. Testosterone, androstanediol glucuronide, estradiol, and sex hormone binding globulin (SHBG) were measured by immunoassay, and IGF-1, IGF-2, and IGF binding protein (BP)-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed. Results Androstanediol glucuronide, estradiol, and SHBG concentrations did not differ by race; however, the molar ratio of testosterone to SHBG was higher in African-American than white male babies after adjustment (p=0.01). Both before and after adjustment, whites had higher concentrations of IGF-1 (adjusted; white, African-American: 93.1, 71.9 ng/mL), IGF-2 (537.3, 474.8 ng/mL), and IGFBP-3 (1673, 1482 ng/mL) than African-Americans (p<0.05), although the molar ratio of IGF-1 plus IGF-2 to IGFBP-3 did not differ by race. Conclusion The higher cord blood testosterone to SHBG ratio in African-American compared with white male babies after taking into account maternal and birth factors is compatible with the hypothesis that differences in androgen levels in utero contribute to their higher prostate cancer risk, although we would have expected crude differences as well. Lower cord blood IGF-1 and IGF-2 levels in African-American compared with white male babies are not consistent with the hypothesis that differences in growth factor levels contribute to their higher prostate cancer risk. PMID:19423525

  4. Association between thyroid hormones, insulin resistance, and metabolic syndrome.

    PubMed

    Kumar, Hari K; Yadav, Raj K; Prajapati, Jayaram; Reddy, Challa V K; Raghunath, Manchala; Modi, Kirtikumar D

    2009-07-01

    To determine the association between thyroid hormones, insulin resistance, and metabolic syndrome in euthyroid women. Forty-five women with no past medical history were studied in this cross-sectional study at the Department of Endocrinology, Medwin Hospitals, Hyderabad, India, from August 2008 to September 2008. The body fat was estimated using bio-impedance method, and fasting blood sample was analyzed for total triiodothyronine (T3), total thyroxine (T4), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), lipid profile, insulin, and glucose. The mean age of the participants was 32.6 +/= 9.6 years with a body mass index (BMI) of 29.9 +/= 3.8 kg/m2. Evidence of homeostasis model assessment index for insulin resistance (HOMA-IR) more than 3 was seen in 34 (75%) and metabolic syndrome in 29 (64%) participants. Total T3 showed a positive correlation with triglycerides, low density lipoprotein- cholesterol (LDL-C), total cholesterol, insulin, HOMA-IR and negatively with body fat. Thyroid-stimulating hormone correlated positively with BMI, insulin, HOMA-IR, LDL-C and negatively with HDL-cholesterol (p<0.05). Free triiodothyronine correlated positively with waist circumference and T4 did not correlate with metabolic syndrome parameters. Our preliminary data show an association between thyroid hormones and some components specific of the metabolic syndrome in euthyroid women. Total triiodothyronine and TSH correlated more with variables of metabolic syndrome than FT3 and T4.

  5. Thyroid hormone-dependent formation of a subcortical band heterotopia (SBH) in the neonatal brain is not exacerbated under conditions of low dietary iron (FeD).

    PubMed

    Spring, S R; Bastian, T W; Wang, Y; Kosian, P; Anderson, G W; Gilbert, M E

    2016-01-01

    Thyroid hormones (TH) are critical for brain development and insufficiencies can lead to structural abnormalities in specific brain regions. Administration of the goitrogen propylthiouracil (PTU) reduces TH production by inhibiting thyroperoxidase (TPO), an enzyme that oxidizes iodide for the synthesis of TH. TPO activity is iron (Fe)-dependent and dietary iron deficiency (FeD) also reduces circulating levels of TH. We have previously shown that modest degrees of TH insufficiency induced in pregnant rat dams alters the expression of TH-responsive genes in the cortex and hippocampus of the neonate, and results in the formation of a subcortical band heterotopia (SBH) in the corpus callosum (Royland et al., 2008, Bastian et al., 2014, Gilbert et al., 2014). The present experiment investigated if FeD alone was sufficient to induce a SBH or if FeD would augment SBH formation at lower doses of PTU. One set of pregnant rats was administered 0, 1, 3, or 10ppm of PTU via drinking water starting on gestational day (GD) 6. FeD was induced in a 2nd set of dams beginning on GD2. A third set of dams received the FeD diet from GD2 paired with either 1ppm or 3ppm PTU beginning on GD6. All treatments continued until the time of sacrifice. On PN18, one female pup from each litter was sacrificed and the brain examined for SBH. We observed lower maternal, PN2 and PN18 pup serum T4 in response to PTU. FeD reduced serum T4 in pups on PN16, but did not affect serum T4 in dams or PN2 pups. Neither did FeD in combination with PTU alter T4 levels in dams on PN18 or pups on PN2 compared to PTU treatment alone. By PN16, however more severe T4 reductions were observed in pups when FeD was combined with PTU. SBH increased with increasing dosage of PTU, but counter to our hypothesis, no SBH was detected in the offspring of FeD dams. As such, T4 levels in dams and newborn pups rather than older neonates appear to be a better predictor SBH associated with TH insufficiency. These data indirectly

  6. Endocrine and metabolic changes in neonatal calves in response to growth hormone and long-R3-insulin-like growth factor-I administration.

    PubMed

    Hammon, H; Blum, J W

    1998-01-01

    Postnatal growth is primarily controlled by growth hormone (GH) and insulin-like growth factor-I (IGF-I). We have studied effects of recombinant bovine GH (rbGH) and Long-R3-insulin-like growth factor-I (Long-R3-IGF-I) on metabolic and endocrine characteristics of neonatal calves. Group GrC (control) was fed colostrum as first meal and then milk replacer up to day 7. Groups GrIGFf, GrIGFi and GrGH were fed as GrC. In group GrIGFf, Long-R3-IGF-I (50 micrograms/[kg x day], twice daily for 7 days) was fed together with colostrum or milk replacer and in group GrIGFi, Long-R3-IGF-I (50 micrograms/[kg x day], twice daily for 7 days) was injected subcutaneously at times of feeding. Calves of group GrGH were injected rbGH (1 mg/[kg x day, s.c.], twice daily for 7 days) at times of feeding. While orally administered Long-R3-IGF-I had no effects, subcutaneously administered Long-R3-IGF-I lowered plasma glucose and insulin concentrations (p < 0.05). In group GrGH, day-2 postprandial plasma insulin concentrations were increased more than in Long-R3-IGF-I-treated groups (p < 0.05) and day-2 postprandial prolactin responses were greater in group GrGH than in controls (p < 0.05). Other traits (lactic acid, nonesterified fatty acids, glucagon, cortisol, thyroxine and 3.5.3'-triiodothyronine) exhibited age-dependent changes, but were not significantly affected by rbGH or Long-R3-IGF-I. The study shows, that parenteral, but not oral, Long-R3-IGF-I affects plasma glucose and insulin concentrations, and that rbGH transiently influences plasma prolactin concentrations in neonatal calves.

  7. Organon OD 14 (tibolone) and menopausal dynamic hormone profiles.

    PubMed

    Abdalla, H I; Hart, D M; Lindsay, R; Beastall, G H

    1986-03-01

    Hormonal profiles were studied in 15 post-menopausal women, 7 of whom had been treated with Organon OD 14 (Tibolone) and 8 with placebo tablets for 3 yr. In the Tibolone-treated group, the sex hormone binding globulin (SHBG) levels were significantly lower, while the estimated free testosterone levels, the testosterone/SHBG ratio and the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) were significantly higher than in the placebo group. Prolactin and triiodothyronine (T3) concentrations were lower in the actively treated group, although the differences were not statistically significant. No significant differences were observed with respect to thyroxine (T4), TSH, basal cortisol or cortisol response to synacthen.

  8. Regulation of Seasonal Reproduction by Hypothalamic Activation of Thyroid Hormone

    PubMed Central

    Shinomiya, Ai; Shimmura, Tsuyoshi; Nishiwaki-Ohkawa, Taeko; Yoshimura, Takashi

    2014-01-01

    Organisms living outside the tropics measure the changes in the length of the day to adapt to seasonal changes in the environment. Animals that breed during spring and summer are called long-day breeders, while those that breed during fall are called short-day breeders. Although the influence of thyroid hormone in the regulation of seasonal reproduction has been known for several decades, its precise mechanism remained unknown. Recent studies revealed that the activation of thyroid hormone within the mediobasal hypothalamus plays a key role in this phenomenon. This localized activation of the thyroid hormone is controlled by thyrotropin (thyroid-stimulating hormone) secreted from the pars tuberalis of the pituitary gland. Although seasonal reproduction is a rate-limiting factor in animal production, genes involved in photoperiodic signal transduction pathway could emerge as potential targets to facilitate domestication. PMID:24600435

  9. The somatotropic axis in neonatal calves can be modulated by nutrition, growth hormone, and Long-R3-IGF-I.

    PubMed

    Hammon, H; Blum, J W

    1997-07-01

    Effects on the somatotropic axis [plasma levels of insulin-like growth factors (IGFs) I and II, IGF-binding proteins (IGFBPs), and growth hormone (GH)] of feeding different amounts of colostrum or milk replacer, of Long-R3-IGF-I (administered subcutaneously or orally; 50 micrograms.kg body wt-1.day-1 for 7 days), and of subcutaneously injected recombinant bovine GH (rbGH; 1 mg.kg body wt-1.day-1 for 7 days) were evaluated in calves during the 1st wk of life. Plasma Long-R3-IGF-I increased after subcutaneous application but not with the oral dose. Endogenous IGF-I was higher in calves fed colostrum six times compared with those fed only milk replacer. Native IGF-I was highest in rbGH-injected calves but was lowered by the subcutaneous injection of Long-R3-IGF-I. IGF-II concentrations were not modified by any of the treatments. IGFBP-2 increased in calves fed only milk replacer and those receiving subcutaneous Long-R3-IGF-I. GH was not modulated by differences in nutrition but increased after rbGH administration and similarly in all groups after intravenous injection of GH-releasing factor analog GRF-(1-29). Parenteral administration of Long-R3-IGF-I decreased GH concentration but did not affect the secretory pattern. The data demonstrate that the somatotrophic axis is basically functioning in neonatal calves and is influenced by nutrition, GH, and Long-R3-IGF-I.

  10. Comparison of FT4 with log TSH on the Abbott Architect ci8200: Pediatric reference intervals for free thyroxine and thyroid-stimulating hormone

    PubMed Central

    Soldin, Steven J; Cheng, Luke L; Lam, Lisa Y; Werner, Alice; Le, Alexander D; Soldin, Offie P

    2013-01-01

    Background We evaluated the clinical validity of serum FT4 measurements by assessing its correlation with log TSH. To provide pediatric reference intervals (representative ranges) for FT4, and TSH on the Architect ci8200 integrated system. Methods This population-based study encompassed 6023 children (3369 females and 2654 males). The percentile and Hoffmann approaches for obtaining reference intervals on these analytes were also compared. Results: FT4 correlation with log TSH was poor ( r=0.010 for males and 0.050 for females). Reference intervals were established. TSH and FT4 did not show a significant sex difference; moreover, the intervals decreased with age for FT4 and TSH. Conclusions Whereas in a previous study ultrafiltration tandem mass spectrometry yielded a correlation of r=0.90 for FT4 vs. log TSH this present study reveals a poor FT4 vs. log TSH correlation in the pediatric population studied and indicates the FT4 immunoassay conducted on the Abbott Architect ci8200 is less useful clinically than might have been expected. Reference intervals using the Hoffmann approach for pediatric in- and out-patients compare well with previously published results utilizing the percentile approach. PMID:19931524

  11. [Concentration of thyroid stimulating hormone and activity of N-acetyl-beta-D-hexosaminidase and its isoenzymes, in serum of patients with thyroid cancer].

    PubMed

    Zwierz, Piotr; Szajda, Sławomir D; Snarska, Jadwiga; Supronowicz, Zbigniew B; Zawadzki, Paweł; Zwierz, Krzysztof; Kamińsk, Fabian

    2006-11-01

    Thyroid cancer consists 1% of all malignant neoplasms. It is not known interrelationship between concentration of TSH in blood serum and condition of thyroid cancer. Thyroid cancer is difficult for diagnosis and differentiation. Therefore it is necessary to search for biochemical markers helpful in diagnostics of thyroid cancer. Significant increase in activity of N-acetyl-beta-D-hexosaminidase and its isoenzymes A and B in serum of patients with neoplasms of kidney and pancreas suggest approporiateness of evaluation of HEX and its isoenzymes in diagnostics of thyroid cancer. of the study--evaluation of TSH concentration and activity of HEX and its isoenzymes A and B, in serum of patients with thyroid cancer. Blood was taken from 7 patients with thyroid cancer (6 men and 1 woman). Control consisted of 7 healthy men. In blood serum concentration of TSH was determined with immunoenzymatic method on analyzer Axsym of Abbott and expressed in microU/mL. The activity of HEX and its isoenzymes A and B was determined by method of Chatterjee et al., as modified by Zwierz et.al. Determination of HEX was performed on microplate reader ELX800 BIO-TEK. Activity of HEX, HEX A and B was expressed in pKat/mL, and specific activity in pKat/mg protein). Protein was determined by biuret method and results were expressed in mg/mL. Concentration of HEX A activity in serum of thyroid cancer patients is significantly higherin comparison to healthymen (p = 0.0191). Also specific activity of HEX A in serum of thyroid cancer patients is significantly higher in comparison to healthy men (p = 0.0393). 1. Determination of TSH concentration in serum of thyroid cancer before the operation may confirm euthyreosis. 2. Determination of HEX A activity in serum may be helpful in diagnostics of thyroid cancer.

  12. Screening of Undiagnosed Hypothyroidism in Elderly Persons with Diabetes according to Age-Specific Reference Intervals for Serum Thyroid Stimulating Hormone and the Impact of Antidiabetes Drugs

    PubMed Central

    Teixeira, Patricia de Fatima dos Santos; Vaisman, Mario

    2016-01-01

    Background. Studies have suggested that hypothyroidism is more frequent in the elderly with diabetes mellitus. However, an adaptation of TSH levels to age should be considered in this assessment. Some antidiabetes drugs reportedly interfere with TSH levels. The objectives of this study were to evaluate the prevalence of undiagnosed hypothyroidism in patients with diabetes and the influence of antidiabetes drugs. Material and Methods. 1160 subjects, 60 years and older (751 with diabetes), were studied; results were compared according to diabetes treatment and with persons without diabetes. TSH, FT4, antithyroperoxidase, fasting glucose, and HbA1c were measured. Results and Discussion. 6.4% of patients with diabetes had hypothyroidism, a higher prevalence compared with persons without diabetes (5.1%), but lower than observed in many studies. The use of age-specific TSH reference interval (RI) could explain this difference. Patients taking metformin (MTF) had TSH (showed in medians) slightly lower (2.8 mU/L) than those not on MTF (3.3 mU/L), p < 0.05. MTF doses influenced TSH levels. Conclusions. The use of specific TSH RI could avoid the misdiagnosis of hypothyroidism in elderly with diabetes. Patients in use of MTF as single drug had lower TSH than those using other medications and persons without diabetes. PMID:27403442

  13. Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease.

    PubMed

    Choi, Hoon Sung; Yoo, Won Sang

    2017-06-01

    Anti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole. We included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups. The mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness. In patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

  14. Stimulating and blocking thyroid-stimulating hormone (TSH) receptor autoantibodies from patients with Graves' disease and autoimmune hypothyroidism have very similar concentration, TSH receptor affinity, and binding sites.

    PubMed

    Morgenthaler, Nils G; Ho, Su Chin; Minich, Waldemar B

    2007-03-01

    The distinct biological properties of TSH receptor (TSH-R) autoantibodies (TRAbs) from patients with Graves' disease (GD) are yet unexplained on the molecular level. Here we compare serum concentration, affinity to the TSH-R, and binding sites on the TSH-R of stimulating (TSAb) and blocking (TBAb) TRAbs. Four-step affinity purification using human recombinant TSH-R was performed with 22 TRAb-positive sera from GD patients (11 with only TSAb and 11 with only TBAb) and five control sera. Antibody concentration, TSH binding inhibition (TBII), and TSAb/TBAb activity of the purified TRAb were assessed. Labeled purified TRAbs were used for displacement studies with TRAb and an additional 30 patients and 10 control sera. TRAbs could be purified to 80-93% purity with recovery of the TBII and TSAb and TBAb activity. No TRAbs could be purified from healthy individuals. The mean +/- SD concentration of TRAb was 17.3 +/- 5.4 microg/IU for the TSAb sera (range, 9.6-25.9) and 18.2 +/- 8.5 microg/IU for the TBAb sera (range, 4.6-29.2), respectively (P = 0.79). Affinity was in the picomolar range for both TRAb subtypes with mean +/- sd dissociation constant of 167 +/- 109 pM (60-410 pM) for TSAb and 253 +/- 132 pM (80-410 pM) for TBAb (P = 0.12). Purified and labeled TSAb and TBAb showed a very similar binding pattern to the TSH-R in displacement studies with unlabeled TSAb/TBAb or unpurified patients sera, indicating binding sites on the TSH-R in close proximity to each other. TSAbs and TBAbs in the serum of patients with GD have similar characteristics. They are of low concentration with high affinity and have also similar binding epitopes on the TSH-R.

  15. [Efficacy of quinagolide in the treatment of a patient with hypophyseal resistance to thyroid hormones].

    PubMed

    De Luis, D A; Lahera, M; Botella, J I; Valero, M A; Varela, C

    2001-05-01

    The pituitary resistance to thyroid hormones (PRTH) is not very frequent and well-known entity, their treatment it continues being topic of controversy. In this work we have evaluated the quinagolida effectiveness in the treatment of it unites patient with (PRTH). The relationship among thyroid stimulating hormone (TSH) and free triiodothyronine (FT3) it was used as marker of the thyroid resistance and of the response to the treatment. The concentrations of TSH and FT3 were normalized after adding quinagolida to methimazole. These results suggest that the quinagolida could be an useful drug in the treatment of this pathology, next to the classic treatments.

  16. Developmental Triclosan Exposure Decreases Maternal, Fetal, and Early Neonatal Thyroxine: Dynamic and Kinetic Evaluation of a Putative Mode-of-Action

    PubMed Central

    Paul, Katie B.; Hedge, Joan M.; Bansal, Ruby; Zoeller, R. Thomas; Peter, Robert; DeVito, Michael J.; Crofton, Kevin M.

    2012-01-01

    This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0–300 mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman® qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid-hormone responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300 mg/kg/day). Hepatic PROD activity increased 2- to 3-fold in PND4 pups and PND22 dams, and UGT activity was 1.5-fold higher in PND22 dams only (300 mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS–induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may

  17. Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: a dynamic and kinetic evaluation of a putative mode-of-action.

    PubMed

    Paul, Katie B; Hedge, Joan M; Bansal, Ruby; Zoeller, R Thomas; Peter, Robert; DeVito, Michael J; Crofton, Kevin M

    2012-10-09

    This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0-300mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid-stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman(®) qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid hormone-responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300mg/kg/day). Hepatic PROD activity increased 2-3 fold in PND4 pups and PND22 dams, and UGT activity was 1.5 fold higher in PND22 dams only (300mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS-induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the

  18. Immunohistochemical localization of anterior pituitary hormones in S-100 protein-positive cells in the rat pituitary gland.

    PubMed

    Kikuchi, Motoshi; Yatabe, Megumi; Tando, Yukiko; Yashiro, Takashi

    2011-09-01

    In the anterior and intermediate lobes of the rat pituitary gland, non-hormone-producing cells that express S-100 protein coexist with various types of hormone-producing cells and are believed to function as phagocytes, supporting and paracrine-controlling cells of hormone-producing cells and stem cells, among other functions; however, their cytological characteristics are not yet fully understood. Using a transgenic rat that expresses green fluorescent protein under the promoter of the S100β protein gene, we immunohistochemically detected expression of the luteinizing hormone, thyroid-stimulating hormone, prolactin, growth hormone and proopiomelanocortin by S-100 protein-positive cells located between clusters of hormone-producing cells in the intermediate lobe. These findings lend support to the hypothesis that S-100 protein-positive cells are capable of differentiating into hormone-producing cells in the adult rat pituitary gland.

  19. Molecular basis of thyrotropin and thyroid hormone action during implantation and early development.

    PubMed

    Colicchia, Martina; Campagnolo, Luisa; Baldini, Enke; Ulisse, Salvatore; Valensise, Herbert; Moretti, Costanzo

    2014-01-01

    Implantation and early embryo development are finely regulated processes in which several molecules are involved. Evidence that thyroid hormones (TH: T4 and T3) might be part of this machinery is emerging. An increased demand for TH occurs during gestation, and any alteration in maternal thyroid physiology has significant implications for both maternal and fetal health. Not only overt but also subclinical hypothyroidism is associated with infertility as well as with obstetric complications, including disruptions and disorders of pregnancy, labor, delivery, and troubles in early neonatal life. We searched the PubMed and Google Scholar databases for articles related to TH action on ovary, endometrium, trophoblast maturation and embryo implantation. In addition, articles on the regulation of TH activity at cellular level have been reviewed. The findings are hereby summarized and critically discussed. TH have been shown to influence endometrial, ovarian and placental physiology. TH receptors (TR) and thyrotropin (thyroid-stimulating hormone: TSH) receptors (TSHR) are widely expressed in the feto-maternal unit during implantation, and both the endometrium and the trophoblast might be influenced by TH either directly or through TH effects on the synthesis and activity of implantation-mediating molecules. Interestingly, due to the multiplicity of mechanisms involved in TH action (e.g. differential expression of TR isoforms, heterodimeric receptor partners, interacting cellular proteins, and regulating enzymes), the TH concentration in blood is not always predictive of their cellular availability and activity at both genomic and nongenomic level. In addition to the known role of TH on the hormonal milieu of the ovarian follicle cycle, which is essential for a woman's fertility, evidence is emerging on the importance of TH signaling during implantation and early pregnancy. Based on recent observations, a local action of TH on female reproductive organs and the embryo during

  20. Investigation of the relationship between serum hormones and pilonidal sinus disease: a cross-sectional study.

    PubMed

    Özkan, Z; Aksoy, N; Emir, S; Kanat, B H; Gönen, A N; Yazar, F M; Çimen, A R

    2014-04-01

    The aim of this cross-sectional study was to determine whether pilonidal sinus is influenced by hormones that stimulate body hair growth. Currently, there are insufficient data on the presence of hormonal abnormalities in pilonidal sinus disease. Hormone levels (including those of thyroid-stimulating hormone, follicular-stimulating hormone, luteinizing hormone, prolactin, progesterone, oestradiol, testosterone, cortisol and dehydroepiandrosterone) were measured in 39 patients with pilonodal sinus presenting between February 2013 and March 2013. The results were compared with those of 39 volunteers without this disease. There was no statistically significant difference between men with pilonidal sinus disease (P > 0.05). The prolactin levels of women with pilonoidal sinus were significantly higher than those of women in the control group (P < 0.05). Raised serum prolactin levels in women may be related to the development of pilonidal sinus disease. Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.

  1. A method for identification of the peptides that bind to a clone of thyroid-stimulating antibodies in the serum of Graves' disease patients.

    PubMed

    Na, Chan Hyun; Lee, Mi Hwa; Cho, Bo Youn; Chae, Chi-Bom

    2003-04-01

    A method was developed for identification of the peptide sequences that bind to thyroid-stimulating antibody (TSAb) clones from phage-displayed peptide library. Immunoglobulin G (IgG) was purified from the serum of a Graves' disease patient that stimulates the synthesis of cAMP in the cells that express TSH receptor (TSHR). The IgG that binds to TSHR was purified by an affinity column packed with the resin cross-linked with the extracellular domain of human TSHR. The receptor-binding IgG was then mixed with phages that display linear or cyclic peptides at the end of tail protein pIII. The bound phages were eluted with acidic glycine after extensive washing. From sequencing of the pIII gene of the bound phages, one can deduce the sequences of the peptides that bind to the receptor-binding IgG. Each peptide sequence was then tested for inhibition of the synthesis of cAMP from thyroid cells induced by the serum of a Graves' patient. In this way, one can obtain the peptides that bind to a clone of TSAb. We obtained a peptide sequence that inhibits the action of TSAb at an extremely low concentration (<10(-14) M). Such a peptide will be useful for various studies on TSAb.

  2. Occurrence of perchlorate and thiocyanate in human serum from e-waste recycling and reference sites in Vietnam: association with thyroid hormone and iodide levels.

    PubMed

    Eguchi, Akifumi; Kunisue, Tatsuya; Wu, Qian; Trang, Pham Thi Kim; Viet, Pham Hung; Kannan, Kurunthachalam; Tanabe, Shinsuke

    2014-07-01

    Perchlorate (ClO4 (-)) and thiocyanate (SCN(-)) interfere with iodide (I(-)) uptake by the sodium/iodide symporter, and thereby these anions may affect the production of thyroid hormones (THs) in the thyroid gland. Although human exposure to perchlorate and thiocyanate has been studied in the United States and Europe, few investigations have been performed in Asian countries. In this study, we determined concentrations of perchlorate, thiocyanate, and iodide in 131 serum samples collected from 2 locations in Northern Vietnam, Bui Dau (BD; electrical and electronic waste [e-waste] recycling site) and Doung Quang (DQ; rural site) and examined the association between serum levels of these anions with levels of THs. The median concentrations of perchlorate, thiocyanate, and iodide detected in the serum of Vietnamese subjects were 0.104, 2020, and 3.11 ng mL(-1), respectively. Perchlorate levels were significantly greater in serum of the BD population (median 0.116 ng mL(-1)) than those in the DQ population (median 0.086 ng mL(-1)), which indicated greater exposure from e-waste recycling operations by the former. Serum concentrations of thiocyanate were not significantly different between the BD and DQ populations, but increased levels of this anion were observed among smokers. Iodide was a significant positive predictor of serum levels of FT3 and TT3 and a significant negative predictor of thyroid-stimulating hormone in males. When the association between serum levels of perchlorate or thiocyanate and THs was assessed using a stepwise multiple linear regression model, no significant correlations were found. In addition to greater concentrations of perchlorate detected in the e-waste recycling population, however, given that lower concentrations of iodide were observed in the serum of Vietnamese females, detailed risk assessments on TH homeostasis for females inhabiting e-waste recycling sites, especially for pregnant women and their neonates, are required.

  3. Reference intervals for thyroid hormones in pregnant Chinese women.

    PubMed

    Panesar, N S; Li, C Y; Rogers, M S

    2001-07-01

    To establish gestation-related reference intervals for thyroid hormones in a Chinese population. A prospective study with 343 healthy pregnant women (5-41 weeks) and 63 non-pregnant controls. Thyroid stimulating hormone (TSH), free thyroxine (T4) and tri-iodothyronine (T3) (and human chorionic gonadotrophin) were measured by immunoassays. The median, 2.5th and 97.5th percentiles at 4-week intervals were calculated. Data were also analysed for significant trends using ANOVA. Free T3 decreased during pregnancy, whereas free T4 initially increased, peaking between 9-13 weeks and then decreased, the decline becoming significant by week 21. TSH mirrored changes in free T4. The gestation-related reference intervals for thyroid hormones should alleviate the misinterpretation of thyroid function in pregnancy.

  4. Purification and characterization of chicken follicle-stimulating hormone.

    PubMed

    Krishnan, K A; Proudman, J A; Bahr, J M

    1992-05-01

    1. Highly purified chicken follicle-stimulating hormone (cFSH) was isolated from chicken pituitaries by differential extraction, sequential chromatography on HPLC cation and anion exchange columns, and gel filtration chromatography. 2. Purified cFSH (USDA-cFSH-K-1) had a potency of 77.44 units/mg in a chicken testes radioreceptor assay, and was biologically active in stimulating the secretion of progesterone by chicken granulosa cells. 3. Purified cFSH contained negligible luteinizing hormone and thyroid stimulating hormone activity. 4. The apparent molecular weight of cFSH was 38,000 Da and a single band on isoelectric focusing had a pI of 4.65.

  5. Thyroid Hormone Replacement in Patients Following Thyroidectomy for Thyroid Cancer

    PubMed Central

    Hannoush, Zeina C.; Weiss, Roy E.

    2016-01-01

    Thyroid hormone replacement therapy in patients following thyroidectomy for thyroid cancer, although a potentially straightforward clinical problem, can present the clinician and patient with a variety of challenges. Most often the problems are related to the dose and preparation of thyroid hormone (TH) to use. Some patients feel less well following thyroidectomy and/or radioiodine ablation than they did before their diagnosis. We present evidence that levothyroxine (L-T4) is the preparation of choice, and keeping the thyroid-stimulating hormone (TSH) between detectable and 0.1 mU/L should be the standard of care in most cases. In unusual circumstances, when the patient remains clinically hypothyroid despite a suppressed TSH, we acknowledge there may be as yet unidentified factors influencing the body’s response to TH, and individualized therapy may be necessary in such patients. PMID:26886951

  6. Rotating shift-related changes in hormone levels in intensive care unit nurses.

    PubMed

    Korompeli, Anna; Sourtzi, Panayota; Tzavara, Chara; Velonakis, Emmanouel

    2009-06-01

    This paper is a report of a study to investigate if an irregular rotating shift system, including night shifts, can cause changes to the secretion of hormones in nurses. In 2006, 32 healthy intensive care unit nurses completed the Standard Shiftwork Index (SSI) and blood samples were collected from each participant at the beginning and end of each shift. Change in hormone levels between the beginning and end of morning shifts were examined and compared between nurses on morning only and rotating shifts. Correlations between change in hormone concentrations and scores from the SSI are presented. The mean reduction of cortisol level between the two measurements was statistically significantly greater for the 'rotating' than 'morning' shift group (P = 0.032). There were no statistically significant differences between the two groups in overall mean change from the first to the second measurement of prolactin, triiodothyronine and thyroid-stimulating hormone. Levels of thyroxine increased statistically significantly in the 'rotating' group (P = 0.049) but not in the 'morning' group. The morningness scale score was greater for the 'rotating' group, while greater job satisfaction levels were found in the 'morning' group. Statistically significant correlations were found between thyroid-stimulating hormone, triiodothyronine, thyroxine and prolactin changes and specific scales of the SSI questionnaire. Ergonomic shift schedules sympathetic to the body clock and nurses' preferences should be adopted to mitigate the adverse effects on health.

  7. Improved response of growth hormone to growth hormone-releasing hormone and reversible chronic thyroiditis after hydrocortisone replacement in isolated adrenocorticotropic hormone deficiency.

    PubMed

    Inagaki, Miho; Sato, Haruhiro; Miyamoto, Yoshiyasu; Hirukawa, Takashi; Sawaya, Asako; Miyakogawa, Takayo; Tatsumi, Ryoko; Kakuta, Takatoshi

    2009-07-20

    We report a 44-year-old Japanese man who showed a reversible blunted response of growth hormone (GH) to GH-releasing hormone (GRH) stimulation test and reversible chronic thyroiditis accompanied by isolated ACTH deficiency. He was admitted to our hospital because of severe general malaise, hypotension, and hypoglycemia. He showed repeated attacks of hypoglycemia, and his serum sodium level gradually decreased. Finally, he was referred to the endocrinology division, where his adrenocorticotropic hormone (ACTH) and cortisol values were found to be low, and his GH level was slightly elevated. An increased value of thyroid stimulating hormone (TSH) and decreased values of free triidothyronine and free thyroxine were observed along with anti-thyroglobulin antibody, suggesting chronic thyroiditis. Pituitary stimulation tests revealed a blunted response of ACTH and cortisol to corticotropin-releasing hormone, and a blunted response of GH to GRH. Hydrocortisone replacement was then started, and this improved the patient's general condition. His hypothyroid state gradually ameliorated and his titer of anti-thyroglobulin antibody decreased to the normal range. Pituitary function was re-evaluated with GRH stimulation test under a maintenance dose of 20 mg/day hydrocortisone and showed a normal response of GH to GRH. It is suggested that re-evaluation of pituitary and thyroid function is useful for diagnosing isolated ACTH deficiency after starting a maintenance dose of hydrocortisone in order to avoid unnecessary replacement of thyroid hormone.

  8. [Heart failure as early manifestation of neonatal hyperthyroidism. Case report].

    PubMed

    Alvarado S, Jorge Luis; Fernández V, Zhirly Andrea

    2014-04-01

    Neonatal hyperthyroidism is usually a self-limited condition frequently associated with transplacental passage of thyroid stimulating antibodies secondary to maternal autoimmune disorders. To timely detect mothers with this medical antecedents decreases the risk for fetal adverse events. To report a case of neonatal hyperthyroidism associated with intrauterine growth restriction and heart failure. A 36 week-old newborn with birth weight of 1,240 g. Symptoms were tachycardia, distal coldness, exophthalmos, hepatomegaly and tremors. Echocardiogram ruled out structural heart disorders. Due to maternal symptoms suggestive of hyperthyroidism, TSH tests were performed showing 0.01 ulU/ml, free T4 7.7 ng/dl, so the diagnosis of neonatal hyperthyroidism was confirmed. It was treated with methimazole and propanol, alleviating the symptoms and decreasing the levels of free T4. To know the maternal history helps identify and manage neonatal complications of hyperthyroidism. Heart failure and other cardiopulmonary disorders are determinants of mortality during early neonatal period. High-risk newborns should receive follow up assessments.

  9. Differential action of glycoprotein hormones: significance in cancer progression.

    PubMed

    Govindaraj, Vijayakumar; Arya, Swathy V; Rao, A J

    2014-02-01

    Growth of multicellular organisms depends on maintenance of proper balance between proliferation and differentiation. Any disturbance in this balance in animal cells can lead to cancer. Experimental evidence is provided to conclude with special reference to the action of follicle-stimulating hormone (FSH) on Sertoli cells, and luteinizing hormone (LH) on Leydig cells that these hormones exert a differential action on their target cells, i.e., stimulate proliferation when the cells are in an undifferentiated state which is the situation with cancer cells and promote only functional parameters when the cell are fully differentiated. Hormones and growth factors play a key role in cell proliferation, differentiation, and apoptosis. There is a growing body of evidence that various tumors express some hormones at high levels as well as their cognate receptors indicating the possibility of a role in progression of cancer. Hormones such as LH, FSH, and thyroid-stimulating hormone have been reported to stimulate cell proliferation and act as tumor promoter in a variety of hormone-dependent cancers including gonads, lung, thyroid, uterus, breast, prostate, etc. This review summarizes evidence to conclude that these hormones are produced by some cancer tissues to promote their own growth. Also an attempt is made to explain the significance of the differential action of hormones in progression of cancer with special reference to prostate cancer.

  10. Thyroid-stimulating immunoglobulins as measured in a reporter bioassay are not detected in patients with Hashimoto's thyroiditis and ophthalmopathy or isolated upper eyelid retraction.

    PubMed

    Wall, Jack R; Lahooti, Hooshang; El Kochairi, Ilhem; Lytton, Simon D; Champion, Bernard

    2014-01-01

    Although ophthalmopathy is mainly associated with Graves' hyperthyroidism, milder eye changes are also found in about 25% of patients with Hashimoto's thyroiditis (HT). The recent finding of negative thyrotropin receptor (TSHR) antibodies, as measured in the Thyretain™ thyroid-stimulating immunoglobulin (TSI) reporter bioassay, in patients with euthyroid Graves' disease raises the possibility that TSHR antibodies are not the cause of ophthalmopathy in all situations. Here, we have tested serum from patients with HT with and without ophthalmopathy or isolated upper eyelid retraction (UER) for TSHR antibodies, using the TSI reporter bioassay and collagen XIII as a marker of autoimmunity against the orbital fibroblast. Study groups were 23 patients with HT with ophthalmopathy, isolated UER, or both eye features and 17 patients without eye signs. Thyretain™ TSI results were expressed as a percentage of the sample-to-reference ratio, with a positive test being taken as a sample-to-reference ratio of more than 140%. Serum collagen XIII antibodies were measured in standard enzyme-linked immunosorbent assay. TSI tests were positive in 22% of patients with HT with no eye signs but in no patient with eye signs. In contrast, TSI tests were positive in 94% of patients with Graves' ophthalmopathy. Tests were negative in all normal subjects tested. Collagen XIII antibodies were detected in 83% of patients with ophthalmopathy, UER, or both eye features, but in only 30% of patients with no eye signs. Our findings suggest that TSHR antibodies do not play a major role in the pathogenesis of ophthalmopathy or isolated UER in patients with HT. Moreover, the role of TSHR antibodies in the development of ophthalmopathy in patients with Graves' disease remains to be proven. In contrast, collagen XIII antibodies appear to be a good marker of eye disease in patients with HT.

  11. The combination of absent thyroid peroxidase antibodies and high thyroid-stimulating immunoglobulin levels in Graves' disease identifies a group at markedly increased risk of ophthalmopathy.

    PubMed

    Khoo, D H; Ho, S C; Seah, L L; Fong, K S; Tai, E S; Chee, S P; Eng, P H; Aw, S E; Fok, A C

    1999-12-01

    Among Graves' Disease (GD) patients, we have observed an unexpectedly high prevalence of antithyroperoxidase antibody (TPOAb) and antithyroglobulin antibody (TgAb) negativity in those with severe ophthalmopathy. To study the possible role of thyroid autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO), TPOAb, TgAb, thyroid-stimulating immunoglobulin (TSI), and thyrotropin-binding inhibitory immunoglobulin (TBII) levels were measured, and the presence or absence of GO was assessed by a single observer in 100 consecutive patients with newly diagnosed, untreated GD who were nonsmokers. Ophthalmopathy was present in 43 patients. TSI levels (p = 0.001), and the prevalence of TPOAb-negativity (p = 0.002) were significantly higher in patients with ophthalmopathy compared to those without. Logistic regression analysis showed that TSI levels (p = 0.005) and the absence of TPOAb (p = 0.0025) were independent predictors of GO. No correlation between TBII or TgAb and eye disease was found. The prevalence of GO increased with each quartile of TSI levels. The prevalence was 20%, 36%, 52%, and 64% in the first, second, third and fourth quartiles of TSI, respectively. The odds ratio of GO (with 95% confidence intervals) when TSI levels were above the median level (1640%) was 3.6 (1.5-8.0), when TPOAb was negative it was 5.0 (1.7-14.4), and with both risk factors it was 36.6 (4.3-313.5). The prevalence of ophthalmopathy in this last group was 92.9%. The combination of negative TPOAb and high TSI levels appears to be associated with a markedly increased risk of clinically evident ophthalmopathy.

  12. Female sexual dysfunction and hormonal status in multiple sclerosis patients.

    PubMed

    Lombardi, Giuseppe; Celso, Maria; Bartelli, Mario; Cilotti, Antonio; Del Popolo, Giulio

    2011-04-01

    Literature holds no information on a correlation between blood hormonal levels, in particular sex hormones and the sexual response of women with multiple sclerosis (MS). To investigate a possible correlation between hormonal status and the sexual response of females with MS. The Female Sexual Function Index (FSFI) questionnaire was used to determine sexual dysfunctions (SDs). Methods for measuring blood hormones were chemiluminescence immunoassay, electrochemiluminescence immunoassay, enzyme immunoassay, and radioimmunoassay. During the screening phase, 55 women of reproductive age were recruited and completed the FSFI. In the first phase of the study females underwent a hematic hormonal evaluation on the third day of their menstrual cycle. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyroid stimulating hormone (TSH), cortisol, dehydroepiandrosterone sulphate (DHEA-S), androstenedione, 17[alpha]-hydroxyprogesterone, total and free testosterone, 17 beta estradiol, inhibin and sex hormone binding globulin (SHBG), and thyroid hormones (fT3 and fT4) were checked. On the day 20-21 into their menstrual cycle the progesterone hematic value was noted. Patients with amenorrhea had all hormones tested once with a random blood drawing. After a 3-month period patients began phase 2, completing the FSFI again. The same blood hormones were investigated. Fifty-four females completed the study. Thirty-one continued to manifest at least one SD: desire (57.4%) was the most common. Overall, 36.4% showed abnormal hormonal alterations. The most frequent was 40% for 17 beta-estradiol. None of the FSFI domains, including the total score, revealed any statistically significant correlation to the hormones investigated. No statistically significant clinical predictive factors for blood hormone abnormalities were detected; comparing females with and without SD, P = 0.250 using chi-squared test was reached. Notable percentages of blood hormonal

  13. Effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on serum hormone levels in rats

    PubMed Central

    Jin, Yeung Bae; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Lee, Yun-Sil

    2013-01-01

    Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method. PMID:23239176

  14. Effects of simultaneous combined exposure to CDMA and WCDMA electromagnetic fields on serum hormone levels in rats.

    PubMed

    Jin, Yeung Bae; Choi, Hyung-Do; Kim, Byung Chan; Pack, Jeong-Ki; Kim, Nam; Lee, Yun-Sil

    2013-05-01

    Despite more than a decade of research on the endocrine system, there have been no published studies about the effects of concurrent exposure of radiofrequency electromagnetic fields (RF-EMF) on this system. The present study investigated the several parameters of the endocrine system including melatonin, thyroid stimulating hormone, stress hormone and sex hormone after code division multiple access (CDMA, 849 MHz) and wideband code division multiple access (WCDMA, 1.95 GHz) signals for simultaneous exposure in rats. Sprague-Dawley rats were exposed to RF-EMF signals for 45 min/day, 5 days/week for up to 8 weeks. The whole-body average specific absorption rate (SAR) of CDMA or WCDMA was 2.0 W/kg (total 4.0 W/kg). At 4 and 8 weeks after the experiment began, each experimental group's 40 rats (male 20, female 20) were autopsied. Exposure for 8 weeks to simultaneous CDMA and WCDMA RF did not affect serum levels in rats of melatonin, thyroid stimulating hormone (TSH), triiodothyronine (T3) and thyroxin (T4), adrenocorticotropic hormone (ACTH) and sex hormones (testosterone and estrogen) as assessed by the ELISA method.

  15. Predicting gestational age using neonatal metabolic markers

    PubMed Central

    Ryckman, Kelli K.; Berberich, Stanton L.; Dagle, John M.

    2016-01-01

    Background Accurate gestational age estimation is extremely important for clinical care decisions of the newborn as well as for perinatal health research. Although prenatal ultrasound dating is one of the most accurate methods for estimating gestational age, it is not feasible in all settings. Identifying novel and accurate methods for gestational age estimation at birth is important, particularly for surveillance of preterm birth rates in areas without routine ultrasound dating. Objective We hypothesized that metabolic and endocrine markers captured by routine newborn screening could improve gestational age estimation in the absence of prenatal ultrasound technology. Study Design This is a retrospective analysis of 230,013 newborn metabolic screening records collected by the Iowa Newborn Screening Program between 2004 and 2009. The data were randomly split into a model-building dataset (n = 153,342) and a model-testing dataset (n = 76,671). We performed multiple linear regression modeling with gestational age, in weeks, as the outcome measure. We examined 44 metabolites, including biomarkers of amino acid and fatty acid metabolism, thyroid-stimulating hormone, and 17-hydroxyprogesterone. The coefficient of determination (R2) and the root-mean-square error were used to evaluate models in the model-building dataset that were then tested in the model-testing dataset. Results The newborn metabolic regression model consisted of 88 parameters, including the intercept, 37 metabolite measures, 29 squared metabolite measures, and 21 cubed metabolite measures. This model explained 52.8% of the variation in gestational age in the model-testing dataset. Gestational age was predicted within 1 week for 78% of the individuals and within 2 weeks of gestation for 95% of the individuals. This model yielded an area under the curve of 0.899 (95% confidence interval 0.895−0.903) in differentiating those born preterm (<37 weeks) from those born term (≥37 weeks). In the subset of

  16. DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats.

    PubMed

    Liu, Changjiang; Zhao, Letian; Wei, Li; Li, Lianbing

    2015-08-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. Limited studies suggest that exposure to DEHP may be associated with altered thyroid function, but detailed mechanisms are unclear. In order to elucidate potential mechanisms by which DEHP disturbs thyroid hormone homeostasis, Sprague-Dawley (SD) rats were dosed with DEHP by gavage at 0, 250, 500, and 750 mg/kg/day for 30 days and sacrificed within 24 h after the last dose. Gene expressions of thyroid hormone receptors, deiodinases, transthyretin, and hepatic enzymes were measured by RT-PCR; protein levels of transthyretin were also analyzed by Western blot. Results showed that DEHP caused histological changes in the thyroid and follicular epithelial cell hypertrophy and hyperplasia were observed. DEHP significantly reduced thyroid hormones (T3, T4) and thyrotropin releasing hormone (TRH) levels, whereas thyroid stimulating hormone (TSH) was not affected. After exposure to DEHP, biosynthesis of thyroid hormones was suppressed, and sodium iodide symporter (NIS) and thyroid peroxidase (TPO) levels were significantly reduced. Additionally, levels of deiodinases and transthyretin were also affected. TSH receptor (TSHr) level was downregulated, while TRH receptor (TRHr) level was upregulated. Metabolism of thyroid hormones was accelerated due to elevated gene expression of hepatic enzymes (UDPGTs and CYP2B1) by DEHP. Taken together, observed findings indicate that DEHP could reduce thyroid hormones through influencing biosynthesis, biotransformation, biotransport, receptor levels, and metabolism of thyroid hormones.

  17. Bromine and thyroid hormone activity.

    PubMed Central

    Allain, P; Berre, S; Krari, N; Laine, P; Barbot, N; Rohmer, V; Bigorgne, J C

    1993-01-01

    AIMS--To examine the possible consequences of high plasma concentrations of bromine on thyroid hormone. METHODS--Bromine was measured by inductively coupled plasma mass spectrometry in the plasma of 799 patients consulting for thyroid disorders. Because the mean (SD) bromine concentration in the plasma of healthy subjects is 4 (1) mg/l, concentrations above 6 mg/l were regarded as outside the normal range. Bromine, free thyroxine (FT4), and thyroid stimulating hormone (TSH) values were compared. RESULTS--The percentage of patients with normal, low, and high FT4 and TSH plasma activities, measured separately, did not differ between patients with low and high bromine concentrations. The percentage of patients with high TSH but normal FT4 values was significantly higher in the group with bromine values of more than 6 mg/l than in the group with bromine concentrations below this (p < 0.02). CONCLUSION--An increase in plasma bromine could potentiate an increase in plasma TSH concentration, probably as a consequence of a minor inhibitory effect on thyroid activity. PMID:8320326

  18. Thyroid hormone transporters in health and disease: advances in thyroid hormone deiodination.

    PubMed

    Köhrle, Josef

    2007-06-01

    Thyroid hormone metabolism by the three deiodinase selenoproteins -- DIO1, DIO2, and DIO3 -- regulates the local availability of various iodothyronine metabolites and thus mediates their effects on gene expression, thermoregulation, energy metabolism, and many key reactions during the development and maintenance of an adult organism. Circulating serum levels of thyroid hormone and thyroid-stimulating hormone, used as a combined indicator of thyroid hormone status, reflect a composite picture of: thyroid secretion; tissue-specific production of T(3) by DIO1 and DIO2 activity, which both contribute to circulating levels of T(3); and degradation of the prohormone T4, of the thyromimetically active T(3), of the inactive rT(3), of other iodothyronines metabolites with a lower iodine content and of thyroid hormone conjugates. Degradation reactions are catalyzed by either DIO1 or DIO3. Aberrant expression of individual deiodinases in disease, single nucleotide polymorphisms in their genes, and novel regulators of DIO gene expression (such as bile acids) provide a more complex picture of the fine tuning and the adaptation of systemic and local bioavailability of thyroid hormones.

  19. Neonatal treatment with capsaicin influences hormonal regulation of blood pressure in adult, water-deprived Long-Evans but not Brattleboro rats.

    PubMed

    Bennett, T; Gardiner, S M

    1986-01-16

    Conscious, adult, water-deprived Brattleboro rats treated neonatally with capsaicin or vehicle showed similar hypotensive responses to sequential inhibition of the renin-angiotensin system (with captopril) and antagonism of ganglionic transmission (with pentolinium). Following a comparable experimental protocol, Long-Evans rats treated neonatally with capsaicin showed a more marked hypotensive response to captopril administration than did vehicle-injected animals. Furthermore, following administration of captopril and pentolinium, the capsaicin-treated animals showed marked impairment of the vasopressin-dependent recovery of blood pressure. These results indicate that the greater hypotensive response to captopril in water-deprived. Long-Evans rats treated neonatally with capsaicin may be due to less effective compensation for inhibition of the renin-angiotensin system when vasopressin release is impaired.

  20. H9c2 cardiomyoblasts produce thyroid hormone.

    PubMed

    Meischl, Christof; Buermans, Henk P; Hazes, Thierry; Zuidwijk, Marian J; Musters, René J P; Boer, Christa; van Lingen, Arthur; Simonides, Warner S; Blankenstein, Marinus A; Dupuy, Corrine; Paulus, Walter J; Hack, C Erik; Ris-Stalpers, Carrie; Roos, Dirk; Niessen, Hans W M

    2008-05-01

    Thyroid hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of 125 I, we found that 125 I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, 125 I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment.

  1. Thyroid Hormone Regulation of Metabolism

    PubMed Central

    Mullur, Rashmi; Liu, Yan-Yun

    2014-01-01

    Thyroid hormone (TH) is required for normal development as well as regulating metabolism in the adult. The thyroid hormone receptor (TR) isoforms, α and β, are differentially expressed in tissues and have distinct roles in TH signaling. Local activation of thyroxine (T4), to the active form, triiodothyronine (T3), by 5′-deiodinase type 2 (D2) is a key mechanism of TH regulation of metabolism. D2 is expressed in the hypothalamus, white fat, brown adipose tissue (BAT), and skeletal muscle and is required for adaptive thermogenesis. The thyroid gland is regulated by thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH). In addition to TRH/TSH regulation by TH feedback, there is central modulation by nutritional signals, such as leptin, as well as peptides regulating appetite. The nutrient status of the cell provides feedback on TH signaling pathways through epigentic modification of histones. Integration of TH signaling with the adrenergic nervous system occurs peripherally, in liver, white fat, and BAT, but also centrally, in the hypothalamus. TR regulates cholesterol and carbohydrate metabolism through direct actions on gene expression as well as cross-talk with other nuclear receptors, including peroxisome proliferator-activated receptor (PPAR), liver X receptor (LXR), and bile acid signaling pathways. TH modulates hepatic insulin sensitivity, especially important for the suppression of hepatic gluconeogenesis. The role of TH in regulating metabolic pathways has led to several new therapeutic targets for metabolic disorders. Understanding the mechanisms and interactions of the various TH signaling pathways in metabolism will improve our likelihood of identifying effective and selective targets. PMID:24692351

  2. Universal salt iodization is successful in Kashmiri population as iodine deficiency no longer exists in pregnant mothers and their neonates: Data from a tertiary care hospital in North India.

    PubMed

    Charoo, Bashir Ahmed; Sofi, Riyaz Ahmed; Nisar, Sobia; Shah, Parvaiz A; Taing, Shenaz; Jeelani, Henaan; Ahmed, Fayaz; Parveen, Shameem; Shah, Zaffar Amin; Mudasir, Syed; Malik, Masood; Ganie, Mohd Ashraf

    2013-03-01

    Normal pregnancy results in a number of important physiological and hormonal changes that alter thyroid function. In pregnancy, the thyroid gland being subjected to physiological stress undergoes several adaptations to maintain sufficient output of thyroid hormones for both mother and fetus. Consequently, pregnant women have been found to be particularly vulnerable to iodine deficiency disorders (IDD), and compromised iodine status during pregnancy has been found to affect the thyroid function and cognition in the neonates. Two decades after successful universal salt iodization (USI) in the country, there is scarce data on the iodine status of the pregnant women and their neonates. This is more relevant in areas like Kashmir valley part of sub-Himalayan belt, an endemic region for IDD in the past. The objective was to estimate Urinary Iodine status in pregnant women, the most vulnerable population. We studied thyroid function [free T3 (FT3), T3, free T4 (FT4), T4, thyroid stimulating hormone (TSH)] and urinary iodine excretion (UIE) in the 1(st), 2(nd), and 3(rd) trimesters and at early neonatal period in neonates in 81 mother-infant pairs (hypothyroid women on replacement) and compared them with 51 control mother-infant pairs (euthyroid). Mean age of cases (29.42 + 3.56 years) was comparable to that of controls (29.87 + 3.37 years). The thyroid function evaluation done at baseline revealed the following: FT3 2.92 ± 0.76 versus 3.71 ± 0.54 pg/ml, T3 1.38 ± 0.37 versus 1.70 ± 0.35 ng/dl, FT4 1.22 ± 0.33 versus 1.52 ± 0.21 ng/dl, T4 9.54 ± 2.34 versus 13.55 ± 2.16 μg/dl, and TSH 7.92 ± 2.88 versus 4.14 ± 1.06 μIU/ml in cases versus controls (P > 0.01), respectively. The 2(nd) to 6(th) day thyroid function of neonates born to case and control mothers revealed T3 of 1.46 ± 0.44 versus 1.48 ± 0.36 ng/dl, T4 of 12.92 ± 2.57 versus 11.76 ± 1.78 μg/dl, and TSH of 3.64 ± 1.92 versus 3.82 ± 1.45 μIU/ml, respectively. UIE was similar (139.12 ± 20.75 vs

  3. Effect of thyroid hormone replacement therapy on ovarian volume and androgen hormones in patients with untreated primary hypothyroidism.

    PubMed

    Muderris, Iptisam Ipek; Boztosun, Abdullah; Oner, Gokalp; Bayram, Fahri

    2011-01-01

    Primary hypothyroidism may be associated with ovarian enlargement and/ or cyst formation. We evaluated the effect of thyroid hormone replacement therapy on hormonal changes, ovarian volume and sonographic appearance. Open, prospective study of women admitted to university gynecology clinic. The study included 26 patients with untreated hypothyroidism who had polycystic (n=10) or normal-appearing (n=16) ovaries and 20 euthyroidic controls. Basal serum total testosterone, free testosterone, androstenedione, dehydroepiandosterone-sulfate, prolactin, estradiol, luteinizing hormone, follicle-stimulating hormone, free T3, free T4 and thyroid-stimulating horone, together with ovarian volumes, were determined and repeated after euthyroidism was achieved. Ovarian volumes of patients with hypothyroidism were significantly greater compared with controls, and their magnitudes diminished significantly during thyroid hormone replacement therapy. Hypothyroidic patients with polycystic ovaries had significantly higher serum free testosterone and dehydroepiandosterone-sulfate, but lower androstenodione levels compared with those who had normal-appearing ovaries. Serum total testosterone concentrations were significantly higher in hypothyroidic patients without polycystic ovaries, and thyroid hormone replacement therapy achieved a significant reduction in total as well as free testosterone. Severe longstanding hypothyroidism leads to increased ovarian volume and/or cyst formation. A decrease in ovarian volume, resolution of ovarian cysts and reversal of the polycystic ovary syndrome-like appearance, together with improvement in serum hormone levels, occurred after euthyroidism was achieved.

  4. Emergence of an Ancestral Glycoprotein Hormone in the Pituitary of the Sea Lamprey, a Basal Vertebrate.

    PubMed

    Sower, Stacia A; Decatur, Wayne A; Hausken, Krist N; Marquis, Timothy J; Barton, Shannon L; Gargan, James; Freamat, Mihael; Wilmot, Michael; Hollander, Lian; Hall, Jeffrey A; Nozaki, Masumi; Shpilman, Michal; Levavi-Sivan, Berta

    2015-08-01

    The gnathostome (jawed vertebrates) classical pituitary glycoprotein hormones, FSH, LH, and TSH, consist of a common α-subunit (GpA1) and unique β-subunits (Gpβ1, -2, and -3), whereas a recently identified pituitary glycoprotein hormone, thyrostimulin, consists of GpA2 and GpB5. This paper reports the identification, expression, and function of an ancestral, nonclassical, pituitary heterodimeric glycoprotein hormone (GpH) consisting of the thyrostimulin A2 subunit with the classical β-subunit in the sea lamprey, Petromyzon marinus, a jawless basal vertebrate. Lamprey (l) GpA2, and lGpHβ were shown to form a heterodimer by coimmunoprecipitation of lGpA2 with FLAG-tagged lGpHβ after the overexpression in transiently transfected COS7 cells using a bipromoter vector. Dual-label fluorescent in situ hybridization and immunohistochemistry showed the coexpression of individual subunits in the proximal pars distalis of the pituitary. GnRH-III (1μΜ) significantly increased the expression of lGpHβ and lGpA2 in in vitro pituitary culture. Recombinant lamprey GpH was constructed by tethering the N terminal of lGpA2 to the C terminal of lGpHβ with a linker region composed of six histidine residues followed by three glycine-serine repeats. This recombinant lamprey GpH activated the lamprey glycoprotein hormone receptor I as measured by increased cAMP/luciferase activity. These data are the first to demonstrate a functional, unique glycoprotein heterodimer that is not found in any other vertebrate. These data suggest an intermediate stage of the structure-function of the gonadotropin/thyroid-stimulating hormone in a basal vertebrate, leading to the emergence of the highly specialized gonadotropin hormones and thyroid stimulating hormones in gnathostomes.

  5. Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron

    EPA Science Inventory

    Thyroid hormones (TH) are critical for brain development. Modest TH insufficiency in pregnant rats induced by propylthiouracil (PTU) results in formation of a structural abnormality, a subcortical band heterotopia (SBH), in brains of offspring. PTU reduces TH by inhibiting the s...

  6. Thyroid Hormone-Dependent Formation of a Subcortical Band Heterotopia (SBH) in the Neonatal Brain is not Exacerbated Under Conditions of Low Dietary Iron

    EPA Science Inventory

    Thyroid hormones (TH) are critical for brain development. Modest TH insufficiency in pregnant rats induced by propylthiouracil (PTU) results in formation of a structural abnormality, a subcortical band heterotopia (SBH), in brains of offspring. PTU reduces TH by inhibiting the s...

  7. Neonatal sepsis.

    PubMed

    Stefanovic, Iva Mihatov

    2011-01-01

    Neonatal sepsis is the most common cause of neonatal deaths with high mortality despite treatment. Neonatal sepsis can be classified into two subtypes depending upon onset of symptoms. There are many factors that make neonates more susceptable to infection. Signs of sepsis in neonates are often non-specific and high degree of suspicion is needed for early diagnosis. Some laboratory parameters can be helpful for screening of neonates with neonatal sepsis, but none of it is specific and sensitive enough to be used singly. Diagnostic approach mostly focuses on history and review of non specific signs and symptoms. Antibiotic treatment is the mainstay of treatment and supportive care is equally important. The aim of this review is to give an overview of neonatal sepsis, including incidence, etiology, clinical picture, diagnostics and therapy.

  8. The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome.

    PubMed

    Schwartz, Charles E; Stevenson, Roger E

    2007-06-01

    Thyroid hormone is essential for the proper development and function of the brain. The active form of thyroid hormone is T(3), which binds to nuclear receptors. Recently, a transporter specific for T(3), MCT8 (monocarboxylate transporter 8) was identified. MCT8 is highly expressed in liver and brain. The gene is located in Xq13 and mutations in MCT8 are responsible for an X-linked condition, Allan-Herndon-Dudley syndrome (AHDS). This syndrome is characterized by congenital hypotonia that progresses to spasticity with severe psychomotor delays. Affected males also present with muscle hypoplasia, generalized muscle weakness, and limited speech. Importantly, these patients have elevated serum levels of free T(3), low to below normal serum levels of free T(4), and levels of thyroid stimulating hormone that are within the normal range. This constellation of measurements of thyroid function enables quick screening for AHDS in males presenting with cognitive impairment, congenital hypotonia, and generalized muscle weakness.

  9. External quality control results for hormones, tumor markers and CRP testing.

    PubMed

    Tatsumi, N; Kawano, K; Takubo, T; Nakamura, H; Tsuda, I

    1999-01-01

    Most hormones, tumor markers, C-reactive protein, and rheumatoid factor (RF) are measured immunologically. Immunological methods based on the antigen-antibody reaction have certain specific problems, including their principle of determination, character of antibodies used, reaction conditions, and others. Free thyroxine (FT4) and thyroid stimulating hormone (TSH), as well as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), prostate antigen, carcinoantigen 19-9 (CA 19-9), and CA 125 are very commonly measured in the routine medical laboratory. Authentic materials can be obtained for hormones and CRP, and efforts to improve quality control and standardization have been made for years. Results of surveillance for FT4, TSH, and AFP were not poor, but inter-laboratory differences for CEA, CA 19-9, and RF were not insignificant.

  10. Discovery of substituted benzamides as follicle stimulating hormone receptor allosteric modulators.

    PubMed

    Yu, Henry N; Richardson, Thomas E; Nataraja, Selva; Fischer, David J; Sriraman, Venkataraman; Jiang, Xuliang; Bharathi, Pandi; Foglesong, Robert J; Haxell, Thomas F N; Heasley, Brian H; Jenks, Mathew; Li, Jane; Dugas, Melanie S; Collis, Regina; Tian, Hui; Palmer, Stephen; Goutopoulos, Andreas

    2014-05-01

    Follicle-stimulating hormone (FSH), acting on its receptor (FSHR), plays a pivotal role in the stimulation of follicular development and maturation. Multiple injections of protein formulations are used during clinical protocols for ovulation induction and for in vitro fertilization that are followed by a selection of assisted reproductive technologies. In order to increase patient convenience and compliance several research groups have searched for orally bioavailable FSH mimetics for innovative fertility medicines. We report here the discovery of a series of substituted benzamides as positive allosteric modulators (PAM) targeting FSHR. Optimization of this series has led to enhanced activity in primary rat granulosa cells, as well as remarkable selectivity against the closely related luteinizing hormone receptor (LHR) and thyroid stimulating hormone receptor (TSHR). Two modulators, 9j and 9k, showed promising in vitro and pharmacokinetic profiles.

  11. The MCT8 thyroid hormone transporter and Allan--Herndon--Dudley syndrome

    PubMed Central

    Schwartz, Charles E.; Stevenson, Roger E.

    2007-01-01

    Thyroid hormone is essential for the proper development and function of the brain. The active form of thyroid hormone is T3, which binds to nuclear receptors. Recently, a transporter specific for T3, MCT8 (monocarboxylate transporter 8) was identified. MCT8 is highly expressed in liver and brain. The gene is located in Xq13 and mutations in MCT8 are responsible for an X-linked condition, Allan--Herndon--Dudley syndrome (AHDS). This syndrome is characterized by congenital hypotonia that progresses to spasticity with severe psychomotor delays. Affected males also present with muscle hypoplasia, generalized muscle weakness, and limited speech. Importantly, these patients have elevated serum levels of free T3, low to below normal serum levels of free T4, and levels of thyroid stimulating hormone that are within the normal range. This constellation of measurements of thyroid function enables quick screening for AHDS in males presenting with mental retardation, congenital hypotonia, and generalized muscle weakness. PMID:17574010

  12. Response to thyrotropin-releasing hormone stimulation tests in preterm infants with transient hypothyroxinemia of prematurity.

    PubMed

    Yamamoto, A; Kawai, M; Iwanaga, K; Matsukura, T; Niwa, F; Hasegawa, T; Heike, T

    2015-09-01

    Whether hormone supplementation is necessary for infants with transient hypothyroxinemia of prematurity (THOP) remains controversial, and further analysis of the hypothalamus-pituitary-thyroid axis of infants with THOP is necessary. Thyrotropin-releasing hormone (TRH) stimulation tests were performed at 2 weeks of age in 50 infants with a gestational age of 30 weeks or less, and the data were analyzed retrospectively. Subjects were divided into three groups; group A consisted of euthyroid infants, group B consisted of infants with THOP and group C consisted of hypothyroid infants. The basal and peak thyroid-stimulating hormone level of group C in response to TRH stimulation tests was significantly higher than the others, but no differences were observed between groups A and B. The response of infants with THOP to the TRH stimulation test was not different from that of euthyroid infants, which suggested that their hypothalamic-pituitary-thyroid axis was appropriately regulated in infants with THOP.

  13. Effects of Long-Term In Vivo Exposure to Di-2-Ethylhexylphthalate on Thyroid Hormones and the TSH/TSHR Signaling Pathways in Wistar Rats

    PubMed Central

    Dong, Xinwen; Dong, Jin; Zhao, Yue; Guo, Jipeng; Wang, Zhanju; Liu, Mingqi; Zhang, Yunbo; Na, Xiaolin

    2017-01-01

    Di-(2-ethylhexyl)phthalate (DEHP) was a widely used chemical with human toxicity. Recent in vivo and in vitro studies suggested that DEHP-exposure may be associated with altered serum thyroid hormones (THs) levels, but the underlying molecular mechanisms were largely unknown. To explore the possible molecular mechanisms, 128 Wistar rats were dosed with DEHP by gavage at 0, 150, 300, and 600 mg/kg/day for 3 months (M) and 6 M, respectively. After exposure, expression of genes and proteins in the thyroid, pituitary, and hypothalamus tissues of rats were analyzed by Q-PCR and western blot, while the sera and urine samples were assayed by radioimmunoassay and ELISA. Results showed that serum THs levels were suppressed by DEHP on the whole. DEHP treatment influenced the levels of rats’ thyrotropin releasing hormone receptor (TRHr), Deiodinases 1 (D1), thyroid stimulating hormone beta (TSHβ), sodium iodide symporter (NIS), thyroid stimulating hormone receptor (TSHr), thyroperoxidase (TPO), thyroid transcription factor 1 (TTF-1), and thyroglobulin (TG) mRNA/protein expression in the hypothalamus-pituitary-thyroid (HPT) axis and decreased urine iodine. Taken together, observed findings indicate that DEHP could reduce thyroid hormones via disturbing the HPT axis, and the activated TSH/TSHR pathway is required to regulate thyroid function via altering TRHr, TSHβ, NIS, TSHr, TPO, TTF-1 and TG mRNA/protein expression of the HPT axis. PMID:28054989

  14. Differential effects of thyroid hormone manipulation and β adrenoceptor agonist administration on uncoupling protein mRNA abundance in adipose tissue and thermoregulation in neonatal pigs

    PubMed Central

    Bos, Petra M; Litten, Jennie C; Laws, John; Symonds, Michael E; Clarke, Lynne

    2008-01-01

    We have shown that there is significant disparity in the expression of uncoupling proteins (UCP) 2 and 3 between modern-commercial and ancient-Meishan porcine genotypes, commercial pigs also have higher plasma triiodothyronine (T3) in on the first day of life. T3 and the sympathetic nervous system are both known to regulate UCPs in rodents and humans; their role in regulating these proteins in the pig is unknown. This study examined whether thyroid hormone manipulation or administration of a selective β3 adrenoceptor agonist (ZD) influenced plasma hormones, colonic temperature and UCP expression in adipose tissue of two breeds of pig. To mimic the differences observed in thyroid hormone status, piglets from Meishan and commercial litters were randomly assigned to control (1 ml/kg water), T3 (10 mg/kg) (Meishan only), methimazole (a commonly used antithyroid drug) (50 mg/kg) (commercial only) or ZD (10 mg/kg) oral administration for the first 4 days of postnatal life. Adipose tissue UCP2/3 mRNA abundance was measured on day 4 using PCR. T3 administration raised plasma T3 concentrations and increased colonic temperature on day 4. UCP3 mRNA abundance was higher in Meishan, than commercial piglets (p = 0.042) and was downregulated following T3 administration (p = 0.014). Irrespective of genotype, ZD increased UCP2 mRNA abundance (Meishan p = 0.05, commercial p = 0.03). Expression of neither UCP2 nor 3 was related to colonic temperature, regardless of treatment. In conclusion, we have demonstrated a dissociation between thyroid hormones and the sympathetic nervous system in the regulation of UCPs in porcine adipose tissue. We have also suggested that expression of adipose tissue UCP2 and 3 are not related to body temperature in piglets. PMID:19279731

  15. 2,4,6-Tribromophenol Interferes with the Thyroid Hormone System by Regulating Thyroid Hormones and the Responsible Genes in Mice

    PubMed Central

    Lee, Dongoh; Ahn, Changhwan; Hong, Eui-Ju; An, Beum-Soo; Hyun, Sang-Hwan; Choi, Kyung-Chul; Jeung, Eui-Bae

    2016-01-01

    2,4,6-Tribromophenol (TBP) is a brominated flame retardant (BFR). Based on its affinity for transthyretin, TBP could compete with endogenous thyroid hormone. In this study, the effects of TBP on the thyroid hormone system were assessed in mice. Briefly, animals were exposed to 40 and 250 mg/kg TBP. Thyroid hormones were also administered with or without TBP. When mice were treated with TBP, deiodinase 1 (Dio1) and thyroid hormone receptor β isoform 2 (Thrβ2) decreased in the pituitary gland. The levels of deiodinase 2 (Dio2) and growth hormone (Gh) mRNA increased in response to 250 mg/kg of TBP, and the relative mRNA level of thyroid stimulating hormone β (Tshβ) increased in the pituitary gland. Dio1 and Thrβ1 expression in the liver were not altered, while Dio1 decreased in response to co-treatment with thyroid hormones. The thyroid gland activity decreased in response to TBP, as did the levels of free triiodothyronine and free thyroxine in serum. Taken together, these findings indicate that TBP can disrupt thyroid hormone homeostasis and the presence of TBP influenced thyroid actions as regulators of gene expression. These data suggest that TBP interferes with thyroid hormone systems PMID:27420076

  16. 2,4,6-Tribromophenol Interferes with the Thyroid Hormone System by Regulating Thyroid Hormones and the Responsible Genes in Mice.

    PubMed

    Lee, Dongoh; Ahn, Changhwan; Hong, Eui-Ju; An, Beum-Soo; Hyun, Sang-Hwan; Choi, Kyung-Chul; Jeung, Eui-Bae

    2016-07-12

    2,4,6-Tribromophenol (TBP) is a brominated flame retardant (BFR). Based on its affinity for transthyretin, TBP could compete with endogenous thyroid hormone. In this study, the effects of TBP on the thyroid hormone system were assessed in mice. Briefly, animals were exposed to 40 and 250 mg/kg TBP. Thyroid hormones were also administered with or without TBP. When mice were treated with TBP, deiodinase 1 (Dio1) and thyroid hormone receptor β isoform 2 (Thrβ2) decreased in the pituitary gland. The levels of deiodinase 2 (Dio2) and growth hormone (Gh) mRNA increased in response to 250 mg/kg of TBP, and the relative mRNA level of thyroid stimulating hormone β (Tshβ) increased in the pituitary gland. Dio1 and Thrβ1 expression in the liver were not altered, while Dio1 decreased in response to co-treatment with thyroid hormones. The thyroid gland activity decreased in response to TBP, as did the levels of free triiodothyronine and free thyroxine in serum. Taken together, these findings indicate that TBP can disrupt thyroid hormone homeostasis and the presence of TBP influenced thyroid actions as regulators of gene expression. These data suggest that TBP interferes with thyroid hormone systems.

  17. Isolated Adrenocorticotropic Hormone or Thyrotropin Deficiency Following Mild Traumatic Brain Injury: Three Cases with Long-Term Follow-Up

    PubMed Central

    Baek, Cho-Ok; Kim, Yu Ji; Kim, Ji Hye

    2015-01-01

    Few studies have examined the clinical features and long-term outcomes of isolated pituitary hormone deficiencies after traumatic brain injury (TBI). Such deficiencies typically present at time intervals after TBI, especially after mild injuries such as concussions, which makes their diagnosis difficult without careful history taking. It is necessary to improve diagnosis and prevent life threatening or morbid conditions such as those that may occur in deficiencies of adrenocorticotropic hormone (ACTH) or thyroid-stimulating hormone (as known as thyrotropin, TSH), the two most important pituitary hormones in hypopituitarism treatment. Here, we report two cases of isolated ACTH deficiency and one case of isolated TSH deficiency. These patients presented at different time points after concussion and underwent long-term follow-ups. PMID:27169080

  18. Isolated Adrenocorticotropic Hormone or Thyrotropin Deficiency Following Mild Traumatic Brain Injury: Three Cases with Long-Term Follow-Up.

    PubMed

    Baek, Cho-Ok; Kim, Yu Ji; Kim, Ji Hye; Park, Ji Hyun

    2015-10-01

    Few studies have examined the clinical features and long-term outcomes of isolated pituitary hormone deficiencies after traumatic brain injury (TBI). Such deficiencies typically present at time intervals after TBI, especially after mild injuries such as concussions, which makes their diagnosis difficult without careful history taking. It is necessary to improve diagnosis and prevent life threatening or morbid conditions such as those that may occur in deficiencies of adrenocorticotropic hormone (ACTH) or thyroid-stimulating hormone (as known as thyrotropin, TSH), the two most important pituitary hormones in hypopituitarism treatment. Here, we report two cases of isolated ACTH deficiency and one case of isolated TSH deficiency. These patients presented at different time points after concussion and underwent long-term follow-ups.

  19. Hormone levels

    MedlinePlus

    Blood or urine tests can determine the levels of various hormones in the body. This includes reproductive hormones, thyroid hormones, adrenal hormones, pituitary hormones, and many others. For more information, see: ...

  20. Dose-response characteristics of neonatal exposure to genistein on pituitary responsiveness to gonadotropin releasing hormone and volume of the sexually dimorphic nucleus of the preoptic area (SDN-POA) in postpubertal castrated female rats.

    PubMed

    Faber, K A; Hughes, C L

    1993-01-01

    Estrogen exposure during critical periods of development promotes androgenization of the brain, which is reflected in altered morphology, behavior, and cyclic hormone secretion in females. Previous work in our laboratory demonstrated that neonatal female rats injected with pharmaceutical or naturally occurring estrogens had decreased GnRH-induced LH secretion and increased volume of the SDN-POA as 42 day castrates. The current experiment defines the dose-response characteristics of neonatal exposure to the isoflavonoid phytoestrogen genistein (G) on pituitary sensitivity to GnRH and SDN-POA volume. Litters of rat pups received subcutaneous injections of either corn oil, 1, 10, 100, 200, 400, 500, or 1000 micrograms of G on days 1 to 10 of life. The litters were ovariectomized and weaned on day 21. On day 42 blood was drawn from right atrial catheters immediately prior to, 5, 10, 15, and 30 min following a single injection of 50 ng/kg of GnRH. Only the 10 micrograms dose of G was associated with increased pituitary response to GnRH, while progressive increases in exposure levels of G were associated with decreasing LH secretion. The SDN-POA volume was increased in only the 500 micrograms and 1000 micrograms exposure groups compared to controls. The results confirm that low doses of G have nonandrogenizing, pituitary-sensitizing effects, while higher doses of G mimic the more typical effects of estrogens. The use of both morphologic and physiologic end points more completely defines the reproductive consequences of environmental estrogen exposure during critical periods of CNS development.

  1. Characteristic location and growth patterns of functioning pituitary adenomas: correlation with histological distribution of hormone-secreting cells in the pituitary gland.

    PubMed

    Baik, Jun Seung; Lee, Mi Hyun; Ahn, Kook-Jin; Choi, Hyun Seok; Jung, So Lyung; Kim, Bum-Soo; Jeun, Sin Soo; Hong, Yong-Kil

    2015-01-01

    To evaluate the correlation between the magnetic resonance imaging findings of functional pituitary adenomas and histological distribution of hormone-secreting cells in pituitary gland. Forty-nine patients with pathologically confirmed functional micro and macro pituitary adenomas were retrospectively reviewed for its location and growth direction. Micro-prolactin, micro-adrenocorticotropic hormone (ACTH), and micro-growth hormone (GH) producing adenomas showed specific location (P-value <.01). Macro-GH and macro-thyroid-stimulating hormone producing adenomas showed specific growth direction (P-value <.05), whereas macro-prolactin and macro-ACTH producing adenomas did not. The functional pituitary microadenomas' location and macroadenomas' growth pattern correlate well with histological distribution of hormone-secreting cells in pituitary gland. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Thyroid hormones in the elderly sick: "T4 euthyroidism".

    PubMed Central

    Burrows, A W; Shakespear, R A; Hesch, R D; Cooper, E; Aickin, C M; Burke, C W

    1975-01-01

    Thyroid function and serum levels of triiodothyronine (T3) and thyroxine (T4) were investigated in 79 euthyroid geriatric patients. Of the 59 inpatients and 20 outpatients 35 (59%) and 2, respectively, had low T3 levels. In contrast, 7 (12%) and 6 (30%), respectively, had raised T4 levels. Two further patients were excluded from the study because of raised levels of thyroid-stimulating hormone. Thyroxine-binding globulin was greatly increased in both groups of patients, but low serum albumin levels were present in 31 (39%). Despite these changes free T3 and T4 indices closely followed total T3 and T4 levels. The difference between the two groups of patients did not correlate with body weight, diagnostic categories, age, drug treatment, or duration of stay in hospital. PMID:811313

  3. Thyroid hormones in the elderly sick: "T4 euthyroidism".

    PubMed

    Burrows, A W; Shakespear, R A; Hesch, R D; Cooper, E; Aickin, C M; Burke, C W

    1975-11-22

    Thyroid function and serum levels of triiodothyronine (T3) and thyroxine (T4) were investigated in 79 euthyroid geriatric patients. Of the 59 inpatients and 20 outpatients 35 (59%) and 2, respectively, had low T3 levels. In contrast, 7 (12%) and 6 (30%), respectively, had raised T4 levels. Two further patients were excluded from the study because of raised levels of thyroid-stimulating hormone. Thyroxine-binding globulin was greatly increased in both groups of patients, but low serum albumin levels were present in 31 (39%). Despite these changes free T3 and T4 indices closely followed total T3 and T4 levels. The difference between the two groups of patients did not correlate with body weight, diagnostic categories, age, drug treatment, or duration of stay in hospital.

  4. [Thyroid hormones and cardiovascular system].

    PubMed

    Límanová, Zdeňka; Jiskra, Jan

    Cardiovascular system is essentially affected by thyroid hormones by way of their genomic and non-genomic effects. Untreated overt thyroid dysfunction is associated with higher cardiovascular risk. Although it has been studied more than 3 decades, in subclinical thyroid dysfunction the negative effect on cardiovascular system is much more controversial. Large meta-analyses within last 10 years have shown that subclinical hyperthyroidism is associated with higher cardiovascular risk than subclinical hypothyroidism. Conversely, in patients of age > 85 years subclinical hypothyroidism was linked with lower mortality. Therefore, subclinical hyperthyroidism should be rather treated in the elderly while subclinical hypothyroidism in the younger patients and the older may be just followed. An important problem on the border of endocrinology and cardiology is amiodarone thyroid dysfunction. Effective and safe treatment is preconditioned by distinguishing of type 1 and type 2 amiodarone induced hyperthyroidism. The type 1 should be treated with methimazol, therapeutic response is prolonged, according to recent knowledge immediate discontinuation of amiodarone is not routinely recommended and patient should be usually prepared to total thyroidectomy, or rather rarely 131I radioiodine ablation may be used if there is appropriate accumulation. In the type 2 there is a promt therapeutic response on glucocorticoids (within 1-2 weeks) with permanent remission or development of hypothyroidism. If it is not used for life-threatening arrhytmias, amiodarone may be discontinuated earlier (after several weeks). Amiodarone induced hypothyroidism is treated with levothyroxine without amiodarone interruption.Key words: amiodarone induced thyroid dysfunction - atrial fibrillation - cardiovascular risk - heart failure - hyperthyroidism - hypothyroidism - thyroid stimulating hormone.

  5. Influence of electromagnetic fields emitted by GSM-900 cellular telephones on the circadian patterns of gonadal, adrenal and pituitary hormones in men.

    PubMed

    Djeridane, Yasmina; Touitou, Yvan; de Seze, René

    2008-03-01

    The potential health risks of radiofrequency electromagnetic fields (RF EMFs) emitted by mobile phones are currently of considerable public interest. The present study investigated the effect of exposure to 900 MHz GSM radiofrequency radiation on steroid (cortisol and testosterone) and pituitary (thyroid-stimulating hormone, growth hormone, prolactin and adrenocorticotropin) hormone levels in 20 healthy male volunteers. Each subject was exposed to RF EMFs through the use of a cellular phone for 2 h/day, 5 days/ week, for 4 weeks. Blood samples were collected hourly during the night and every 3 h during the day. Four sampling sessions were performed at 15-day intervals: before the beginning of the exposure period, at the middle and the end of the exposure period, and 15 days later. Parameters evaluated included the maximum serum concentration, the time of this maximum, and the area under the curve for hormone circadian patterns. Each individual's pre-exposure hormone concentration was used as his control. All hormone concentrations remained within normal physiological ranges. The circadian profiles of prolactin, thyroid-stimulating hormone, adrenocorticotropin and testosterone were not disrupted by RF EMFs emitted by mobile phones. For growth hormone and cortisol, there were significant decreases of about 28% and 12%, respectively, in the maximum levels when comparing the 2-week (for growth hormone and cortisol) and 4-week (for growth hormone) exposure periods to the pre-exposure period, but no difference persisted in the postexposure period. Our data show that the 900 MHz EMF exposure, at least under our experimental conditions, does not appear to affect endocrine functions in men.

  6. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies.

    PubMed

    Hsu, S M; Raine, L; Fanger, H

    1981-05-01

    A highly sensitive immunoenzymatic technic is presented. The method involves three sequential steps: (1) primary antibody, (2) biotin-labeled secondary antibody, and (3) avidin-biotin-peroxidase complex. Avidin, an egg white protein, has four binding sites for the low-molecular-weight vitamin biotin. Many moieties of biotin can be coupled to the peroxidase molecule. Thus, since a relatively large amount of avidin is incubated with biotin-labeled peroxidase, avidin serves as a link between biotin-peroxidase molecules; in turn, biotin-peroxidase serves as a link between avidin molecules. Consequently, this large lattice-like complex with biotin-binding capability can be attracted to the sites of biotin-labeled antibody, producing a superior staining sensitivity. Several commercially available radioimmunoassay antibodies (e.g., antiglucagon, prolactin, gastrin, growth hormone, and thyroid-stimulating hormone antibodies) were tested for immunohistochemical staining. The unlabeled antibody peroxidase-antiperoxidase method fails to stain gastrin or thyroid-stimulating secretory cells when using these antibodies, and a relatively high antibody concentration is required to produce a positive reaction for glucagon, prolactin, and growth hormone. In contrast, the avidin-biotin-peroxidase complex method successfully demonstrates polypeptide hormones even when antibodies are diluted 20 to 40 times.

  7. Neonatal jaundice.

    PubMed

    McKiernan, Pat

    2012-06-01

    Neonatal jaundice lasting greater than 2 weeks should be investigated. Pale stools and dark or yellow urine are evidence of liver disease, which should be urgently investigated. The neonatal hepatitis syndrome has many causes, and a structured approach to investigation is mandatory. It should be possible to confirm or exclude biliary atresia within one week, so that definitive surgery is not delayed unnecessarily. Babies with the neonatal hepatitis syndrome should have vigorous fat-soluble vitamin supplementation, including parenteral vitamin K if coagulation is abnormal. The prognosis for infants with idiopathic neonatal hepatitis and multifactorial cholestasis is excellent.

  8. Neonatal anemia.

    PubMed

    Aher, Sanjay; Malwatkar, Kedar; Kadam, Sandeep

    2008-08-01

    Neonatal anemia and the need for red blood cell (RBC) transfusions are very common in neonatal intensive care units. Neonatal anemia can be due to blood loss, decreased RBC production, or increased destruction of erythrocytes. Physiologic anemia of the newborn and anemia of prematurity are the two most common causes of anemia in neonates. Phlebotomy losses result in much of the anemia seen in extremely low birthweight infants (ELBW). Accepting a lower threshold level for transfusion in ELBW infants can prevent these infants being exposed to multiple donors.

  9. Transcriptomics analysis and hormonal changes of male and female neonatal rats treated chronically with a low dose of acrylamide in their drinking water.

    PubMed

    Collí-Dulá, Reyna Cristina; Friedman, Marvin A; Hansen, Benjamin; Denslow, Nancy D

    2016-01-01

    Acrylamide is known to produce follicular cell tumors of the thyroid in rats. RccHan Wistar rats were exposed in utero to a carcinogenic dose of acrylamide (3 mg/Kg bw/day) from gestation day 6 to delivery and then through their drinking water to postnatal day 35. In order to identify potential mechanisms of carcinogenesis in the thyroid glands, we used a transcriptomics approach. Thyroid glands were collected from male pups at 10 PM and female pups at 10 AM or 10 PM in order to establish whether active exposure to acrylamide influenced gene expression patterns or pathways that could be related to carcinogenesis. While all animals exposed to acrylamide showed changes in expected target pathways related to carcinogenesis such as DNA repair, DNA replication, chromosome segregation, among others; animals that were sacrificed while actively drinking acrylamide-laced water during their active period at night showed increased changes in pathways related to oxidative stress, detoxification pathways, metabolism, and activation of checkpoint pathways, among others. In addition, thyroid hormones, triiodothyronine (T3) and thyroxine (T4), were increased in acrylamide-treated rats sampled at night, but not in quiescent animals when compared to controls. The data clearly indicate that time of day for sample collection is critical to identifying molecular pathways that are altered by the exposures. These results suggest that carcinogenesis in the thyroids of acrylamide treated rats may ensue from several different mechanisms such as hormonal changes and oxidative stress and not only from direct genotoxicity, as has been assumed to date.

  10. Analysis of the GH content within archived dried blood spots of newborn screening cards from children diagnosed with growth hormone deficiency after the neonatal period.

    PubMed

    Binder, G; Hettmann, S; Weber, K; Kohlmüller, D; Schweizer, R

    2011-12-01

    It is unknown whether GH secretion of children with growth hormone deficiency (GHD) is already diminished at birth. We aimed to determine the GH content within archived dried blood spots of newborn screening cards from children diagnosed with GHD at childhood. At our hospital, all children with the diagnosis of GHD and an actual age <10years were identified. For 16 patients (mean age, 7.4years; range, 1.0-9.7), screening cards were available. The archived dried blood from the first 48 to 96h of life was eluated in buffer of a highly sensitive hGH-ELISA to measure the GH content. Reference values were calculated based on 600 anonymous newborn screening cards of different ages. Median GH content within the archived dried blood spots of the reference had declined by 30% during the first year and by further 35% during the next 8.5years of storage. After correction for time of storage, four out of the 16 archived dried blood spots of the GHD children contained low amounts of GH (≤5th percentile). Diminished GH secretion at birth was absent in isolated GHD, but associated with multiple pituitary hormone deficiency (MPHD) (P=0.0013), ectopic neurohypophysis (P=0.0013), lower GH test peak values (P=0.02) and higher weight at diagnosis (P=0.015). Children with isolated GHD have normal GH secretory capacity during the first week of life while the majority of children with MPHD and pituitary malformation were GH deficient immediately after birth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Neonatal treatment with ovarian hormones and suckling among distinct litter sizes: Differential effects on recognition memory and spreading depression at adulthood.

    PubMed

    Accioly, Noranege Epifânio; Guedes, Rubem Carlos Araújo

    2017-09-10

    Ovarian hormones (OH) and early malnutrition may affect the developing brain, with repercussions on behavioral and excitability-dependent processes. However, the possible synergistic effects of both factors have not been analyzed. In this study, we investigated the effect of treatment in early life with OH and suckling among distinct litter sizes on recognition memory, anxiety behavior, and the excitability-dependent phenomenon known as cortical spreading depression (CSD). Female Wistar rats were suckled under favorable and unfavorable lactation, corresponding to litters with 9 and 15 pups (L9 and L15 groups, respectively). From postnatal days (P) 7 to 21, the animals received 50 µg/kg of β-estradiol or progesterone. From P80 to P84, we tested behavioral reactions. From P90 to P120, we analyzed CSD parameters. Compared with the corresponding L9 groups, the OH-treated L15 groups performed worse in recognition memory tasks. No intergroup difference in the anxiety parameters was observed. Compared with naive and vehicle-treated controls, OH-treated groups displayed higher CSD velocities and amplitudes and shorter CSD durations. Early treatment with OH facilitates recognition memory and CSD, and in association with unfavorable lactation (L15) impaired recognition memory, but not anxiety behavior, in the adult brain. OH treatment and L15 lactation condition seem to interact regarding OH action on memory, but not on CSD. Data suggest a long-lasting differential effect that might be related to the lasting hormonal action on brain excitability. We postulate and discuss the possibility that these findings may be implicated in human neurological diseases.

  12. Modulating the function of the immune system by thyroid hormones and thyrotropin.

    PubMed

    Jara, Evelyn L; Muñoz-Durango, Natalia; Llanos, Carolina; Fardella, Carlos; González, Pablo A; Bueno, Susan M; Kalergis, Alexis M; Riedel, Claudia A

    2017-04-01

    Accumulating evidence suggests a close bidirectional communication and regulation between the neuroendocrine and immune systems. Thyroid hormones (THs) can exert responses in various immune cells, e.g., monocytes, macrophages, natural killer cells, and lymphocytes, affecting several inflammation-related processes (such as, chemotaxis, phagocytosis, reactive oxygen species generation, and cytokines production). The interactions between the endocrine and immune systems have been shown to contribute to pathophysiological conditions, including sepsis, inflammation, autoimmune diseases and viral infections. Under these conditions, TH therapy could contribute to restoring normal physiological functions. Here we discuss the effects of THs and thyroid stimulating hormone (TSH) on the immune system and the contribution to inflammation and pathogen clearance, as well as the consequences of thyroid pathologies over the function of the immune system.

  13. Diagnostic Dilemma in Discordant Thyroid Function Tests Due to Thyroid Hormone Autoantibodies

    PubMed Central

    Srichomkwun, Panudda; Scherberg, Neal H.; Jakšić, Jasminka; Refetoff, Samuel

    2016-01-01

    Objective Assay interference could be the cause of abnormal thyroid function tests. Early recognition prevents inappropriate patient management. The objective of this report is to present a case with discordant thyroid function tests in different thyroid assay platforms due to thyroid autoantibodies. Methods We present a case her family, laboratory data and methods that investigate immunoassay interference. Results A 21-year-old woman with autoimmune thyroid disease was treated for hypothyroidism with levothyroxine and noted to have elevated total and free thyroxine, free triiodothyronine but normal thyroid-stimulating hormone. Repeat thyroid function tests using different platforms revealed discrepant results. Further investigation showed that the patient had positive thyroid hormone autoantibodies (THAAbs). Conclusion We demonstrates abnormal thyroid function tests caused by THAAbs. The latter were the cause of interference with assays resulting in discrepant test results inconsistent with the clinical presentation. Early recognition would prevent inappropriate patient management. PMID:28078322

  14. Neonatal teeth.

    PubMed

    Kovac, J; Kovac, D

    2011-01-01

    Teeth that are present at birth are called natal teeth, and teeth that emerge through the gingiva during the first 4 weeks of life are called neonatal teeth. The incidence of the appearance of natal and neonatal teeth has been reported to be between once every 800 and once every 6000 births. Natal and neonatal teeth may be uncomfortable for a nursing mother and present a risk of aspiration and swallowing by the infant if they are loose. Also, they may cause irritation and trauma to the infant's soft tissues. Under these circumstances, natal and neonatal teeth need to be extracted. In this article, a case report of two neonatal teeth in a five week old girl is presented. The teeth were present in the mandibular incisor region and were excessively mobile and caused discomfort for the nursing mother. They were extracted because of the fear of aspiration (Fig. 4, Ref. 10).

  15. Thyrotropin-Blocking Autoantibodies and Thyroid-Stimulating Autoantibodies: Potential Mechanisms Involved in the Pendulum Swinging from Hypothyroidism to Hyperthyroidism or Vice Versa

    PubMed Central

    Rapoport, Basil

    2013-01-01

    Background Thyrotropin receptor (TSHR) antibodies that stimulate the thyroid (TSAb) cause Graves' hyperthyroidism and TSHR antibodies which block thyrotropin action (TBAb) are occasionally responsible for hypothyroidism. Unusual patients switch from TSAb to TBAb (or vice versa) with concomitant thyroid function changes. We have examined case reports to obtain insight into the basis for “switching.” Summary TBAb to TSAb switching occurs in patients treated with levothyroxine (LT4); the reverse switch (TBAb to TSAb) occurs after anti-thyroid drug therapy; TSAb/TBAb alterations may occur during pregnancy and are well recognized in transient neonatal thyroid dysfunction. Factors that may impact the shift include: (i) LT4 treatment, usually associated with decreased thyroid autoantibodies, in unusual patients induces or enhances thyroid autoantibody levels; (ii) antithyroid drug treatment decreases thyroid autoantibody levels; (iii) hyperthyroidism can polarize antigen-presenting cells, leading to impaired development of regulatory T cells, thereby compromising control of autoimmunity; (iv) immune-suppression/hemodilution reduces thyroid autoantibodies during pregnancy and rebounds postpartum; (v) maternally transferred IgG transiently impacts thyroid function in neonates until metabolized; (vi) a Graves' disease model involving immunizing TSHR-knockout mice with mouse TSHR-adenovirus and transfer of TSHR antibody-secreting splenocytes to athymic mice demonstrates the TSAb to TBAb shift, paralleling the outcome of maternally transferred “term limited” TSHR antibodies in neonates. Finally, perhaps most important, as illustrated by dilution analyses of patients' sera in vitro, TSHR antibody concentrations and affinities play a critical role in switching TSAb and TBAb functional activities in vivo. Conclusions Switching between TBAb and TSAb (or vice versa) occurs in unusual patients after LT4 therapy for hypothyroidism or anti-thyroid drug treatment for Graves

  16. Differential relationships between chronic hormone profiles in pregnancy and maternal investment in rhesus monkey mothers with hair loss in the neonatal period.

    PubMed

    Dettmer, Amanda M; Rosenberg, Kendra; Menard, Mark T; El-Mallah, Saif N; Woodward, Ruth A; Suomi, Stephen J; Meyer, Jerrold S

    2017-01-01

    Hair loss is commonly used as an indicator of well being in primate facilities, yet it has been shown to also occur in otherwise healthy pregnant and postpartum females. There is significant variability in the incidence of hair loss during these important developmental periods, reasons for which remain unclear. We studied female rhesus monkeys (Macaca mulatta, n = 47) with and without hair loss in pregnancy/postpartum. We hypothesized that, similar to previously published reports, pregnancy would result in an increased likelihood of hair loss, and that hair loss would be correlated with higher hair cortisol concentrations (HCCs). We further hypothesized that hair loss among pregnant females is related to differential maternal investment. We studied a subset of monkeys (n = 26) from mid-to-late pregnancy through peak lactation, some of which exhibited hair loss in the perinatal period (n = 15), and some of which did not (n = 11). We examined fetal measurements, infant birth weight, infant growth rate, and milk yield volume (MYV) in the first 30 days as indices of investment. We found that pregnant monkeys showed a greater incidence of hair loss across the study year (χ(2)(2)  = 6.55, P = 0.038), and that mothers with hair loss had significantly higher HCCs in pregnancy than those without (F(2,28)  = 3.8, P = 0.017, ηp(2)  = 0.21). HCCs in pregnancy were correlated with severity of hair loss in the neonatal period (r(37)  = 0.42, P = 0.008). Moreover, HCCs in pregnancy were positively correlated with infant birth weight (r(12)  = 0.56, P = 0.038), infant growth rate (r(12)  = 0.64, P = 0.014), and MYV (r(11)  = 0.85, P < 0.001) for alopecic but not non-alopecic mothers. These mothers did not differ in fetal measurements, infant birth weight/growth rate, or MYV. Our results suggest that hair loss in some monkeys, especially during the birthing season, may be a signal of greater physiological stress

  17. Alterations in thyroid hormone economy in patients with hydatidiform mole

    PubMed Central

    Galton, Valerie Anne; Ingbar, Sidney H.; Jimenez-Fonseca, Jesus; Hershman, Jerome M.

    1971-01-01

    Studies of several aspects of thyroid hormone economy have been conducted in 11 patients before and after removal of a molar pregnancy. Before evacuation of the mole, all patients demonstrated moderately to greatly elevated values for thyroidal 131I uptake, absolute iodine uptake, and serum protein-bound-131I. Values for serum PBI and serum thyroxine (T4) concentration were consistently and often greatly increased, averaging more than twice those found in normal pregnancy and three times those in normal controls. On the other hand, the maximum binding capacity of the T4-binding globulin (TBG) was variably affected, and ranged between the values found in normal controls and those found in normal pregnancy. Values for the absolute concentration of free T4 in serum were, on the average, only moderately elevated, since the proportion of free T4 was moderately low, although not as low as in normal pregnancy. Sera of patients with molar pregnancy contained high levels of thyroid stimulating activity, as assessed in the McKenzie mouse bioassay system. The stimulator displayed a more prolonged duration of action than that of TSH and did not reveal a major immunological cross-reactivity with either human or bovine TSH, differing in the latter respect from the chorionic thyrotropin of normal human placenta. Abnormalities in iodine metabolism were rapidly ameliorated after removal of the molar pregnancy, and this was associated with the disappearance from serum of the thyroid stimulator. Despite the foregoing evidence of thyroid hyperfunction and hypersecretion of T4, patients with molar pregnancy were neither goitrous nor overtly thyrotoxic. They did display, however, high values of the urinary pigment/creatinine ratio, a possible indication of the presence of a hypermetabolic state. It is concluded that in patients with molar pregnancy, thyroid function and T4 secretion are stimulated, often greatly so, by an unusual thyroid stimulator which is demonstrable in the blood and

  18. Neonatal medications.

    PubMed

    Ward, Robert M; Stiers, Justin; Buchi, Karen

    2015-04-01

    Neonatal abstinence syndrome (NAS) is reaching epidemic proportions related to perinatal use of opioids. There are many approaches to assess and manage NAS, including one we have outlined. A standardized approach is likely to reduce length of stay and variability in practice. Circumcision is a frequent, painful procedure performed in the neonatal period. The rationale for providing analgesia is presented as well as a review of methods. Pharmacogenomics and pharmacogenetics have expanded our understanding of diseases and their drug therapy. Some applications of pharmacogenomics to the neonatal period are presented, along with pediatric challenges of developmental expression of drug-metabolizing enzymes.

  19. Chronic exposure to pentachlorophenol alters thyroid hormones and thyroid hormone pathway mRNAs in zebrafish.

    PubMed

    Yu, Li-Qin; Zhao, Gao-Feng; Feng, Min; Wen, Wu; Li, Kun; Zhang, Pan-Wei; Peng, Xi; Huo, Wei-Jie; Zhou, Huai-Dong

    2014-01-01

    Pentachlorophenol (PCP) is frequently detected in the aquatic environment and has been implicated as an endocrine disruptor in fish. In the present study, 4-month-old zebrafish (Danio rerio) were exposed to 1 of 4 concentrations of PCP (0.1, 1, 9, and 27 µg/L) for 70 d. The effects of PCP exposure on plasma thyroid hormone levels, and the expression levels of selected genes, were measured in the brain and liver. The PCP exposure at 27 µg/L resulted in elevated plasma thyroxine concentrations in male and female zebrafish and depressed 3, 5, 3'-triiodothyronine concentrations in males only. In both sexes, PCP exposure resulted in decreased messenger RNA (mRNA) expression levels of thyroid-stimulating hormone β-subunit (tshβ) and thyroid hormone receptor β (trβ) in the brain, as well as increased liver levels of uridine diphosphoglucuronosyl transferase (ugt1ab) and decreased deiodinase 1 (dio1). The authors also identified several sex-specific effects of PCP exposure, including changes in mRNA levels for deiodinase 2 (dio2), cytosolic sulfotransferase (sult1 st5), and transthyretin (ttr) genes in the liver. Environmental PCP exposure also caused an increased malformation rate in offspring that received maternal exposure to PCP. The present study demonstrates that chronic exposure to environmental levels of PCP alters plasma thyroid hormone levels, as well as the expression of genes associated with thyroid hormone signaling and metabolism in the hypothalamic-pituitary-thyroid (HPT) axis and liver, resulting in abnormal zebrafish development.

  20. [Regulatory mechanism of hormones of the pituitary-target gland axes in kidney-Yang deficiency based on a support vector machine model].

    PubMed

    Xiufeng, Wang; Lei, Zhang; Rongbo, Huang; Qinghua, Wu; Jianxin, Min; Na, Ma; Laicheng, Luo

    2015-04-01

    To study the development mechanism of kidney-Yang deficiency through the establishment of support vector machine models of relevant hormones of the pituitary-target gland axes in rats with kidney-Yang deficiency syndrome. The kidney-Yang deficiency rat model was created by intramuscular injection of hydrocortisone, and contents of the hormones of the pituitary-thyroid axis: thyroid stimulating hormone (TSH), 3,3',5-triiodothyronine (T3) and thyroxine (T4); hormones of the pituitary-adrenal gland axis: adrenocorticotropic hormone (ACTH) and cortisol (CORT); and hormones of the pituitary-gonadal axis: luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T), were determined in the early, middle, and advanced stages. Ten support vector regression (SVR) models of the hormones were established to analyze the mutual relationships among the hormones of the three axes. The feedback control action of the pituitary-adrenal axis began to lose efficacy from the middle stage of kidney-Yang deficiency. The contents all hormones of the three pituitary-target gland axes decreased in the advanced stage. Relative errors of the jackknife test of the SVR models all were less than 10%. Imbalances in mutual regulation among the hormones of the pituitary-target gland axes, especially loss of effectiveness of the pituitary-adrenal axis, is one pathogenesis of kidney-Yang deficiency. The SVR model can accurately reflect the complicated non-linear relationships among pituitary-target gland axes in rats with of kidney-Yang deficiency.

  1. Sleep deprivation alters thyroid hormone economy in rats.

    PubMed

    Rodrigues, Nayana Coutinho; da Cruz, Natália Santos; de Paula Nascimento, Cristine; da Conceição, Rodrigo Rodrigues; da Silva, Alba Cenélia Matos; Olivares, Emerson Lopes; Marassi, Michelle Porto

    2015-02-01

    What is the central question of this study? The relationship between the thyroid system and sleep deprivation has seldom been assessed in the literature, and mounting evidence exists that sleep disturbances influence human lifestyles. The aim of this study was to investigate the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism in sleep-deprived and sleep-restricted rats. What is the main finding and its importance? Central hypothyroidism and high thyroxine (T4 ) to 3,5,3'-triiodothyronine (T3 ) activation in brown adipose tissue were observed following sleep deprivation. Sleep-restricted rats exhibited normal thyroid-stimulating hormone and T4 concentrations despite increased circulating T3 . Sleep recovery for 24 h did not normalize the high T3 concentrations, suggesting that high T3 is a powerful counterregulatory mechanism activated following sleep deprivation. Modern life has shortened sleep time, and the consequences of sleep deprivation have been examined in both human subjects and animal models. As the relationship between thyroid function and sleep deprivation has not been fully investigated, the aim of this study was to assess the hypothalamic-pituitary-thyroid axis and thyroid hormone metabolism following paradoxical sleep deprivation (PSD) and sleep restriction (SR) in rats. The effects of a 24 h rebound period were also studied. Male Wistar rats (200-250 g, n = 10 per group) were subjected to sleep deprivation via the modified multiple platform method. Rats were assigned to the following seven groups: control, PSD for 24 or 96 h, 24 or 96 h of sleep deprivation with rebound (PSD24R and PSD96R), SR for 21 days (SR21) and SR21 with rebound (SR21R). Blood samples were collected to determine the 3,5,3'-triiodothyronine (T3 ), thyroxine (T4 ) and thyroid-stimulating hormone concentrations. Brown adipose tissue iodothyronine deiodinase type 2 (D2) activity was also evaluated. Body weight gain was dramatically reduced (by ∼50-100%) in all

  2. Serum copper as a novel biomarker for resistance to thyroid hormone.

    PubMed

    Mittag, Jens; Behrends, Thomas; Nordström, Kristina; Anselmo, Joao; Vennström, Björn; Schomburg, Lutz

    2012-04-01

    Thyroid hormone action is mediated by the thyroid hormone receptors TRα1 and TRβ. Defects in TRβ lead to RTH (resistance to thyroid hormone) β, a syndrome characterized by high levels of thyroid hormone and non-suppressed TSH (thyroid-stimulating hormone). However, a correct diagnosis of RTHβ patients is difficult as the clinical picture varies. A biochemical serum marker indicative of defects in TRβ signalling is needed and could simplify the diagnosis of RTHβ, in particular the differentiation to TSH-secreting pituitary adenomas, which present with clinically similar symptoms. In the present paper we show that serum copper levels are regulated by thyroid hormone, which stimulates the synthesis and the export of the hepatic copper-transport protein ceruloplasmin into the serum. This is accompanied by a concerted reduction in the mRNA levels of other copper-containing proteins such as metallothioneins 1 and 2 or superoxide dismutase 1. The induction of serum copper is abolished in genetically hyperthyroid mice lacking TRβ and human RTHβ patients, demonstrating an important role of TRβ for this process. Together with a previously reported TRα1 specific regulation of serum selenium, we show that the ratio of serum copper and selenium, which is largely independent of thyroid hormone levels, volume changes or sample degradation, can constitute a valuable novel biomarker for RTHβ. Moreover, it could also provide a suitable large-scale screening parameter to identify RTHα patients, which have not been identified to date.

  3. Neonatal conjunctivitis

    MedlinePlus

    Newborn conjunctivitis; Conjunctivitis of the newborn; Ophthalmia neonatorum; Eye infection - neonatal conjunctivitis ... diseases spread through sexual contact to prevent newborn conjunctivitis caused by these infections. Putting eye drops into ...

  4. Single vagus nerve stimulation reduces early postprandial C-peptide levels but not other hormones or postprandial metabolism.

    PubMed

    Tang, M W; van Nierop, F S; Koopman, F A; Eggink, H M; Gerlag, D M; Chan, M W; Zitnik, R; Vaz, F M; Romijn, J A; Tak, P P; Soeters, M R

    2017-04-08

    A recent study in rheumatoid arthritis (RA) patients using electrical vagus nerve stimulation (VNS) to activate the inflammatory reflex has shown promising effects on disease activity. Innervation by the autonomic nerve system might be involved in the regulation of many endocrine and metabolic processes and could therefore theoretically lead to unwanted side effects. Possible effects of VNS on secretion of hormones are currently unknown. Therefore, we evaluated the effects of a single VNS on plasma levels of pituitary hormones and parameters of postprandial metabolism. Six female patients with RA were studied twice in balanced assignment (crossover design) to either VNS or no stimulation. The patients selected for this substudy had been on VNS therapy daily for at least 3 months and at maximum of 24 months. We compared 10-, 20-, and 30-min poststimulus levels to baseline levels, and a 4-h mixed meal test was performed 30 min after VNS. We also determined energy expenditure (EE) by indirect calorimetry before and after VNS. VNS did not affect pituitary hormones (growth hormone, thyroid stimulating hormone, adrenocorticotropic hormone, prolactin, follicle-stimulating hormone, and luteinizing hormone), postprandial metabolism, or EE. Of note, VNS reduced early postprandial insulin secretion, but not AUC of postprandial plasma insulin levels. Cortisol and catecholamine levels in serum did not change significantly. Short stimulation of vagal activity by VNS reduces early postprandial insulin secretion, but not other hormone levels and postprandial response. This suggests VNS as a safe treatment for RA patients.

  5. Neonatal magnetocardiography.

    PubMed

    Anastasiadis, P G; Anninos, P; Kotini, A; Koutlaki, N; Garas, A; Galazios, G

    2001-01-01

    The aim of the present study was to test the validity of magnetocardiography (MCG) in the estimation of neonatal cardiac rhythm using a single channel superconductive quantum interference device (SQUID). Our study population consisted of 50 neonates who were delivered normally between 37-41 weeks of gestation from clinically uncomplicated pregnancies. There was also a neonate included in the study in which the diagnosis of "hypoplastic left heart syndrome" was demonstrated by U/S Doppler examination. Maternal age ranged from 18 to 39 years (mean=29.15, SD=6.13). Our study results revealed 44 neonates with normal cardiac rhythm, four with ventricular tachycardia (VT), one with ventricular tachycardia (VT) and extrasystolic beats and one with bradycardia. The neonate with the hypoplastic left heart syndrome presented frequent episodes of ventricular bigeminy in the magnetocardiographic trace. M-mode echocardiography confirmed the diagnosis of the seven cases of arrhythmia in our study group. Results gained from the study lead us to believe that MCG could provide clinical practice with a non-invasive, rapid and easy to perform method, which could be used as an adjunct to conventional methods for the evaluation of neonatal cardiac rhythm.

  6. Development of additional pituitary hormone deficiencies in pediatric patients originally diagnosed with isolated growth hormone deficiency due to organic causes.

    PubMed

    Child, Christopher J; Blum, Werner F; Deal, Cheri; Zimmermann, Alan G; Quigley, Charmian A; Drop, Stenvert L S; Cutler, Gordon B; Rosenfeld, Ron G

    2016-05-01

    To determine characteristics of children initially diagnosed with isolated growth hormone deficiency (IGHD) of organic aetiology, who later developed multiple pituitary hormone deficiencies (MPHD). Data were analysed for 716 growth hormone-treated children with organic IGHD, who were growth hormone-naïve at baseline in the multinational, observational Genetics and Neuroendocrinology of Short Stature International Study. Development of MPHD was ascertained from investigator-provided diagnoses, adverse events and concomitant medications. Analyses were performed for all patients and separately for those who developed MPHD within 4.5 years or had >3.5 years follow-up and continued to have IGHD (4-year cohort). MPHD developed in 71/716 (9.9%) children overall, and in 60/290 (20.7%) in the 4-year cohort. The most frequent additional deficiencies were thyroid-stimulating hormone (47 patients) and gonadotropins (23 patients). Compared with those who remained with IGHD, children who developed MPHD had more severe GHD at study entry, significantly lower baseline insulin-like growth factor1, peak stimulated growth hormone, and more frequent diagnosis of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Multivariate logistic regression analyses identified female gender, longer follow-up, higher baseline age and lower peak stimulated growth hormone as predictors of MPHD development. MPHD is more likely to develop in patients with severe organic IGHD, especially those with history of intracranial tumour or mutation of gene(s) controlling hypothalamic-pituitary development and/or function. Older baseline age, female gender and longer follow-up duration were also associated with higher incidence of MPHD. Long-term monitoring of pituitary function is recommended, irrespective of the aetiology of GHD. © 2016 European Society of Endocrinology.

  7. Coupling between Nutrient Availability and Thyroid Hormone Activation*

    PubMed Central

    Lartey, Lattoya J.; Werneck-de-Castro, João Pedro; O-Sullivan, InSug; Unterman, Terry G.; Bianco, Antonio C.

    2015-01-01

    The activity of the thyroid gland is stimulated by food availability via leptin-induced thyrotropin-releasing hormone/thyroid-stimulating hormone expression. Here we show that food availability also stimulates thyroid hormone activation by accelerating the conversion of thyroxine to triiodothyronine via type 2 deiodinase in mouse skeletal muscle and in a cell model transitioning from 0.1 to 10% FBS. The underlying mechanism is transcriptional derepression of DIO2 through the mTORC2 pathway as defined in rictor knockdown cells. In cells kept in 0.1% FBS, there is DIO2 inhibition via FOXO1 binding to the DIO2 promoter. Repression of DIO2 by FOXO1 was confirmed using its specific inhibitor AS1842856 or adenoviral infection of constitutively active FOXO1. ChIP studies indicate that 4 h after 10% FBS-containing medium, FOXO1 binding markedly decreases, and the DIO2 promoter is activated. Studies in the insulin receptor FOXO1 KO mouse indicate that insulin is a key signaling molecule in this process. We conclude that FOXO1 represses DIO2 during fasting and that derepression occurs via nutritional activation of the PI3K-mTORC2-Akt pathway. PMID:26499800

  8. Does Ventriculoperitoneal Shunting Improve Thyroid Hormone Levels in Hydrocephalic Newborns?

    PubMed

    Ucler, Necati; Erol, Fatih Serhat; Ozturk, Sait; Akgun, Bekir; Kaplan, Metin; Sen, Yasar

    2017-01-01

    The aim of this report was to investigate the effect of ventriculoperitoneal shunt insertion for the treatment of hydrocephalus on thyroid hormones in the first 3 months of life. Thyroid-stimulating hormone (TSH), free T3 (fT3), and free T4 (fT4) levels were compared at 7 days (preoperatively) and at 30 and 90 days (postoperatively) after birth between 25 ventriculoperitoneal shunt-inserted hydrocephalic newborns and 20 healthy newborns. The TSH level at 7 days was higher in the hydrocephalic patient group (6.33 µIU) compared to the control group (3.76 µIU). This value was significantly decreased at 90 days in the ventriculoperitoneal shunt-inserted newborns (2.35 µIU) compared to the control group (3.33 µIU; p < 0.05). There were no significant differences between time points for fT4 and fT3 values in the patient group or for TSH, fT4, and fT3 values in the control group. We propose that a ventriculoperitoneal shunt inserted in the early period of life may have beneficial effects on thyroid hormones. © 2016 S. Karger AG, Basel.

  9. Discovery and Development of Small Molecule Allosteric Modulators of Glycoprotein Hormone Receptors

    PubMed Central

    Nataraja, Selvaraj G.; Yu, Henry N.; Palmer, Stephen S.

    2015-01-01

    Glycoprotein hormones, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) are heterodimeric proteins with a common α-subunit and hormone-specific β-subunit. These hormones are dominant regulators of reproduction and metabolic processes. Receptors for the glycoprotein hormones belong to the family of G protein-coupled receptors. FSH receptor (FSHR) and LH receptor are primarily expressed in somatic cells in ovary and testis to promote egg and sperm production in women and men, respectively. TSH receptor is expressed in thyroid cells and regulates the secretion of T3 and T4. Glycoprotein hormones bind to the large extracellular domain of the receptor and cause a conformational change in the receptor that leads to activation of more than one intracellular signaling pathway. Several small molecules have been described to activate/inhibit glycoprotein hormone receptors through allosteric sites of the receptor. Small molecule allosteric modulators have the potential to be administered orally to patients, thus improving the convenience of treatment. It has been a challenge to develop a small molecule allosteric agonist for glycoprotein hormones that can mimic the agonistic effects of the large natural ligand to activate similar signaling pathways. However, in the past few years, there have been several promising reports describing distinct chemical series with improved potency in preclinical models. In parallel, proposal of new structural model for FSHR and in silico docking studies of small molecule ligands to glycoprotein hormone receptors provide a giant leap on the understanding of the mechanism of action of the natural ligands and new chemical entities on the receptors. This review will focus on the current status of small molecule allosteric modulators of glycoprotein hormone receptors, their effects on common signaling pathways in cells, their utility for clinical application as demonstrated in preclinical models

  10. Long-term effects of growth hormone replacement therapy on thyroid function in adults with growth hormone deficiency.

    PubMed

    Losa, Marco; Scavini, Marina; Gatti, Elisa; Rossini, Alessandro; Madaschi, Sara; Formenti, Ilaria; Caumo, Andrea; Stidley, Christine A; Lanzi, Roberto

    2008-12-01

    Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH). The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels. During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years. We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.

  11. Neonatal pain

    PubMed Central

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback. PMID:24330444

  12. Neonatal pain.

    PubMed

    Walker, Suellen M

    2014-01-01

    Effective management of procedural and postoperative pain in neonates is required to minimize acute physiological and behavioral distress and may also improve acute and long-term outcomes. Painful stimuli activate nociceptive pathways, from the periphery to the cortex, in neonates and behavioral responses form the basis for validated pain assessment tools. However, there is an increasing awareness of the need to not only reduce acute behavioral responses to pain in neonates, but also to protect the developing nervous system from persistent sensitization of pain pathways and potential damaging effects of altered neural activity on central nervous system development. Analgesic requirements are influenced by age-related changes in both pharmacokinetic and pharmacodynamic response, and increasing data are available to guide safe and effective dosing with opioids and paracetamol. Regional analgesic techniques provide effective perioperative analgesia, but higher complication rates in neonates emphasize the importance of monitoring and choice of the most appropriate drug and dose. There have been significant improvements in the understanding and management of neonatal pain, but additional research evidence will further reduce the need to extrapolate data from older age groups. Translation into improved clinical care will continue to depend on an integrated approach to implementation that encompasses assessment and titration against individual response, education and training, and audit and feedback.

  13. JNK pathway decreases thyroid hormones via TRH receptor: a novel mechanism for disturbance of thyroid hormone homeostasis by PCB153.

    PubMed

    Liu, Changjiang; Ha, Mei; Cui, Yushan; Wang, Chengmin; Yan, Maosheng; Fu, Wenjuan; Quan, Chao; Zhou, Jun; Yang, Kedi

    2012-12-08

    PCBs, widespread and well-characterized endocrine disruptors, cause the disruption of thyroid hormone (TH) homeostasis in humans and animals. In order to verify the hypotheses that MAPK pathways would play roles in disturbance of TH levels caused by PCBs, and that TH-associated receptors could function in certain MAPK pathway, Sprague-Dawley rats were dosed with PCB153 intraperitoneally (i.p.) at 0, 4, 16 and 32mg/kg for 5 consecutive days, and Nthy-ori 3-1 cells were treated with PCB153 (0, 1, 5, 10μM) for 30min. Results showed that after the treatment with PCB153, serum total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3) and thyrotropin releasing hormone (TRH) were decreased, whereas free triiodothyronine (FT3) and serum thyroid stimulating hormone (TSH) were not altered. In vivo and in vitro studies indicated that JNK pathway was activated after PCB153 exposure. Moreover, TRH receptor (TRHr) level was suppressed after the activation of JNK pathway and was elevated after the inhibition of JNK pathway, but TSH receptor (TSHr) level was not affected by the status of JNK pathway though it was reduced after PCB153 treatment. The activated signs of ERK and P38 pathways were not observed in this study. Taken together, observed effects suggested that JNK pathway could decrease TH levels via TRHr, and that would be one novel mechanism of PCB153-mediated disruption of THs.

  14. Association of thyroid hormones with obesity and metabolic syndrome in Japanese children.

    PubMed

    Minami, Yukako; Takaya, Ryuzo; Takitani, Kimitaka; Ishiro, Manabu; Okasora, Keisuke; Niegawa, Tomomi; Tamai, Hiroshi

    2015-09-01

    Obesity is associated with health consequences, and thyroid dysfunction may be an adaption to the increased energy expenditure in obesity. With the rising prevalence of obesity in childhood, the prevalence of metabolic syndrome may also increase. In the current study, we have shown gender differences in the association of thyroid hormones with obesity, and attempted to elucidate the relationship between thyroid hormones and anthropometric parameters and biochemical data in obese Japanese children. We analyzed anthropometric measurements, blood pressure, body composition, thyroid hormones, and lipid profiles in 283 obese children. The association between thyroid hormones and several parameters differed by gender. The free T3 to free T4 ratio (fT3/fT4) in boys was negatively associated with the quantitative insulin sensitivity check index, whereas in girls, thyroid-stimulating hormone levels were positively correlated with levels of glucose, diastolic blood pressure, and non-high density lipoprotein-cholesterol, and fT3/fT4 was positively correlated with uric acid levels. FT3/fT4 in boys with metabolic syndrome was relatively higher than in those without metabolic syndrome. The cause of gender differences is unknown. Therefore, further studies with larger sample sizes and a long-term follow-up period are needed to address the influence of thyroid hormones on various parameters.

  15. Association of thyroid hormones with obesity and metabolic syndrome in Japanese children

    PubMed Central

    Minami, Yukako; Takaya, Ryuzo; Takitani, Kimitaka; Ishiro, Manabu; Okasora, Keisuke; Niegawa, Tomomi; Tamai, Hiroshi

    2015-01-01

    Obesity is associated with health consequences, and thyroid dysfunction may be an adaption to the increased energy expenditure in obesity. With the rising prevalence of obesity in childhood, the prevalence of metabolic syndrome may also increase. In the current study, we have shown gender differences in the association of thyroid hormones with obesity, and attempted to elucidate the relationship between thyroid hormones and anthropometric parameters and biochemical data in obese Japanese children. We analyzed anthropometric measurements, blood pressure, body composition, thyroid hormones, and lipid profiles in 283 obese children. The association between thyroid hormones and several parameters differed by gender. The free T3 to free T4 ratio (fT3/fT4) in boys was negatively associated with the quantitative insulin sensitivity check index, whereas in girls, thyroid-stimulating hormone levels were positively correlated with levels of glucose, diastolic blood pressure, and non-high density lipoprotein-cholesterol, and fT3/fT4 was positively correlated with uric acid levels. FT3/fT4 in boys with metabolic syndrome was relatively higher than in those without metabolic syndrome. The cause of gender differences is unknown. Therefore, further studies with larger sample sizes and a long-term follow-up period are needed to address the influence of thyroid hormones on various parameters. PMID:26388669

  16. Localization and synthesis of the hormone-binding regions of the human thyrotropin receptor

    SciTech Connect

    Atassi, M.Z.; Manshouri, T. ); Sakata, Shigeki )

    1991-05-01

    Two regions of human thyrotropin (thyroid-stimulating hormone, TSH) receptor (TSHR) were selected on the basis that they exhibit no sequence resemblance to luteinizing hormone/chorionic gonadotropin receptor. Five synthetic overlapping peptides (12-30, 24-44, 308-328, 324-344, and 339-364) were studied for their ability to bind {sup 125}I-labeled human TSH (hTSH), its isolated {alpha} and {beta} subunits, bovine TSH, ovine TSH, human luteinizing hormone, and human follicle-stimulating hormone. The human TSHR peptides 12-30 and 324-344 exhibited remarkable binding activity to human, bovine, and ovine TSH and to the {beta} chain of hTSH. Lower binding activity resided in the adjacent overlapping peptides, probably due to the contribution of the shared overlap to the binding. The specificity of TSH binding to these peptides was confirmed by their inability to bind human luteinizing hormone, human follicle-stimulating hormone, and the {alpha} chain of hTSH. Thyrotropins did not bind to bovine serum albumin or to peptide controls unrelated to the TSHR system. It is concluded that the binding of TSH to its receptor involves extensive contacts and that the TSHR peptides 12-30 and 324-344 contain specific binding regions for TSH that might be either independent sites or two faces (subsites) within a large binding site.

  17. Leucine-enkephalin-like immunoreactivity is localized in luteinizing hormone-producing cells in the axolotl (Ambystoma mexicanum) pituitary.

    PubMed

    Suzuki, Hirohumi; Yamamoto, Toshiharu

    2014-02-01

    In this study, we used immunohistochemical techniques to determine the cell type of leucine-enkephalin (Leu-ENK)-immunoreactive cells in the axolotl (Ambystoma mexicanum) pituitary. Immunoreactive cells were scattered throughout the pars distalis except for the dorso-caudal portion. These cells were immuno-positive for luteinizing hormone (LH), but they were immuno-negative for adrenocorticotrophic, growth, and thyroid-stimulating hormones, as well as prolactin. Immunoelectron microscopy demonstrated that Leu-ENK-like substance and LH co-localized within the same secretory granules. Leu-ENK secreted from gonadotrophs may participate in LH secretion in an autocrine fashion, and/or may participate in the release of sex steroids together with LH. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Factors related to endocrine changes and hormone substitution treatment during pre- and post-operation stages in craniopharyngioma

    PubMed Central

    Sun, Fenglei; Sun, Xintang; Du, Xiaolong; Xing, Hongshun; Yang, Bin

    2017-01-01

    Factors related to endocrine changes and hormone substitution treatment during pre- and post-operation periods in craniopharyngioma cases were examined. Twenty patients who underwent tumor resection from January 2012 to January 2015 were included in the study. We monitored factors related to endocrine changes and hormone substitution treatment during pre- and post-operation periods. Blood thyroid-stimulating hormone, triiodothyronine, thyroxine, prolactin, follicle-stimulating hormone, luteinizing hormone and cortisol levels were measured in the patients. Urinary volume and urine specific gravity were also measured before and after the operation. After the operation, we observed diabetes insipidus and a decrease in TSH and gonadal hormone levels more frequently compared to pre-operation. However, incidence of high prolactin was markedly reduced following surgery. The number of hypothyroidism cases before and after surgery had no statistical significance. In conclusion, surgery for craniopharyngioma aggravated endocrine dysfunction. Craniotomy and total tumor resection had considerable effects on the endocrine system. Routine hormone therapy as an alternative treatment was necessary after operation. Alternative treatment of adrenal cortex hormones reduced the incidence on low blood cortisol. PMID:28123549

  19. Functional role of the heterodimeric glycoprotein hormone, GPA2/GPB5, and its receptor, LGR1: An invertebrate perspective.

    PubMed

    Rocco, David A; Paluzzi, Jean-Paul V

    2016-08-01

    In vertebrates, follicle-stimulating hormone (FSH), luteinizing hormone (LH), chorionic gonadotropin (CG) and thyroid-stimulating hormone (TSH) are glycoprotein hormones that play central roles in metabolism, reproduction and development. Recently, a novel heterodimeric glycoprotein hormone, called GPA2/GPB5, was discovered in humans; however, contrary to its vertebrate glycoprotein hormone relatives, the physiological role of GPA2/GPB5 has not yet been fully elucidated in any vertebrate or invertebrate. Moreover, it is unclear as to whether GPA2/GPB5 functions as a heterodimer or as individual GPA2 and GPB5 monomers in these organisms. GPA2- and GPB5-like subunits have been identified or predicted in a wide array of animal phyla including the nematodes, chordates, hemichordates, arthropods, molluscs, echinoderms and annelids. So far, molecular studies on transcript expression of the GPA2/GPB5 subunits and its putative receptor, the leucine-rich repeat-containing G protein-coupled receptor 1 (LGR1), suggests this glycoprotein hormone system plays a developmental role and may also function in hydromineral balance in invertebrates. This mini-review summarizes the current state of knowledge on the physiological actions and activity of this evolutionarily ancient heterodimeric glycoprotein hormone with a particular focus on its known functions in the invertebrates.

  20. Neonatal Cholestasis

    PubMed Central

    Feldman, Amy G.; Sokol, Ronald J.

    2013-01-01

    Cholestatic jaundice is a common presenting feature of neonatal hepatobiliary and metabolic dysfunction. Any infant who remains jaundiced beyond age 2 to 3 weeks should have the serum bilirubin level fractionated into a conjugated (direct) and unconjugated (indirect) portion. Conjugated hyperbilirubinemia is never physiologic or normal. The differential diagnosis of cholestasis is extensive, and a step-wise approach based on the initial history and physical examination is useful to rapidly identify the underlying etiology. Early recognition of neonatal cholestasis is essential to ensure timely treatment and optimal prognosis. Even when specific treatment is not available, infants who have cholestasis benefit from early medical management and optimization of nutrition. Future studies are necessary to determine the most reliable and cost-effective method of universal screening for neonatal cholestasis. PMID:24244109

  1. Recessive resistance to thyroid hormone in mice lacking thyroid hormone receptor beta: evidence for tissue-specific modulation of receptor function.

    PubMed Central

    Forrest, D; Hanebuth, E; Smeyne, R J; Everds, N; Stewart, C L; Wehner, J M; Curran, T

    1996-01-01

    The diverse functions of thyroid hormone (T3) are presumed to be mediated by two genes encoding the related receptors, TRalpha and TRbeta. However, the in vivo functions of TRalpha and TRbeta are undefined. Here, we report that targeted inactivation of the mouse TRbeta gene results in goitre and elevated levels of thyroid hormone. Also, thyroid-stimulating hormone (TSH), which is released by pituitary thyrotropes and which is normally suppressed by increased levels of thyroid hormone, was present at elevated levels in homozygous mutant (Thrb-/-) mice. These findings suggest a unique role for TRbeta that cannot be substituted by TRalpha in the T3-dependent feedback regulation of TSH transcription. Thrb-/- mice provide a recessive model for the human syndrome of resistance to thyroid hormone (RTH) that exhibits a similar endocrine disorder but which is typically caused by dominant TRbeta mutants that are transcriptional inhibitors. It is unknown whether TRalpha, TRbeta or other receptors are targets for inhibition in dominant RTH; however, the analysis of Thrb-/- mice suggests that antagonism of TRbeta-mediated pathways underlies the disorder of the pituitary-thyroid axis. Interestingly, in the brain, the absence of TRbeta may not mimic the defects often associated with dominant RTH, since no overt behavioural or neuroanatomical abnormalities were detected in Thrb-/- mice. These data define in vivo functions for TRbeta and indicate that specificity in T3 signalling is conferred by distinct receptor genes. Images PMID:8670802

  2. A vital region for human glycoprotein hormone trafficking revealed by an LHB mutation.

    PubMed

    Potorac, Iulia; Rivero-Müller, Adolfo; Trehan, Ashutosh; Kiełbus, Michał; Jozwiak, Krzysztof; Pralong, Francois; Hafidi, Aicha; Thiry, Albert; Ménagé, Jean-Jacques; Huhtaniemi, Ilpo; Beckers, Albert; Daly, Adrian F

    2016-12-01

    Glycoprotein hormones are complex hormonally active macromolecules. Luteinizing hormone (LH) is essential for the postnatal development and maturation of the male gonad. Inactivating Luteinizing hormone beta (LHB) gene mutations are exceptionally rare and lead to hypogonadism that is particularly severe in males. We describe a family with selective LH deficiency and hypogonadism in two brothers. DNA sequencing of LHB was performed and the effects of genetic variants on hormone function and secretion were characterized by mutagenesis studies, confocal microscopy and functional assays. A 20-year-old male from a consanguineous family had pubertal delay, hypogonadism and undetectable LH. A homozygous c.118_120del (p.Lys40del) mutation was identified in the patient and his brother, who subsequently had the same phenotype. Treatment with hCG led to pubertal development, increased circulating testosterone and spermatogenesis. Experiments in HeLa cells revealed that the mutant LH is retained intracellularly and showed diffuse cytoplasmic distribution. The mutated LHB heterodimerizes with the common alpha-subunit and can activate its receptor. Deletion of flanking glutamic acid residues at positions 39 and 41 impair LH to a similar extent as deletion of Lys40. This region is functionally important across all heterodimeric glycoprotein hormones, because deletion of the corresponding residues in hCG, follicle-stimulating hormone and thyroid-stimulating hormone beta-subunits also led to intracellular hormone retention. This novel LHB mutation results in hypogonadism due to intracellular sequestration of the hormone and reveals a discrete region in the protein that is crucial for normal secretion of all human glycoprotein hormones.

  3. Neonatal sepsis

    PubMed Central

    Shah, Birju A; Padbury, James F

    2014-01-01

    Neonatal sepsis continues to be a common and significant health care burden, especially in very-low-birth-weight infants (VLBW <1500 g). Though intrapartum antibiotic prophylaxis has decreased the incidence of early-onset group B streptococcal infection dramatically, it still remains a major cause of neonatal sepsis. Moreover, some studies among VLBW preterm infants have shown an increase in early-onset sepsis caused by Escherichia coli. As the signs and symptoms of neonatal sepsis are nonspecific, early diagnosis and prompt treatment remains a challenge. There have been a myriad of studies on various diagnostic markers like hematological indices, acute phase reactants, C-reactive protein, procalcitonin, cytokines, and cell surface markers among others. Nonetheless, further research is needed to identify a biomarker with high diagnostic accuracy and validity. Some of the newer markers like inter α inhibitor proteins have shown promising results thereby potentially aiding in early detection of neonates with sepsis. In order to decrease the widespread, prolonged use of unnecessary antibiotics and improve the outcome of the infants with sepsis, reliable identification of sepsis at an earlier stage is paramount. PMID:24185532

  4. Neonatal sepsis

    MedlinePlus

    ... better the outcome. Possible Complications Complications may include: Disability Death When to Contact a Medical Professional Seek medical help right away for an infant that shows symptoms of neonatal sepsis. Prevention Pregnant women may need preventive antibiotics if they have: Chorioamnionitis ...

  5. Neonatal hematology.

    PubMed

    Diaz-Miron, Jose; Miller, Jacob; Vogel, Adam M

    2013-11-01

    Neonatal hematology is a complex and dynamic process in the pediatric population. Surgeons frequently encounter hematologic issues regarding hemostasis, inflammation, and wound healing. This publication provides a surgeon-directed review of hematopoiesis in the newborn, as well as an overview of the current understanding of their hemostatic profile under normal and pathologic conditions. © 2013 Published by Elsevier Inc.

  6. Thyrotropic activity of salmon pituitary glycoprotein hormones in the Hawaiian parrotfish thyroid in vitro.

    PubMed

    Swanson, P; Grau, E G; Helms, L M; Dickhoff, W W

    1988-02-01

    The thyrotropic activities of salmon pituitary extract, thyroid-stimulating hormone (TSH), gonadotropins (GTH), and glycoprotein fractions obtained during purification of salmon TSH and GTH were measured using the parrotfish thyroid culture system. Purified salmon TSH was approximately 1,000 times more potent than bovine TSH in stimulating thyroxine release into the culture medium. Most of the forms of salmon GTH had no thyrotropic activity. One of the forms of salmon GTH (GTH-F) and three chromatofocusing fractions (CF-B, -C, and -E) that were devoid of activity in the coho salmon in vivo had some thyrotropic activity in the parrotfish thyroid culture. Whether the activity of these fractions was due to contamination with TSH, less potent forms of TSH, or inherent thyrotropic activity of a form of GTH is discussed. These results indicate that the parrotfish thyroid culture system can be used to detect thyrotropic activity of fractions obtained during the purification of teleost TSH.

  7. Neonatal Infectious Diseases: Evaluation of Neonatal Sepsis

    PubMed Central

    Spearman, Paul W.; Stoll, Barbara J.

    2015-01-01

    Synopsis Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation and early initiation of therapy are required to prevent adverse outcomes. The following chapter reviews recent trends in epidemiology, and provides an update on risk factors, diagnostic methods and management of neonatal sepsis. PMID:23481106

  8. Neonatal infectious diseases: evaluation of neonatal sepsis.

    PubMed

    Camacho-Gonzalez, Andres; Spearman, Paul W; Stoll, Barbara J

    2013-04-01

    Neonatal sepsis remains a feared cause of morbidity and mortality in the neonatal period. Maternal, neonatal, and environmental factors are associated with risk of infection, and a combination of prevention strategies, judicious neonatal evaluation, and early initiation of therapy are required to prevent adverse outcomes. This article reviews recent trends in epidemiology and provides an update on risk factors, diagnostic methods, and management of neonatal sepsis. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Imbalance between thyroid hormones and the dopaminergic system might be central to the pathophysiology of restless legs syndrome: a hypothesis.

    PubMed

    Pereira, Jose Carlos; Pradella-Hallinan, Marcia; Lins Pessoa, Hugo de

    2010-05-01

    Data collected from medical literature indicate that dopaminergic agonists alleviate Restless Legs Syndrome symptoms while dopaminergic agonists antagonists aggravate them. Dopaminergic agonists is a physiological regulator of thyroid-stimulating hormone. Dopaminergic agonists infusion diminishes the levels of thyroid hormones, which have the ability to provoke restlessness, hyperkinetic states, tremors, and insomnia. Conditions associated with higher levels of thyroid hormones, such as pregnancy or hyperthyroidism, have a higher prevalence of Restless Legs Syndrome symptoms. Low iron levels can cause secondary Restless Legs Syndrome or aggravate symptoms of primary disease as well as diminish enzymatic activities that are involved in dopaminergic agonists production and the degradation of thyroid hormones. Moreover, as a result of low iron levels, dopaminergic agonists diminishes and thyroid hormones increase. Iron therapy improves Restless Legs Syndrome symptoms in iron deprived patients. Medical hypothesis. To discuss the theory that thyroid hormones, when not counterbalanced by dopaminergic agonists, may precipitate the signs and symptoms underpinning Restless Legs Syndrome. The main cause of Restless Legs Syndrome might be an imbalance between the dopaminergic agonists system and thyroid hormones.

  10. Analysis of the correlation between lipotoxicity and pituitary-thyroid axis hormone levels in men and male rats

    PubMed Central

    Yang, Jianmei; Zhou, Xiaoming; Zhang, Xu; Hu, Jianting; Gao, Ling; Song, Yongfeng; Yu, Chunxiao; Shao, Shanshan; Yuan, Zhongshang; Sun, Yan; Yan, Huili; Li, Guimei; Zhao, Jiajun

    2016-01-01

    Lipotoxicity seriously harms human health, but it is unclear whether lipotoxicity is detrimental to the pituitary. We investigated the correlation between serum triglyceride and pituitary axis hormone levels in epidemiological and animal studies. In the epidemiological study, serum thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were greater in male patients with isolated hypertriglyceridemia than in controls, whereas adrenocorticotropin (ACTH) levels were lower in the patients with hypertriglyceridemia. Pituitary hormone levels correlated with triglyceride levels, even after adjustment for potential confounders. In the animal study, male rats were fed a high-fat or control diet for 28 weeks. As the duration of high-fat feeding increased, the serum and pituitary triglyceride concentrations increased. At early times, the high-fat diet elevated serum TSH and triiodothyronine. At later times, much higher serum TSH levels coupled with reduced thyroxine were observed in the high-fat group. Serum levels of pituitary-gonadal and pituitary-adrenal axis hormones were not affected by the diet. The mRNA and protein expression of Tshβ were greater in the high-fat group than in the control group, whereas expression of Fshβ, Lhβ and Acth had no difference between the groups. Overall, serum triglyceride levels were associated with pituitary-thyroid axis hormone levels. PMID:27322428

  11. The influence of organophosphate and carbamate on sperm chromatin and reproductive hormones among pesticide sprayers.

    PubMed

    Jamal, Farrukh; Haque, Quazi S; Singh, Sangram; Rastogi, S K

    2016-08-01

    This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes. © The Author(s) 2015.

  12. Correlation between ovarian morphology and biochemical and hormonal parameters in polycystic ovary syndrome

    PubMed Central

    Inan, Cihan; Karadag, Cihan

    2016-01-01

    Objective: To determine the biochemical and hormonal differences in polycystic ovary syndrome (PCOS) patients with and without polycystic ovary (PCO) morphology and to evaluate the outcomes resulting from those differences. Methods: The study included a total of 83 patients with PCOS; 43 of them had PCO morphology (Group-I) and 40 did not (Group-II). Serum LDL, HDL, total cholesterol, triglyceride (TG), total testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), 17b-estradiol (E2), prolactin (PRL), thyroid stimulating hormone (TSH), sex hormone binding globulin (SHBG), glucose and insulin levels were determined. Homoeostatic model assessment insulin resistance (HOMA-IR) index was calculated. Results: The two groups were similar with respect to BMI. The systolic and diastolic blood pressure measurements of Group-I were significantly lower (p<0.01). Serum mean level of LH (p=0.026) and the mean LH/FSH (p=0.001) level of Group-I were significantly higher than Group-II. The total cholesterol and triglyceride levels of Group-I were significantly lower (p<0.05, p<0.01). The mean HOMA-IR level of Group-I was significantly lower than Group-II (p=0.004). Conclusions: The group without PCO morphology had a higher risk than the other group in terms of increased insulin resistance, dyslipidemia and cardiovascular diseases due to effects of hyperandrogenism. PMID:27375725

  13. Exhaustive exercise and vitamins C and E modulate thyroid hormone levels at low and high altitudes.

    PubMed

    Al-Hashem, Fahaid; Alkhateeb, Mahmoud; Al-Ani, Bahjat; Sakr, Hussein; Khalil, Mohammad

    2012-01-01

    Thyroid hormones play an important role in cell growth and differentiation and regulation of oxygen consumption and thermogenesis. The effect of altitude and vitamin supplementation on thyroid hormone levels in animals or humans performing acute exhaustive exercise have not been investigated before. Therefore, we thought to test whether exhaustive exercise-induced stress with antioxidant supplementation was capable of modulating the level of thyroid hormones at different altitudes. Serum levels of T4 (Thyroxin), T3 (Triiodothyronine), and TSH (Thyroid Stimulating Hormone) were measured in rats (N=36) born and bred in low altitude (600 m above sea level) and high altitude (2200 m above sea level) following forced swimming with or without vitamins C and E (25 mg/kg) pre-treatments. Thyroid levels were significantly decreased in resting rats at high altitude compared to low altitude, and swimming exercise moderately increased T3 and TSH at both high and low altitudes, whereas T4 was markedly increased (62 %) at low altitude compared to a moderate high altitude increase (28 %). Co-administration of vitamins C and E augmented the observed forced swimming-induced thyroid release. However, the conversion of T4 to T3 was reduced in both altitude areas following swimming exercise and vitamin pre-treatment had no effect. We conclude that acute stress induced thyroidal hormones in rats, which was augmented by antioxidant drugs in both high and low altitude areas. These findings may play an important role in the human pathophysiology of thyroid gland at different altitudes.

  14. Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: structural elucidation of the sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

    SciTech Connect

    Green, E.D.; Baenziger, J.U.

    1988-01-05

    The authors have elucidated the structures of the anionic asparagine-linked oligosaccharides present on the glycoprotein hormones lutropin (luteinizing hormone), follitropin (follicle-stimulating hormone), and thyrotropin (thyroid-stimulating hormone). Purified hormones, isolated from bovine, ovine, and human pituitaries, were digested with N-glycanase, and the released oligosaccharides were reduced with NaB(/sup 3/H)/sub 4/. The /sup 3/H-labeled oligosaccharides from each hormone were then fractionated by anion-exchange high performance liquid chromatography (HPLC) into populations differing in the number of sulfate and/or sialic acid moieties. The sulfated, sialylated, and sulfated/sialylated structures, which together comprised 67-90% of the asparagine-linked oligosaccharides on the pituitary glycoprotein hormones, were highly heterogeneous and displayed hormone- as well as animal species-specific features. A previously uncharacterized dibranched oligosaccharide, bearing one residue each of sulfate and sialic acid, was found on all of the hormones except bovine lutropin. In this study, they describe the purification and detailed structural characterizations of the sulfated, sialylated, and sulfated/sialylated oligosaccharides found on lutropin, follitropin, and thyrotropin from several animal species.

  15. Insulin Plant (Costus pictus) Extract Restores Thyroid Hormone Levels in Experimental Hypothyroidism

    PubMed Central

    Ashwini, S.; Bobby, Zachariah; Sridhar, M. G.; Cleetus, C. C.

    2017-01-01

    Background: The aim of the present study was to investigate the preventive effect of Costus pictus leaf extract in experimental hypothyroidism. Materials and Methods: Forty male Wistar rats were randomly divided into four groups with ten rats in each group: Control (C), hypothyroid (H), control+extract (C+E), and hypothyroid+extract (H+E). Rats in C group did not receive any intervention throughout the experimental period. The rats in the C+E and H+E groups received pretreatment with C. pictus leaf extract for 4 weeks. Subsequently, for the next 6 weeks, rats in the H group received 0.05% propylthiouracil in drinking water while C+E group received C. pictus leaf extract and H+E group received propyl thiouracil and C. pictus leaf extract. Results: Hypothyroid group rats exhibited dramatic increase in thyroid-stimulating hormone (TSH) levels with concomitant depletion in the levels of thyroid hormones. Treatment with the extract resulted in remarkable improvement in thyroid profile. Extract produced 10.59-fold increase in plasma free T3, 8.65-fold increase in free T4, and 3.59-fold decrease in TSH levels in H+E group in comparison with H group. Treatment with the extract ameliorated hypercholesterolemia, decreased levels of plasma C-reactive protein and tumor necrosis factor alpha, suppressed tissue oxidative stress and prevented hepatic and renal damage caused due to thyroid hormone depletion in the H+E group. Pentacyclic triterpenes alpha and beta amyrins were identified and quantified in the extract. Conclusions: This is the first study to reveal that C. pictus extract has therapeutic potential to restore thyroid hormone levels and prevent the biochemical complications due to thyroid hormone insufficiency in the animal model of experimental hypothyroidism. SUMMARY The preventive effect of Costus pictus leaf extract in experimental hypothyroidism was evaluated in the present study.Hypothyroidism was induced in the experimental animals by giving 0

  16. [Neonatal hyperthyroidism and maternal Graves disease].

    PubMed

    Ben Ameur, K; Chioukh, F Z; Marmouch, H; Ben Hamida, H; Bizid, M; Monastiri, K

    2015-04-01

    The onset of Graves disease during pregnancy exposes the neonate to the risk of hyperthyroidism. The newborn must be monitored and treatment modalities known to ensure early treatment of the newborn. We report on the case of an infant born at term of a mother with Graves disease discovered during pregnancy. He was asymptomatic during the first days of life, before declaring the disease. Neonatal hyperthyroidism was confirmed by hormonal assays. Hyperthyroidism was treated with antithyroid drugs and propranolol with a satisfactory clinical and biological course. Neonatal hyperthyroidism should be systematically sought in infants born to a mother with Graves disease. The absence of clinical signs during the first days of life does not exclude the diagnosis. The duration of monitoring should be decided according to the results of the first hormonal balance tests. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  17. Perfluoroalkyl substances and thyroid hormones in cord blood.

    PubMed

    Tsai, Meng-Shan; Lin, Ching-Chun; Chen, Mei-Huei; Hsieh, Wu-Shiun; Chen, Pau-Chung

    2017-03-01

    Perfluoroalkyl substances (PFASs) are pollutants that tend to accumulate in the environment and organisms. The animal and human studies to date have focused on thyroid function, but the results are inconsistent. A sample of 118 mother-infant pairs was obtained from the Taiwan Birth Panel Study (TBPS). Cord blood PFASs levels were evaluated using the Waters ACQUITY UPLC system coupled with a Waters Quattro Premier XE triple quadrupole mass spectrometer, and cord blood thyroid hormones were assessed using a Roche Analytics E170 modular analyser (Roche Diagnostics, Mannheim, Germany). PFASs concentrations were analysed in the final models to examine the associations between cord blood PFASs levels and thyroid hormone concentrations. The cord blood perfluorooctane sulfonate (PFOS) concentration was negatively associated with the cord blood thyroxine (T4) concentration [per ln unit: adjusted β (95% confidence interval, CI) = -0.458(-0.916, -0.001)]. Moreover, the level of cord blood thyroid stimulating hormone (TSH) was positively associated with the cord blood PFOS concentration [per ln unit: adjusted β (95% confidence interval, CI) = 0.346(0.101, 0.592)]. The sex stratified effects of PFOS on T4 were suggestive of differential effects in high-exposure groups compared with low-exposure group in boys. We found that cord blood thyroid hormone levels are affected by PFASs, with a negative association between T4 and PFOS and a positive association between TSH and PFOS. The causal associations of thyroid hormones and PFASs require further exploration. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Impairing follicle-stimulating hormone (FSH) signaling in vivo: targeted disruption of the FSH receptor leads to aberrant gametogenesis and hormonal imbalance.

    PubMed

    Dierich, A; Sairam, M R; Monaco, L; Fimia, G M; Gansmuller, A; LeMeur, M; Sassone-Corsi, P

    1998-11-10

    Pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone stimulate the gonads by regulating germ cell proliferation and differentiation. FSH receptors (FSH-Rs) are localized to testicular Sertoli cells and ovarian granulosa cells and are coupled to activation of the adenylyl cyclase and other signaling pathways. Activation of FSH-Rs is considered essential for folliculogenesis in the female and spermatogenesis in the male. We have generated mice lacking FSH-R by homologous recombination. FSH-R-deficient males are fertile but display small testes and partial spermatogenic failure. Thus, although FSH signaling is not essential for initiating spermatogenesis, it appears to be required for adequate viability and motility of the sperms. FSH-R-deficient females display thin uteri and small ovaries and are sterile because of a block in folliculogenesis before antral follicle formation. Although the expression of marker genes is only moderately altered in FSH-R -/- mice, drastic sex-specific changes are observed in the levels of various hormones. The anterior lobe of the pituitary gland in females is enlarged and reveals a larger number of FSH- and thyroid-stimulating hormone (TSH)-positive cells. The phenotype of FSH-R -/- mice is reminiscent of human hypergonadotropic ovarian dysgenesis and infertility.

  19. Prader-Willi syndrome and growth hormone deficiency.

    PubMed

    Aycan, Zehra; Baş, Veysel Nijat

    2014-01-01

    Prader-Willi syndrome (PWS) is a rare multisystem genetic disorder demonstrating great variability with changing clinical features during patient's life. It is characterized by severe hypotonia with poor sucking and feeding difficulties in early infancy, followed by excessive eating and gradual development of morbid obesity in later infancy or early childhood. The phenotype is most probably due to hypothalamic dysfunction which is also responsible for growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies, central adrenal insufficiency and hypogonadism. The multidimensional problems of patients with PWS can be managed with multidisciplinary approach. Reduced GH secretion, low peak GH response to stimulation, decreased spontaneous GH secretion and low serum IGF-1 levels in PWS patients have been documented in many studies. GH therapy has multiple beneficial effects on growth and body composition, motor and mental development in PWS patients. The recommended dosage for GH is 0.5-1 mg/m2/day. GH therapy should not be started in the presence of obstructive sleep apnea syndrome, adenotonsillar hypertrophy, severe obesity and diabetes mellitus. GH treatment should be considered for patients with genetically confirmed PWS in conjunction with dietary, environmental and life-style measures.

  20. Adverse effects of thyroid hormone preparations and antithyroid drugs.

    PubMed

    Bartalena, L; Bogazzi, F; Martino, E

    1996-07-01

    Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.

  1. Neonatal hemochromatosis.

    PubMed

    Feldman, Amy G; Whitington, Peter F

    2013-12-01

    Neonatal hemochromatosis is a clinical condition in which severe liver disease in the newborn is accompanied by extrahepatic siderosis. Gestational alloimmune liver disease (GALD) has been established as the cause of fetal liver injury resulting in nearly all cases of NH. In GALD, a women is exposed to a fetal antigen that she does not recognize as "self" and subsequently begins to produce IgG antibodies that are directed against fetal hepatocytes. These antibodies bind to fetal liver antigen and activate the terminal complement cascade resulting in hepatocyte injury and death. GALD can cause congenital cirrhosis or acute liver failure with and without iron overload and siderosis. Practitioners should consider GALD in cases of fetal demise, stillbirth, and neonatal acute liver failure. Identification of infants with GALD is important as treatment is available and effective for subsequent pregnancies.

  2. [Neonatal intussusception].

    PubMed

    Cuervo, J L

    2015-01-13

    Intussusception in infants and young children is a relatively common entity with a well defined clinical picture and a favorable outcome in most cases.The neonatal intussusceptions is extremely rare and does not have a well-defined clinical picture since its clinical manifestations vary according to the gestational time it occurs, the response of the injured intestine and the gestational age of the child concerned. Two new cases of neonatal intussusceptions are presented and a review of the world literature is performed. Given the stage of intussusceptions (pre- or postnatal) occurs and gestational age of the affected infant (preterm or term), there are three entities with clinical characteristics, topography and evolution rather different: prenatal or intrauterine intussusception, postnatal intussusception in the preterm and postnatal intussusception in the term infant.

  3. Effect of hypothyroidism on female reproductive hormones

    PubMed Central

    Saran, Sanjay; Gupta, Bharti Sona; Philip, Rajeev; Singh, Kumar Sanjeev; Bende, Sureshrao Anoop; Agroiya, Puspalata; Agrawal, Pankaj

    2016-01-01

    Objective: Objective was to evaluate reproductive hormones levels in hypothyroid women and impact of treatment on their levels. Materials and Methods: A total of 59 women with untreated primary hypothyroidism were included in this prospective study. Venous blood was taken at baseline and after euthyroidism was achieved for measuring serum free thyroxine, free triiodothyronine (FT3), thyroid stimulating hormone (TSH), prolactin (PRL), follicular stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), testosterone (T), and thyroid peroxidase antibody. Thirty-nine healthy women with regular menstrual cycles without any hormonal disturbances served as controls. The statistical analysis was performed using the Statistical Package for the Social Sciences Version 20 ([SPSS] IBM Corporation, Armonk, NY, USA). P < 0.05 was considered statistically significant. Results: On an average at diagnosis cases have more serum TSH (mean [M] = 77.85; standard error [SE] = 11.72), PRL (M = 39.65; SE = 4.13) and less serum E2 (M = 50.00; SE = 2.25) and T (M = 35.40; SE = 2.31) than after achieving euthyroidism (M = 1.74; SE = 0.73), (M = 16.04; SE = 0.84), (M = 76.25; SE = 2.60), and (M = 40.29; SE = 2.27), respectively. This difference was statistically significant t (58) = 6.48, P <0.05; t (58) = 6.49, P < 0.05; t (58) = 12.47; P < 0.05; and t (58) = 2.04, P < 0.05; respectively. Although average serum FSH (M = 12.14; SE = 0.40) and LH (M = 5.89; SE = 0.27) were lower in cases at diagnosis than after achieving euthyroidism (M = 12.70; SE = 0.40), (M = 6.22; SE = 0.25), respectively, but these differences were statistically insignificant t (58) = 1.61, P = 0.11; t (58) = 1.11, P = 0.27, respectively. Conclusion: The study has demonstrated low E2 and T levels in hypothyroid women which were increased after achieving euthyroidism. Although average serum FSH and LH were increased in hypothyroid women after achieving euthyroidism but this difference was statistically

  4. Hormonal Programming Across the Lifespan

    PubMed Central

    Tobet, Stuart A; Lara, Hernan E; Lucion, Aldo B; Wilson, Melinda E; Recabarren, Sergio E; Paredes, Alfonso H

    2013-01-01

    Hormones influence countless biological processes across the lifespan, and during developmental sensitive periods hormones have the potential to cause permanent tissue-specific alterations in anatomy and physiology. There are numerous critical periods in development wherein different targets are affected. This review outlines the proceedings of the Hormonal Programming in Development session at the US-South American Workshop in Neuroendocrinology in August 2011. Here we discuss how gonadal hormones impact various biological processes within the brain and gonads during early development and describe the changes that take place in the aging female ovary. At the cellular level, hormonal targets in the brain include neurons, glia, or vasculature. On a genomic/epigenomic level, transcription factor signaling and epigenetic changes alter the expression of hormone receptor genes across development and following ischemic brain insult. In addition, organizational hormone exposure alters epigenetic processes in specific brain nuclei and may be a mediator of sexual differentiation of the neonatal brain. During development of the ovary, exposure to excess gonadal hormones leads to polycystic ovarian syndrome (PCOS). Exposure to excess androgens during fetal development also has a profound effect on the development of the male reproductive system. In addition, increased sympathetic nerve activity and stress during early life have been linked to PCOS symptomology in adulthood. Finally, we describe how age-related decreases in fertility are linked to high levels of nerve growth factor (NGF), which enhances sympathetic nerve activity and alters ovarian function. PMID:22700441

  5. Effects of oral chlortetracycline and dietary protein level on plasma concentrations of growth hormone and thyroid hormones in beef steers before and after challenge with a combination of thyrotropin-releasing hormone and growth hormone-releasing hormone.

    PubMed

    Rumsey, T S; McLeod, K; Elsasser, T H; Kahl, S; Baldwin, R L

    1999-08-01

    The objective of this study was to determine the effect of a subtherapeutic level of chlortetracycline (CTC) fed to growing beef steers under conditions of limited and adequate dietary protein on plasma concentrations of GH, thyroid-stimulating hormone (TSH), and thyroid hormones before and after an injection of thyrotropin-releasing hormone (TRH) + GHRH. Young beef steers (n = 32; average BW = 285 kg) were assigned to a 2x2 factorial arrangement of treatments of either a 10 or 13% crude protein diet (70% concentrate, 15% wheat straw, and 15% cottonseed hulls) and either a corn meal carrier or carrier + 350 mg of CTC daily top dressed on the diet. Steers were fed ad libitum amounts of diet for 56 d, and a jugular catheter was then placed in each steer in four groups (two steers from each treatment combination per group) during four consecutive days (one group per day). Each steer was injected via the jugular catheter with 1.0 microg/kg BW TRH + .1 microg/kg BW GHRH in 10 mL of saline at 0800. Blood samples were collected at -30, -15, 0, 5, 10, 15, 20, 30, 45, 60, 120, 240, and 360 min after releasing hormone injection. Plasma samples were analyzed for GH, TSH, thyroxine (T4), and triiodothyronine (T3). After 84 d on trial, the steers were slaughtered and the pituitary and samples of liver were collected and analyzed for 5'-deiodinase activity. Feeding CTC attenuated the GH response to releasing hormone challenge by 26% for both area under the response curve (P<.03) and peak response (P<.10). Likewise, CTC attenuated the TSH response to releasing hormone challenge for area under the response curve by 16% (P<.10) and peak response by 33% (P<.02), and attenuated the T4 response for area under the curve by 12% (P<.08) and peak response by 14% (P<.04). Type II deiodinase activity in the pituitary was 36% less (P<.02) in CTC-fed steers than in steers not fed CTC. The results of this study are interpreted to suggest that feeding subtherapeutic levels of CTC to young

  6. Hormone Therapy

    MedlinePlus

    ... of estrogen , a hormone that helps control the menstrual cycle . Changing estrogen levels can bring on symptoms such ... of two hormones—estrogen and progesterone —control your menstrual cycle. These hormones are made by the ovaries . Estrogen ...

  7. High-Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior Pituitary Basophilic Cells.

    PubMed

    Yang, J; Zhang, X; Liu, Z; Yuan, Z; Song, Y; Shao, S; Zhou, X; Yan, H; Guan, Q; Gao, L; Zhang, H; Zhao, J

    2016-03-01

    Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.

  8. Liver X receptor β: new player in the regulatory network of thyroid hormone and 'browning' of white fat.

    PubMed

    Miao, Yifei; Warner, Margaret; Gustafsson, Jan-Ke

    2016-01-01

    The recent discovery of browning of white adipose tissue (WAT) has raised great research interest because of its significant potential in counteracting obesity and type II diabetes. However, the mechanisms underlying browning are still poorly understood. Liver X receptors (LXRs) are one class of nuclear receptors, which play a vital role in regulating cholesterol, triglyceride and glucose metabolism. Following our previous finding that LXRs serve as repressors of UCP1 in classic brown adipose tissue in female mice, we found that LXRs, especially LXRβ, also repress the browning process of subcutaneous adipose tissue (SAT) in male rodents fed a normal diet. Depletion of LXRs activated thyrotropin releasing hormone positive neurons in the paraventricular area of the hypothalamus, and thus stimulated secretion of thyroid-stimulating hormone from the pituitary. Consequently production of thyroid hormones in the thyroid gland and circulating thyroid hormone level were increased. Moreover, the activity of thyroid signaling in SAT was markedly increased. One unexpected finding of our study is that LXRs are indispensable in the thyroid hormone negative feedback loop at the level of the hypothalamus. LXRs maintain expression of thyroid receptors in the brain and when they are inactivated there is no negative feedback of thyroid hormone in the hypothalamus. Together, our findings have uncovered the basis of increased energy expenditure in male LXR knock-out mice and provided support for targeting LXRs in treatment of obesity.

  9. Association of obesity with hormonal imbalance in infertility: a cross-sectional study in north Indian women.

    PubMed

    Seth, Bhavna; Arora, Sarika; Singh, Ritu

    2013-10-01

    Hormones play an important role in the development and regulation of reproductive function and the menstrual cycle of women. Extremes of body weight tend to affect the homeostasis of the hypothalamo-pituitary-gonadal axis. This cross-sectional study was carried out in 113 women (57 with primary infertility and 56 with secondary infertility) in the age group 20-35 years, presenting for hormonal evaluation of infertility in a tertiary care hospital. After preliminary clinical evaluation, anthropometric indices (height, weight, BMI, waist circumference and waist hip ratio) were measured in all subjects. Fasting blood sample drawn on second/third day of menstrual cycle was analysed for serum luteinizing hormone, follicle stimulating hormone (FSH), prolactin and thyroid stimulating hormone (TSH). Serum FSH levels showed a significant positive correlation with indicators of central obesity (waist circumference and waist hip ratio in both the study groups). In primary infertility, significant positive correlation was also observed between serum FSH levels and other markers of obesity like body weight, hip circumference and BMI. In secondary infertility, serum prolactin and serum TSH levels demonstrated a significant positive correlation with body weight and BMI. Obesity is associated with hormonal derangements which are responsible for infertility. In overweight women with infertility, weight loss should be considered as a first line treatment.

  10. Thyroid Hormone Indices in Computer Workers with Emphasis on the Role of Zinc Supplementation

    PubMed Central

    Amin, Ahmed Ibrahim; Hegazy, Noha Mohamed; Ibrahim, Khadiga Salah; Mahdy-Abdallah, Heba; Hammouda, Hamdy A. A.; Shaban, Eman Essam

    2016-01-01

    AIM: This study aimed to investigate the effects of computer monitor-emitted radiation on thyroid hormones and the possible protective role of zinc supplementation. MATERIAL AND METHODS: The study included three groups. The first group (group B) consisted of 42 computer workers. This group was given Zinc supplementation in the form of one tablet daily for eight weeks. The second group (group A) comprised the same 42 computer workers after zinc supplementation. A group of 63 subjects whose job does not entail computer use was recruited as a control Group (Group C). All participants filled a questionnaire including detailed medical and occupational histories. They were subjected to full clinical examination. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4) and zinc levels were measured in all participants. RESULTS: TSH, FT3, FT4 and zinc concentrations were decreased significantly in group B relative to group C. In group A, all tested parameters were improved when compared with group B. The obtained results revealed that radiation emitted from computers led to changes in TSH and thyroid hormones (FT3 and FT4) in the workers. CONCLUSION: Improvement after supplementation suggests that zinc can ameliorate hazards of such radiation on thyroid hormone indices. PMID:27335605

  11. Placental Transfer of Perfluoroalkyl Substances and Associations with Thyroid Hormones: Beijing Prenatal Exposure Study

    PubMed Central

    Yang, Lin; Li, Jingguang; Lai, Jianqiang; Luan, Hemi; Cai, Zongwei; Wang, Yibaina; Zhao, Yunfeng; Wu, Yongning

    2016-01-01

    Perfluoroalkyl substances (PFASs) have been detected in wildlife and human samples worldwide. Toxicology research showed that PFASs could interfere with thyroid hormone homeostasis. In this study, eight PFASs, fifteen PFAS precursors and five thyroid hormones were analyzed in 157 paired maternal and cord serum samples collected in Beijing around delivery. Seven PFASs and two precursors were detected in both maternal and cord sera with significant maternal-fetal correlations (r = 0.336 to 0.806, all P < 0.001). The median ratios of major PFASs concentrations in fetal versus maternal serum were from 0.25:1 (perfluorodecanoic acid, PFDA) to 0.65:1 (perfluorooctanoic acid, PFOA). Spearman partial correlation test showed that maternal thyroid stimulating hormone (TSH) was negatively correlated with most maternal PFASs (r = −0.261 to −0.170, all P < 0.05). Maternal triiodothyronin (T3) and free T3 (FT3) showed negative correlations with most fetal PFASs (r = −0.229 to −0.165 for T3; r = −0.293 to −0.169 for FT3, all P < 0.05). Our results suggest prenatal exposure of fetus to PFASs and potential associations between PFASs and thyroid hormone homeostasis in humans. PMID:26898235

  12. Frequency of mutations in PROP-1 gene in Turkish children with combined pituitary hormone deficiency.

    PubMed

    Kandemir, Nurgün; Vurallı, Doğuş; Taşkıran, Ekim; Gönç, Nazlı; Özön, Alev; Alikaşifoğlu, Ayfer; Yılmaz, Engin

    2012-01-01

    Mutations in the prophet of Pit-1 (PROP-1) gene are responsible for most of the cases of combined pituitary hormone deficiencies (CPHD). We performed this study to determine the prevalence of PROP-1 mutations in a group of Turkish children with CPHD. Fifty-three children with the diagnosis of CPHD were included in this study. Clinical data were obtained from medical files, and hormonal evaluation and genetic screening for PROP-1 mutations were performed. A homozygous S109X mutation was found in the second exon in two brothers, and they had growth hormone (GH) and thyroid-stimulating hormone (TSH) deficiencies and normal prolactin levels. In the third exon of the PROP-1 gene, a heterozygous A142T polymorphism was found in 14 patients and a homozygous A142T polymorphism was found in 3 patients. In the first exon, a homozygous A9A polymorphism was found in 7 patients and a heterozygous A9A polymorphism was found in 31 patients. We assumed that mutations in the PROP-1 gene in cases with CPHD were expected to be more prevalent in our population due to consanguinity, but it was found that these mutations were far less than expected and that it was rare in non-familial cases.

  13. Effects of thyroid hormone on serum glycated albumin levels: study on non-diabetic subjects.

    PubMed

    Koga, M; Murai, J; Saito, H; Matsumoto, S; Kasayama, S

    2009-05-01

    Glycated albumin (GA) is used alongside glycated hemoglobin (HbA(1C)) as an indicator of glycemic control. Although serum GA levels are affected mainly by plasma glucose, they are also influenced by serum albumin metabolism. Thyroid hormone is known to promote albumin catabolism, and it is thus thought to affect serum GA levels. In the present study, the effects of thyroid hormone on serum GA measurements were investigated in patients with thyroid dysfunction. Six patients with untreated hypothyroidism and 17 patients with untreated thyrotoxicosis were investigated. Patients who had anemia or diabetes were excluded. A total of 25 non-diabetic, euthyroid individuals were enrolled as controls. HbA(1C), serum GA, thyroid-stimulating hormone (TSH), free triiodothyronine (T(3)), and free thyroxine (T(4)) levels were measured in all these subjects, and their relationships were examined. Although no intergroup differences were observed for HbA(1C), serum GA was significantly higher among patients with hypothyroidism than controls, and significantly lower among patients with thyrotoxicosis. Serum GA had a significant positive correlation with serum TSH and significant inverse correlations with free T(3) and free T(4). Thyroid hormone levels are inversely associated with serum GA levels. Cautions are necessary when evaluating serum GA levels in patients with thyroid dysfunction.

  14. The heterochronic gene Lin28 regulates amphibian metamorphosis through disturbance of thyroid hormone function.

    PubMed

    Faunes, Fernando; Gundermann, Daniel G; Muñoz, Rosana; Bruno, Renzo; Larraín, Juan

    2017-05-15

    Metamorphosis is a classic example of developmental transition, which involves important morphological and physiological changes that prepare the organism for the adult life. It has been very well established that amphibian metamorphosis is mainly controlled by Thyroid Hormone (TH). Here, we show that the heterochronic gene Lin28 is downregulated during Xenopus laevis metamorphosis. Lin28 overexpression before activation of TH signaling delays metamorphosis and inhibits the expression of TH target genes. The delay in metamorphosis is rescued by incubation with exogenous TH, indicating that Lin28 works upstream or parallel to TH. High-throughput analyses performed before any delay on metamorphosis or change in TH signaling showed that overexpression of Lin28 reduces transcript levels of several hormones secreted by the pituitary, including the Thyroid-Stimulating Hormone (TSH), and regulates the expression of proteins involved in TH transport, metabolism and signaling, showing that Lin28 disrupts TH function at different levels. Our data demonstrates that the role of Lin28 in controlling developmental transitions is evolutionary conserved and establishes a functional interaction between Lin28 and thyroid hormone function introducing a new regulatory step in perinatal development with implications for our understanding of endocrine disorders. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. The Effect of Central Injection of Ghrelin and Bombesin on Mean Plasma Thyroid Hormones Concentration

    PubMed Central

    Mahmoudi, Fariba; Mohsennezhad, Fatemeh; Khazali, Homayoun; Ehtesham, Haleh

    2011-01-01

    Ghrelin increases food intakes and body weight. Bombesin decreases food intakes and inhibits the stimulatory effect of Ghrelin on food intakes. Thyroid hormones have a crucial role in the regulation of body weight and yet the effect of bombesin on thyroid axis activity is not fully clear. Therefore, the goal of this study was to determine the effect of different doses of Ghrelin or bombesin on mean plasma thyroid-stimulating hormone (TSH), Triiodothyronine (T3) and Thyroxin (T4) concentration and also, the effect of interaction between Ghrelin and bombesin on thyroid axis activity. Forty-nine rats in seven groups received saline or different doses of Ghrelin (4, 10 or 15 nmol) and bombesin ( 2.5, 5 or 10 nmol) and forty-two rats in six groups received simultaneous injection of Ghrelin (10 or 15 nmol) and different doses of bombesin (2.5, 5 or 10 nmol) via lateral cerebral ventricle. Blood samples were collected via decapitation 20 min after the injection and plasma was assayed for plasma TSH, T3 and T4 concentration by Radioimmunoassay (RIA). Ghrelin significantly decreased the concentration of mean plasma thyroid hormones compared to saline. Bombesin did not significantly increase thyroid hormones concentration compared to saline but bombesin blocked the inhibitory effect of Ghrelin on thyroid axis activity. Bombesin may be the antagonist of Ghrelin action. PMID:24250396

  16. Placental Transfer of Perfluoroalkyl Substances and Associations with Thyroid Hormones: Beijing Prenatal Exposure Study

    NASA Astrophysics Data System (ADS)

    Yang, Lin; Li, Jingguang; Lai, Jianqiang; Luan, Hemi; Cai, Zongwei; Wang, Yibaina; Zhao, Yunfeng; Wu, Yongning

    2016-02-01

    Perfluoroalkyl substances (PFASs) have been detected in wildlife and human samples worldwide. Toxicology research showed that PFASs could interfere with thyroid hormone homeostasis. In this study, eight PFASs, fifteen PFAS precursors and five thyroid hormones were analyzed in 157 paired maternal and cord serum samples collected in Beijing around delivery. Seven PFASs and two precursors were detected in both maternal and cord sera with significant maternal-fetal correlations (r = 0.336 to 0.806, all P < 0.001). The median ratios of major PFASs concentrations in fetal versus maternal serum were from 0.25:1 (perfluorodecanoic acid, PFDA) to 0.65:1 (perfluorooctanoic acid, PFOA). Spearman partial correlation test showed that maternal thyroid stimulating hormone (TSH) was negatively correlated with most maternal PFASs (r = -0.261 to -0.170, all P < 0.05). Maternal triiodothyronin (T3) and free T3 (FT3) showed negative correlations with most fetal PFASs (r = -0.229 to -0.165 for T3; r = -0.293 to -0.169 for FT3, all P < 0.05). Our results suggest prenatal exposure of fetus to PFASs and potential associations between PFASs and thyroid hormone homeostasis in humans.

  17. Role of thyrotropin-releasing hormone in prolactin-producing cell models.

    PubMed

    Kanasaki, Haruhiko; Oride, Aki; Mijiddorj, Tselmeg; Kyo, Satoru

    2015-12-01

    Thyrotropin-releasing hormone (TRH) is a hypothalamic hypophysiotropic neuropeptide that was named for its ability to stimulate the release of thyroid-stimulating hormone in mammals. It later became apparent that it exerts a number of species-dependent hypophysiotropic activities that regulate other pituitary hormones. TRH also regulates the synthesis and release of prolactin, although whether it is a physiological regulator of prolactin that remains unclear. Occupation of the Gq protein-coupled TRH receptor in the prolactin-producing lactotroph increases the turnover of inositol, which in turn activates the protein kinase C pathway and the release of Ca(2+) from storage sites. TRH-induced signaling events also include the activation of extracellular signal-regulated kinase (ERK) and induction of MAP kinase phosphatase, an inactivator of activated ERK. TRH stimulates prolactin synthesis through the activation of ERK, whereas prolactin release occurs via elevation of intracellular Ca(2+). We have been investigating the role of TRH in a pituitary prolactin-producing cell model. Rat pituitary somatolactotroph GH3 cells, which produce and release both prolactin and growth hormone (GH), are widely used as a model for the study of prolactin- and GH-secreting cells. In this review, we describe the general action of TRH as a hypophysiotropic factor in vertebrates and focus on the role of TRH in prolactin synthesis using GH3 cells.

  18. 42 CFR 493.933 - Endocrinology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... categorized as waived tests) T3 Uptake Triiodothyronine Thyroid-stimulating hormone Thyroxine (c) Evaluation.... Triiodothyronine Target value ±3 SD. Thyroid-stimulating hormone Target value ±3 SD. Thyroxine Target value ±20%...

  19. 42 CFR 493.933 - Endocrinology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... categorized as waived tests) T3 Uptake Triiodothyronine Thyroid-stimulating hormone Thyroxine (c) Evaluation.... Triiodothyronine Target value ±3 SD. Thyroid-stimulating hormone Target value ±3 SD. Thyroxine Target value ±20%...

  20. 42 CFR 493.933 - Endocrinology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... categorized as waived tests) T3 Uptake Triiodothyronine Thyroid-stimulating hormone Thyroxine (c) Evaluation.... Triiodothyronine Target value ±3 SD. Thyroid-stimulating hormone Target value ±3 SD. Thyroxine Target value ±20%...

  1. 42 CFR 493.933 - Endocrinology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... categorized as waived tests) T3 Uptake Triiodothyronine Thyroid-stimulating hormone Thyroxine (c) Evaluation.... Triiodothyronine Target value ±3 SD. Thyroid-stimulating hormone Target value ±3 SD. Thyroxine Target value ±20%...

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

    SciTech Connect

    Romano, Megan E.; Webster, Glenys M.; Vuong, Ann M.; Thomas Zoeller, R.; Chen, Aimin; Hoofnagle, Andrew N.; Calafat, Antonia M.; Karagas, Margaret R.; Yolton, Kimberly; Lanphear, Bruce P.; Braun, Joseph M.

    2015-04-15

    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

  3. Bioidentical Hormones and Menopause

    MedlinePlus

    ... Center Pacientes y Cuidadores Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ... Learn About Clinical Trials Hormones and Health The Endocrine System Hormones Endocrine Disrupting Chemicals (EDCs) Steroid and Hormone ...

  4. Hormones and Obesity

    MedlinePlus

    ... Chemicals (EDCs) Endocrine Glands and Types of Hormones Brainy Hormones What Do Hormones Do? Infographics Myth vs ... Chemicals (EDCs) Endocrine Glands and Types of Hormones Brainy Hormones What Do Hormones Do? Infographics Myth vs ...

  5. Polychlorinated biphenyl exposure, diabetes and endogenous hormones: a cross-sectional study in men previously employed at a capacitor manufacturing plant

    PubMed Central

    2012-01-01

    Background Studies have shown associations of diabetes and endogenous hormones with exposure to a wide variety of organochlorines. We have previously reported positive associations of polychlorinated biphenyls (PCBs) and inverse associations of selected steroid hormones with diabetes in postmenopausal women previously employed in a capacitor manufacturing plant. Methods This paper examines associations of PCBs with diabetes and endogenous hormones in 63 men previously employed at the same plant who in 1996 underwent surveys of their exposure and medical history and collection of bloods and urine for measurements of PCBs, lipids, liver function, hematologic markers and endogenous hormones. Results PCB exposure was positively associated with diabetes and age and inversely associated with thyroid stimulating hormone and triiodothyronine-uptake. History of diabetes was significantly related to total PCBs and all PCB functional groupings, but not to quarters worked and job score, after control for potential confounders. None of the exposures were related to insulin resistance (HOMA-IR) in non-diabetic men. Conclusions Associations of PCBs with specific endogenous hormones differ in some respects from previous findings in postmenopausal women employed at the capacitor plant. Results from this study, however, do confirm previous reports relating PCB exposure to diabetes and suggest that these associations are not mediated by measured endogenous hormones. PMID:22931295

  6. Polychlorinated biphenyl exposure, diabetes and endogenous hormones: a cross-sectional study in men previously employed at a capacitor manufacturing plant.

    PubMed

    Persky, Victoria; Piorkowski, Julie; Turyk, Mary; Freels, Sally; Chatterton, Robert; Dimos, John; Bradlow, H Leon; Chary, Lin Kaatz; Burse, Virlyn; Unterman, Terry; Sepkovic, Daniel W; McCann, Kenneth

    2012-08-29

    Studies have shown associations of diabetes and endogenous hormones with exposure to a wide variety of organochlorines. We have previously reported positive associations of polychlorinated biphenyls (PCBs) and inverse associations of selected steroid hormones with diabetes in postmenopausal women previously employed in a capacitor manufacturing plant. This paper examines associations of PCBs with diabetes and endogenous hormones in 63 men previously employed at the same plant who in 1996 underwent surveys of their exposure and medical history and collection of bloods and urine for measurements of PCBs, lipids, liver function, hematologic markers and endogenous hormones. PCB exposure was positively associated with diabetes and age and inversely associated with thyroid stimulating hormone and triiodothyronine-uptake. History of diabetes was significantly related to total PCBs and all PCB functional groupings, but not to quarters worked and job score, after control for potential confounders. None of the exposures were related to insulin resistance (HOMA-IR) in non-diabetic men. Associations of PCBs with specific endogenous hormones differ in some respects from previous findings in postmenopausal women employed at the capa