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Student Number : 9600048X - MSc (Med) research report - Faculty of Health Sciences / Disorders of the thyroid gland are amongst the most common endocrine disorders. The diagnosis of thyroid disease consists of a history and clinical examination, followed by specific confirmatory investigations. These investigations are an important diagnostic component in thyroid disease and are amongst the most common investigations ordered in clinical laboratories. Although these tests are relatively inexpensive individually, they account for a disproportionately large amount of health care expenditure for diagnostic testing. Appropriate laboratory investigation is critical to establish the diagnosis and cause of thyroid disease in the most costeffective way. Discovery Health released a set of evidence-based guidelines in order to educate the clinician with regard to the selection of thyroid function tests. According to these guidelines a TSH (Thyroid Stimulating Hormone) test is the investigation of choice in suspected thyroid disease. This study is a retrospective investigation that compares the difference in ordering patterns of laboratory investigations by clinicians before and after the publication of the guidelines. Two data sets were generated from the data bank of Discovery Health. The first data set (I) was based on records compiled before March 2003 whereas the second data set (II) was based on records compiled from April 2003. Following use of the exclusion and inclusion criteria the sample size totaled 73 850 cases. An analysis was made with regard to the requesting frequency of specific tests. This study will focus solely on the appropriateness of thyroid function tests ordered. It is beyond the scope of this study to attach a specific clinical diagnosis to the results. The thyroid function tests requested before the publication of the evidence-based guidelines were often requested without careful thought and consideration on the part of the clinician. Some of the combination tests ordered (Free T3 and Free T4) are not advocated as an initial investigation in the evaluation of thyroid function and waste funds in this instance. The ordering of inappropriate thyroid function tests often leads to the depletion of funds available to a patient within the financial year. The results revealed that after publication of the guidelines there was an increase in the requesting frequency of TSH as a first line investigation, as well as Free T4 while a decrease in requests for Free T3 was noted. The publication of evidence-based guidelines as a guide to requesting the correct thyroid function tests in order to diagnose suspected thyroid disease appears to have impacted in increasing awareness amongst clinicians with regard to the tests required to diagnose and monitor thyroid disease.

Thyroid hormones are well known important to be in development and growth in birds and that signaling of thyrotropin (TSH) regulates the photo induced seasonal reproduction. A mutation at the thyroid stimulating hormone receptor (TSHR) gene in domestic breeds of chicken could be involved in the release of the photoperiodic regulation. Furthermore, TSH can affect a wide range of domestication related phenotypes, such as behaviour, growth rate and pigmentation. The aim of this study was to investigate the behaviours expressed in the different genotypes on the TSHR gene in chickens. Four standard tests were conducted, aerial predator, fear of human, social dominance and tonic immobility. An advanced intercross line of chickens between red junglefowl and White leghorn was used. Male domestic type chickens explored more, showed more less fear behaviours and showed least fear behaviours in the fear of human test. Increased activity and flight response has been interpreted as a lower fear response, which is in line with this study. The wild type chickens showed more social dominance than domestic type chickens which are in line with previous results. In tonic immobility there was a difference between the wild type male and heterozygous male chickens in latency until first head movement. The conclusion of this study is that there is a difference between the wild type and domestic type chickens. This indicates that the TSHR gene is involved in behavioural changes during domestication, but whether it is due to passive or active selection is the question.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

It has been shown that thyroid hormones are important in development and growth in birds and further that thyrotropin (TSH) signaling regulated photoinduced seasonal reproduction. In addition to controlling the development of certain physiological traits, TSH can affect a wide range of phenotypes related to domestication such as behaviour, growth rate, more frequent reproductive cycle’s, pigmentation and also behaviour. Studies indicate that thyroid hormone physiology could potentially be responsible for differences in individual stress response as well as differences in social dominance. This project investigated behaviours expressed in the different genotypes on the Thyroid stimulating hormone receptor (TSHR) gene in chickens. Standard test such as Fear of human, Aerial predator, Tonic immobility and Social hierarchy were carried out with White leghorn (WL) as a domesticated species and Red Junglefowl (Rjf) as their wild counterpart; these were considered to be the control group. There was no significant result on genotype effect for the TSHR animals observed in those variables tested. The TSHR mutants were expected to mirror the White leghorn behavioural response and the TSHR wildtype the behaviour of Rjf. This was however not confirmed. There were a significant interaction between genotype effect and sex effect for TSHR for stand alert in the Aerial predator test which mirrored the results seen in the control groups. The male wildtype followed the male Rjf pattern however the mutant did not mirror the WL male. This study would benefit from more individuals to be tested, for stronger statistical results, plus also to have all genotypes represented to fully investigate the affect the TSHR mutation have on domesticated chickens and potentially the domestication process in a range of species. / TSHR

Background: Paraben exposure occurs everyday to most people unknowingly. Parabens are present in most personal care products in varying amounts. Presently, parabens are not listed as endocrine disruptors; however, some research has shown parabens associated with decreases in thyroid hormone levels. The chemical and adsorption mechanism for parabens in association with thyroid hormones is not well understood. Determining whether parabens are associated with a change in thyroid hormone levels can help reduce the incidence of possible adverse health effects with exposure to parabens. Methodology: The selected study variables were analyzed using SAS version 9.2. Data were obtained from the 2007-2008 National Health and Nutrition Examination Survey (NHANES). Analyses were performed separately for adolescent females (12-19) and adult females (20+). Weighted means were performed for the main independent and dependent variables of interest stratified by race/ethnicity groups and by smoking status. Independent samples t-test and ANOVA was used to test significance of differences of weighted means. Weighted bivariate linear regression was performed for each dependent variable (Thyroid Stimulating Hormone [TSH], Triiodothyronine [T3], and Thyroxine [T4]) regressed on butylparaben. Weighted multiple linear regressions were performed and parameter estimates with 95% confidence intervals were used to ascertain the measure of effect. Separate regression models stratified by age group (adolescent vs. adult) were ran for each dependent variable (TSH, T3, and T4) regressed on butylparaben level and covariates, race/ethnicity and smoking status (ever smoked). Results: Weighted bivariate linear regression showed that among adult females, for each ng/ml increase in butylparaben, there was a -1.07 decrease in ng/dL T3 (p Weighted multiple linear regression showed higher butylparaben levels among adult females were associated with 0.12 ug/dL lower than average T4 levels (p Conclusion: While parabens are currently not considered endocrine disruptors, the human metabolism of and effects from exposure to parabens are not well understood. Results from this study showing decreased levels of some thyroid hormone levels (TSH, T3, and T4) associated with increased levels of butylparaben was found, as well as differences in thyroid hormone levels among racial/ethnic groups. Although not many human studies have found significant results, 10 some rodent studies have found butylparaben associations with thyroid hormone changes.4, 6, 19, 54 The results of this study indicating no statistically significant association between butylparaben and decreases in thyroid hormone levels are consistent with results of some rodent studies.7, 8, 54, 55 In light of these findings, additional human studies with paraben exposure and thyroid hormone levels are needed to increase knowledge of the mechanism and effect of parabens in the human body.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

Iodine is necessary for thyroid hormones synthesis which in turn are essential for brain development during fetal and early postnatal life. In these critical periods, severe iodine deficiency can induce irreversible brain damage in the fetus and the infant, resulting in retarded cognitive and/or psychomotor development. Despite the introduction of salt iodization programs such as national measures to control iodine deficiency, some European countries, including Belgium, are still affected by Mild Iodine Deficiency (MID) and MID during pregnancy may affect neurodevelopment of the offspring. Elevated thyroid stimulating hormone (TSH) concentration (>5mU/l) at birth has been used as an indicator of iodine deficiency during late pregnancy and at the population level. This doctoral research aimed to investigate the association between neonatal TSH level, used as a surrogate marker of MID during late pregnancy, and cognitive, psychomotor and psychosocial development of preschool children. It was hypothesized that elevation of TSH at birth is associated with impaired intellectual and psychomotor development and with behavioral problems at 4-5 years. As the use of TSH as an indicator of iodine deficiency has been criticized, we have also set out to assess the potential factors influencing neonatal TSH level measured through neonatal screening using a representative sample of TSH values between 0 and 15 mIU/L. Additionally, we aimed to reevaluate the neonatal TSH cut-off (5mIU/L) used to monitor iodine status in the population. The objective was to evaluate the cut-off point from which we can observe the impairment of children’s neurodevelopment. We hypothesized that this is a good way to establish the best cut-off value for identifying iodine deficiency.The study included 315 Belgian preschool children with a TSH concentration between 0 and 15 mU/L at screening. For each sex and TSH-interval (0-1 mU/L, 1-2 mU/L, 2-3 mU/L, 3-4 mU/L, 4-5 mU/L, 5-6 mU/L, 6-7 mU/L, 7-8 mU/L, 8-9 mU/L, 9-15 mU/L) 19 newborns were randomly selected after excluding infants with congenital hypothyroidism, low birth weight and premature infants. Neonatal TSH was measured in dried blood spots collected by heel stick 3 to 5 days after birth using the Autodelphia method. Cognitive abilities and psychomotor development were assessed using respectively the Wechsler Preschool and Primary Scale of Intelligence-III and the Charlop-Atwell scale of motor coordination. Psychosocial development was measured using the Child Behavior Check List for ages 1½-5 years. In addition, the mothers completed a self-administered questionnaire in order to account for confounding factors. No association between neonatal TSH within the range of 0 to 15 mIU/L - a surrogate marker for mild iodine deficiency during pregnancy and neurocognitive development was present in Belgian preschool children. The current level of iodine deficiency in Belgium is probably not severe enough to affect the neurodevelopment of children. In this study, we were able to identify several maternal and pregnancy related determinants of neonatal TSH levels. Higher TSH levels were associated with a lifetime (up to child birth) smoking behavior in the mother, a lower weight gain during pregnancy, a longer pregnancy duration. Higher TSH levels were found in spring and winter compared to summer and autumn. It is not advised to use elevated neonatal TSH levels at birth as an indicator of iodine deficiency during late pregnancy without taking potential covariates into account. Given the fact that no association was found between TSH and developmental scores in the children, we cannot evaluate the cut-off point from which we can observe the impairment of children’s neurodevelopment. / Doctorat en Sciences psychologiques et de l'éducation / info:eu-repo/semantics/nonPublished

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.