Thyroid Metabolism Research Articles

Serum Thyroid Hormone Levels in Healthy Children from Birth to Adulthood and in Short Children Born Small for Gestational Age

Age-appropriate reference ranges for thyroid hormones are required for detecting pediatric thyroid dysfunction. Data on thyroid hormones and peripheral thyroid metabolism in short children born small for gestational age (SGA) before and during GH treatment are lacking. Our objectives were to obtain pediatric thyroid hormone reference ranges; to investigate thyroid hormones in short SGA children before puberty, during puberty, and during postponement of puberty by GnRH analog; and to evaluate thyroid hormones during GH treatment. In 512 healthy children (225 females; 0-18 yr), free T(4) (FT(4)), TSH, total T(4), T(3), rT(3), and T(4)-binding globulin were determined. Reference ranges were calculated using the linearity, median, and skewness method. In 125 short SGA children (62 females; mean age 11.3 yr), thyroid hormones were analyzed before and after 2 yr of GH treatment and additional GnRH analog. Thyroid references showed wide ranges postnatally and age-specific patterns thereafter, similar in boys and girls. Untreated short SGA children had similar FT(4) and T(4) levels as the reference population but significantly higher T(3), rT(3), and T(4)-binding globulin levels. During puberty and during GH treatment, FT(4) and rT(3) significantly decreased, whereas T(3) significantly increased. Age-specific thyroid reference ranges are presented. Puberty and GH treatment both induce changes in peripheral thyroid metabolism, resulting in more biologically active T(3) at the expense of less inactive rT(3), possibly mediated by IGF-I. GH treatment induces altered peripheral thyroid metabolism but does not result in thyroid dysfunction.

Thyroid hormone metabolism and environmental chemical exposure

BackgroundPolychlorinated dioxins and –furans (PCDD/Fs) and polychlorinated-biphenyls (PCBs) are environmental toxicants that have been proven to influence thyroid metabolism both in animal studies and in human beings. In recent years polybrominated diphenyl ethers (PBDEs) also have been found to have a negative influence on thyroid hormone metabolism. The lower brominated flame retardants are now banned in the EU, however higher brominated decabromo-diphenyl ether (DBDE) and the brominated flame retardant hexabromocyclododecane (HBCD) are not yet banned. They too can negatively influence thyroid hormone metabolism. An additional brominated flame retardant that is still in use is tetrabromobisphenol-A (TBBPA), which has also been shown to influence thyroid hormone metabolism.Influences of brominated flame retardants, PCDD/F’s and dioxin like-PCBs (dl-PCB’s) on thyroid hormone metabolism in adolescence in the Netherlands will be presented in this study and determined if there are reasons for concern to human health for these toxins. In the period 1987-1991, a cohort of mother-baby pairs was formed in order to detect abnormalities in relation to dioxin levels in the perinatal period. The study demonstrated that PCDD/Fs were found around the time of birth, suggesting a modulation of the setpoint of thyroid hormone metabolism with a higher 3,3’, 5,5’tetrathyroxine (T4) levels and an increased thyroid stimulating hormone (TSH). While the same serum thyroid hormone tests (- TSH and T4) were again normal by 2 years of age and were still normal at 8-12 years, adolescence is a period with extra stress on thyroid hormone metabolism. Therefore we measured serum levels of TSH, T4, 3,3’,5- triiodothyronine (T3), free T4 (FT4), antibodies and thyroxine-binding globulin (TBG) in our adolescent cohort.MethodsVena puncture was performed to obtain samples for the measurement of thyroid hormone metabolism related parameters and the current serum dioxin (PCDD/Fs), PCB and PBDE levels.ResultsThe current levels of T3 were positively correlated to BDE-99. A positive trend with FT4 and BDE-99 was also seen, while a positive correlation with T3 and dl-PCB was also seen. No correlation with TBG was seen for any of the contaminants. Neither the prenatal nor the current PCDD/F levels showed a relationship with the thyroid parameters in this relatively small group.ConclusionOnce again the thyroid hormone metabolism (an increase in T3) seems to have been influenced by current background levels of common environmental contaminants: dl-PCBs and BDE-99. T3 is a product of target organs and abnormalities might indicate effects on hormone transporters and could cause pathology. While the influence on T3 levels may have been compensated, because the adolescents functioned normal at the time of the study period, it is questionable if this compensation is enough for all organs depending on thyroid hormones.

Resistance to Thyroid Hormone and Down Syndrome: Coincidental Association or Genetic Linkage?

ThyroidVol. 22, No. 9 Letters to the EditorResistance to Thyroid Hormone and Down Syndrome: Coincidental Association or Genetic Linkage?José Carlos Fernández-García, José Antonio López-Medina, Mohammed Berchid-Debdi, and Francisco José TinahonesJosé Carlos Fernández-GarcíaSearch for more papers by this author, José Antonio López-MedinaSearch for more papers by this author, Mohammed Berchid-DebdiSearch for more papers by this author, and Francisco José TinahonesSearch for more papers by this authorPublished Online:27 Aug 2012https://doi.org/10.1089/thy.2011.0316AboutSectionsView articleView Full TextSupplemental MaterialPDF/EPUBView Supplemental Data ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Resistance to Thyroid Hormone and Down Syndrome: Coincidental Association or Genetic Linkage?." , 22(9), pp. 973–974FiguresReferencesRelatedDetailsCited ByScreening of potential biomarkers for prenatal diagnosis of trisomy 2125 December 2016 | Journal of Obstetrics and Gynaecology, Vol. 37, No. 4Down Syndrome and Thyroid FunctionEndocrinology and Metabolism Clinics of North America, Vol. 41, No. 4 Volume 22Issue 9Sep 2012 InformationCopyright 2012, Mary Ann Liebert, Inc.To cite this article:José Carlos Fernández-García, José Antonio López-Medina, Mohammed Berchid-Debdi, and Francisco José Tinahones.Resistance to Thyroid Hormone and Down Syndrome: Coincidental Association or Genetic Linkage?.Thyroid.Sep 2012.973-974.http://doi.org/10.1089/thy.2011.0316Published in Volume: 22 Issue 9: August 27, 2012Online Ahead of Print:July 23, 2012PDF download

Iodotyrosine Deiodinase Defect Identified via Genome-Wide Approach

Diagnosis of congenital hypothyroidism is hampered by the heterogeneity of inborn errors of thyroid metabolism and the possible delay in hypothyroidism development leading to missed cases by neonatal screen. In the current study, we used a whole-genome approach to identify the mutation responsible for severe hypothyroidism and a huge goiter in the eldest child born to healthy first cousins. We identified a homozygous mutation of the iodotyrosine deiodinase gene (IYD). We delineated the phenotype of this defect in detail, including urinary monoiodotyrosine (MIT) and diiodotyrosine (DIT) excretion. Moreover, a 4.5-yr-old sister was found homozygous for the mutation. Her clinical and biological data were normal, except for elevated MIT and DIT excretion. The urinary loss of MIT and DIT iodine observed in most affected individuals was quite limited compared to the total iodine loss, except for the hypothyroid homozygote. Hypothyroidism could therefore be partially induced by a relative iodine deficiency caused by urinary iodine loss through MIT and DIT excretion, even in cases of normal iodine intake. The wide inter- and intrafamilial variability of the disease severity remains unclear. Besides refining the phenotype of the IYD defect, our observation shows that a global, genome-wide approach to the heterogeneous inborn thyroid defects was efficient in rapidly identifying the mutation in the proband and the disease recurrence in the still euthyroid sister. Although facilitated by consanguinity in this family, novel sequencing techniques will soon make whole-genome approaches readily amenable to more common cases.

Consumo de micronutrientes e excesso de peso: existe relação?

In past decades, the growth in obesity has been associated with changes in the lifestyle of the population, including comprehensive dietary changes, especially in the intake of micronutrients. To describe micronutrient intake and review its consequences on nutritional status. A literature review was performed covering domestic and international articles published over the past 11 years, on the SciELO, LILACS, MEDLINE and governmental databases, using descriptors such as "micronutrients", "food consumption", "excess weight", "health", "nutritional status" in Portuguese and in English. Micronutrient intake deficiency is a global health problem, affecting about 2 billion people and seems to be associated with an increased risk for non-communicable diseases and disorders, including obesity. Insufficient intake of vitamin A favors overweight by altering thyroid metabolism, while vitamin C is related to the synthesis of carnitine and fat oxidation; vitamin D favors the control of satiety and energy expenditure. As for minerals, calcium helps the regulation of thermogenesis and lipogenesis / lipolysis, and zinc is involved in regulating insulin and leptin. The promotion of healthy eating habits through educational practices is necessary for greater public awareness of the implications of micronutrient intake on nutritional status, and should be included in Public Health strategies in order to control obesity and its complications.

The Imprinted Gene DIO3 Is a Candidate Gene for Litter Size in Pigs

Genomic imprinting is an important epigenetic phenomenon, which on the phenotypic level can be detected by the difference between the two heterozygote classes of a gene. Imprinted genes are important in both the development of the placenta and the embryo, and we hypothesized that imprinted genes might be involved in female fertility traits. We therefore performed an association study for imprinted genes related to female fertility traits in two commercial pig populations. For this purpose, 309 SNPs in fifteen evolutionary conserved imprinted regions were genotyped on 689 and 1050 pigs from the two pig populations. A single SNP association study was used to detect additive, dominant and imprinting effects related to four reproduction traits; total number of piglets born, the number of piglets born alive, the total weight of the piglets born and the total weight of the piglets born alive. Several SNPs showed significant () additive and dominant effects and one SNP showed a significant imprinting effect. The SNP with a significant imprinting effect is closely linked to DIO3, a gene involved in thyroid metabolism. The imprinting effect of this SNP explained approximately 1.6% of the phenotypic variance, which corresponded to approximately 15.5% of the additive genetic variance. In the other population, the imprinting effect of this QTL was not significant (), but had a similar effect as in the first population. The results of this study indicate a possible association between the imprinted gene DIO3 and female fertility traits in pigs.

THYROID FUNCTION TEST IMBALANCE IN EPILEPTIC CHILDREN UNDER ANTICONVULSIVE THERAPY

How to Cite this Article: Ravi Torkaman M, Amirsalari S, Saburi A. Thyroid Function Test Imbalance in Epileptic ChildrenUnder Anticonvulsive Therapy. Iranian Journal of Child Neurology 2012;6(1):43-44. Dear Editor, There have been many studies regarding the impact of antiepileptic drugs(AEDs) on thyroid function. There are some challenging scopes which must beconsidered for conducting the study adressing the focused question. “Which oneof the thyroid hormones is related to the AEDs consumption?”. Some studiesdemonstrated that there may be alterations in all thyroid function tests (T3, T4 andTSH) after antiepileptic therapy in children (1). Some studies concluded that longtermprescription of anticonvulsive medications resulted in a decline in serum T4levels, although it had no effect on serum TSH levels. However, changes in serumT3 level was challenging and it must be investigated further (2).There were some confounding factors which may interfere with the conclusion.One of them is the type of the study. There are various study plans for this purposesuch as cross-sectional, case-control, experimental, self-controlled cohort anddouble-blind randomized clinical trial studies. It seems that the proper protocol ofstudy for this propose is a double-blind randomized clinical trial study. By usingother designs, the authors cannot interpret the effect of AEDs on thyroid function;however, they can discuss the prevalence of thyroid hormone imbalance and thecoordination among T3, T4 and TSH.Moreover, one of the confounding factors is the thyroid binding globulin (TBG)effect. It has appeared that some of the AEDs may change the amount of TBGand in this way may affect the amount of thyroid hormones (3). Clonazepamand valproic acid do not have any enzyme inducing effects, but phenobarbital,carbamazepine, phenytoin and primidone may induce the hepatic enzyme (4-6). Therefore, it seems necessary to analyze each group of patients based on thetype of drug which is prescribed and also by using the free amount of thyroidhormones, the researcher will be able to exclude the TBG effect. In addition, ageis an important factor which should be considered. The epileptic patients showextra-thyroid adverse effects such as vitamin D and bone metabolism disordersdue to antiepileptic drugs (7). Other secondary clinical disorders which interactwith the thyroid metabolism should be considered and overruled in the study withthe mentioned proposal, especially in the older population.It appears that the confounding effect of the duration of AED intake mustbe adjusted regarding the children’s age using multivariate analysis such asregression model or partial correlation test. The etiological mechanism of serumconcentrations of thyroid hormone change by AEDs has not been clarified clearlyand besides, patients with a personal or family history of thyroid disorders mayprogress to overt thyroid hormone imbalance secondary to AED consumption (6). Therefore, it is suggested that the pure etiologicalmechanism of thyroid disorders due to AEDs shouldbe studied in such cases. Previous reports suggestedthat return to normal of all parameters was observedafter withdrawal of anticonvulsive therapy and thisreversibility of the thyroid hormone imbalance may bea clue for further investigations in order to study thepatho-physiologic mechanism of this disorder (6).Recently, new pharmaceutical drugs have beensuccessfully used for epileptic patients. It is expectedthat the therapeutic role of these new medications willbecome more prominent in these patients in the futureand future studies should be focused on their adverseeffects. Disclosures: None.

Investigation of Thyroid Metabolism Diseases in Kütahya Region

Investigation of Thyroid Metabolism Diseases in Kütahya Region

Maternal Thimerosal Exposure Results in Aberrant Cerebellar Oxidative Stress, Thyroid Hormone Metabolism, and Motor Behavior in Rat Pups; Sex- and Strain-Dependent Effects

Methylmercury (Met-Hg) and ethylmercury (Et-Hg) are powerful toxicants with a range of harmful neurological effects in humans and animals. While Met-Hg is a recognized trigger of oxidative stress and an endocrine disruptor impacting neurodevelopment, the developmental neurotoxicity of Et-Hg, a metabolite of thimerosal (TM), has not been explored. We hypothesized that TM exposure during the perinatal period impairs central nervous system development, and specifically the cerebellum, by the mechanism involving oxidative stress. To test this, spontaneously hypertensive rats (SHR) or Sprague-Dawley (SD) rat dams were exposed to TM (200μg/kg body weight) during pregnancy (G10-G15) and lactation (P5-P10). Male and female neonates were evaluated for auditory and motor function; cerebella were analyzed for oxidative stress and thyroid metabolism. TM exposure resulted in a delayed startle response in SD neonates and decreased motor learning in SHR male (22.6%), in SD male (29.8%), and in SD female (55.0%) neonates. TM exposure also resulted in a significant increase in cerebellar levels of the oxidative stress marker 3-nitrotyrosine in SHR female (35.1%) and SD male (14.0%) neonates. The activity of cerebellar type 2 deiodinase, responsible for local intra-brain conversion of thyroxine to the active hormone, 3',3,5-triiodothyronine (T3), was significantly decreased in TM-exposed SHR male (60.9%) pups. This coincided with an increased (47.0%) expression of a gene negatively regulated by T3, Odf4 suggesting local intracerebellar T3 deficiency. Our data thus demonstrate a negative neurodevelopmental impact of perinatal TM exposure which appears to be both strain- and sex-dependent.

The possible roles of environmental factors and the aryl hydrocarbon receptor in the prevalence of thyroid diseases in Vietnam era veterans

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) profoundly affects the immune system in experimental animals. TCDD was a contaminant in defoliants used in the Vietnam War, and is known to cause prolonged activation of the aryl hydrocarbon receptor (AhR) in humans. Chronic exposure to TCDD is associated with an increased prevalence of certain chronic diseases, lymphomas and leukemias. The AhR is a transcription factor that responds to cellular metabolites as well as to environmental substances. We review how TCDD and the AhR alter thyroid metabolism directly, and how recent experimental and clinical findings on TCDD and immunity are related to autoimmune thyroid diseases. TCDD exaggerates the normal responses of the AhR to endogenous activators, affecting dendritic cells, regulatory T cells (T(reg)), T(helper)17 (T(h)17) and T(helper)22 (T(h)22) cells. A recent study on approximately 225 000 veterans of the Vietnam era found that those who served in Vietnam or were otherwise exposed to defoliants had a 2.5-fold to three-fold higher prevalence of the diagnosis of Graves' disease, compared to Veterans who served elsewhere. The balance between T(reg), T(h)17 and T(h)22 cells is disrupted by TCDD, resembling what has been found clinically in Graves' disease and Hashimoto's thyroiditis, and in animal models of these diseases. By altering the immune balance in susceptible individuals, chronic TCDD exposure may influence the prevalence of autoimmune thyroid diseases.

Mood Disorders in Pregnant Women With Thyroid Dysfunction

Both mood disorders and thyroid dysfunction are common in pregnancy and the postpartum period and have significant short and long-term implications to the mothers and their infants. Thyroid hormones have a multitude of effects on the central nervous system, undergo significant changes during pregnancy, and it is now widely recognized that disturbances of mood and cognition often emerge in association with putative disturbance of thyroid metabolism in the brain. Several small studies have shown associations between clinical and subclinical thyroid dysfunction and depression during pregnancy or the postpartum period. Unfortunately, this relationship between maternal thyroid dysfunction and perinatal depression is not well studied.

Developmental aspects of environmental neurotoxicology: Lessons from lead and polychlorinated biphenyls

The particular vulnerability of the developing nervous system for low-level exposure to chemicals is well established. It has been argued that some degree of developmental neurotoxicity was found for a large number of industrial chemicals. However, for only few of these, namely inorganic lead, arsenic, organic mercury and polychlorinated biphenyls (PCBs), human evidence is available to suggest that these may cause neurodevelopmental adversity and may, thus, be involved in contributing to neurodevelopmental disorders like autism, attention-deficit disorder, mental retardation or cerebral palsy. The focus of this overview is on PCBs and inorganic lead as developmental neurotoxicants at environmental levels of exposure. The adverse effects of inorganic lead on the developing brain have long been studied, and much emphasis has been on subtle degrees of mental retardation in terms of intelligence (IQ). The evidence is consistent, but the effect sizes are typically small. Research interest has also been devoted to studying aspects of "attention-deficit hyperactivity disorder" (ADHD) in children in relation to environmental exposure to lead in both cross-sectional and case-control studies. More recently, we have also studied core elements of ADHD according to ICD-10 and DSM-IV in relation to environmental exposure to lead, mercury and aluminum in asymptomatic school children in Romania. Both, performance measures (several attention tasks) and questionnaire-based behavior ratings from parents and teachers showed that lead, but not Hg or Al, was consistently and adversely associated with core elements of ADHD. These findings in asymptomatic children nicely fit into the overall pattern of observations and suggest that, apart from genetic influences, low-level exposure to lead contributes to this neurodevelopmental disorder. Polychlorinated biphenyls (PCBs) are persistent organic pollutants with lipophilic properties. Due to their persistence, they are still present in environmental media at potentially harmful concentrations, although production and use of PCBs was already banned in the early 1980s. Several prospective cohort studies-including our Düsseldorf study-have demonstrated that pre- and early postnatal exposure to PCBs is associated with deficit or retardation of mental and/or motor development, even after adjusting for maternal intelligence and developmental effects of the quality of the home environment. The pathophysiology is still unclear, although interference with thyroid metabolism during brain development is being discussed. Based on these reviews, three aspects, namely pre- vs. postnatal impact, effect scaling for comparative purposes, and integration of neurobehavioral findings into clinical and neuroscience contexts, are outlined as lessons learned from neurodevelopmental observations in children environmentally exposed to lead or PCBs.

Stress and the thyroid gland

The review highlights the effects of acute and chronic stress on thyroid metabolism. Special attention is paid to the influence of stress and the direct effects of glucocorticoids on the thyroid status, the activities of thyrocyte iodine uptake, oxidation and organification as well as peripheral metabolism of thyroid hormones (deposition and transport of thyroid hormones, deiodinase activities in different tissues). The role of stress in the development of thyroid pathology is analysed and characteristic features of thyroid function alterations during impaired functioning of the pitiutary-adrenal system are established. The mechanisms of the stress-induced impairments in thyroid functions are of interest for further research, taking into consideration serious consequences of thyroid deficiency for the body, even in subclinical thyroid insufficiency.

D2 Thr92Ala and PPARγ2 Pro12Ala Polymorphisms Interact in the Modulation of Insulin Resistance in Type 2 Diabetic Patients

Type 2 deiodinase (D2) converts T4 into its active metabolite T3, an essential step in thyroid metabolism. A Thr92Ala polymorphism in the gene encoding D2 has been inconsistently associated with insulin resistance (IR). Recently, it was reported that the D2 Thr92Ala (rs225014) and the peroxisome proliferator-activated receptor (PPAR) γ2 Pro12Ala (rs1801282) polymorphisms interact in the modulation of metabolic syndrome in nondiabetic subjects. Here, we investigated the effect of both polymorphisms, isolated or in combination, on IR in patients with type 2 diabetes mellitus (DM2). The D2 Thr92Ala and PPARγ2 Pro12Ala polymorphisms were genotyped in 721 DM2 patients. IR was evaluated using the homeostasis model assessment-IR (HOMA(IR)) index in a subgroup of 246 DM2 subjects. The frequencies of D2 Ala92 and PPARγ2 Ala12 variants were 0.390 and 0.074, respectively. Patients carrying D2 Ala/Ala genotype had a higher fasting plasma insulin and HOMA(IR) index as compared to patients carrying Thr/Ala or Thr/Thr genotypes (P = 0.022 and P = 0.001, respectively). A significant synergistic effect was observed between D2 Thr92Ala and PPARγ2 Pro12Ala polymorphisms on HOMA(IR) index, with carriers of both D2 Ala/Ala genotype and PPARγ2 Ala12 allele showing the highest HOMA(IR) values, after adjusting for age, gender, BMI, and use of medication for DM2 (P = 0.010). In conclusion, DM2 patients harboring both D2 Ala/Ala genotype and PPARγ2 Ala12 allele seem to present more severe IR than those with other D2/PPARγ2 genotype combinations. These findings suggest that these polymorphisms interact in the IR modulation, which may constitute a potential therapeutic target.

CHANGING COURSE ON PERCHLORATE

THE ENVIRONMENTAL Protection Agency will set a national limit for the amount of perchlorate—a component of rocket fuel—and of several volatile organic compounds allowed in drinking water, agency Administrator Lisa P. Jackson announced last week. EPA’s decision on perchlorate reverses a policy of the George W. Bush Administration not to regulate it. The substance is used in solid rocket fuel, flares, and fireworks, and it occurs naturally in some areas. The conclusion to regulate perchlorate is “based on extensive review of the best available science and the health needs of the American people,” Jackson said. Perchlorate interferes with thyroid metabolism. This can cause damage to the developing nervous systems of babies and young children. Between 5 million and 17 million Americans across 26 states may be exposed to perchlorate in their drinking water, according to EPA. A national drinking water standard for the chemical may lead to sizable cleanup liability for the Defense Department, ...

Thyroidology and public health: The challenges ahead

Thyroidology and public health: The challenges ahead

Cigotica programme: pediatric experiences

Introduction The alarming spread of obesity epidemic in children and adolsecents, as well as the absence of tested and efficient measures and programmes on obesity preven­tion indicate the necessity for the establishment of the Centre for the prevention, treatment and rehabilitation of obesity in children and adolescents and the 'Cigotica Programme' at the Special Hospital 'Zlatibor'. The advantage of the 'Cigotica' Programme is the multidisciplinary approach to treating obese children, which implies specific education, dietetic interventions with the reduction in the total daily calorie intake, physical activity, medical, educational and psychological support, change of behavior and lifestyle. Objective To define obesity complications, metabolic risk factors and treatment effects on body composition and metabolic parameters in adolescents participating in the 'Cigotica' Programme. Method 1,030 adolescents were examined (498 girls and 532 boys), aged 12 to 18, average age 15.45, diagnosed with primary obesity, hospitalized at the Centre for the prevention, treatment and rehabilitation of obesity in children and adolescents at the Special Hospital 'Zlatibor', in the period from 27/07/2008 to 03/10/2010. Hospitalization lasted 21 days. Obesity criterion was body mass index (BMI) > +2 SD . Body The Special Hospital for the Thyroid Gland and Metabolism Zlatibor mass, BMI, % of fat were obtained by means of Tanita scales for determining body composition using the impendence method. Apart from medical examination, blood pressure was also taken. The levels of triglycerides, total HDL and LDL cholesterols, uric acids and glycemia were determined on the second and twenty-first day of hospitalization after a 12-day fasting period. Results After the multidisciplinary treatment, the average reduction in body mass (p< 0.05 ) in all adolescents was 5.92 ± 2.71 kg, in boys - 6.24 ±3.24 kg, and in girls -5.86±2.4. During the 21-day hospitalization, the average BMI (p< 0.05) was reduced by -2.12 ± 0.31 in all examinees, in boys by -2.33 ± 48 and in girls by -2.04 ± 0.41 kg/m2. The BMI z-score was considerably lower in all examinees upon release and it was (p<0.05)-0.26 ±0.08, in girls 0.28 ±0.06 and in boys 0.31 ± 0.08. % of fat was considerably lower (p< 0.05) in all examinees -1.65 ± 0.23, in girls 1.72 ± 0.32 and in boys 1.50% ± 0.20. The waist circumference was reduced by -7.85 ±3.01 in all examinees, in girls -8.20 ± 4.3 and in boys -7.25 ± 2.6. Hypertension was observed in 28% of adolescents. Two factors of metabolic syndrome were present in 27.6%, and metabolic syndrome was present in 18.3% of the examinees. The disorder in sugar transport was observed in 8.9% of the examinees. Conclusion The effects of the 'Cigotica' Programme are very encouraging and they show that the multidisciplinary approach directed towards the reduction in energetic intake, education, change of lifestyle and habits related to nutrition and physical activity, leads to a considerable reduction in body mass, improvement in blood pressure, laboratory analyses, aerobic capacities and self-confidence in obese adolescents. There are obe­sity complications in a large number of adolescents, which indicates that the obesity problem has not been duly detected by parents or medical workers and that more efficient prevention programmes are needed. A great interest of children, parents, doctors and their participation in the 'Cigotica' Programme are going to contribute to raising awareness of obesity risks and the importance of health prevention in ado­lescents in our region.

234 Autism Spectrum (ASD) and Attention Deficit Hyperactivity (ADHD) Disorders Epidemics: Does Fetal Exposure to Endocrine Disrupting Chemicals Play a Role?

Background: The prevalence of neurodevelopmental disorders, such as ASD and ADHD, is increasing. This might at least partly be explained by an increased awareness of symptoms and a shift in diagnosis. However, further studies of the incidence of ASD and ADHD are warranted. Evidence has been accumulating that fetal exposure to endocrine disrupting chemicals (EDCs) can cause neurodevelopmental damage. Objective: To determine a link between fetal EDCs exposure and ASD and/or ADHD. Methods: A systemic review of the literature (PubMed) was performed. The primary search terms were: ‘prenatal exposure delayed effects’ and ‘EDCs’, and ‘autistic disorder’ or ‘attention deficit disorder with hyperactivity’. Secondary search terms were combinations of ‘maternal exposure’ with ‘developmental disabilities/chemically induced’ and ‘neurotoxins’, all with the limiters ‘child’, ‘English’, and ‘human’. Results: Fetal exposure to EDCs appears to affect the HPA-axis, leading to disturbed fetal thyroid metabolism and androgen and estrogen homeostasis and therefore possibly disturbed neurodevelopment. Furthermore, fetal exposure to EDCs, organochlorine pesticides in particular, is associated with an elevated risk of ASD and ADHD. Different gene expression in those children due to fetal EDCs exposure is reported. Conclusion: Evidence is emerging that fetal exposure to EDCs contributes to the increasing prevalence of ASD and ADHD. However, prospective long term cohort studies are necessary to confirm these observations.

Can bone loss be reversed by antithyroid drug therapy in premenopausal women with Graves' disease?

ContextHyperthyroidism can lead to reduced bone mineral density (BMD) and increased fracture risk particularly in postmenopausal women, but the mechanism behind is still unclear.ObjectiveProspective examination of the influence of thyroid hormones and/or thyroid autoantibodies on BMD in premenopause.DesignWe have examined 32 premenopausal women with untreated active Graves' disease from time of diagnosis, during 18 months of antithyroid drug therapy (ATD) and additionally 18 months after discontinuing ATD. Variables of thyroid metabolism, calcium homeostasis and body composition were measured every 3 months. BMD of lumbar spine and femoral neck were measured at baseline, 18 ± 3 and 36 ± 3 months. Data were compared to base line, a sex- and age matched control group and a group of patients with Hashimoto's thyroiditis treated with non-suppressive doses of levothyroxine.ResultsThe study showed significantly (p < 0.002) lower BMD in the thyrotoxic state compared to the control group with subsequent significant improvement during 18 ± 3 months of ATD compared to baseline (p < 0.001). However, during the following 18 months after stopping ATD femoral neck BMD decreased again unrelated to age (more than 0.4% per year, p < 0,002). The wellestablished effect of thyrotoxicosis on calcium homeostasis was confirmed. The positive predictor for best BMD was TSH receptor antibodies (TRAb) while free T4 correlated negatively in the thyrotoxic female Graves' patients (p < 0.02 and p < 0.003). In healthy controls and patients with treated Graves' disease both TSH and T4 correlated negatively to the bone mass (BMC) (p < 0.003).ConclusionThe results indicated a clinically relevant impact of thyroid function on bone modulation also in premenopausal women with Graves' disease, and further indicated the possibility for a direct action of TRAb on bones.

The Challenges and Complexities of Thyroid Hormone Replacement

Hypothyroidism is an endocrine disorder affecting 1%-10% of the population. Symptoms of hypothyroidism include fatigue, lethargy, and decreased cognitive performance. The mainstay therapy for hypothyroidism is synthetic thyroxine (T4) because of its long half-life and conversion to the bioactive form 3-5-3' triiodothyronine (T3). Recently, treatment research has re-emerged from clinicians who found that patients still experienced significant psychological morbidity, such as decreases in cognitive performance, mood, and physical status, despite appropriate standard T4 therapy. It was subsequently reported that patients treated with both T3 and T4 experienced better cognitive functioning compared to patients treated with T4 alone. This review discusses the current literature comparing cognitive improvement in combination T3/T4 therapies to T4 monotherapy in the context of the most recent biological research on thyroid metabolism and signaling in neurons that might help explain the conflicting cognitive results in these studies and help develop new paradigms to test in the future.