Paracetamol overdose in Danish children and adolescents during the Covid-19 restrictions.

INTRODUCTION: To assess the effect of long-term isolation on the mental state of Danish youth. This study aimed to investigate trends in paracetamol overdoses among people under 18 years of age in Denmark during Covid-19 restrictions as an indicator of mental health. METHODS: All patients under the age of 18 years presenting with paracetamol overdose at one of the 18 paediatric departments in Denmark from 2016 to 2021 were included. They were identified in all Danish hospital databases using specific diagnostic codes. RESULTS: From 2016 to 2021, a total of 3,217 people under 18 years of age were admitted for paracetamol overdose. Among these, 86% (n = 2,755) were girls and 14% (n = 462) were boys. During 2020, a slight (7%) decrease in admissions was observed among both boys and girls compared with the preceding four-year mean value. In 2021, the number of overdoses among girls exceeded by 35% the former all-time high from 2016. Furthermore, the number of overdoses among girls exceeded the pre-four-year period mean value by 43%. Among boys, an 8% increase was seen from the highest ever previous value recorded in 2019 and a 23% increase compared with the previous four-year mean value. CONCLUSIONS: During the first year of restrictions, a slight decrease in paracetamol overdoses was observed, possibly associated with limited accessibility. The second year showed a considerable increase in paracetamol overdoses, which may imply an affected mental state among youth during the prolonged lockdown restrictions as seen in previous epidemics. Therefore, further studies are warranted to develop a pandemic preparedness plan to protect general mental health. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Hospitalized children experience: Play heroes to build bridges between hospital days and everyday life.

Play has positive effects on children's well-being and development. Play heroes, in Danish, called "Legeheltene", have worked, for the last 7 years, to improve play and movement for hospitalized children in Danish hospitals. However, the significance of this novel Danish intervention is insufficiently researched. This phenomenological-hermeneutic study explored how children experience interacting with a play hero when hospitalized at a Danish paediatric unit. Combined observations and interviews were performed with children from two paediatric departments. Data were analyzed with inspiration from the French philosopher Paul Ricoeur. Three themes were identified: "A sense of familiarity," "From loneliness to connectedness," and "Becoming more powerful." Children experience that interaction with play heroes is existentially meaningful. Through playful activities, children experience that they are connected to their daily lives outside the hospital and their true selves. Bridges to children's everyday lives are built, leading to an improved sense of freedom, security, and the ability to manage difficult aspects of their hospital stay. Engagement with play heroes provides children with an experience of well-being and can be a positive direction in care provided to hospitalized children.

A common deletion in the growth hormone receptor gene (d3-GHR) in the offspring is related to maternal placental GH levels during pregnancy.

BACKGROUND: A common growth hormone receptor polymorphism with deletion of exon 3 (d3-GHR) has previously been linked to increased postnatal growth on the one hand and decreased fetal growth on the other. Regulation of fetal growth is positively dependent on secretion of placental GH (hGH-V). OBJECTIVE: We explored the effect of the fetal d3-GHR genotype on maternal serum levels of hGH-V and fetal growth. The cellular localization of hGH-V synthesis and the GH receptors were determined in normal placentas. METHODS: 43 healthy mother-child pairs were examined during pregnancy with measurements of hGH-V during third trimester, and serial ultrasound measurements determined fetal growth rate. Birth anthropometrics were obtained. The GHR genotype of the child was analysed postnatally. Immunohistochemical (IHC) analysis was conducted on four placentas. RESULTS: The presence of the d3-GHR genotype was associated with a markedly reduced concentration of hGH-V in maternal serum (ß -0.52, SE 0.24, p = 0.04) compared to those who had a fl/fl genotype. Accordingly, a tendency towards reduced fetal growth rate during third trimester (ß -25.8, SE 12.7, p = 0.05) and a lower birth weight were found among carriers of the d3-GHR allele, but these associations did not reach statistical significance (p = 0.08). IHC analysis showed expression of placental GH and GHR in the villous syncytiotrophoblast, the extravillous trophoblast, and the decidual cells and smooth muscle cells in chorionic vessels. CONCLUSIONS: The presence of the d3-GHR polymorphism in the fetus was associated with lower maternal serum levels of hGH-V, decreased fetal growth rate in third trimester and lower birth weight compared to the wildtype.

Corrigendum to "Challenges in Interpretation of Thyroid Function Tests in Pregnant Women with Autoimmune Thyroid Disease".

[This corrects the article DOI: 10.4061/2011/598712.].

Increase in thyroglobulin antibody and thyroid peroxidase antibody levels, but not preterm birth-rate, in pregnant Danish women upon iodine fortification.

OBJECTIVE: The presence of thyroid antibodies in pregnancy has been associated with preterm birth. In the non-pregnant population, the implementation of the Danish iodine fortification program has increased the prevalence of thyroid antibodies. This study investigated the prevalence of thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) in pregnant Danish women before, during and after implementation of the iodine fortification program and association with preterm birth. DESIGN: Comparative cohort study of 1368 pregnancies from three cohorts gathered before (1996-1998), during (2000-2003) and after (2008-2009) the iodine fortification program. METHODS: In cohort 1 (n = 297), TPOAbs were measured (DYNOtest (BRAHMS)). In cohorts 2 (n = 148) and 3 (n = 923), both TPOAbs and TgAbs were measured (Kryptor immunofluorescent assay (BRAHMS)). The prevalence and effect of antibody positivity were explored using three cut-offs: TPOAbs and/or TgAbs >100 kU/L, TPOAbs and/or TgAbs >60 kU/L and TPOAbs >30 and/or TgAbs >20 kU/L. National preterm birth data were extracted from the National Birth Registry. RESULTS: In the three cohorts, TPOAb levels >60 kU/L were found in 5.4, 8.1 and 12.0% (χ2(2, n = 1367) = 11.7, P = 0.003) respectively, and TPOAbs and/or TgAbs >60 kU/L in 8.1 and 16.2% in cohorts 2 and 3 respectively (χ2(2, n = 1070) = 6.5, P = 0.01). TgAb levels (>20 kU/L) had increased plenty-fold from cohort 2 to 3 (χ2(1, n = 1071) = 136.5, P < 0.001). Preterm birth occurred in 4.1% of all pregnancies with no effect from antibody positivity (TPOAbs and/or TgAbs >60 kU/L, χ2(1, n = 1039) = 0.0, P = 0.98, aOR = 1.1, 95% CI (0.4-2.7)). The national preterm birth-rate showed no increase over the same period. CONCLUSIONS: Thyroid antibody positivity in Danish pregnant women has more than doubled upon the implementation of the iodine fortification program without an increase in preterm birth-rate.

Pubertal Onset in Boys and Girls Is Influenced by Pubertal Timing of Both Parents.

CONTEXT: Epidemiological evidence on maternal and paternal heritability of the wide normal variation within pubertal timing is sparse. OBJECTIVE: We aimed to estimate the impact of parental pubertal timing on the onset of puberty in boys and girls. DESIGN: Annual pubertal examinations of healthy children in a longitudinal cohort study. Information on parental timing of puberty (earlier, comparable to, or later compared to peers) and menarche age was retrieved from questionnaires. PARTICIPANTS: A total of 672 girls and 846 boys. MAIN OUTCOME MEASURES: Age at onset of pubic hair (PH2+), breasts (B2+), and menarche in girls; and PH2+, genital stage (G2+), and testis >3 mL with orchidometer (Tvol3+) in boys. RESULTS: In boys, pubertal onset was significantly associated with pubertal timing of both parents. PH2+ and Tvol3+ were earlier: -11.8 months (95% confidence interval, -16.8, -6.8)/-8.9 (-12.8, -4.9), and -9.5 (-13.9, -5.1)/-7.1 (-10.4, -3.7) if the father/mother, respectively, had early pubertal development compared to late. In girls, menarche was significantly associated with both parents' pubertal timing: -10.5 months (-15.9, -5.1)/-10.1 (-14.3, -6.0) if father/mother had early pubertal development compared to late. For the onset of PH2+ and B2+ in girls, estimates were -7.0 months (-12.6, -1.4) and -4.1 (-10.6, +2.4)/-6.7 (-11.0, -2.5), and -6.7 (-11.0, -2.0) for fathers/mothers, respectively. Maternal age of menarche was significantly associated with the onset of all pubertal milestones except PH2+ in girls. CONCLUSIONS: Maternal as well as paternal pubertal timing was a strong determinant of age at pubertal onset in both girls and boys. Age at breast and pubic hair development in girls, which has declined most during recent years, seemed to be least dependent on heritability.

Phthalates Are Metabolised by Primary Thyroid Cell Cultures but Have Limited Influence on Selected Thyroid Cell Functions In Vitro.

Phthalates are plasticisers added to a wide variety of products, resulting in measurable exposure of humans. They are suspected to disrupt the thyroid axis as epidemiological studies suggest an influence on the peripheral thyroid hormone concentration. The mechanism is still unknown as only few in vitro studies within this area exist. The aim of the present study was to investigate the influence of three phthalate diesters (di-ethyl phthalate, di-n-butyl phthalate (DnBP), di-(2-ethylhexyl) phthalate (DEHP)) and two monoesters (mono-n-butyl phthalate and mono-(2-ethylhexyl) phthalate (MEHP)) on the differentiated function of primary human thyroid cell cultures. Also, the kinetics of phthalate metabolism were investigated. DEHP and its monoester, MEHP, both had an inhibitory influence on 3'-5'-cyclic adenosine monophosphate secretion from the cells, and MEHP also on thyroglobulin (Tg) secretion from the cells. Results of the lactate dehydrogenase-measurements indicated that the MEHP-mediated influence was caused by cell death. No influence on gene expression of thyroid specific genes (Tg, thyroid peroxidase, sodium iodine symporter and thyroid stimulating hormone receptor) by any of the investigated diesters could be demonstrated. All phthalate diesters were metabolised to the respective monoester, however with a fall in efficiency for high concentrations of the larger diesters DnBP and DEHP. In conclusion, human thyroid cells were able to metabolise phthalates but this phthalate-exposure did not appear to substantially influence selected functions of these cells.

Migration of phthalates on culture plates - an important challenge to consider for in vitro studies.

Phthalates are endocrine disruptors of the reproductive system and suspected to influence many other organ and hormone systems. They are also semi-volatile organic compounds present in the gas phase in the environment. Their mode of action has been investigated in numerous in vitro studies. Multi-well culture plates are typically used to study phthalates in cell cultures. In a pilot study, we observed evidence of phthalate migration in 24-well culture plates. As this has not previously been described, we investigated the phenomenon in more detail. Primary human thyroid epithelial cell cultures (n = 8 cultures) were exposed to either di-ethyl phthalate (DEP), di-n-butyl phthalate (DnBP), mono-n-butyl phthalate (MnBP) or di-(2-ethylhexyl) phthalate (DEHP). Measurement of phthalate metabolites by mass spectrometry demonstrated that the short-branched DEP was able to migrate to adjacent wells when added to cell culture plates. DnBP also seemed to be able to migrate, unlike the long-branched DEHP or the monoester MnBP which did not seem to have this ability. High background levels of phthalate metabolites were also observed, which might compromise results from low dose phthalate studies. In conclusion, the migration of phthalates which is probably caused by their volatile properties might lead to false interpretation of study results.

Thyroid function and autoimmunity in Danish pregnant women after an iodine fortification program and associations with obstetric outcomes.

OBJECTIVE: Aberrations in maternal thyroid function and autoimmunity during pregnancy have been associated with negative obstetric outcome. In Denmark, a national iodine fortification program was implemented in the year 2000 with the aim to alleviate the mild-moderate iodine deficiency. Following the iodine implementation, there has been an increase in thyroid autoimmunity in the background population. This study investigates the thyroid status of pregnant Danish women following the iodine fortification program, and a possible association with preterm delivery. DESIGN: Historical cohort study of 1278 randomly selected pregnant Danish women attending the national Down's syndrome screening program. METHODS: The main outcome measures were thyroid status according to laboratory- and gestational-age-specific reference intervals, and association with risk of abnormal obstetric outcome. Antibody-positivity was defined as an antibody-level (thyroid peroxidase and/or thyroglobulin antibodies) above 60 U/ml. RESULTS: Establishing laboratory-specific gestational-age-dependent reference intervals, we found a prevalence of maternal thyroid dysfunction of 10%-15.8% by use of the cut-off suggested by the American Thyroid Association. Thyroid dysfunction was significantly associated with antibody-positivity (P<0.05). No associations were found between preterm delivery and thyroid dysfunction (adjusted OR 0.6, 95% CI: 0.1-2.3) or autoimmunity (adjusted OR 1.1, 95% CI: 0.4-2.7). CONCLUSIONS: After the implementation of the Danish iodine fortification program, the prevalence of thyroid dysfunction and autoimmunity in Danish pregnant women is high - even higher by use of pre-established reference intervals from international consensus guidelines. However, no associations were found with abnormal obstetric outcome. Large randomized controlled trials are needed to clarify the benefit of treating slight aberrations in pregnant women's thyroid function.

Influence of phthalates on cytokine production in monocytes and macrophages: a systematic review of experimental trials.

BACKGROUND: Phthalates are a group of endocrine disrupting chemicals suspected to influence the immune system. The aim of this systematic review is to summarise the present knowledge on the influence of phthalates on monocyte and macrophage production and secretion of cytokines, an influence which could affect both pro- and anti-inflammatory abilities of these cells. STRATEGY AND RESULTS: A systematic search was performed in Medline, Embase and Toxline in June 2013, last updated 3rd of August 2014. Criteria used to select studies were described and published beforehand online on Prospero (http://www.crd.york.ac.uk/NIHR_PROSPERO, registration number CRD42013004236). In vivo, ex vivo and in vitro studies investigating the influence of phthalates on cytokine mRNA expression and cytokine secretion in animals and humans were included. A total of 11 reports, containing 12 studies, were found eligible for inclusion. In these, a total of four different phthalate diesters, six primary metabolites (phthalate monoesters) and seven different cytokines were investigated. Though all studies varied greatly in study design and species sources, four out of five studies that investigated di-2-ethylhexyl phthalate found an increased tumour necrosis factor-α secretion/production from monocytes or macrophages. A summary of cytokine measurements was not possible since few studies were comparable in study design and due to insufficient reporting of raw data for most of the included studies. CONCLUSION: Results from this review have suggested that at least one phthalate (di-2-ethylhexyl phthalate) has the ability to enhance tumour necrosis factor-α production/secretion from monocytes/macrophages in vitro, but also observed ex vivo. Influence of other phthalates on other cytokines has only been investigated in few studies. Thus, in vitro studies on primary human monocytes/macrophages as well as more in vivo studies are needed to confirm or dispute these findings.

Gestational age-specific reference ranges from different laboratories misclassify pregnant women's thyroid status: comparison of two longitudinal prospective cohort studies.

OBJECTIVES: Correct interpretation of thyroid status during pregnancy is vital to secure fetal development. Pregnancy-related changes in maternal thyroid status necessitate the use of gestational age-specific reference ranges. In this study, we investigated between-laboratory reproducibility of thyroid reference ranges in pregnant women. DESIGN: Comparison of two longitudinal prospective cohort studies including 255 (cohort 1) and 101 (cohort 2) healthy antibody-negative Danish pregnant women attending prenatal care at Copenhagen University Hospital. METHODS: Different immunoassays were used to measure thyroid hormone levels in the two cohorts. Thyroid hormone reference ranges were established for every 5 weeks of gestation. Differences between cohorts were explored through mixed-model repeated measures regression analyses. By applying reference ranges from one cohort to the other, the proportion of women who would be misclassified by doing so was investigated. RESULTS: TSH increased and free thyroxine (FT4) decreased as pregnancy progressed. Results indicated highly significant differences between cohorts in free triiodothyronine (F=21.3, P<0.001) and FT4 (F=941, P<0.001). TSH levels were comparable (P=0.09). Up to 90.3% of the women had FT4 levels outside their laboratory's nonpregnant reference range, and up to 100% outside the other cohort's gestational-age-specific reference ranges. Z-score-based reference ranges markedly improved comparison between cohorts. CONCLUSION: Even in the same region, the use of gestational-age-specific reference ranges from different laboratories led to misclassification. Up to 100% of maternal FT4 levels fell outside the other cohort's reference range despite similar TSH levels. In clinical practice, thyroid testing of pregnant women without adding method specificity to gestational age-dependent reference ranges will compromise patient safety.

[Multiple mini interviews before the occupation of main training posts in paediatrics]. / Multiple miniinterview før besættelse af pædiatriske hoveduddannelsesstillinger er gennemførlige.

Interviews are mandatory in Denmark when selecting doctors for training positions. We used multiple mini interviews (MMI) at four recruitment rounds for the main training posts in paediatrics. In total, 125 candidates were evaluated and assessed by CV and MMI (4-5 stations). Reliability for individual stations in MMI assessed by Cronbach's alpha was adequate (0.63-0.92). The overall reliability assessed by G-theory was lower, suggesting that different skills were tested. The acceptability was high. Our experiences with MMI suggest good feasibility and reliability. An increasing number of stations may improve the overall reliability.

Thyroid effects of endocrine disrupting chemicals.

In recent years, many studies of thyroid-disrupting effects of environmental chemicals have been published. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing organism may have deleterious effects on neurological outcome. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some animal experiments and in vitro studies have focused on elucidating the mode of action of specific chemical compounds. Long-term human studies on effects of environmental chemicals on thyroid related outcomes such as growth and development are still lacking. The human exposure scenario with life long exposure to a vast mixture of chemicals in low doses and the large physiological variation in thyroid hormone levels between individuals render human studies very difficult. However, there is now reasonably firm evidence that PCBs have thyroid-disrupting effects, and there is emerging evidence that also phthalates, bisphenol A, brominated flame retardants and perfluorinated chemicals may have thyroid disrupting properties.

Lower birth weight and increased body fat at school age in children prenatally exposed to modern pesticides: a prospective study.

BACKGROUND: Endocrine disrupting chemicals have been hypothesized to play a role in the obesity epidemic. Long-term effects of prenatal exposure to non-persistent pesticides on body composition have so far not been investigated. The purpose of this study was to assess possible effects of prenatal exposure to currently used pesticides on children's growth, endocrine and reproductive function. METHODS: In a prospective study of 247 children born by women working in greenhouses in early pregnancy, 168 were categorized as prenatally exposed to pesticides. At three months (n = 203) and at 6 to 11 years of age (n = 177) the children underwent a clinical examination and blood sampling for analysis of IGF-I, IGFBP3 and thyroid hormones. Body fat percentage at age 6 to 11 years was calculated from skin fold measurements. Pesticide related associations were tested by linear multiple regression analysis, adjusting for relevant confounders. RESULTS: Compared to unexposed children birth weight and weight for gestational age were lower in the highly exposed children: -173 g (-322; -23), -4.8% (-9.0; -0.7) and medium exposed children: -139 g (-272; -6), -3.6% (-7.2; -0.0). Exposed (medium and highly together) children had significantly larger increase in BMI Z-score (0.55 SD (95% CI: 0.1; 1.0) from birth to school age) and highly exposed children had 15.8% (0.2; 34.6) larger skin folds and higher body fat percentage compared to unexposed. If prenatally exposed to both pesticides and maternal smoking (any amount), the sum of four skin folds was 46.9% (95% CI: 8.1; 99.5) and body fat percentage 29.1% (95% CI: 3.0; 61.4) higher. There were subtle associations between exposure and TSH Z-score -0.66(-1.287; -0.022) and IGF-I Z-score (girls: -0.62(-1.0; -0.22), boys: 0.38(-0.03; 0.79)), but not IGFBP3. CONCLUSIONS: Occupational exposure to currently used pesticides may have adverse effects in spite of the added protection offered to pregnant women. Maternal exposure to combinations of modern, non-persistent pesticides during early pregnancy was associated with affected growth, both prenatally and postnatally. We found a biphasic association with lower weight at birth followed by increased body fat accumulation from birth to school age. We cannot rule out some residual confounding due to differences in social class, although this was adjusted for. Associations were stronger in highly exposed than in medium exposed children, and effects on body fat content at school age was potentiated by maternal smoking in pregnancy.

Do Thyroid Disrupting Chemicals Influence Foetal Development during Pregnancy?

Maternal euthyroidism during pregnancy is crucial for normal development and, in particular, neurodevelopment of the foetus. Up to 3.5 percent of pregnant women suffer from hypothyroidism. Industrial use of various chemicals-endocrine disrupting chemicals (EDCs)-has been shown to cause almost constant exposure of humans with possible harmful influence on health and hormone regulation. EDCs may affect thyroid hormone homeostasis by different mechanisms, and though the effect of each chemical seems scarce, the added effects may cause inappropriate consequences on, for example, foetal neurodevelopment. This paper focuses on thyroid hormone influence on foetal development in relation to the chemicals suspected of thyroid disrupting properties with possible interactions with maternal thyroid homeostasis. Knowledge of the effects is expected to impact the general debate on the use of these chemicals. However, more studies are needed to elucidate the issue, since human studies are scarce.

Challenges in interpretation of thyroid function tests in pregnant women with autoimmune thyroid disease.

Physiological changes during gestation are important to be aware of in measurement and interpretation of thyroid function tests in women with autoimmune thyroid diseases. Thyroid autoimmune activity is decreasing in pregnancy. Measurement of serum TSH is the first-line screening variable for thyroid dysfunction also in pregnancy. However, using serum TSH for control of treatment of maternal thyroid autoimmunity infers a risk for compromised foetal development. Peripheral thyroid hormone values are highly different among laboratories, and there is a need for laboratory-specific gestational age-related reference ranges. Equally important, the intraindividual variability of the thyroid hormone measurements is much narrower than the interindividual variation (reflecting the reference interval). The best laboratory assessment of thyroid function is a free thyroid hormone estimate combined with TSH. Measurement of antithyroperoxidase and/or TSH receptor antibodies adds to the differential diagnosis of autoimmune and nonautoimmune thyroid diseases.

Serum concentrations of Anti-Müllerian Hormone (AMH) in 95 patients with Klinefelter syndrome with or without cryptorchidism.

AIM: Anti-Müllerian hormone (AMH) is produced by foetal Sertoli cells at the time of sexual differentiation and is responsible for the regression of the Müllerian ducts in the male foetus. AMH is a testis-specific marker of diagnostic value in infants with ambiguous genitalia or with bilateral cryptorchidism. However, little is known about AMH in boys and adult men with normal or abnormal gonadal function. We therefore aimed at determining circulating AMH concentrations in patients with 47,XXY Klinefelter syndrome (KS) with or without cryptorchidism. METHODS: AMH was determined in 95 47,XXY patients aged 0.2-64.5 years, of which 12 patients had a history of cryptorchidism. RESULTS: AMH was within the normal range in boys with Klinefelter syndrome until puberty. The pubertal decline was delayed, especially in patients with a history of cryptorchidism. AMH was below -2 SD in 85% of adult KS. CONCLUSION: AMH secretion in patients with 47,XXY KS was within normal limits during mini-puberty and until puberty. Thereafter, AMH declined to subnormal levels in all patients. We hypothesize that this decline was a result of the hyalinization of seminiferous tubules in relation to puberty, rather than caused by disrupted regulatory mechanisms at the level of the pituitary-gonadal axis.

Serum levels of anti-Müllerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients.

CONTEXT: In adult women, anti-Müllerian hormone (AMH) is related to the ovarian follicle pool. Little is known about AMH in girls. OBJECTIVE: The objective of the study was to provide a reference range for AMH in girls and adolescents and to evaluate AMH as a marker of ovarian function. SETTING: The study was conducted at a tertiary referral center for pediatric endocrinology. MAIN OUTCOME MEASURES: We measured AMH in 926 healthy females (longitudinal values during infancy) as well as in 172 Turner syndrome (TS) patients according to age, karyotype (A: 45,X; B: miscellaneous karyotypes; C: 45,X/46,XX), and ovarian function (1: absent puberty; 2: cessation of ovarian function; 3: ongoing ovarian function). RESULTS: AMH was undetectable in 54% (38 of 71) of cord blood samples (<2; <2-15 pmol/liter) (median; 2.5th to 97.5th percentile) and increased in all (37 of 37) infants from birth to 3 months (15; 4.5-29.5 pmol/liter). From 8 to 25 yr, AMH levels were stable (19.9; 4.7-60.1 pmol/liter), with the lower level of the reference range clearly above the detection limit. AMH levels were associated with TS-karyotype groups (median A vs. B: <2 vs. 3 pmol/liter, P = 0.044; B vs. C: 3 vs. 16 pmol/liter, P < 0.001) as well as with ovarian function (absent puberty vs. cessation of ovarian function: <2 vs. 6 pmol/liter, P = 0.004; cessation of ovarian function vs. ongoing ovarian function: 6 vs. 14 pmol/liter, P = 0.001). As a screening test of premature ovarian failure in TS, the sensitivity and specificity of AMH less than 8 pmol/liter was 96 and 86%, respectively. CONCLUSION: AMH seems to be a promising marker of ovarian function in healthy girls and TS patients.

Childhood exposure to phthalates: associations with thyroid function, insulin-like growth factor I, and growth.

BACKGROUND: Phthalates are widely used chemicals, and human exposure is extensive. Recent studies have indicated that phthalates may have thyroid-disrupting properties. OBJECTIVE: We aimed to assess concentrations of phthalate metabolites in urine samples from Danish children and to investigate the associations with thyroid function, insulin-like growth factor I (IGF-I), and growth. METHODS: In 845 children 4-9 years of age, we determined urinary concentrations of 12 phthalate metabolites and serum levels of thyroid-stimulating hormone, thyroid hormones, and IGF-I. RESULTS: Phthalate metabolites were detected in all urine samples, of which monobutyl phthalate was present in highest concentration. Phthalate metabolites were negatively associated with serum levels of free and total triiodothyronine, although statistically significant primarily in girls. Metabolites of di(2-ethylhexyl) phthalate and diisononyl phthalate were negatively associated with IGF-I in boys. Most phthalate metabolites were negatively associated with height, weight, body surface, and height gain in both sexes. CONCLUSIONS: Our study showed negative associations between urinary phthalate concentrations and thyroid hormones, IGF-I, and growth in children. Although our study was not designed to reveal the mechanism of action, the overall coherent negative associations between urine phthalate and thyroid and growth parameters may suggest causative negative roles of phthalate exposures for child health.

Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women.

BACKGROUND: Adaptive alterations in maternal physiology cause changes in thyroid hormone levels throughout pregnancy, and precise biochemical evaluation is thus highly dependent on gestation-specific reference intervals and expected intra-individual variation. OBJECTIVE: The aim of the study was the assessment of the intra-individual variation as well as the longitudinal course of thyroid hormones during normal pregnancy and factors that influence the normal reference range for thyroid function. For this purpose, a longitudinal statistical model was applied. DESIGN: In a cohort of 132 pregnant women, serial blood samples were obtained and ultrasound scans were performed throughout pregnancy. METHODS: Serum levels of TSH, free and total thyroxine (T(4)), free and total triiodothyronine (T(3)) as well as autoantibodies against thyroid peroxidase and thyroglobulin were measured in 979 serum samples. RESULTS: Intra-individual variations of thyroid hormone concentrations were smaller than inter-individual variations (individuality index range: 0.38-0.71). Maternal height was positively associated with free T(4) (FT(4)) (b=0.003; P=0.031) and pre-pregnancy body mass index with T(3) and free T(3) (b=0.017; <0.001 and b=0.007; P<0.001). Smoking was positively associated with T(4) and FT(4), but it was modulated by gestational age. Gestation-specific reference intervals for thyroid function variables from autoantibody-negative participants are presented. CONCLUSIONS: In accordance with the data from nonpregnant adults, intra-individual variations of thyroid hormones were smaller than inter-individual variations also during pregnancy. In the evaluation of thyroid function in pregnancy, the individual longitudinal course of thyroid hormones rather than absolute values should be considered. We present a longitudinal model for the prediction of maternal thyroid function tests in pregnant women.