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Phthalates are ubiquitous environmental chemicals with endocrine disrupting properties and potentially obesogenic effects. We hypothesised that antenatal phthalate exposure may influence growth and adiposity patterns in girls through childhood into adolescence. Among 1342 Raine Study singleton females, 462 had maternal serum and at least one outcome available up to 20 years of age. Individuals’ maternal serum collected at 18 and 34 weeks gestation was pooled and analyzed for concentrations of 32 metabolites of 15 phthalate diesters. Cox regression and linear models were used to determine associations between maternal phthalate levels and age at menarche, change in height and weight z-scores between birth and two years, height from birth to 20 years, BMI from two to 20 years, deviation from mid-parental height at age 20 and DEXA scan measures at age 20. Weak negative associations were detected with some phthalate metabolites and change in height and weight z-score during infancy. Weak positive associations between some of the high molecular weight phthalate metabolites and height z-score were detected during childhood. While still within the normal range, age at menarche was slightly delayed in girls with higher prenatal exposure to the higher molecular weight phthalate metabolites. We derived some associations between prenatal phthalate exposure with early growth patterns and age at menarche.

Phthalates are ubiquitous environmental endocrine-disrupting chemicals suspected to interfere with developmental androgen action leading to adverse effects on male reproductive function. Prenatal exposure studies in rodents show cryptorchidism, hypospadias and reduced testicular volume (TV), testosterone and anogenital distance in males. It is postulated that there is a developmental window in utero when phthalate exposure has the most potent adverse effects. Some human studies show associations between prenatal phthalate exposure and reduced calculated "free" serum testosterone in infant boys and shorter anogenital distance. However, there are no data available yet which link antenatal exposure to long-term effects in men. We aimed to correlate antenatal phthalate exposure with adult TV, semen parameters and serum reproductive hormone concentrations. 913 men from the Western Australian (Raine) Pregnancy Cohort were contacted aged 20-22 years. 423 (56%) agreed to participate; 404 underwent testicular ultrasound examination; 365 provided semen samples, and reproductive hormones were measured in 384. Maternal antenatal serum phthalate metabolite measurements were available for 185 and 111 men, who provided serum and semen, respectively. Maternal serum collected at 18 and 34 weeks gestation, stored at -80degreeC, was pooled and analyzed for 32 phthalate metabolites by liquid chromatography-tandem mass spectrometry. TV was calculated, semen analysis performed by WHO approved methods, and serum concentrations of gonadotrophins, inhibin B, and testosterone measured. Eleven phthalate metabolites were detected. Primary and secondary metabolites of di-(2-ethyl-hexyl) phthalate (DEHP) and di-iso-nonyl phthalate (DiNP) were positively correlated. After correction for adult height, BMI, presence of a varicocele and exposure to maternal smoking mono-iso-nonyl phthalate (MiNP) (r = -0.22) and sums of DEHP and DiNP metabolites (r = -0.24) and the sum of the metabolites of the high

Context: Anti-Mullerian hormone (AMH), which is secreted by immature Sertoli cells, triggers the involution of the fetal Mullerian ducts. AMH is a testis-specific marker used for diagnosis in infants with ambiguous genitalia or bilateral cryptorchidism. Aim: The aim of the study was to describe the ontogeny of AMH secretion through life in healthy males. Setting:This was a population-based study of healthy volunteers. Participants: Participants included 1027 healthy males from birth (cord blood) to 69 yr. A subgroup was followed up longitudinally through the infantile minipuberty [(in cord blood, and at 3 and 12 months), n = 55] and another group through puberty [(biannual measurements), n = 83]. Main Outcome Measures: Serum AMH was determined by a sensitive immunoassay. Serum testosterone, LH, and FSH were measured, and pubertal staging was performed in boys aged 6 to 20 yr (n = 616). Results: Serum AMH was above the detection limit in all samples with a marked variation according to age and pubertal status. The median AMH level in cord blood was 148 pmol/liter and increased significantly to the highest observed levels at 3 months (P <0.0001). AMH declined at 12 months (P <0.0001) and remained at a relatively stable level throughout childhood until puberty, when AMH declined progressively with adults exhibiting 3-4% of infant levels. Conclusion: Based on this extensive data set, we found detectable AMH serum levels at all ages, with the highest measured levels during infancy. At the time of puberty, AMH concentrations declined and remained relatively stable throughout adulthood. The potential physiological role of AMH and clinical applicability of AMH measurements remain to be determined

PURPOSE OF REVIEW: To overview the effects of endocrine disrupters on thyroid function. RECENT FINDINGS: Studies in recent years have revealed thyroid-disrupting properties of many environmentally abundant chemicals. Of special concern is the exposure of pregnant women and infants, as thyroid disruption of the developing fetus may have deleterious effects on neurological outcome. Evidence is reviewed for the following groups of chemicals: polychlorinated biphenyls, dioxins, flame retardants, pesticides, perfluorinated chemicals, phthalates, bisphenol A and ultraviolet filters. Chemicals may exert thyroid effects through a variety of mechanisms of action, and some publications have focused on elucidating the mechanisms of specific (groups of) chemicals. SUMMARY: A large variety of ubiquitous chemicals have been shown to have thyroid-disrupting properties, and the combination of mechanistic, epidemiological and exposure studies indicates that the ubiquitous human and environmental exposure to industrial chemicals may impose a serious threat to human and wildlife thyroid homeostasis. Currently, available evidence suggests that authorities need to regulate exposure to thyroid-disrupting chemicals of pregnant women, neonates and small children in order to avoid potential impairment of brain development. Future studies will indicate whether adults also are at risk of thyroid damage due to these chemicals Udgivelsesdato: 2009/10

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 Udgivelsesdato: 2009/12

CONTEXT AND OBJECTIVE: Few studies have focused on the interrelation between thyroid size, anthropometric variables, and IGF-I in adults, but such data are lacking for children. We have investigated thyroid gland volume and several hormonal and anthropometric variables in prepubertal children. DESIGN AND PARTICIPANTS: A total of 859 prepubertal euthyroid Danish children aged 4-9 yr underwent a thorough clinical investigation, including anthropometrical measurements and determination of TSH, thyroid hormones, autoantibodies, urinary iodine excretion, and thyroid volume (TV) by ultrasound. Longitudinal growth data from birth were available. RESULTS: TV increased significantly with age (r = 0.487; P < 0.001). Mean TV +/- sd for different age groups were as follows: 4 yr, 2.2 +/- 1.4 ml; 5 yr, 2.5 +/- 1.3 ml; 6 yr, 2.8 +/- 1.3 ml; 7 yr, 3.2 +/- 1.3 ml; 8 yr, 3.5 +/- 1.3 ml; 9 yr, 3.7 +/- 1.3 ml. We found a significant positive association between IGF-I and TV (P < 0.001). Furthermore, in multiple regression analyses, TSH (P < 0.013), free T(4) (P < 0.001), lean body mass (P < 0.001), and body surface area (P < 0.001) as well as other anthropometrical measurements were identified as factors significantly associated with TV. Family history of thyroid disease and presence of incidental abnormal ultrasound findings were also positively associated with TV (P = 0.025 and 0.022, respectively). CONCLUSIONS: In our cohort of prepubertal Danish children, the GH/IGF-I-axis was positively correlated with thyroid size, suggesting a role in the regulation of thyroid growth. Moreover, anthropometric measurements, in particular body surface area, were the best predictors of TV Udgivelsesdato: 2009/10

An international workshop tided "Assessing Endocrine-Related Endpoints within the First Years of Life" was held 30 April-1 May 2007, in Ottawa, Ontario, Canada. Representatives from a number of pregnancy cohort studies in North America and Europe presented options for measuring various endocrine-sensitive endpoints in early life and discussed issues related to performing and using those measures. The workshop focused on measuring reproductive tract developmental endpoints [e.g., anogenital distance (AGD)], endocrine status, and infant anthropometry. To the extent possible, workshop participants strove to develop or recommend standardized measurements that would allow comparisons and pooling of data across studies. The recommended outcomes include thigh fat fold, breast size, vaginal cytology, AGD, location of the testis, testicular size, and growth of the penis, with most of the discussion focusing on the genital exam. Although a number of outcome measures recommended during the genital exam have been associated with exposure to endocrine-disrupting chemicals, little is known about how predictive these effects are of later reproductive health or other chronic health conditions.

BACKGROUND: A significantly reduced male reproductive health status, including a higher prevalence of cryptorchidism and hypospadias, has been documented in Danish men compared with Finnish men. Exposure to environmental pollutants with endocrine disrupting activities has been suggested as a possible contributing factor. In this study, we investigated whether there was a difference in milk and placental concentrations of persistent organohalogen compounds, between the two countries. METHODS: Organohalogens were analysed by high-resolution gas chromatography-high-resolution mass spectrometry in human milk samples from Finland (n = 65) and Denmark (n = 65) and in placentas from Finland (n = 112) and Denmark (n = 168). RESULTS: 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDE) was the dominant pollutant. beta-Hexa-chloro-cyclohexane (beta-HCH), hexachlorobenzene (HCB), endosulfan-I, dieldrin, oxychlordane (OXC), cis-heptachloroepoxide (c-HE) and 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDT) were the other main organochlorines detected. Danish samples had significantly higher concentrations of p,p'-DDE, p,p'-DDT, beta-HCH, HCB, dieldrin, c-HE and OXC than did the Finnish samples. Levels of organobrominated compounds were very low and most were undetectable in the majority of samples. BB-153 and BB-155 were the most abundant polybromobiphenyl congeners. BB-153 was more abundant in Danish milk samples compared with Finnish samples, whereas BB-155 was more abundant in the Finnish milk. CONCLUSIONS: The organochlorine levels were higher in Danish, than in Finnish, samples, suggesting a higher exposure for Danish infants Udgivelsesdato: 2008/1

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Many aspects of hormonal regulation and mechanisms of normal infancy growth are poorly understood.