Endocrine-Disrupting Chemicals in Human Fetal Growth.

Fetal growth is regulated by a complex interaction of maternal, placental, and fetal factors. The effects and outcomes that chemicals, widely distributed in the environment, may have on the health status of both the mother and the fetus are not yet well defined. Mainly mixtures of chemical substances are found in the mothers and placenta. Exposure to endocrine-disrupting chemicals (EDCs) can be associated with fetal growth retardation, thyroid dysfunction, and neurological disorders. EDCs mostly interfere with insulin, glucocorticoid, estrogenic, and thyroid pathways, with subsequent effects on normal endocrine and metabolic functions, which cause changes in the epigenome and state of inflammation with life-long effects and consequences. International scientific societies recommend the implementation of research and of all possible preventive measures. This review briefly summarizes all these aspects.

Fetal thyroid disorders: Pathophysiology, diagnosis and therapeutic approaches.

Fetal thyroid disorders while uncommon in general, have significant morbidity and profound effects in the neonate. Pregnancy provides the opportunity not only for the diagnosis of these conditions but also for therapeutic interventions. In careful balance, these disorders range from hypothyroidism to hyperthyroidism, both may manifest with fetal thyroid goiters as well. The intrauterine therapeutic approach of these must also weight the balance in this range as well as the maternal well being which may also express thyroid dysfunction. In this review we explore the different fetal manifestations of thyroid disease, describe the pathophysiology and therapeutic approaches both in practice and in development.

Cigarette smoking during pregnancy is associated with alterations in maternal and fetal thyroid function.

CONTEXT: Studies in the general population have shown lower serum TSH levels in smokers as compared with nonsmokers. AIM: Our aim was to examine whether smoking is associated with changes in thyroid function of pregnant women and their fetus. SUBJECTS AND METHODS: We examined the relationship between smoking and thyroid function (serum TSH, free T4, and free T3) in two independent cohorts of pregnant women without a history of thyroid disorder or an overt biochemical thyroid dysfunction: 1) first-trimester cohort (median gestation 9 wk) (n = 1428) and 2) third-trimester cohort (gestation 28 wk) (n = 927). We also analyzed the relationship between maternal smoking and thyroid hormone levels in cord serum of 618 full-term babies born to the women in the third-trimester cohort. RESULTS: In smokers compared with nonsmokers, median serum TSH was lower (first-trimester cohort: 1.02 vs. 1.17 mIU/liter, P = 0.001; third-trimester cohort: 1.72 vs. 1.90 mIU/liter, P = 0.037), and median serum FT3 was higher (first-trimester cohort: 5.1 vs. 4.9 pmol/liter, P < 0.0001; third-trimester cohort: 4.4 vs. 4.1 pmol/liter, P < 0.0001). In both cohorts, serum FT4 in smokers and nonsmokers were similar. The prevalence of anti-thyroperoxidase antibodies was also similar in smokers and nonsmokers in both cohorts. Cord serum TSH of babies born to smokers was lower than of those born to nonsmokers (6.7 vs. 8.1 mIU/liter, P = 0.009). CONCLUSIONS: Cigarette smoking is associated with changes in maternal thyroid function throughout the pregnancy and in fetal thyroid function as measured in cord blood samples.

[Thyroid C cells are decreased in experimental CDH]. / Las células C tiroideas están disminuidas en la hernia diafragmática experimental.

BACKGROUND/AIM: Experimental CDH is often associated with malformations of neural crest origin. Several of these features are present in human CDH and therefore likely similar pathogenic mechanisms should be explored. The aim of the present study is to examine whether thyroid C-cells, another neural crest derivative, are abnormal in this rat model. METHODS: Pregnant rats were exposed either to 100 mg of 2-4-dichlorophenyl-p-nitrophenyl ether (nitrofén) or vehicle (controls) on 9.5 day of gestation. Fetuses were recovered on day 21st and the thyroids of those with CDH (68%) were immuno-histochemically stained with anti-calcitonin antibody. The number of positively stained cells per high power field were counted using a computer-assisted image analysis method in at least 5 sections per thyroid. The distribution of the cells within the gland was assessed as well. Comparisons between CDH and control rats were made by non-parametric tests with a significance threshold of p<0.05. RESULTS: The number of c-cells was dramatically reduced in CDH animals in comparison with controls (101.2 +/- 61.3 vs 23.1 +/- 37, p<0.0001). Histology of the thyroid was similar in both groups, but the distribution of positive C-cells within the gland followed an abnormal pattern in CDH rats with the cells tending to be located at the periphery rather than at the core of the lobes. CONCLUSIONS: Nitrofén induces a severe decrease in thyroid C cells accompanied by abnormal distribution patterns. These results add further evidence of the involvement of a neural crest dysregulation as a component of the pathogenesis of experimental CDH. Whether there is or not a clinical counterpart to these findings is still unknown, but the nature of the cardiovascular and craneo-facial malformations in some babies with CDH strongly support further research in this field.

Morphology of the human thyroglossal tract: a histologic and macroscopic study in infants and children.

The anatomic development of thyroglossal tract remnants is not understood at present. For analysis of morphology and growth patterns of thyroglossal tract remnants, we used histologic whole organ serial sections to determine developmental changes through the first years of life. Larynges of 58 infants and children ages 1 month to 13 years were obtained in whole organ serial step-sections in an axial plane. The slides were stained with hematoxylin and eosin, Alcian blue, and periodic acid-Schiff stains. Altogether, 3,247 histologic slices were examined. The resulting data were then correlated with the age and sex of the specimens. We found, in 24 cases (41.3%), remnants of the thyroglossal tract or ectopic thyroid tissue. In 4 specimens (16.6%), a complete thyroglossal tract could be observed that presented a ventral path in relation to the hyoid bone with no contact with the perichondrium of the cartilage. Hormonal activity of ectopic thyroid tissue was proven in 20 cases (34.5%). Thyroid follicles were located in 2 cases (3.5%) in the hyoid bone. The thyroglossal ducts revealed a modest tendency for a left-sided pathway, whereas thyroid follicles were located more on the right paramedian side. Morphometric data on the development and structure of the thyroglossal tract and the thyroid follicles during infancy and childhood are presented. The study provides quantitative data of clinical interest that elucidate the anatomy of thyroglossal tract remnants. In addition, our investigation supports Sistrunk's operative approach for avoiding recurrences in the treatment of thyroglossal duct cysts.

Diagnosis and management of maternal and fetal thyroid disorders.

Thyroid diseases in pregnancy are a group of disorders with different clinical manifestations which require a rational approach in their diagnosis and management. In many cases, this involves a team approach including different specialties. Several topics have received particular attention in recently published reports. The syndrome of transient hyperthyroidism of hyperemesis gravidarum, more frequently recognized and considered to be caused by inappropriate concentrations of human chorionic gonadotropin in plasma, has been reported for the first time to be secondary to a mutation in the thyrotropin-releasing hormone receptor. Mutations in the thyrotropin-releasing hormone receptor have also being found in cases, most of them familiar, of congenital hypothyroidism caused by resistance to thyrotropin-releasing hormone. However, other cases of congenital hypothyroidism with resistance to thyrotropin-releasing hormone were not caused by mutations in the thyrotropin-releasing hormone receptor. This is a fascinating new field in molecular medicine, stimulated by clinical observations in infants born with congenital hypothyroidism that did not fulfill the classical clinical descriptions. New studies in the metabolism and transfer of anti-thyroid drugs from mother to fetus have indicated no differences between propylthiouracil and methimazole. Finally, changes in titers and the biological action of thyrotropin-releasing hormone receptors antibodies appear to explain the clinical observation of improvement in Graves' hyperthyroidism during the second half of pregnancy and its recurrence during the postpartum period.

The development of the foetal thyroid: in utero ultrasonographic measurements.

OBJECTIVE: The early recognition of potentially treatable thyroid disease in the foetus frequently depends on the detection of abnormal growth of the foetal thyroid gland. We have therefore established nomograms for foetal thyroid transverse width and circumference from 14 weeks of gestation until term, using transvaginal and transabdominal high-resolution ultrasound techniques. DESIGN: A prospective, cross-sectional study of 193 normal singleton pregnancies was performed. MEASUREMENTS: Thyroid size was measured by transvaginal ultrasonography between 14 and 17 weeks, and by abdominal ultrasound from 18 to 37 weeks of gestation. RESULTS: Data was accurately obtained for 193 foetuses. The mean +/- SD thyroid width and circumference were 11.7 +/- 4.1 mm (95% confidence interval 11.1-12.3) and 39.5 +/- 14.1 mm (95% confidence interval 37.4-41.6), respectively. Thyroid size as a function of gestational age was expressed by the regression equations: thyroid width (mm) = -3.94 + 0.68 x gestational age (weeks), and thyroid circumference (mm) = -1.38 + 0.23 x gestational age (weeks). The correlation coefficients, r = 0.91 and r = 0.93, for thyroid width and circumference, respectively, were found to be highly statistically significant (p < 0.0001). The normal mean of thyroid width and circumference for each week of gestational age and the 95% prediction limits were defined. CONCLUSIONS: The present data offer normative measurements of the foetal thyroid that may facilitate the prenatal diagnosis of foetal goitre and make early administration of in utero treatment possible.

Pathologic intrathyroidal parathyroid glands.

BACKGROUND: Parathyroid glands originate from the third and fourth branchial pouches and migrate caudally to their final positions. Aberrations during migration result in anomalous locations. Intrathyroidal location is not common. METHODS: We reviewed cervical explorations performed from 1974 to 1993 in hyperparathyroidism patients. RESULTS: We found pathological intrathyroidal glands in six patients. Three patients had adenomas (left superior, left inferior and right inferior glands). The hyperplastic glands were left inferior in one patient and right inferior in the remaining two. Intraoperative diagnosis was made in three cases in which palpation of the thyroid gland showed a nodule that was suspected to be the parathyroid missing gland. In three patients it was a finding in thyroidectomy or hemithyroidectomy specimens, two of them with associated thyroid nodular disease. CONCLUSIONS: Ipsilateral thyroidotomy on the side of a palpable thyroid mass or blind hemithyroidectomy are justified if a presumably pathological intrathyroidal gland is suspected, when all other sites in the neck have been excluded.

Fourth branchial arch fistula.

A case is presented of a rare congenital anomaly of the fourth branchial arch, which presented as an abscess in the anterior triangle, related to a fistula communicating with the pyriform fossa. Histopathological examination showed the fistula to be associated with thyroid tissue supporting the hypothesis that the ventral wing of the fourth pouch contributes to the thyroid gland.

Piriform sinus fistula and the ultimobranchial body.

Piriform sinus fistulae are an underlying abnormality common in patients with acute suppurative thyroiditis. The fistulae arise from the hypopharynx, and end in or adjacent to the thyroid lobe. These congenital fistulae seem to be remnants of one of the pharyngeal pouches in embryonic development, but their exact origin is still controversial. Resected specimens of the thyroid glands and fistulae from 15 patients were examined immunohistochemically with rabbit antisera to human calcitonin and thyroglobulin. The fistulae were lined by squamous, columnar or ciliated epithelium, and sometimes formed branches in the thyroid lobe. Near the branches solid cell nests existed. Mucous glands, follicular structures and thymic tissue were found in the fistula. The follicular structures stained for thyroglobulin. Immunostaining for calcitonin revealed aggregates of many C cells in the thyroid near the fistula. A few calcitonin-positive cells were also found in the fistula. These findings, along with the anatomical relation of the fistulae to major structures of the neck, strongly suggest that the fistulae are remnants related to the ultimobranchial body, and that the fistulae trace the migration route of the ultimobranchial body to the thyroid gland.