Transport Across the Cell Membrane
The deiodinases involved in T4 to T3 conversion and T4 and T3 degradation as well as the T3 receptors are located intracellularly. Therefore, both action and metabolism of thyroid hormones are intracellular events requiring transport of iodothyronines across the cell membrane. For a long time it was believed that TH diffused passively over the cell membrane, but recent years of research has made it increasingly clear that cellular transmembrane transport of TH is mediated by transporters, that...
Clinical Outcomes of Congenital Hypothyroidism
Longitudinal growth, final height and pubertal development are typically normal in male and female individuals with CH in whom L-T4 therapy is maintained as recommended 15, 16 . Pubertal timing and final height are independent of etiology, severity of CH and the start of L-T4 treatment, but girls with a higher initial dose L-T4 (> 8 xg kg d) had an earlier onset of puberty 15 . In contrast to physical signs, the neurodevelopmental outcome of patients with CH largely depends on the early...
Fetal Thyroid Function and Maternal Thyroid Hormones
The onset of active fetal thyroid function (FTF) coincides with full maturation of the pituitary portal vessels at 16-20 weeks of gestation 1 . Before the period of FTF, the neocortex of the fetal brain undergoes important phases of development which are largely dependent on the presence of thyroxine (T4) and triiodothyronine (T3) 1, 2 . Low concentrations of T4 and T3 are present in early embryonic and fetal tissue before the onset of FTF in concentrations that are directly influenced...
References
1 Wagner RL, Apriletti JW, McGrath ME, West BL, Baxter JD, Fletterick RJ A structural role for hormone in the thyroid hormone receptor. Nature 1995 378 690-697. 2 Refetoff S, DeWind LT, DeGroot LJ Familial syndrome combining deaf-mutism, stuppled epiphyses, goiter and abnormally high PBI possible target organ refractoriness to thyroid hormone. J Clin Endocrinol Metab 1967 27 279-294. 3 Beck-Peccoz P, Chatterjee VK The variable clinical phenotype in thyroid hormone resistance syndrome. Thyroid...
Child Development
Thyroid hormones are major factors for the normal development of the brain. The mechanisms of actions of thyroid hormones in the developing brain are mainly mediated through two ligand-activated thyroid hormone receptor isoforms 50 . It is known that thyroid hormone deficiency may cause severe neurological disorders resulting from the deficit of neuronal cell differentiation and migration, axonal and dendritic outgrowth, myelin formation and synapto-genesis 23 . This is the situation well...
Thyroid Disease in Turner Syndrome
An association between Turner syndrome (TS) and thyroid disease was first suggested by Atria et al. 1 in 1948 when they reported post mortem findings of a small thyroid gland with lymphocytic infiltration in a young woman with Turner syndrome. Many authors reported on a higher prevalence of hypothyroidism and an association with positive thyroid antibodies in TS patients (table 2) 2, 6, 7, 24, 29, 32, 37 . Hypothyroidism is found in up to 35 of TS patients. Thyroid autoimmunity seems to be even...
Diagnostic WorkUp of Congenital Hypothyroidism
A positive newborn screening result calls for immediate diagnostic work-up. Information on maternal medication or morbidity should be obtained to assess the infant's prenatal thyroid status. Clinical examination should be performed to document signs and symptoms of CH and possible associated malformations. There is an increased risk for other congenital anomalies (8.4 ), including cardiovascular, musculoskeletal and CNS malformations 3 . Confirmatory serum measurements of TSH and T4 are...
Hormones Thyroid Agent
1 Weetman AP Autoimmune thyroid disease propagation and progression. Eur J Endocrinol 2003 148 1-9. 2 Dechairo BM, Zabaneh D, Collins J, Brand O, Dawson GJ, Green AP, Mackay I, Franklyn JA, Connell JM, Wass JA, Wiersinga WM, Hegedus L, Brix T, Robinson BG, Hunt PJ, Weetman AP, Carey AH, Gough SC Association of the TSHR gene with Graves' disease the first disease specific locus. Eur J Hum Genet 2005 13 1223-1230. 3 Simmonds MJ, Gough SCL Genetic insights into disease mechanisms of autoimmunity....
During Gestation
Thyrotropin-releasing hormone (TRH) in the fetal hypothalamus regulates the thyroid-stimulating hormone (TSH) in the pituitary gland early on in the fetus. Pituitary TSH can be detected for the first time around the 10-12th week of gestation. Its concentrations in the serum of the fetus are approximately 3-8mIU l from week 12 and increase gradually during the final weeks of gestation to 10-12 mlU l. This is accompanied by a parallel increase in fetal thyroid radioiodine uptake and by a...
Post 131I Cancer Risks
The increased risk of thyroid cancer after thyroid irradiation in childhood has been recognized for nearly 50 years 70 . Thus, a major concern of 131I therapy relates to the risk of thyroid cancer. Detractors of 131I therapy point to the increased rates of thyroid cancer and thyroid nodules observed in young children exposed to radiation from nuclear fallout at Hiroshima or after the Chernobyl nuclear reactor explosion. The thyroid gland is unique in its developmental sensitivity to malignancy...
Iodine Deficiency
When the aforementioned physiological requirements are not met in a given population, a series of functional and developmental abnormalities occur, including thyroid function abnormalities. Iodine deficiency is now accepted as the most common cause of preventable brain damage in the world. According to the World Health Organization (WHO), iodine deficiency disorders (IDD) affect 740 million people throughout the world, and nearly 50 million people suffer from some degree of IDD-related brain...
The Thyroid and Autoimmunity in Children and Adolescents
School of Medicine and Biomedical Science, University of Sheffield, Sheffield, UK Thyroid autoimmunity is the commonest disease process to affect thyroid function. The prevalence of thyroid autoimmunity increases throughout life, with a possible decline in frequency in the very old as a 'healthy survivor' effect. The mere presence of thyroid autoimmunity, as demonstrated by the presence of thyroid autoantibodies or focal thyroiditis, for example, does not equal thyroid disease, since the...
Hypothyroidism in Infancy Childhood and Adolescence
Hypothyroidism during childhood and adolescence can result from a variety of congenital or acquired defects (table 2). Table 3. Symptoms of childhood hypothyroidism Growth and developmental delay Short stature Infantilism in anthropometric ratios Bone age delay Motor developmental delay Skin and hair Pale, coarse, dry and cold skin Hypertricosis in forehead and neck Rare, dry, thick hair Myopathy and muscular pseudohypertrophy Sluggish motor performance, sleepiness, cold intolerance Some...
Iodine Excess
The thyroid gland has intrinsic regulatory mechanisms that maintain normal thyroid function even in the presence of iodine excess. When large amounts of iodine are given to subjects with normal thyroid function a transient decrease in the synthesis of the thyroid hormones occurs for 48 h. This acute inhibitory effect of iodine on thyroid hormone synthesis is called the acute Wolff-Chaikoff effect and is due to increased intrathyroid iodine concentrations. The escape from or adaptation to the...
Nongenomic Actions Extranuclear Actions
A number of T3 effects occur rapidly and are unaffected by inhibitors of transcription and protein synthesis. The site of these actions has been localized to the plasma membrane, cytoplasm and cellular organelles. The nongenomic actions often have a short latency. Cell culture studies suggest that thyroid hormones rapidly, and nongenomically regulate the Ca2 ATPase enzyme, the Na channel via protein kinase C PKC , the K channel via phosphatidyl-inositol 3 PI3 -kinase, the Na H antiporter via...
Fetal Thyroid Development and Function
The fetal thyroid begins concentrating iodine at 10-12 weeks of gestation and is under control of fetal pituitary thyroid-stimulating hormone TSH by about 20 weeks of gestation 19 . Despite the fetus not possessing a functioning thyroid in early pregnancy there is good evidence that thyroid hormone is important in the development of many organs including the brain. It is now well accepted that maternal circulating T4 crosses the placenta into the fetus at all stages of pregnancy, first shown by...
Clinical Syndrome
The hallmark of Pendred syndrome is the combination of sensorineural deafness and goiter in the presence of a positive perchlorate discharge test. The clinical manifestations of this syndrome can be highly variable between affected families and even within the same family 5 . The true incidence of the syndrome is not known, and depends in part on whether it is defined on a purely clinical basis, or on a genetic basis. The incidence of congenital deafness has been reported to be between 1 1,000...
Pendrins Function in the Thyroid
The exact mechanism by which pendrin functions in the thyroid is still debated. Based on homology with sulfate transporters, it was initially hypothesized that Fig. 4. Structure of the pendrin protein showing 12 transmembrane domains as proposed by Royaux et al. 18 . Circles show some of the more than 100 different mutations identified in patients with Pendred syndrome and DNFB4. The black circles indicate missense and non-sense mutations whereas the gray circles indicate other mutations types...
Hyperthyroidism and Pregnancy
While the commonest cause of hyperthyroidism in pregnancy which affects up to 0.2 of pregnant women is Graves' disease 85-90 , other Table 3. Causes of hyperthyroidism in pregnancy Transient gestational hyperthyroidism associated with hyperemesis gravidarum causes such as hyperemesis gravidarum, toxic multinodular goitre, toxic adenoma and subacute thyroiditis may occur. It should be noted that most women with nausea and vomiting in pregnancy do not have hyperthyroidism. Rarer causes include...
Treatment Approaches for Children
Based on what is now known about the risks and benefits of different treatments and the pathogenesis of Graves' disease, we can now be more selective in our approach to therapy. To reduce treatment risks and expedite cures, the treatment of the child or adolescent with Graves' disease can be guided by the patient's age and the nature of the intrinsic autoimmune disease. For children less than 5 years of age, we consider antithyroid medications as a first line therapy. Although radioactive...
Antithyroid Drug Therapy
Medical treatment in the first half of the century consisted of bed rest, quinine, and iodine in the form of Lugol's solution 98 . Partial thyroidectomy was used to provide permanent cures 98 . With the advent of thiouracil and propylthiouracil PTU in the mid-1940s, medical therapy of Graves' improved markedly 99 . Because of the relatively high incidence of toxic reactions that developed following the administration of thiouracil including agranulocyto-sis, leukopenia, and drug fever, PTU...
Roussel And Dunn 2004 Thyroid Function
1 Delange F The role of iodine in brain development. Proc Nutr Soc 2000 59 1-5. 2 Hetzel BS, Clugston GA Iodine in Shils M, Olson JA, Shike M, Ross AC eds Nutrition in Health and Disease. Baltimore, Williams amp Wilkins, 1999, vol 9, pp 253-264. 3 Dunn JT What's happening to our iodine J Clin Endocrinol Metab 1998 83 3398-3400. 4 Semba RD, Delange F Iodine in human milk perspectives of infant health. Nutr Rev 2001 59 269-278. 5 Dorea JG Iodine nutrition and breast-feeding. J Trace Elem Med Biol...
Effects of Hyperthyroidism on Mother and Child
Several reviews of this subject are available 27-29 . Maternal complications of hyperthyroidism include miscarriage, placenta abruptio and preterm delivery. Congestive heart failure and thyroid storm may also occur and the risk of pre-eclampsia is significantly higher in women with poorly controlled hyperthyroidism and low birth weight may be up to nine times as common. Neonatal hyperthyroidism, prematurity and intra-uterine growth retardation may be observed. A retrospective review documented...
Mechanisms of Thyroid Autoimmunity
It is well established that a complex interplay of diverse environmental and genetic susceptibility factors interact in predisposing an individual to autoimmune thyroid disease fig. 1 . Moreover, the contribution that each factor makes varies from patient to patient, and as yet there are no clear genotype-phenotype correlations. We have shown that polymorphisms in the thyroid stimulating hormone receptor TSH-R are associated with Graves' disease but not autoimmune Genetic factors HLA CTLA-4...
