The Natural Thyroid Diet

The Natural Thyroid Diet

The Natural Thyroid Diet is a guide written to show people suffering from thyroid how to treat it the most natural and effective way. The guide was put together to be something that can be done at home without a need to visit an expert as regards its use. This program is a proven home method useful in eliminating Thyroid rapidly and permanently. It is a combination of useful diets system to help you permanently get rid of your thyroid within 4 weeks. The foods have been tested and have been proven to solve this problem for you. The book is a quick fix that has been designed to help you get a cure for your Thyroid in 4 Weeks. The methods employed in this book are natural ones that have been proven by many specialists. The book is in a digital format (PDF) and has been created at a very affordable price. There are a lot of stress, frustrations and disappointments that come with trying programs after programs. This is one thing that happens in the name of fighting Thyroid; however, this program has been designed to help you stop worrying about programs after programs. The creator is assured of its work that you are allowed to ask for a refund if nothing happens after 4 weeks of its usage. Read more here...

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The Hypothalamic PituitaryThyroid Axis

Thyroid hormones play an important role in normal growth and development of the maturing human. In the adult, thyroid hormones maintain metabolic homeostasis by regulating oxygen consumption, body weight and intermediate metabolism. Thyroid function is under hypothalamic-pituitary control. Thus, thyroid hormones are produced by the thyroid gland in response to stimulation by thyroid-stimulating hormone (TSH) produced by the anterior pituitary. TSH, in turn is regulated by the hypothalamic peptide, thyrotropin-releasing hormone (TRH). The function of the entire complex is modified by the availability of the thyroid hormones in a typical negative feedback manner leading to the concept of a functional unit, the hypothalamic-pituitary-thyroid (HPT) axis. This chapter focuses on the ontogenesis and functional anatomy of the hypothalamic-pituitary system first, and the thyroid gland itself. Emphasis is placed on the molecular aspects regarding the morphogenesis of the functionally linked...

Thyroid Disease during Pregnancy

The prevalence of hyperthyroidism is around 5 per 1,000 and hypothyroidism about 3 per 1,000 in women. As the conditions are generally much more common in the female it is to be expected that they will appear during pregnancy. Developments in our understanding of thyroid physiology 1 and immunology 2 in pregnancy as well as improvements in thyroid function testing 3 have highlighted the importance of recognising and providing appropriate therapy to women with gestational thyroid disorders. Before considering the clinical entities occurring during and after pregnancy it is useful to briefly review thyroid physiology and immunology in relation to pregnancy.

Management of Graves Hyperthyroidism

Guidelines for measurements of thyroid-stimulating hormone-receptor antibodies in a pregnant woman with Graves' disease (reproduced from Laurberg et al. 37 , with permission from the Society of the European Journal of Endocrinology) allay fears which are commonly present in these women. The patient's thyroid status should be checked frequently to minimise risk of miscarriage should she be hyperthyroid at the time of conception. If treatment had been commenced with methimazole or carbimazole a change to propylthiouracil (PTU) is recommended to reduce the admittedly rare occurrence of aplasia cutis 35 and the equally rare methimazole embryopathy 36 reported following the administration of the former drugs. The patient may have been rendered euthyroid by partial thyroidectomy or radioiodine therapy. However, if these procedures are performed the patient may require thyroxine therapy (with a requirement for an increase in dose and monitoring during gestation) in addition, there...

Thyroid Function in the Newborn and Infant

The thyroid gland is an endocrine organ of vital importance for the neonate since normal thyroxine concentrations are essential for the normal neurodevelopment of the newborn and subsequently the infant and child. The recent advances in our understanding of fetal thyroid hormone physiology have also shown the importance of the placental transfer of maternal thyroid hormones and the normal function of the fetal thyroid gland for normal brain development of the fetus with subtle differences in the outcome of the term newborn as opposed to the preterm newborn.

Maternal Fetal Unit and the Function of the Fetal Thyroid Gland

Grows and obliterates the exocoelomic cavity (fig. 1b) considerably changing the maternal-fetal exchange pathways. From the 11 to 12th weeks of gestation and onward, maternal nutrients, including thyroid hormone, are transferred by the placenta directly into the fetal circulation. The placenta plays an important role in the development and function of the thyroid gland in the fetus. The placenta produces various hormones that can influence the fetal thyroid gland (e.g. chorionic gonadotropin, TRH). The most important role of the placenta though is in regulating the passage of hormones and drugs, from the mother to the embryo, which influence the fetal thyroid gland. For many years its was unknown how the very small amounts of maternal T4 which are allowed to pass the placental barrier (sometimes as low as 1 of the maternal concentrations in the first trimester) can play such a major role in the normal fetal physiology of the developing brain and fetal tissues. The answer came from...

Action of the Thyroid Hormones

The action of the thyroid hormones in the adipose tissue, the liver, the heart, the muscles and the bones are expressed during neonatal but not fetal life. It is not known whether this delay in the action of the thyroid hormones in these tissues is related to the maturation of the thyroid hormone signaling pathway at a molecular level or related to the maturation of thyroid hormone metabolism. The actions of the thyroid hormones, which are specific to each individual tissue, depend on the prevalent isoform of the thyroid hormone receptor (TR) which is expressed in each tissue and on cofactors at the site of action of the thyroid hormones. The highest concentrations of TRs are found in developing neurons and in various regions in the brain of the fetus and the neonate such as cortex, cerebellum, and visual and auditory cortices. There are many indications that the TR 1 isoform of the receptor is the one which promotes, via T3, the vital development of the central nervous system in the...

Thyroid Synthesis in the Full Term Newborn

During the birth process many changes occur in the function of the thyroid gland in the full-term neonate. The most dramatic change is the abrupt increase in TSH which takes place in the first 30 min after parturition which can reach levels of 60-70 mlU l. This increase causes a major stimulation of the thyroid gland with an increase in T4 in the serum by about 50 and a 3- to 4-fold increase in T3 within 24h 36, 37 . Studies in experimental animals have shown that the increase in TSH is a consequence of the relative hypothermia that exists in the environment outside of the uterus. The increase in T3 occurs not only because TSH levels increase but also because of an increase in the action of type I deiodinase during birth. The high levels of reverse T3 (rT3) decrease relatively quickly during the neonatal period. The increase in the action of type II deiodi-nase causes an increase in T3 in the adipose tissue of the neonate which is necessary for thermogenesis and the synthesis of...

Thyroid Synthesis in the Pre Term Newborn

The function of the thyroid gland in the pre-term neonate reflects the immaturity of the hypothalamic-pituitary-thyroid axis which corresponds to the week of gestation of the pre-term neonate. There is a gradual increase in the concentration of TSH, TBG, T3 and T4 during gestation 42, 43 . After parturition there is an increase in T4 and TSH just as in full-term neonates, but the increase is much smaller in pre-term neonates than what it is in the full-term neonates and there is a dramatic decrease in the concentration of T4 during the following 1-2 weeks 44 . This decrease in T4 is more important in low birthweight and significantly premature neonates (< 1.5 kg and < 30 weeks of gestation) where the level of T4 may not be detectable 44, 45 . In most cases though total T4 is influenced and not FT4 as much since TBG is low in pre-term neonates due to immaturity of the liver. Another reason for the fall in T4 in pre-term neonates is the reduced storage of iodine which exists due to...

Function of the Thyroid Gland in the Neonate and Infant

After the large increase in the serum concentrations of the thyroid hormones and TSH which occur during the first days of neonatal life there is a gradual decrease in the levels of T4, T3 and TSH during the life of the neonate and infant. The most important difference between this period and adult life is that there is a larger production and utilization of T4 in the neonates and infants. The neonates produce 5-6 xg kg day of T4 with a gradual decrease during the first years of life to reach levels of 2-3 xg kg day of T4 at 3-9 years of age. This is in contrast to adults who produce 1.5 xg kg day of T4 42 . The weight of the neonatal thyroid gland is a good indicator of maternal iodine intake during pregnancy. On an adequate maternal iodine intake, the weight of the neonatal thyroid is less than 1.5 g 48 . Due to the increased turnover of iodine and consequently of thyroglobulin in the early neonatal period, decreased iodine intake will bring about an increased consumption of reserve...

Thyroid Hormone Transport

More than 99 of the circulating thyroid hormone is bound to plasma proteins but can be liberated with great rapidity for entry into cells. The thyroid hormone-binding proteins are comprised of thyroxine-binding globulin (TBG), transthyretin (TTR or thyroxine-binding prealbumin), human serum albumin (HSA) and lipoproteins. Their functions are most probably to ensure a constant supply of TH to the cells and tissues by preventing urinary loss 3 , protect the organism against abrupt changes in thyroid hormone production and degradation, protect against iodine deficiency 2 and target the amount of TH delivery by ensuring a site-specific, enzymatic alteration of TBG 4 . TBG has by far the highest affinity for T4, the result of which being that TBG binds 75 of serum T4, whereas TTR binds 20 and HSA 5 2 . Some of the properties of the binding proteins are displayed in table 1. Table 1. Some properties and metabolic parameters of the prinicpal thyroid hormone-binding proteins in serum...

Causes of hypothyroidism

Hashimoto's thyroiditis most common cause associated with other autoimmune diseases (e.g., pernicious anemia, vitiligo, lupus). Look for positive antimicrosomal antibodies. Histology shows lymphocyte infiltration of the gland. 2. Subacute thyroiditis acute viral inflammation with fever and enlarged, tender thyroid gland. History of upper respiratory infection or mumps is common. Give NSAIDs for symptom relief. Patients often recover without treatment. Hyperthyroidism symptoms include nervousness, anxiety, insomnia, tachycardia, palpitations, atrial fibrillation, heat intolerance, weight loss, diarrhea, menstrual irregularities (hypomenorrhea), increased appetite, and thyroid stare. Check thyroid function tests. Usually TSH is low, andT4 (primary) is high. Exophthalmos and pretibial myxedema are specific for Graves' disease. Treatment begins with antithyroid drugs (propylthiouracil or metliimazole). Most patients eventually require further therapy. Use surgery for patients under 25 or...

Genomic and Nongenomic Actions of Thyroid Hormones

As mentioned above, the biological activity of thyroid hormones is largely exerted by T3 and is determined by the intracellular T3 concentration, which is Most thyroid hormone actions are initiated by an interaction of T3 with specific nuclear receptors, which act largely as transcription factors exerting a modifying effect on the expression of a variety of genes, the genomic actions. However, extranuclear processes may also contribute to the overall biologic actions of thyroid hormones 88-90 . These effects occur rapidly and are shown to be unaffected by inhibitors of transcription and translation suggesting that thyroid hormones may also mediate non-genomic actions reviewed in 91 . The heart is a major target organ for thyroid hormone action, and the T3 effects are shown to be mediated by both nuclear and extranuclear mechanisms leading to enhanced velocity of cardiac contraction and increased speed of diastolic relaxation reviewed in 92 .

Genetic and Other Causes of Congenital Hypothyroidism

CH represents a heterogeneous group of thyroidal and non-thyroidal disorders (fig. 1), leading to decreased or absent thyroid hormone action and clinical sequelae. In 70-80 of the cases thyroid dysgenesis is found due to agenesis (30 ), ectopic gland (48 ) or hypoplastic, eutopic gland (5 ) 3 . A normal (11 ) or enlarged thyroid gland (6 ) is observed in children with disorders of thyroid hormone synthesis. Up to 15 of cases with CH occur on a hereditary basis (table 1), while the remaining majority of cases are considered sporadic forms. Isolated thyroid dysgenesis may be caused by inactivating ('loss-of-function') mutations of the TSH receptor (TSHR) (fig. 2). CH in association with various complex syndromes is found in patients carrying mutations of thyroid transcription factors PAX8, TITF1, TITF2 or the stimulatory G protein a-subunit Gene Protein Heredity Thyroid Associated

Clinical Outcomes of Congenital Hypothyroidism

Children with CH may have selective deficits on visual, language, motor, attention and memory abilities 21 . Auditory brainstem evoked potentials were abnormal in 25 of early-treated patients with CH 22 . Recent studies have comprehensively analyzed the temporal patterns of thyroid hormone action in the developing brain 21 . Hypothyroidism in early pregnancy is related to impaired visual attention and processing as well as gross motor abilities. It has to be considered that syndromatic forms of CH due to functional defects of thyroidal transcription factors or the iodothyronine transporter (table 1) may adversely affect CNS development independent of circulating thyroid hormone levels. The long-term perspective for normal mental and neurologic development is poor for infants with CH not detected by newborn screening. Physical symptoms and growth may normalise when L-T4 treatment is started later but within the first months of life but infants with severe perinatal hypothyroidism...

Resistance to Thyroid Hormone in Childhood

Occasionally, a patient is seen in the clinic with apparent hypo- and or hyperthyroid symptoms but with conflicting results of thyroid function tests they have a nonsuppressed or even slightly increased TSH inappropriate for the invariably increased free T4 in serum. This combination of hormone levels can have several causes but there are two major ones namely a TSH-producing pituitary adenoma and resistance to thyroid hormone (RTH). The latter will be the subject of this chapter. The basic problem in RTH is a decreased sensitivity of tissues to thyroid hormone. The decreased sensitivity is also present in the pituitary, where it leads to a blunting of the feedback of thyroid hormone on the pituitary. This in turn results in the above mentioned increased secretion of TSH and thereby of T4. As will be explained below, the insensitivity is caused by mutations in the thyroid hormone receptor beta isoform that reduce thyroid hormone binding affinity. This does not just lead to a...

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 Clinical autoimmune thyroid disease Clinical autoimmune thyroid disease Fig. 1. Interaction of factors predisposing to autoimmune thyroid disease. hypothyroidism 2 . The other known genetic loci associated with thyroid autoimmunity, namely HLA, CTLA-4 and PTPN22, are shared between these 2 thyroid conditions, as well as many other autoimmune diseases reviewed in 3 . Several environmental factors have been delineated but some of these remain controversial and of unknown action, such as smoking and stress 4, 5 . Evidence...

Thyroid Gland Capillary Network

An extraordinarily rich vascularization is the common characteristic of all endocrine organs. A capillary network encircles the thyroid follicles (see Fig.360). This figure provides a vivid image of the capillary network at the surface of feline thyroid follicles. An interlobular artery is seen in the lower part of the figure. It continues in interfollicular vessels. In this preparation, the vessel system of the thyroid gland was only partially filled with resin. The capillary network is in reality much more elaborate.

Antithyroid drugs for longterm therapy C Thiourea derivatives

Antithyroid Drugs Action

Perchlorate, given orally as the sodium salt, inhibits the iodide pump. Adverse reactions include aplastic anemia. Compared with thioamides, its therapeutic importance is low but it is used as an adjunct in scintigraphic imaging of bone by means of technetate when accumulation in the thyroid gland has to be blocked. Short-term thyroid suppression (C). Iodine in high dosage (> 6000 jg d) exerts a transient thyrostatic effect in hyperthyroid, but usually not in euthyr-oid, individuals. Since release is also blocked, the effect develops more rapidly than does that of thioamides. Clinical applications include preoperative suppression of thyroid secretion according to Plummer with Lugol's solution (5 iodine + 10 potassium iodide, 50-100 mg iodine d for a maximum of 10 d). In thyrotoxic crisis, Lugol's solution is given together with thioamides and p-blockers. Adverse effects allergies contraindications iodine-induced thyrotoxicosis. Lithium ions inhibit thyroxine release. Lithium salts...

Effects of Hyperthyroidism on Mother and Child

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 a 5.6 incidence of fetal death or stillbirth in 249 pregnancies from hyperthyroid mothers and a further 5 fetal and neonatal abnormalities. Women with thyroid hormone resistance who, despite being euthyroid, had high levels of circulating T4 had a significantly increased miscarriage rate compared to euthyroid unaffected couples 30 . However, a recent study of women with subclinical hyperthyroidism, comprising 1.7 of women, showed no significant adverse pregnancy outcomes suggesting that treatment of this condition in pregnancy is not warranted 31 . Nevertheless, there is no doubt that overt clinical and biochemical hyperthy-roidism should...

Treatment of Hyperthyroidism Due to Graves Disease in Children

Yale Pediatric Thyroid Center, Department of Pediatrics, Yale University School of Medicine, New Haven, Conn., USA Total thyroidectomy is an effective treatment of Graves' disease, with a low rate of disease recurrence. Long-term complications include recurrent laryn-geal nerve paresis in 2 or more of individuals, permanent hypoparathy-roidism in 1 or more, and hypertrophic and non-hypertrophic scars. Surgery is the preferred definitive treatment for the very large thyroid gland and when the individual is considered too young for 131I. When used at doses that deliver 150 Gy, or more (> 150 xCi 131I g thyroid tissue), radioactive iodine is an effective cure for Graves disease and is associated with few acute side effects. Potential long-term adverse side effects, including thyroid cancer and genetic damage, have yet to be observed in individuals treated as children or adolescents with 131I.

Roussel And Dunn 2004 Thyroid Function

14 Morreale de Escobar G, Obregon MJ, Escobar del Rey F Role of thyroid hormone during early brain development. Eur J Endocrinol 2004 151 U25-U37. 15 Pemberton HN, Franklyn JA, Kilby MD Thyroid hormones and fetal brain development. Minerva Ginecol 2005 57 367-378. 17 Vulsma T, Gons MH, de Vijlder J Maternal-fetal transfer of thyroxine in congenital hypothy-roidism due to a total organification defect or thyroid agenesis. N Engl J Med 1989 321 13-16. 19 Glinoer D The regulation of thyroid function in pregnancy pathways of endocrine adaptation from physiology to pathology. Endocr Rev 1997 18 404-433. 22 Delange F Screening for congenital hypothyroidism used as an indicator of IDD control. Thyroid 1998 8 1185-1192. 29 Bernal J Thyroid hormones and brain development. Vitam Horm 2005 71 95-122. 33 Hetzel BS, Potter BJ Iodine deficiency and the role of thyroid hormones in brain development in Dreosti JE, Smith RM (eds) Neurobiology of the Trace Elements. Clifton, Humana, 1983, pp 83-133. 34...

Childhood Hyperthyroidism

Hyperthyroidism occurs much less commonly in children than hypothyroidism, yet is a far more virulent condition 7, 8 . In children the most common cause of childhood thyrotoxicosis is Graves' disease, which is characterized by diffuse goiter, hyperthyroidism and occasionally ophthalmopathy 6, 9-11 . Other causes of childhood hyperthyroidism include toxic nodules, toxic multinodular goiters, acute and subacute thyroiditis, and the ingestion of thyroid hormone 6, 9-11 . Untreated, hyperthyroidism is associated with excessive activity, tremor, tachycardia, flushing, palpitations, accelerated linear growth, weight loss, impaired skeletal mineralization, and poor school performance 6, 9-11 . Because Graves' disease, toxic nodules and toxic multinodular goiters only rarely spontaneously resolve within a short period, treatment of hyper-thyroidism is essential. Current treatment options include the use of radioactive iodine, surgery, and antithyroid medications.

Experimental Autoimmune Thyroiditis in the Mouse

Experimental autoimmune thyroiditis (EAT) in mice is an excellent model for Hashimoto's thyroiditis (HT). It is induced with thyroglobulin (Tg), a known thyroid autoantigen that is common to both mouse and human and for which several conserved, thyroiditogenic epitopes have been identified. Basic Protocol 1 describes induction and evaluation of EAT. A homologous antigen, mouse (MTg), is used because it has additional unique epitope(s) and induces more severe and long-lasting thyroid inflammation than heterologous mammalian Tg induces. Susceptibility of mouse strains is based on major histocompatibility complex (MHC) class II genes H-2 haplotypes k and s are susceptible, b, d, and f are resistant, and q is intermediate. EAT is evaluated using appropriate assay parameters thyroid histology and in vitro proliferative response (see Support Protocol 2). Thyroid histology distinguishes susceptible from resistant strains and shows the extent of mononuclear cell infiltration and destruction...

Induction And Evaluation Of Experimental Autoimmune Thyroiditis

Two adjuvants, bacterial lipopolysaccharide (LPS) and supplemented complete Freund's adjuvant (CFA see Alternate Protocol), are widely used to facilitate induction of experimental autoimmune thyroiditis (EAT) with mouse thyroglobulin (MTg). These adjuvants are particularly useful if spleen cells (LPS) and lymph node cells (CFA) are to be used for adoptive transfer (see Basic Protocol 2). LPS is preferred to CFA because there is no antigen loss associated with preparing an emulsion, and the use of LPS as an adjuvant results in more uniform disease induction (see Background Information). Moreover, two injections of MTg are generally required to induce EAT, and some institutional animal care and use committees (IACUC) do not permit two CFA doses per animal. Of the three parameters to evaluate EAT, the most important is histologic evaluation of mononuclear cell infiltration of the thyroid gland. Second is the in vitro T cell proliferative response to MTg (see Support Protocol 2), which...

Adoptive Transfer Of Experimental Autoimmune Thyroiditis

Adoptive transfer of experimental autoimmune thyroiditis (EAT) has recently been used to characterize T cell epitopes of thyroglobulin (Tg). Clones of the Tg gene have provided complete (human and bovine) or partial (porcine, rat, and mouse) amino acid sequences for the entire or large portions of the 660-kDa molecule (Kong et al., 1995). Thus far, no immunodominant epitopes have been uncovered, and the role of Tg peptides in patho-genesis can only be ascertained if they expand T cells in vitro and transfer thyroiditis to normal syngeneic recipients. This protocol can be used to examine conserved epitopes, the role of iodination of Tg peptides in immunogenicity, T cell receptor (TCR) VP gene usage, and the role of adhesion molecules in infiltration. The interval between immunization (Basic Protocol 1) and removal of lymphoid organs is similar to that listed for T cell proliferation assay (Support Protocol 2). After immunization with MTg and lipopolysaccharide (LPS), spleen cells can...

Induction Of Tolerance To Experimental Autoimmune Thyroiditis

Susceptible mice are normally unresponsive when immunized with mouse thyroglobulin (MTg) without adjuvant. However, they become resistant to experimental autoimmune thyroiditis (EAT) induction after pretreatment with two doses of deaggregated MTg (dMTg) given 7 days apart. Within 3 days after the second dose, EAT induction is virtually suppressed, and resistance lasts for > 73 days. Suppression is mediated by CD4+ cells. Thus, this protocol permits the study of regulatory T cell mechanisms in an autoimmune disease it simulates the endogenous release of circulatory MTg following thyroid-stimulating hormone infusion which also leads to CD4+ T-cell-mediated suppression. Note that two groups of mice are used tolerized and nontolerized mice.

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 PTU and MMI reduce thyroid hormone synthesis by inhibiting the oxidation and organic binding of thyroid iodide 100, 101 . These medications are not curative. Rather, they palliate the hyperthyroid state until it spontaneously resolves or definitive treatment is rendered. In contrast to oral iodine therapy (see below), thiouracil drugs do not prevent thyroid gland hyperplasia. Thus, thyroid enlargement may occur during therapy. The thyroid gland may become softer and the outlines of the gland more difficult to distinguish 99 . Because radioactive iodine is less effective in large than in small glands 59, 99, 107 , thyroid size should be continuously monitored for progressive thyroid...

Hyperthyroidism and Pregnancy

Subacute thyroiditis 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 struma ovarii, hydatidiform mole and one reported case of a TSH receptor mutation activated only during pregnancy 27 (table 3). The clinical suspicion of hyperthyroidism may not be obvious as symptoms of tachycardia, sweating, dyspnoea and nervousness are seen in normal pregnancy as are cardiac systolic flow murmurs. The diagnosis should always be confirmed by estimation of circulating thyroid hormone concentrations. It should be noted that serum thyroxine (both total and free) varies during normal gestation. Recent national and internationally agreed guidelines suggest that laboratories should be encouraged to develop normal ranges for total but more particularly free T4 and T3, as well as TSH after the 1st trimester during...

Immunopathogenesis of Thyroid Eye Disease

The orbital fibroblasts are widely viewed as the target cells of the autoimmune attack in GO. During the early stages of the disease, macrophages, highly specialized T cells, mast cells, and occasional plasma cells infiltrate the orbital connective, adipose, and muscle tissues 4, 5 . Activation of T cells directed against a thyroid follicular cell antigen(s) that then recognizes and binds to a similar antigen(s) in orbital tissue is a probable but yet unproven theory 2 . The orbital fibroblasts do express functional TSH receptors (TSH-R). This recent finding has led to the currently favored view that the TSH-R is the long sought after shared antigen between the thyroid and the orbit and that the TSH-R is the autoantigen involved in GO. Indeed, cytokine-induced differentiation of a particular subset of orbital fibroblasts into adipocytes is associated with increased TSH-R expression and adipogenesis 16 . A causative role of stimulating TSH-R antibodies (TSI) in the development of GO is...

Pendrins Function in the Thyroid

Thyroid Pendrin

The exact mechanism by which pendrin functions in the thyroid is still debated. Based on homology with sulfate transporters, it was initially hypothesized that 29 reported that pendrin is responsible for iodide efflux from the follicular cells into the colloid. They also report that in the thyroid, iodine is transported in exchange for chloride, whereas in other tissues, it is hypothesized that pen-drin's main function is to transport chloride through exchange with other anions In normal thyroid, pendrin is expressed at low levels on the apical membrane of follicular cells. Thyroids from patients with Graves' disease display a similar, albeit more extensive, expression of pendrin when compared to normal thyroid tissue, especially in areas with increased proliferation of the follicular cells. In contrast, immunohistochemical staining was absent and mRNA levels were significantly lower in papillary carcinoma when compared to normal and other neoplastic diseases of the thyroid. These...

Synthesis and Release of Thyroid Hormones

Follicle cells synthesize and secrete thyroglobulin from their apical surfaces into the follicle lumen where it is stored. The follicle lumen is an extracellular compartment and, thus, secretion of thyroglobulin constitutes the exocrine secretion of the follicle cells and accounts for the polarity of the cells. The tyrosines of thyroglobulin are iodinated in the follicle lumen and rearranged to form the thyroid hormones (T3 and T4), which are modified tyrosines that are retained in the primary structure of thyroglobulin. embedded in the posterior surface of the thyroid gland. Cell types

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 Vulsma et al. 20 . The precise mechanism of placental T4 transport is not clear but the important role of both the type 2 and type 3 deiodinase enzymes, both expressed in the placenta, has been recognised. Type 2 deiodinase is also located in the uterus and other parts of the genital tract and may have a role in fetal implantation 21 . In the fetus it is expressed in the brain and its action supplies that developing organ with T3. Type 3 deiodinase (D3), which degrades thyroid hormones, is...

Thyroid hormone synthesis

* Iodide trapping by the thyroid gland (iodide pump in the basolateral membranes of the follicular epithelial cells sodium-iodide co-transport-symport) * Iodide oxidation to free iodine (peroxidase-H2O2 system). Thyroid peroxidase is a membrane-bound glycoprotein with a molecular weight of 102 000 and a hame compound as the prosthetic group. It is synthesised in the rough endoplasmic reticulum. * Thyreoglobulin synthesis by the endoplasmic reticulum of the thyroid cells. Thyroglobulin is a homo-dimeric glycoprotein with 5496 amino acids and a molecular weight of 660 000. The glycosylation of thyroglobulin is completed in the Golgi apparatus prior to secretion into the colloid of the follicular lumen. * Coupling of the iodotyrosines to give iodothyronines MIT + DIT triiodothyrosine (T3) DIT + DIT thyroxine (T4). The iodination and subsequent coupling reactions are catalysed by thyroid peroxidase. * The synthesis of thyroid hormone occurs at the apical membranes of the follicular...

Hypothalamicpituitarythyroid axis

The hypothalamic-pituitary-thyroid axis is an integrated organ complex providing for the regulated production of thyroid hormones. It is affected by the following factors Hypothalamic TRH production Increased dopamine, noradrenaline Decreased T3, T4, glucocorticoids Pituitary TSH production Increased TRH Decreased dopamine, oestrogens, T3, T4, glucocorticoids Thyroid gland hormone production Increased TSH, iodine, human chorionic gonadotrophin (HCG), catechol-amines Thyroid function tests e Serum thyroid hormones T4, free T4, T3, free T3, thyroglobulin. h Tests of the thyroid-pituitary axis Dynamic tests of thyroid activity Table 10.1 Hypothalamic-pituitary-thyroid axis dysfunction Decreased iodine, medications (lithium anti-thyroid medication) dietary goitrogens Thyroid stimulating hormone is a glycoprotein, with an alpha chain of 89 amino acids and a beta chain of 112 amino acids.

Imaging of the Normal and Affected Thyroid in Childhood

Imaging has undergone major advances over the past three decades and has revolutionized the evaluation of patients with thyroid disease. However, the use of thyroid imaging is in general not evidence-based, and there have been few cost-benefit evaluations of medical imaging 1 . The thyroid gland can be evaluated by several imaging techniques (1) radionuclide imaging, and (2) nonisotopic imaging comprising (a) ultrasonography (US) (b) computed tomography (CT), and (c) magnetic resonance imaging (MRI). A recent development has been the combination of PET (positron emission tomography) and CT for oncologic imaging. Each has advantages and limitations, and there is no absolute clinical indication for performing any of them in the majority of patients 1, 2 . In this chapter emphasis will be on the clinical use of US in childhood.

Thyroid Disease in Diabetes Mellitus

The most frequent autoimmune disease in type 1 diabetes affects the thyroid. The etiology of autoimmunity in pancreas and thyroid is a T cell-mediated disease and seems to be due to common genetic susceptibility. Two immune regulatory genes (HLA human leukocyte antigen and CTLA-4 cytotoxic T lymphocyte-associated protein 4) contribute to the susceptibility for both diseases 5, 23 . This locus, also known as the IDDM 12 gene, seems to play a major role in development of autoimmune polyglandular syndrome type 2 (APS-2). Autoimmunthyroiditis describes a group of thyroid diseases with destruction of thyroid tissue due to an autoimmune reaction. Classification of these diseases is not consistent in the literature. Most frequently, Hashimoto thyroidi-tis with antibodies against thyroid antigens is found. These antibodies are directed towards thyroid peroxidase (TPO-Ab), thyreoglobulin (TG-Ab) and or TSH-receptor antigen (TRAK). Positivity for thyroid auto antibodies in children with type 1...

Description Surgical Thyroid Procedures

I hyroid cancer is the most common endocrine cancer, and the number of new cases in the United States is increasing annually by 3 per 100,000. Most thyroid nodules or tumors develop from thyroid follicular cells 95 of these nodules and tumors are benign. The remaining 5 of 896 Thyroid Cancer thyroid nodules or tumors are cancerous, and there are several forms of thyroid cancer. Papillary carcinoma is the most common form of primary thyroid cancer. It is also the slowest-growing thyroid cancer and is usually multifocal and bilateral in distribution. Papillary carcinoma metastasizes slowly into the cervical lymph nodes and the nodes of the mediastinum and lungs. Follicular cancer is the next most common form. It is more likely to recur than other forms it generally metastasizes to the regional lymph nodes and is spread by the blood to distant areas such as the bones, liver, and lungs. More than 90 of patients treated for either papillary or follicular carcinoma will live for 15 years or...

Hypothyroidism Introduction

Hypothyroidism is the result of inadequate thyroid hormone production to maintain body processes. It may be the result of congenital thyroid abnormality and therefore present in infancy or it may become notable during the first two years of life. It appears later when production is inadequate to maintain body processes as rapid growth increases the need for hormones. Acquired causes of the condition may be thyrotoxicosis, thyroidectomy, irradiation, infections, and dietary deficiency of iodine. Secretions of the thyroid gland include thyroid hormone (thyroxine, T4 and triiodothyronine, T3) which are bound to proteins in the blood (thyroxine-binding globulin, TBG) and thyrocalcitonin (maintains calcium levels in blood). The hormones are controlled by the thyroid-stimulating hormone (TSH) that is secreted by the anterior pituitary gland. Treatment of hypothyroidism is by thyroid hormone replacement, which involves prompt intervention in the infant and gradually increasing amounts of...

Thyroid Hormone Therapy

Effect Thyroid Hormornes Cells

Thyroid hormones accelerate metabolism. Their release (A) is regulated by the hypophyseal glycoprotein TSH, whose release, in turn, is controlled by the hypothalamic tripeptide TRH. Secretion of TSH declines as the blood level of thyroid hormones rises by means of this negative feedback mechanism, hormone production is automatically adjusted to demand. The thyroid releases predominantly thyroxine (T4). However, the active form appears to be triiodothyronine (T3) T4 is converted in part to T3, receptor affinity in target organs being 10-fold higher for T3. The effect of T3 develops more rapidly and has a shorter duration than does that of T4. Plasma elimination t1 2 for T4 is about 7 d that for T3, however, is only 1.5 d. Conversion of T4 to T3 releases iodide 150 jig T4 contains 100 jig of iodine. Replacement therapy of hypothyroidism. Whether primary, i.e., caused by thyroid disease, or secondary, i.e., resulting from TSH deficiency, hypothy-roidism is treated by oral administration...

Hypothyroidism in Infancy Childhood and Adolescence

The child with severe primary hypothyroidism may develop enlargement of the cella tursica. After radiologic examination, the detected mass represents hypertrophy and hyperplasia of thyrotrophs in response to lack of negative feedback by thyroid hormones 43 . In laboratory evaluation they have high levels of TSH with low levels of T4. Measurement of TSH and thyroid hormones, antithyroid antibodies namely thyroperoxidase (TPOAb) and thyroglobulin (TGAb) should be obtained. The presence of the antibodies permits the diagnosis of autoimmune thyroiditis. A hypothalamic cause vs. pituitary origin of the hypothyroidism with low serum free T4 and TSH levels can be distinguished by TRH testing. In children with hypothalamic hypothyroidism the peak serum TSH response to TRH is often delayed beyond 30min, and the TSH response may be prolonged with serum TSH values that remain elevated for 2-3 h. In hypopituitarism, there is little or no TSH response to TRH. Thyroid hormone resistance is...

The Thyroid and Autoimmunity in Children and Adolescents

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 majority of people with focal thyroiditis do not become hypothyroid 1 . On the other hand, as far as we know the formation of thyroid-stimulating antibodies (TSAb) leads to Graves' disease in the great majority of subjects, even if in rare cases their levels may oscillate and be associated with a fluctuating clinical course. After a brief review of the basic immunological mechanisms which underlie autoimmune thyroid diseases, this chapter will focus on the comparatively few studies which have looked specifically at the pathogenic mechanisms in these disorders in children and...

Hormones Thyroid Agent

1 Weetman AP Autoimmune thyroid disease propagation and progression. Eur J Endocrinol 2003 148 1-9. 4 Vestergaard P Smoking and thyroid disorders. Eur J Endocrinol 2002 146 153-161. 9 Penhale WI, Farmer A, McKenna RP, Irvine WJ Spontaneous thyroiditis in thymectomized and irradiated Wistar rats. Clin Exp Immunol 1973 15 225-236. 11 Chen F, Day SL, Metcalfe RA, Sethi G, Moses S, Kapembwa M, Brook G, Churchill D, de Ruiter A, Robinson S, Lacey CJ, Weetman AP Characteristics of autoimmune thyroid disease occurring as a late complication of immune reconstitution in patients with advanced human immunodeficiency virus (HIV) disease. Medicine (Baltimore) 2005 84 98-106. 13 McIntosh RS, Asghar MS, Weetman AP The antibody response in human autoimmune thyroid disease. Clin Sci 1997 92 529-541. 14 Gilbert JA, Gianoukakis AG, Salehi S, Moorhead J, Rao PV Khan MZ, McGregor AM, Smith TJ, Banga JP Monoclonal pathogenic antibodies to the thyroid-stimulating hormone receptor in Graves' disease with...

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 required, along with thyroid hormone binding proteins and serum free T4. In cases of maternal autoimmune thyroid disorder, assessment of TSHR blocking antibodies may indicate a transient form of CH. Thyroglobulin levels tend to be high in dyshormonogenesis and low in thyroid agenesis. Thyroid ultrasonography and or thyroid scan are considered optional for management of CH 1 but are necessary to clarify the underlying source of CH, to distinguish between thyroid aplasia, ectopy or inborn errors of T4...

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 more common in females with Turner syndrome with a prevalence of up to 52 15 . A positive family history was reported by Wilson et al. 37 . This group found an increased incidence of thyroid antibodies in patients with TS and their first degree relatives. The incidence of thyroid antibodies was 30 in patients compared to 1.7 in an age matched control group and 22 in the mothers of the TS patients (vs. 6.6 in the controls). Larissa et al. 21 found a preferential parental segregation of...

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 (especially the T4 levels) by those in the maternal circulation 3-14 . When maternal T4 and T3 concentrations are abnormally low in the first trimester, fetal brain development is adversely affected and there is a defect in the histogenesis and cerebral cortex cytoarchitecture, defective neuronal migration at the beginning of fetal neocorticogenesis, and a defective cortical expression of several genes in the fetal brain such as neuroendocrine-specific protein A 15, 16 . At the time of neural tube...

Thyroid Drugs

Levothyroxine sodium Action Kinetics The thyroid manufactures two active hormones thy-roxine and triiodothyronine, both of which contain iodine. These thyroid hormones are released into the bloodstream, where they are bound to protein. Synthetic derivatives include liothyronine (T3), levothyro-nine (T4), and liotrix (a 4 1 mixture of T4 and T3). The thyroid hormones regulate growth by controlling protein synthesis and regulating energy metabolism by increasing the resting or basal metabolic rate. This results in increases in respiratory rate body temperature CO oxygen consumption HR blood volume enzyme system activity rate of fat, carbohydrate, and protein metabolism and growth and maturation. Excess thyroid hormone causes a decrease in TSH, and a lack of thyroid hormone causes an increase in the production and secretion of TSH. Normally, the ratio of T4 to T3 released from the thyroid gland is 20 1 with about 35 of T4 being converted in the periphery (e.g., kidney, liver) to T3. Uses...

Thyroid Gland

Thyroid follicles are mostly round or ovoid. They are encased by a single-layered epithelium of various heights (cf. Figs. 358-362). First, a liquid secretion of low viscosity is released into the follicular lumen. This secretory product is called colloid (mostly thyroglobulin) 2. It is the carrier for thyroid hormones. Colloid secretion leads to the storage of thyroid hormones inside the follicle (thyroid hormone is entrapped in a thyroglobulin scaffolding). In on the process, the heights of the epithelial cells decrease (see Fig. 358,359). The c basal lamina underneath the follicular epithelium can only be seen on the -2 level of electron microscopy. Dense nets of blood and lymph capillaries sur- round the follicles. The epithelial cells around the capillaries are fenestrated 3, as is the case in other endocrine organs. The connective tissue 4 (see b Fig. 160) between the thyroid follicles contains nerve fibers. C-cells El, also - known as parafollicular cells, occur dispersed in...

Thyroidectomy

Surgery is the oldest form of definitive therapy of Graves' disease with the Nobel Prize in Physiology and Medicine awarded to Koker in 1909 for developments in this field 90 . Whether total or subtotal thyroidectomy should be performed has been the focus of past and recent debate. The higher relapse rates seen with subtotal thyroidectomy have resulted in the recommendation that total thyroidectomy is the procedure of choice for Graves' disease 68, 91, 92 . New surgical techniques, such as minimally invasive thyroidectomy and minimally invasive video-assisted thyroidectomy have recently been described 93 . Whereas it can take several months for the hyperthyroid state to remit after 131I treatment, the hypothyroid state occurs much sooner after surgery, being dependent on the clearance of circulating thyroid hormone. Following subtotal thyroidectomy, relief of hyperthyroidism is achieved in about 80 of children and adults, and hypothyroidism develops in about 60 of individuals 94, 95 ....

Fetal Maternal Relationships

Thyroid Function during Pregnancy Pregnancy affects thyroid homeostasis. An increased excretion of iodine in the urine accounts for the increase in thyroid volume even in areas of moderate dietary iodine intake 4 . Some studies, however, do not show an increase in urinary iodine during pregnancy. In either case the increase in thyroid volume is the result of imbalance between the intake and increased requirements of iodine during pregnancy 5 . Iodine deficiency during pregnancy is associated with maternal goitre and reduced maternal thyroxine (T4) level. While thyroid size increases in areas of iodine deficiency it does not do so in those regions that are iodine sufficient even in moderate iodine-deficient regions urinary iodine excretion is higher in all trimesters than in non-pregnant women and may be causative in maternal goitre formation as assessed by ultrasound. The increase in thyroid volume already referred to is substantially greater in iodine-deficient areas. This...

Monitoring of the Fetus in a Mother with Graves Disease

As neonatal thyrotoxicosis is known to be associated with neurological impairment in some cases there is a requirement to monitor the fetus rather than wait till birth to diagnose thyroid dysfunction. The use of serial in utero ultrasonographic measurements has been shown to accurately measure fetal thyroid size 42 . If the fetal thyroid does not reduce in size in response to antithyroid drug administration then transplacental passage of TsAb causing fetal hyper-thyroidism should be suspected. A recent comprehensive study by Luton et al. 43 showed that the sensitivity and specificity of fetal thyroid ultrasound at 32 weeks for the diagnosis of clinically relevant fetal thyroid dysfunction was 92 and 100 , respectively. Subtotal thyroidectomy is indicated if control of the hyperthyroidism is poor on account of poor compliance or inability to take drugs. Patients with a very large goitre may also require surgery because of pressure symptoms. Surgery is preferred in the second trimester...

Optimal Iodine Intake

These recommendations derive from consensus statements by several groups, including the International Council for Control of Iodine Deficiency Disorders, the World Health Organization, UNICEF, and the Food and Nutrition Board of the US National Academy of Sciences. The amounts are based on the following the calculated daily thyroid hormone turnover in euthyroidism, the iodine intake producing the lowest values for serum thyrotropin (TSH) and for serum thyroglobulin (TG), the amount of thyroid hormone replacement necessary to restore euthyroidism to athyreotic subjects, the iodine intake associated with the smallest thyroid volumes in populations, and the lowest incidence of transient hypothyroidism in neonatal screening with blood spot TSH. About 90 of iodine is eventually excreted in the urine. The median urinary iodine concentration in casual ('spot') samples, expressed as micrograms per liter ( g l), is currently the most practical biochemical laboratory marker of community iodine...

More Than Adequate Iodine Intake

Although not excessive, studies in more than adequate iodine intake (see table 4) following iodine prophylaxis, also pointed out the possible development of thyroid autoantibodies. Zois et al. 85 investigated the iodine status and the impact of iodine prophylaxis on the prevalence of autoimmune thyroiditis among schoolchildren in a formerly iodine-deficient community in northwestern Greece. The findings were compared to those obtained from a similar survey carried out 7 years previously in the same area. A total of 302 schoolchildren (12-18 years of age) from a mountainous area of northwestern Greece were examined for the presence of goiter, and blood and urine samples were collected for assessment of thyroid function, antithyroid antibodies and urinary iodine excretion. Median urinary iodine concentration in the children was 200 xg l. Thyroid function was normal in all but 7 children, who had subclinical hypothyroidism (2.5 ). Antithyroid antibodies (antithyroid peroxidase and or...

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 these transporters determine the availability of iodothyronines to the intracellular sites for metabolism and action 19 , and that the TH transport is energy dependent 20 (fig. 1). Recently, specific transporters (organic anion transporters and amino acid transporters) known to facilitate cellular thyroid hormone uptake have been identified 20-22 . Hennemann and Visser 22 have defined requirements for (patho)physiological significance of thyroid These mediate uptake of iodothyronines and their...

Deiodination of lodothyronines

Deiodination is the foremost pathway of thyroid hormone metabolism both in quantitative terms but also through activation of T4 by outer ring deiodination to T3, as well as inactivation of both T4 and T3 by inner ring deiodination reviewed in 50 . Three iodothyronine deiodinases (D1-D3) are identified as seleno cysteino-containing membrane proteins with their active enzymatic sites located in the cytoplasma. D1 and D2 convert T4 to T3, while D3 has only inner ring deiodination activity and inactivates T4 and T3 to rT3 and T2, respectively (fig. 1). D1 is expressed in liver, kidney and the thyroid, while D2 is expressed in the brain, pituitary, thyroid gland and skeletal muscle. In contrast to the rat, humans do not express D1 in the central nervous system. D3 is expressed in brain and fetal tissues, placenta and pregnant uterus. Other characteristics of the deiodinases are presented in table 3. D1 has both outer and inner ring deiodination activities, but appears particularly...

Receptor Specific Nuclear Actions Genomic Actions

Thyroid hormone receptors belong to a large superfamily of nuclear hormone receptors that include the steroid hormone, retinoic acid, vitamin D and peroxysomal proliferator receptors (PPARs). The receptors have a central DNA-binding domain and a carboxy-terminal ligand-binding domain (fig. 4). The two major isoforms, the thyroid hormone receptor a-1, a-2 (TRa) and (-1, (3-2, (3-3 (TR() have a high homology in these two domains, while the amino-terminal regions are more variable. Two thyroid hormone receptor genes located on chromosomes 17 and 3, respectively 89, 93-94 encoding for TRa and TR(, respectively. TRa-1, TRa-2, TR(-1 and TR(-3 are expressed widely, whereas TR(-2 is predominantly restricted to the hypothalamic pituitary axis in the negative feedback regulation of TSH. T3 binds to TR-a and TR-( resulting in nuclear gene expression. The receptors are ligand-regulatable transcription factors that recognize and interact with specific DNA sequences (thyroid hormone response...

Summary and Conclusions

Deficient supply of e.g. iodine, and possibly also a protection of urinary loss of the smaller molecules of unbound TH compared to the bound forms 2 . The normal human organism has a high capacity for compensating to a maintained normal thyroid function by almost any reduction in the plasma binding proteins. Several transporters that mediate the cellular entry of TH have been identified, but most of them are not specific for thyroid hormones. Up to now only two truly TH-specific transporters have been found OATP1C1 with high preference for T4 and MCT8 with preference for T3 as the ligand 21 . Since delivery of TH to the cells is a crucial mechanism for subsequent TH action, abnormalities in these transporters probably result in disease, e.g. a described mutation in the MCT8 caused tissue-specific hypothyroidism in the brain with milder affection of other organs 39 . In both qualitative and quantitative terms, deiodination is by far the most important pathway of thyroid hormone...

Debate on Newborn Screening Programs

Although both screening strategies detect CH of thyroidal origin, they may miss patients with central CH because T4 may be only moderately decreased and TSH is not elevated. In such patients, however, early diagnosis is crucial not only for early and appropriate thyroxine replacement (fig. 3), but Preterm infants with CH may have a delayed TSH increase owing to the immaturity of the hypothalamic-pituitary-thyroid axis, and may thus be missed by laboratory screening procedures. Therefore, a routine second screening between 2 and 6 weeks of age has been suggested in preterm neonates 14 leading to a reported additional 10 of cases.

Treatment Recommendations

To ensure optimal dosage and compliance, frequent evaluations of thyroid hormone serum levels are necessary. These tests should be obtained 2 and 4 weeks after L-T4 start, every 1-2 months during the first year of life, every 3-4 months between 1-3 years of age and 2-4 weeks after any change in dosage 1 . During L-T4 therapy, 4 or more episodes of elevated TSH (> 5mU l) after the age of 6 months were associated with inferior school performance 27 . These episodes may be caused by poor parental empowerment or impaired T4 bioavailability. The latter may be caused by inhibited intestinal uptake of T4 through soy or fiber and medications with iron or calcium, malabsorption or increased degradation by anticonvulsants. 10 Moreno JC, Bikker H, Kempers MJ, et al Inactivating mutations in the gene for thyroid oxidase 2 (THOX2) and congenital hypothyroidism. N Engl J Med 2002 347 95-102. 12 Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S A novel syndrome combining thyroid and...

Directions for the Future

The discovery of the genetic cause of Pendred syndrome opened up new opportunities in the study of thyroid, ear and kidney physiology. The next challenge is to translate these findings into clinically relevant interventions. Genetic testing can identify carriers in high-risk populations, and this information can then be used for genetic counseling and family planning. The thyroid disease per se does not cause overwhelming disability however, early, complete thyroid

Treatment Approaches for Children

For children less than 5 years of age, we consider antithyroid medications as a first line therapy. Although radioactive iodine has also been successfully used in this age group without an apparent increase in cancer rates, it may be best to defer radioactive iodine therapy because of the possible increased risks of thyroid cancer after radiation exposure in very young children in the event that any thyroid tissue remains after radioactive iodine therapy. Because young children are less likely to have remission than older children on drug treatment 15, 16 , prolonged drug therapy may be needed. If there are no toxic effects, continuing antithyroid drugs is reasonable until the child is considered old enough for radioactive iodine therapy. Alternatively, thyroidec-tomy or ablative radioactive iodine therapy can be considered if reactions to medications develop or there is the desire to avoid prolonged drug use. Fifteen percent of children with Graves' disease will present between 6 and...

Activity and Severity of TED

The decision of whether ophthalmopathy must be treated should rely on the assessment of two different parameters, the activity and severity of the disease. The activity of the disease is neither synonymous nor coincident with the severity of the disease. In other words, an individual patient may have severe ocular manifestations but the disease may be inactive (fig. 1). To assess the activity of ophthalmopathy, Mourits et al. 22 proposed a clinical activity score (CAS), which in its original formulation included 10 different items (table 1) mainly, but not solely, reflecting inflammatory changes giving one point to each manifestation, a score is obtained, with a range from 0 (no activity) to 10 (highest activity). A slightly modified CAS which does not include some of the items originally proposed by Mourits et al. 22 was proposed by an ad hoc committee of the four thyroid societies as a tool to record ocular changes over time after treatment of ophthalmopathy 23 (table 1). Definition...

Juvenile Graves Ophthalmopathy Incidence and Symptomatology

The incidence rates start to increase as of the age of 20 years. Below the age of 20 years the occurrence of GO is a rare event. Incidence rates (cases per 100,000 population per year) are in the age groups 5-9, 10-14, and 15-19 years for females 3.5, 1.8 and 3.3, respectively, and for males 0, 1.7 and 0, respectively. Only 6 of the 120 incident cases of GO observed in this cohort study were below the age of 20 years. A more detailed study published recently from the same department found that of 1,662 cases ages < 18 years, with thyroid-related abnormalities, evaluated at the Mayo Clinic in Rochester, Minn., USA, during the 15-year interval (1985 to 1999), 35 children with GO were identified. Of these, 6 had received radioactive iodine (RAI), 1 patient had RAI plus antithyroid drugs, 9 had partial or total thyroidectomy, and the rest antithyroid medications for their thyroid problem. Four patients did not require treatment. Of the 35 children with GO, 31...

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 PKC and mitogen-activated protein kinase (MAPK) 98 . The nongenomic actions thus presumably include the regulation of ion channels, oxidative phosphorylation and mitochondrial gene transcription and involve the generation of intracellular secondary messengers signaling pathways including induction of calcium, cyclic AMP or protein kinase signaling cascades 91, 98-100 . Recently, integrin aVp3, has been identified as a plasma membrane TH-binding site 101 . Furthermore, it has been shown that...

Clinical Presentation

The most common clinical presentation of childhood thyroid cancer is a palpable thyroid nodule it is the first sign of the disease in 73-87 of the cases 8, 18 . Most thyroid cancers in children are asymptomatic, but palpable thyroid nodules are more frequently malignant in children than in adults 19, 34 . As with adults, hoarseness, dysphagia or a hard fixed nodule may be indicative of an underlying thyroid malignancy. Fine-needle aspiration cytology of the nodule should confirm the diagnosis. The size of newly diagnosed papillary thyroid tumors in childhood is larger than in adulthood a size of > 4 cm is found in 36 of children vs. 15 of adults, and a size of < 1 cm occurs in 9 of children vs. 22 of adults 35 . Invasion of contiguous structures in papillary thyroid carcinoma is also more frequent in children than in adults (24 vs. 16 ) 35 . Neck node involvement is quite common in childhood papillary thyroid carcinoma, in the order of 60-90 2-4, 8, 35 palpable cervical...

Iodine Deficiency and Supplementation

Iodine is excreted in the urine and urinary iodine is highly sensitive to recent changes in iodine intake. In eight iodine-deficient countries, urinary iodine concentrations indicate that iodine intakes are clearly inadequate. Studies of thyroid size in pregnancy measured by ultrasonography also indicate iodine nutrition is suboptimal in much of Europe. In countries affected by mild or moderate iodine deficiency (e.g. Germany, Belgium, Italy, Denmark), thyroid volume increases 14-30 during pregnancy, while in iodine-sufficient countries (Finland, Holland), there is no increase in thyroid volume during pregnancy. Six randomized, controlled trials of iodine supplementation in pregnancy have been published, involving 450 women with mild-to-moderate iodine deficiency. In all six trials, supplementation resulted in a significant increase in maternal urinary iodine. Iodine doses varied between 50 and 230 xg day, and the data indicate no clear dose-response relationship for urinary iodine,...

Selenium Deficiency and Supplementation

The essential trace element selenium is involved in thyroid hormone synthesis, metabolism and action. In several regions of the world people are exposed to inadequate selenium supply because selenium contents of surface soils have been depleted by erosion and glacial washout similar to iodine. Therefore, plant and animal food chains contain inadequate amounts of both of these elements. Deficiencies of selenium and iron can act in concert with iodine deficiency to impair thyroid metabolism and modify the response to prophylactic iodine. The effects of selenium and iron status on iodine and thyroid metabolism share certain parallels. Selenium deficiency reduces the activity of the selenium-dependent deiodinase and peroxidase enzymes and thereby impairs thyroid metabolism in iodine-deficient populations 21-24 . Similarly, iron deficiency reduces heme-dependent thyroperoxidase activity, impairs thyroid metabolism, and influences the response to iodine in iodine deficiency disorders....

Iron Deficiency and Supplementation

Iodine deficiencies often coexist in regions of West and North Africa, 20-30 of school-age children suffer from both goiter and iron-deficiency anemia. Data from animal studies indicate that iron deficiency, with or without anemia, impairs thyroid metabolism. Iron deficiency also impairs thyroid metabolism in human trials. Overall, these studies suggest that iron deficiency blunts the thyrotropic response to exogenous TRH lowers serum T3 and T4 levels, and lowers utilization of thyroid hormones 25-30 . Clinical trials were done in primary schools in an area of endemic goiter in the mountains of Cote d'lvoire. At that time, the median urinary iodine concentration and the goiter rate by palpation in school-aged children in this region were 28 xg l and 45 , respectively, indicating moderate to severe iodine deficiency. Goitrous, school-aged children were divided into two groups nonan-emic or with iron deficiency anemia. All children received an oral dose of 0.4 ml iodized poppy seed oil...

Vitamin A Supply and Zinc Status

In developing countries, children are at high risk for vitamin A deficiency, a leading cause of preventable blindness in children and increased morbidity and mortality from serious infections. In rural Cote d'Ivoire, 32-50 of school-age children suffer from both vitamin A deficiency and goiter. In northern Morocco, 41 of children have vitamin A deficiency, and 50 are goitrous. In animals, vitamin A deficiency has multiple effects on thyroid metabolism it decreases thyroidal iodine uptake, impairs thyroglobulin synthesis, and increases thyroid size. In the periphery, vitamin A deficiency increases free and total circulating thyroid hormone, and vitamin A status may modulate T4 feedback of TSH secretion. Finally, vitamin A deficiency in rats increases pituitary TSHp mRNA and TSH secretion both return to normal after treatment with retinoic acid 31 . In a double-blind, randomized clinical trial, children with vitamin deficiency were given iodized salt and either vitamin A or placebo at 0...

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 following radiation exposure. Individuals older than 20 years of age do not have an increased risk of thyroid cancer when exposed to low-level thyroid irradiation 71-73 . Yet, when individuals are less than 20 years of age at the time of low-level thyroid irradiation, the thyroid cancer risks increases the younger one is 71-73 . In addition to age, the radiation dose plays a major role in cancer risk 70-73 . The risk of thyroid cancer and thyroid nodules is highest with exposure to low or...

Historical Note

Five hundred years later Galen of Pergamon described the anatomy of the third ventricle region, the location of the pituitary gland inside the sella turcica embodied in a vascular network, the rete mirabilis, and observed nerves adjoining the 'soft flesh' in the neck, i.e. the thyroid gland 1 . He first proposed that the energy of the body (the vital spirit) was carried through the arteries at the level of the rete mirabilis, where it was transformed into nerve impulse (the animal spirit), eventually transferred by the nerves to the periphery of the body, 'glands' included, raising implicitly the possibility for a nervous influence over the thyroid activity. The Galenic model remained virtually unaltered up to the beginning of the 14th century, when the anatomist Mondino de' Liuzzi suggested that the thyroid gland interacted with the heat of the blood present in the internal carotid arteries due to their anatomical relation with the thyroid. He proposed that the third ventricle serves...

Ligand

So, although propylthiouracil is used to treat hyperthyroidism mainly due to its inhibitory action on the enzyme, thyroid peroxidase, propylthiouracil at high doses also inhibits D1 activity 55 . The production of TH is regulated by the hypothalamo-pituitary-thyroid axis, while the biological activity of TH, i.e. the tissue availability of T3 is mainly regulated by the three deiodinases 56 . The serum concentrations of thyroid function variables are regulated very closely within the individual, while there is a substantial interindividual variation in serum levels of both T4, T3, TSH and thyroglobulin. This was first demonstrated by Feldt-Rasmussen et al. 57 in 1979, and has later been verified by others 58, 59 . This pattern indicates an important genetic component in the regulation of serum concentrations of thyroid function variables, with an individual set-point for thyroid function. A classical twin study demonstrated results to support this...

Conclusion

Autoimmune thyroid disease is uncommon in children and adolescents, but there is a significant prevalence of self-limiting autoimmune thyroiditis with positive thyroid autoantibodies and biochemical thyroid dysfunction. There is some evidence that the genetic predisposition to thyroid autoimmunity differs between adults and children, and there are specific, clinically important associations with other autoimmune disease in children. The area still requires further association studies, in particular examining larger cohorts and directly comparing results to series of adult patients from the same area, to elucidate fully the differences, which might enhance our understanding of how the autoimmune response can be modulated for therapeutic benefit.

Newborn Screening

The first CH screening was performed by Dussault and Laberge 6, 7 , in Quebec, Canada in 1972. They detected 7 hypothyroid infants among 47,000 newborns during 3 years. The high frequency of false-positives delayed the diagnosis and increased the cost and they arranged the cutoffs used for recall. The babies recalled underwent thyroid hormones and TSH blood studies. In the meantime, radioactively labeled antibodies for determining T4 in dried blood spots began regionally in the USA and Europe. They went parallel with screening programs of PKU. In the initial report by Dussault et al. 8 , the method was recommended as a confirmatory test knowing that it would miss cases with hypothlamic-pituitary hypothyroidism which they reported to be 10 of the 1982, a Neonatal Thyroid Screening Conference held in Tokyo recommended NS programs oriented to detect infants with elevated serum concentrations of TSH 15 . They suggested that this could be accomplished by measuring TSH in filter paper blood...

Iodine Deficiency

Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Iodine deficiency disorders (IDD), which was referred to as endemic goiter up to thirty years ago refers to iodine deficiency that can be prevented by ensuring an adequate intake of iodine in population 64 .

Diagnosis

Having ascertained the validity of the obtained hormone test results, a distinction must be made between a TSH-secreting pituitary adenoma and RTH. This can be difficult when imaging of the pituitary does not show a tumor. In both cases TSH is refractory to thyroid hormone feedback. A TRH test can be helpful. In the case of RTH there will be a response of TSH to the TRH which will be less so when an autonomous pituitary tumor is present. Furthermore, the a subunit to TSH ratio is normal in RTH whereas it will be elevated in TSH-secreting tumors 11, 12 . When the differential diagnosis clearly points to RTH, the patients genomic DNA can be sequenced, in particular exons 7-10, to confirm the diagnosis.

Management

Most patients have corrected themselves by increasing their serum thyroid hormones in the presence of normal TSH 12, 14 . No treatment is necessary in these cases. When the patient presents with hyperthyroid symptoms, especially tachycardia, beta-blockers can be used. The thyroid hormone analogue 3,5,3'-triiodothyroacetic acid (TRIAC) has also been used successfully to treat some symptoms of RTH in children such as increased TSH and goiter 15-18 . This is due to the fact that TRIAC has a higher affinity for the TRp then for the TRa, and is metabolized more rapidly then T3. Because of this it has a limited effect on organs like the heart with a predominance of TRa. Similar treatment successes with D-T4 19, 20 have no clear explanation. In cases where previous erroneous diagnosis has occurred resulting in postsurgical or postradiation hypothyroidism, treatment with thyroid hormone can be started. As an outcome for successful therapy serum TSH can be used required T4 doses can be as high...

Molecular Issues

On the basis of this, the interference with the normal way in which the TR works can be envisaged to take place at several different levels. As shown in figure 3 all mutations cluster in three particular areas. When these areas are plotted onto the 3D structure of the TRp, it becomes apparent that they are surrounding the binding site for thyroid hormone (fig. 4). Therefore the first possibility is loss of hormone binding. In this case the hormone cannot bind to Disruption of the TRp gene in mouse models shows a phenotype reminiscent of the first RTH patients identified to harbor a homozygous deletion 31 . These animals also have serious hearing defects. When the deletion is heterozygous, normal thyroid test results are found. The expression of mutant TRp in mice results in an animal model of RTH with lower body weight, hyperactivity and learning problems, similar to the problems found in humans 32-35 . A possible reason for the variability in the symptoms with which patients present...

History

Pendred syndrome is caused by loss-of-function mutations in the novel protein called pendrin, which is encoded by the gene SLC26A4 (PDS). Pendrin functions as an anion transporter and is expressed in the thyroid, the inner ear, the kidney and the placenta. The precise mechanism by which mutations in this single protein cause both defective thyroid function and profound hearing loss has been the topic of extensive research ever since the discovery of the gene.

Molecular Genetics

That the mature protein is expressed on the apical membrane of the follicular thyroid epithelial cells, in cells lining the endolymphatic duct, endolymphatic sac and organ of Corti in the inner ear, in the intercalated cells of the kidney and in trophoblast cells 4, 19, 20 . In the thyroid, pendrin expression is regulated by TTF-1 and thyroglobulin, but not by TSH, sodium iodide or insulin 18, 21, 22 . The pendrin gene, SLC26A4, belongs to a larger family of ion transporters that is currently thought to include 10 members, SLC26A1-11 (SLC26A10 is a pseudogene). Early homology studies suggested the pendrin may function as a sulfate transporter 4 , but this was soon proven unlikely, since sulfate transport was shown to be entirely normal in thyroid cells obtained from Pendred syndrome patients 23 . In vitro expression studies subsequently documented that the protein forms a channel that can function either as a chloride-iodide transporter in the thyroid 24 or a Cl OH HCO3 exchanger in...

Radioactive Iodine

When the US Atomic Energy Commission was allowed to supply uranium fission products for medical use, 131I, with a half-life of 8 days became available for the treatment of Graves' disease. In 1946, a patient at Barnard Hospital in St. Louis with thyroid cancer became the first to be treated with the long halflife nuclide 3 . Because of the inherent advantages the longer half-life isotope, 131I rapidly became the preferred iodine isotope for treating hyperthyroidism and thyroid cancer. About 10 years after the first adult was treated with radioactive iodine for Graves' disease, Drs. John D. Crawford and Chapman at the MGH treated the first child with Graves' disease with radioactive iodine. The child faced unremitting hyperthyroidism in the face of toxic reactions to antithyroid medications. In the 1960s and 1970s, several groups reported their experience using radioactive iodine to treat childhood Graves' disease 22-24 . These reports showed both safety and efficacy in children. When...

Clinical Syndrome

In contrast, the thyroid disease associated with Pendred syndrome rarely presents in infancy, usually appearing in late childhood or early adolescence as diffuse or multinodular goiter. Typically, the patients are clinically euthyroid, although mild, compensated hypothyroidism, characterized by elevated TSH with normal thyroxin and tri-iodothyronine levels, is often present. However, clinical presentation is variable and Massa et al. recently described a case of documented Pendred syndrome in whom the presenting thyroid pathology was a painless, benign solitary thyroid nodule that resolved after hormone replacement 8 . The size of the goiter is also variable, and may be small, detectable only on close physical examination, or may reach massive proportions, causing significant cosmetic problems or even tracheal compression (fig. 1) 9 . Although the goiter tends to recur after surgery, partial thyroidectomy may be required. The histological appearance of the thyroid tissue is...

Conclusions

2 Krassas GE, Heufelder AE Immunosuppressive therapy in patients with thyroid eye disease an overview of current concepts. Eur J Endocrinol 2001 144 311-318. 3 Wiersinga WM Thyroid associated ophthalmopathy pediatric and endocrine aspects. Pediatr Endocrinol Rev 2004 1(suppl 3) 513-517. 5 Perros P, Kendall-Taylor P Pathogenesis of thyroid-associated ophthalmopathy. Trends Endocrinol Metab 1993 4 270-275. 7 Bahn RS Cytokines in thyroid eye disease potential for anticytokine therapy. Thyroid 1998 8 415-418. 11 Krassas GE, Pontikides N, Doukidis D, Heufelder G, Heufelder AE Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1 receptor antagonist in patients with thyroid eye disease undergoing treatment with somatostatin analogues. Thyroid 2001 11 1115-1122. 15 Metcalfe RA, Weetman AP Stimulation of extraocular muscle fibroblasts by cytokines and hypoxia possible role in...

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 acute Wolff-Chaikoff effect is a decrease in the thyroid iodide trap, thereby decreasing the intrathyroid iodide concentration 68 , due to a decrease in the sodium iodide symporter (NIS) mRNA and protein expression 69 . For this reason, most people can tolerate high doses of iodine without developing thyroid abnormalities. Excess iodine ingestion (up to 1.5-3.0 mg day) also decreases the release of T4 and T3 from the thyroid resulting in small decreases in serum T4 and T3 concentrations with...

Epidemiology

Differentiated thyroid carcinoma (papillary and follicular thyroid carcinoma) is rare during childhood and adolescence. It comprises 90-95 of all pediatric thyroid cancers medullary thyroid carcinoma is present in 5-8 , and undifferentiated anaplastic carcinoma is extremely rare. The annual incidence of differentiated thyroid carcinoma in children below 16 years of age is between 0.02 and 0.3 cases per 100,000, whereas the annual incidence per 100,000 in the general population ranges from 1.2 to 2.6 in men and from 2.0 to 3.8 in women 1 . In large retrospective surveys of differentiated thyroid carcinoma, 72 of 1,500 cases (4.8 ) occurred in children of < 16 years at the Institut Gustave-Roussy in Villejuif 2 , and 140 of 1,599 cases (8.8 ) in children of < 19 years at the M.D. Anderson Cancer Center in Houston 3 . Most affected children are older than 10 years, and the occurrence of differentiated thyroid cancer below the age of 10 years is exceptional 1, 4 . Although juvenile...

Pathology

Combining three large surveys of differentiated thyroid carcinoma in children and adolescents, 107 of the 137 cases had papillary carcinoma (78 ) and 30 had follicular carcinoma (22 ) 1, 17, 18 these figures are remarkably similar to 81 papillary and 19 follicular carcinomas among differentiated thyroid cancers in the general population 1, 3 . The data do not support a higher prevalence of papillary thyroid carcinoma in children than in adults, as stated by some authors 19 . Papillary thyroid carcinomas from children and adolescents contain more numerous lymphocytes than those from adults nearly half contain CD4+ T helper cells, CD8+ killer cells or CD19+ B cells 20, 21 . This may be related to the more favorable prognosis of differentiated thyroid cancer in children and adolescents than in adults, in line with the notion that the immune response to thyroid cancer appears to be important in preventing metastasis and recurrence. Pediatric papillary thyroid carcinomas with the most...

Ns Ns Ns 0027

Arising in a synchronous or metachronous (possible due to RET PTC rearrangements) fashion 34 . A second compelling argument is the longer recurrence-free survival after total vs. less than total thyroidectomy (table 1) 4, 40 . Completion thyroidectomy has been associated with lower mortality rates in adults with papillary thyroid carcinoma and children and adolescents with radiation-induced papillary thyroid carcinoma as well 41 . Less extensive surgery has been supported by the outcome of an American multi-institutional cohort of 329 patients diagnosed when < 21 years old progression-free survival did not differ in relation to the extent of surgery 42 however, total thyroidectomy was more often applied to later-stage patients, jeopardizing the claim of no benefit from more intense treatment 4 . Lobectomy for microcar-cinomas (< 1 cm) remains a controversial issue, and is better avoided in radiation-induced cancer. Thyroidectomy should be accompanied routinely by en bloc...

Prognosis

In 1994, Mazzaferri and Jhiang 56 already noticed a very high recurrence rate but low mortality rate in children and adolescents with differentiated thyroid carcinoma. This was confirmed by Samaan et al. 3 in 1992 in a comparative study on 140 patients below 20 years of age and 1,459 patients of > 20 years with differentiated thyroid carcinoma. In both groups the frequency of papillary carcinoma (86 vs. 80 ), thyroidectomy (73 vs. 65 ) and 131I therapy (48 vs. 45 ) was similar, but extrathyroidal spread was more prevalent in the younger age group (74 vs. 57 ). Recurrences were more frequent at age Although the above findings are reconfirmed by many other smaller series, the low mortality rate of pediatric differentiated thyroid carcinoma might to some extent reflect relatively short follow-ups compared with patients' lifespans 4 . Most reports have a median follow-up of < 15 years, but cause-specific deaths may occur after longer time intervals 57 e.g. mortality was 10 in 34...

Radionuclide Imaging

In regions with adequate dietary iodine intake, the 24-hour uptake of oral radioiodine is 10-35 . The trapping mechanism is the sodium-iodide symporter (NIS), which is regulated by thyrotropin (TSH) 3 . There are more than 20 radionuclides of iodine, but only 123I and 131I are in widespread clinical use. 123I has a relatively short half-life and emits only y photons and is used for thyroid uptake measurements and scintigraphy. In contrast, 131I has a half-life of 8 days and emits p particles as well as high-energy y photons. 131I is therefore suited for therapy, but the y photons can be imaged, which explains why 131I is used for diagnostic and post-treatment whole-body scanning in patients with thyroid cancer. The use of 131I for routine thyroid scintigraphy is discouraged because the radiation dose is about 100 times greater than that of 123I. Based on low cost, availability and an even lower radiation dose, technetium (99mTc) pertecnetate is an attractive alternative to 123I and...

Thyreoidea

Fig. 10. 99mTc pertechnetate thyroid scan of a hyperfunctioning nodule in the right lobe with complete suppression of uptake in the remainder of the thyroid. disease. Compared with a normal thyroid, the thyroid lobes are slightly larger in all dimensions, and the early and late uptakes are higher. Figure 10 shows an autonomous hyperfunctioning nodule with suppression of extranodular thyroid tissue. If thyrotoxicosis is confirmed biochemically, in addition to elevated levels of TSH receptor antibodies and a nonpalpable thyroid gland, there is no absolute indication to measure uptake or obtain a scan. Subacute thyroiditis is rare in childhood 35 and most often presents with thyrotoxicosis and elevated erythrocyte sedimentation rate and is associated with neck pain and tenderness. Reduced or no thyroid uptake on a scintiscan supports the diagnosis (fig. 11). Single and Multiple Thyroid Nodules In general, diffuse enlargement of the thyroid is of benign origin, whereas a solitary nodule...

PET and PETCT

Cancer-seeking radiopharmaceuticals have been evaluated for more than a decade to improve differentiation between benign and malignant thyroid nodules. Positron emission tomography with fluorine 18-fluorodeoxyglucose (FDG) is well established as a functional imaging tool for diagnostic oncologic imaging. It yields metabolic information about lesions that is not provided with conventional morphologic imaging modalities such as US, CT and MRI 44 . Studies using FDG PET for tumor staging and restaging, monitoring treatment, and predicting the prognosis in patients with head and neck cancers, have been published 45, 46 . To interpret PET images accurately, it is essential to be fully familiar with the normal patterns, intensities, and frequencies of FDG distribution in the head and neck area. PET evaluations of physiologic tracer uptake in the head and neck region, with or without image fusion techniques involving the use of conventional cross-sectional modalities to assist in locating...

Ultrasonography

Because of the superficial location of the thyroid gland, high-resolution real-time gray-scale and color Doppler sonography can demonstrate the normal thyroid anatomy and pathologic conditions with remarkable clarity 58 . With increasing availability, this technique has come to play an ever more important role in the diagnostic evaluation of thyroid diseases. High-frequency transducers (7.5-15.0 MHz) provide both deep ultrasound penetration (up to 5 cm) and a high-definition image, with a resolution of 0.7-1.0 mm. It can distinguish solid nodules from cysts and allows accurate estimation of size, shows vascular flow (Doppler), and aids in the accurate placing of needles for diagnostic or therapeutic purposes 59 . It is also an excellent tool for use in the follow-up for estimation of changes in size of a lesion or the entire thyroid gland over time. Finally, it allows in utero investigation of the fetal thyroid 60 and can be helpful in fetal diagnosis of thyroid dysfunction 61 . The...

Computed Tomography

Computed tomography offers excellent anatomic resolution because of its ability to identify small differences in density between different tissues 131 . It is highly sensitive for detecting thyroid nodules, but as with US, benign nodules cannot be distinguished from carcinomas 132 . It can distinguish solid from cystic and mixed solid-cystic nodules and thyroid volume can be determined. It is superior to US in detecting thyroid tissue in the retrotracheal, retroclavicular and intrathoracic regions and for evaluation of metastatic disease in the neck and thorax 133 . The limitations of CT are cost, limited availability, length of the procedure, need for patient cooperation, artifacts caused by swallowing or breathing, and exposure to ionizing irradiation (1-4 rad) 132 . It has been suggested that the higher doses and increased lifetime radiation risks in children will actually produce a sharp increase, relative to adults, in estimated risk of lifetime cancer from CT 134 . This fact may...

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 progressive increase in the serum concentrations of both total T4 and FT4. It is intriguing that TSH bioactivity is greatly increased with respect to that circulating in the mother in spite of the increasing FT4 concentrations in the fetus (fig. 2). This confirms the hypotheses that fetal serum TSH is not of maternal origin, that it is not under hypothalamic neuroendocrine control by the fetal hypothalamus and that it is not under negative feedback control by the thyroid hormones 26 . This raises the...

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 documented in iodine-deficient areas where the maternal circulating thyroxine concentrations are too low to provide adequate fetal levels particularly in the first trimester. Recent work has raised concern that in an iodine-sufficient area maternal thyroid dysfunction (hypothyroidism, subclinical hypothyroidism or hypothyroxinaemia) during pregnancy results in neuro-intellectual impairment of the child. Two studies, have shown that a low thyroid hormone concentration in early gestation can be...

Hormones Secreted from the Anterior Pituitary

Thyroid Stimulating Hormone (TSH) TSH is a glycoprotein with 211 amino acids and stimulates production and release of thyroxine (T4) and 3,5,3-triiodothyronine (T3). TSH stimulates iodide transport into thyroid cells and growth of the thyroid gland itself and provides negative feedback to TRH release from the hypothalamus.

Peripherally Secreted Hormones

They stimulate oxygen consumption, increase body heat, metabolism and heart rate. There is an increase in the dissociation of oxygen from hemoglobin by increasing red cell 2,3-diphosphoglycerate (2,3-DPG) Calcitonin is secreted from the parafollicular cells or clear cells (ultimobranchial bodies) in the thyroid gland and inhibits bone resorption and produces hypocalce-mia in experimental animals. Its secretion results in decreases in serum phosphate levels but it has not been demonstrated to be important in the basal control of serum calcium during normal homeostasis in humans. Salmon calcitonin is more than 20 times more active in humans than human calcitonin.

Risk Factors and Cancer

Ionizing radiation is a universal but weak carcinogen.1,39 However, cumulative exposures from medical diagnostic and treatment procedures, commercial, occupational sources, or waste increase the risk of cancer. Leukemias and cancers of the breast, lung, and thyroid are typical but cancers of the stomach, colon, and bladder, and potentially any human tumor may be seen. Radiation can cause most types of cancer, especially myelogenous leukemia and cancers of the breast, thyroid, and lung. Some cancers that have not been linked to radiation include chronic lymphocytic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, and cancers of the cervix, testis, prostate, and pancreas. Despite the massive radiation contamination resulting from the nuclear reactor accidents at Chernobyl and Chelyabinsk thus far the only well-documented increase in cancer is childhood thyroid cancer.40 Finally, genetic predisposition can increase the risk of developing cancer by exposure to radiation, as in the...

Primary Nursing Diagnosis

After surgery, assess the patient's neurological status and report significant changes. Also check for the presence of pain. Antibiotics, antipyretics, and analgesics may be used to control infection and pain. Check nasal drainage for the presence of glucose, which indicates cerebrospinal fluid drainage. Monitor blood glucose. Growth hormone levels generally fall rapidly after surgery, thus removing an insulin-antagonist effect and possibly causing hypo-glycemia. Pituitary dysfunction occurs in about one-fifth of patients after surgery and requires glucocorticoids, gonadotropins, and thyroid replacement hormone therapy. Radiotherapy may also be used postoperatively to prevent tumor regrowth.

Cancer Screening Diagnosis and Prevention

Thus far, biological markers (biomarkers) have been used to diagnose cancer, and to monitor disease progression and recurrence after therapy.59-62 Biomarkers have substantially improved the understanding of the molecular mechanism of action of carcinogenesis and risk, although they are more useful for monitoring the consequences of the disease and therapy rather than assessing the effects of risk factors on the onset of the disease. For example the serum-based markers calcitonin, prostate-specific antigen, and CA-125 are all elevated in medullary thyroid, prostate cancer, and a small subset of ovarian cancers, respectively.63-65 Urine-based biomarkers like bladder tumor antigen, survivin, and calreticulin have been recently used as diagnostic marker for bladder cancer.66 Therefore improved modern molecular screening approaches may identify (1) high-risk patient groups who might benefit from more intensive screening as well as inclusion in trials of preventive agents and (2) indicators...

Palliative and Causative Acting Drugs

By far the largest fraction of today's pharmacopoeia does not target disease at its cause - as these causes are largely unknown - but by modulating a pathway that affects the disease-relevant phenotype or function. We refer to such drugs as symptomatic or palliative agents. The pathways they target are known from more than a century of physiological, biochemical, and pharmacological research. The pathways they modulate are disease phenotype-relevant (albeit not disease cause-relevant), and while they are not dysfunctional, their modulation can effectively be used to counterbalance the effect of a dysfunctional, disease-causing pathway. Thus signs and symptoms of the disease can be alleviated, often with striking success, notwithstanding the fact that the real cause of the disease remains untouched. A classical example of such an approach is the acute treatment of thyrotoxicity with b-adrenergic-blocking agents even though in this case the sympathetic nervous system does not contribute...

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