How To Prevent Hypothyroidism Naturally

The Hypothyroidism Revolution

During Phase 1 of the Hypothyroidism Revolution Program, the magic begins to happen as you begin to notice many positive changes occurring. You will begin your progressive transition towards the ideal thyroid healing diet that will give your thyroid the big boost that it needs to help your cells produce more than enough energy for you. By the end of Phase 1, your energy levels will be rapidly on the rise and you will feel amazingly satisfied with zero food cravings. You will feel in control again as your mood drastically improves and any sign of depression and anxiety begin to disappear. Your family and friends are going to notice some major positive changes in you. You will also begin to experience many of the outer changes that come with improved thyroid function. Youre skin will begin to clear up and glow while your hair and nails will begin to look healthy again. As you ease into the thyroid healing diet, you will progressively remove the foods that suppress your thyroid, disrupt your hormone pathways, cause digestive upset and irritation, and cause toxic byproducts that congest your liver. At the same time, you will be progressively adding the foods that will be supplying your cells with the right balance and combination of nutrients that they need to thrive and produce endless amounts of energy. Continue reading...

The Hypothyroidism Revolution Overview


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Endocrinopathies Congenital hypothyroidism

Congenital hypothyroidism is associated with mental retardation and may be associated with decreased motor activity at birth, hoarse cry, and difficulty with feeding. It is rarely diagnosed at birth from clinical assessment alone, but it is recognized from new-born screening tests with confirmation by measurement in blood samples. Symptoms of hypothyroidism may not be clearly detected until the second month of life. The overall prevalence is 1 in 4000 live births. Neurological and learning disorders associated with untreated congenital hypothyroidism include attention-deficit disorder, hearing loss, speech defects, ataxia, and abnormal muscle tone. (35 Rapid diagnosis in infancy is essential to prevent these complications. Without treatment, severe neurological dysfunction ensues. With initiation of oral thyroid hormone treatment (levothyroxine in a single daily dose of 8 to 10 pg kg per day) in the first 6 weeks of life, IQ is in the normal range. If treatment is delayed until 3 to 6...

Congenital hypothyroidism

This results from loss of thyroid function, usually due to failure of the thyroid gland to develop correctly. The incidence is 1 in 3500 to 4000, which may be higher in Asian families, being 1 in 918 in the north-west of England. Neonates are usually normal at birth. Prior to the establishment of neonatal screening programme, hypothyroidism used to be a major cause of mental retardation. (59 If the condition remains untreated, neonates develop lethargy, difficulty with feeding, constipation, enlargement of the tongue, and umbilical hernia. As the development of the brain and normal growth are dependent upon normal levels of thyroid hormone, congenital hypothyroidism leads to growth retardation and mental retardation. Treatment with thyroxine needs to begin as soon as the diagnosis is made even a delay of 6 months can lead to significant reduction in the IQ. (6,9

Physiological Effects Of Thyroid Hormones

There is no discrete target tissue for thyroid hormones virtually every cell in the body is affected by thyroid hormones in some way. These hormones are intimately involved in the maintenance of normal function in virtually every cell type, including cellular responsiveness to other hormones, to the availability of metabolic substrates, to growth factors, and so on. Thyroid dysfunction can produce dramatic changes in the metabolism of proteins, carbohydrates, and lipids at the cellular level that can have repercussions for the operation of the cardiovascular, gastrointestinal, musculoskeletal, reproductive, and nervous systems. Some of the clinical manifestations of thyroid dysfunction are presented next in the discussions of hypothyroid and hyperthy-roid states.

Clinical Manifestations of Hypothyroidism

Thyroid hormone also plays a major role in the maturation of bone. A deficiency of thyroid hormone in early life leads to both delay in and abnormal development of epiphyseal centers of ossification (epiphyseal dysgenesis). Hypothyroidism-induced impairment of linear growth can lead to dwarfism in which the limbs are disproportionately short in relation to the trunk with the apparent bone age retarded in relation to chronological age. The hallmarks of infantile hypothyroidism (e.g., retardation of mental development and growth) become manifest only in later infancy and are largely irreversible. Consequently, early recognition and initiation of replacement therapy are crucial. In the absence of thyroid hormone therapy, the symptoms of infantile hy-pothyroidism include feeding problems, failure to thrive, constipation, a hoarse cry, and somnolence. In In adults, the signs and symptoms of hypothyroidism include somnolence, slow mentation, dryness and loss of hair, increased fluid in body...

Naturally Existing CD4CD25 T Cells as Peripheral Barrier to Autoimmune Thyroiditis

As we have hypothesized earlier and discussed above, there is a clonal balance of regulatory T cells and autoreactive T cells, with the former keeping the latter in check in normal, susceptible individuals (Kong et al., 1982). This hypothesis has certainly been borne out by transfer experiments in which CD4+CD25- T cells, transferred without CD4+CD25+ T cells, mediated the development of several autoimmune diseases including thyroiditis (Sakaguchi et al., 1995). The depletion of CD4+CD25+ T cells also enabled resistant mice to respond to induction of autoimmune gastritis (McHugh and Shevach, 2002). We have postulated that such a natural barrier to autoimmune thyroiditis development represents the first level of regulatory influence, while mTg-induced resistance to withstand EAT induction represents the second level of regulation (Kong et al., 1989). With the identification of CD4+CD25+ regulatory T cells as mediators of induced resistance, we examined if naturally occurring regulatory...


Hypothyroidism is usually the result of primary failure or ablation of the thyroid gland, hypothalamic dysfunction, pituitary dysfunction, autoimmune thyroiditis, or lithium therapy. Clinical manifestations of hypothyroidism include fatigue, cold intolerance, lethargy, weakness, weight gain, constipation, menstrual irregularities, hair loss, slow reaction time, oedema, delayed reflexes, and bradycardia. Hypothyroidism occurs in as many as 10 per cent of patients taking lithium lithium-induced hypothyroidism is much more likely to occur in women.( .5) The association between clinical hypothyroidism and depression is well known. Gold et al.(66) found that 5 per cent of a series of 250 patients with major depressive syndromes had at least subclinical hypothyroidism. In many patients with hypothyroidism, the depression responds to thyroid hormone replacement alone, (67) but the response may take a long time. When that is the case, antidepressants are indicated and efficacious. (65)

Subacute Thyroiditis

Subacute thyroiditis (or de Quervain's disease) is a relatively uncommon form of thyroiditis characterized pathologically by the presence of extensive follicular cell destruction, extravasation of colloid and aggregation of histiocytes around colloid, coalescing into giant cells. There is strong but indirect evidence that this pathology may result as a reaction to a preceding viral infection, but immune mechanisms may also play a role. Patients often present with cervical pain, tenderness of the thyroid (at times exquisite), symptoms of thyrotoxicosis and in some cases, systemic symptoms of an inflammatory illness. Thyrotoxicosis results from an unregulated release of preformed thyroid hormone from an inflamed gland. As the thyroid gland is depleted of preformed hormone and the thyroiditis subsides, the serum T4 and T3 concentrations fall to normal and in some cases to subnormal levels, before recovery of the gland with normalization of function. The entire course of the illness may...

Hypothyroid States

Hypothyroidism refers to the exposure of body tissues to a subnormal amount of thyroid hormone. This can result from a defect anywhere in the HPTA. As a consequence of the lack of thyroid hormone, a wide variety of physiological and clinical disturbances involving virtually every organ system may result. Primary hypothyroidism results from an inability of the thyroid gland itself to produce and secrete sufficient quantities of T4 and T3 and accounts for most cases of hypothyroidism. In iodine-sufficient areas of the world, the most common cause of primary hypothyroidism is chronic autoimmune thyroiditis (Hashimoto's thyroiditis). Other causes of primary hypothyroidism include spontaneous degeneration of glandular tissue (idiopathic hypothyroidism), thyroid ablation with radioactive iodine uptake (131I), and total or subtotal surgical thyroidectomy. Primary hypothyroidism is accompanied by an elevation in pituitary TSH secretion and circulating TSH levels. An enlargement of the...

Silent Thyroiditis

This form of thyroiditis is dominated by the pathological picture of a prominent lymphocytic infiltration of the gland. The evidence to date suggests that silent thyroiditis is a variant of lymphocytic thyroiditis. Both have a predilection to occur in the post-partum period but are also common in the non-pregnant state. In contrast to subacute thyroiditis, the clinical features are usually (but not invariably) milder. There is usually less or no pain in the cervical region and less or no thyroid tenderness, despite, at times, acute enlargement of the thyroid. There are minimal if any systemic symptoms and the thyrotoxic symptoms, if present, may be quite mild. The subsequent evolution in the thyroid biochemical abnormalities has a similar clinical course to that of subacute thyroiditis. However, in contrast to subacute thyroiditis, patients with silent thyroiditis often have recurrences and up to one-half of the patients may develop permanent hypothyroidism in the future.

Health Promotion And Disease Prevention

The concept of disease prevention is more specific and comprises primary, secondary and tertiary prevention (12). Primary prevention is defined as preventing the disease or stopping individuals from becoming at high risk. Universal and selective preventive interventions are included in primary prevention. Universal primary prevention targets the general public or a whole population group without an identified specific risk (e.g. iodine supplementation programmes to prevent neurological and other disorders caused by iodine deficiency). Selective primary prevention targets individuals or subgroups of the population whose risk of developing disease is significantly higher than average, as evidenced by biological, psychological or social risk factors (e.g. prevention of stroke through adequate management of hypertension, diabetes and hypercholesterolemia). Secondary prevention aims at decreasing the severity of disease or reducing risk level or halting progression of disease through early...

Basic Physiology of Obesity

Before the body stores excess calories as triglycerides, it tries to use the ingested calories as energy. It does this in three ways basal metabolic rate (BMR), thermogenesis, and physical activity 26 . Like the idling of an engine, the basal metabolic rate is the body's constant conversion on the cellular level of ATP to ADP for energy. This continuous utilization of energy accounts for 70 of the body's daily caloric expenditure. BMR is influenced by thyroid conditions. BMR slows with hypothyroid and increases with hyperthyroid conditions. Consequently, people with hypothyroidism are often obese because of a slow metabolism, and people with hyperthyroidism are commonly thin.

Autoreactive Repertoire

Self-reactive T-cell clones should be deleted in the thymus during ontogeny (central tolerance) or inactivated peripherally through anergy by inappropriate antigen presentation (peripheral tolerance). High-affinity interactions of self-reactive T cells in the thymus with self-epitope-loaded MHC molecules on thymic epithelium or medullary dendritic cells result in clonal deletion of the autoreactive clones (negative selection). Interactions between T cells and self-MHC with nonspecific epitopes are not of high enough avidity to cause apoptosis of the developing T cell but provide sufficient signal to retain the lymphocyte in the thymus (positive selection) for further differentiation. The problem with this form of tolerance is that it depends on self-antigens being present in the thymus during T-cell ontogeny. This could be true for common cellular molecules present in all cells, but would not necessarily be true for specialized or sequestered antigens, such as thyroglobulin, cardiac...

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An unusual variant of papillary carcinoma is the hyalinizing trabecular tumour. This tumour was originally described by pioneers such as Zipkin in 1905 (109), Masson in 1922 (110), and Ward et al. in 1982 (111). The terminology hyalinizing trabecular adenoma (HTA) was defined by Carney et al. in 1987 (112). This lesion has also been designated paraganglioma-like adenoma of thyroid (PLAT) by Bronner et al (113) because of its unusual histologic pattern (Figure 12). Since the original descriptions, a malignant counterpart, hyalinizing trabecular carcinoma (HTC), has been described (114-116) and both HTA and HTC are now incorporated under the umbrella of hyalinizing trabecular tumors (HTT). Their main importance lies in the fact that they are sometimes mistaken for other entities such as paraganglioma or medullary carcinoma (112). Immunohistochemical stains for neuroendocrine markers will easily discriminate between HTT and paraganglioma or medullary carcinoma. However, it was noted that...

Introduction And Historical Aspects

Primary thyroid lymphomas have been recognised for many years and have been documented from the 1940s and 1950s. It was deemed to be important to recognise this entity for it seems that about a third of the cases may be treated successfully with X-rays, followed by maintained thyroid medication (1). Thus, the importance of separating lymphomas from its mimics, namely, chronic thyroiditis and small cell carcinoma, was evident at an early stage because of the therapeutic implications. Indeed, the histological difficulty in separating lymphoma from chronic thyroiditis and small cell carcinoma, no doubt led to the under-diagnosis of lymphoma. Even 50 years and more ago, certain peculiarities of thyroid lymphoma were apparent to pathologists the predilection for elderly women, long survival and the tendency for similar lesions to occur in the gastrointestinal tract. These lymphomas were so characteristic that Brewer and Orr coined the term struma reticulosa to describe them (2). The fact...

Clinical Presentation

Women are more frequently affected than men with a ratio of 2.5 to 8.4 1. Most patients are in the 50 to 80 year age range. There is usually rapid enlargement of an already existing goitre, and the mass may extend extra-thyroidally. The rapid growth and extent of invasion may result in dysphagia, hoarseness and dyspnoea (3, 16, 21). Thyroid function is usually normal but hypothyroidism has been documented in a minority of cases (11, 22). If hypothyroidism is present, it is usually due to the preexisting thyroiditis and not due to the obliteration of thyroid parenchyma by the lymphomatous infiltrate. Very rare cases of hyperthyroidism have been encountered where rapid destruction of thyroid follicles with release of colloid and thyroid hormone into the circulation, have been implicated as causative (23, 24).

The electrocardiogram

Q waves are considered to be pathological and indicative of infarction if they are wide (above 0.04 s) or deep (more than one-third the height of the following R wave). So-called 'septal' Q waves (from left to right activation of the septum) are, of course, normal in leads I, AVL, and V4-V6. Pathological Q waves usually develop over the first 24 h. They are absent in the early hours in this case, lack of progression of the precordial R wave from V1 to V4 may be the only early indication of infarction. These changes are more significant if a prior ECG is available. ST depression and or T-wave inversion do not exclude infarction. Widespread ST depression is sometimes due to subendocardial infarction, with a poor prognosis. However, ST depression and or T-wave inversion can be a completely non-specific finding due to various other causes, such as digoxin, electrolyte abnormality, ventricular hypertrophy, anemia, thyroid disease, or cardiomyopathy. The Fibrinolytic Therapy Trialists'...

Genetic Polymorphisms And Type A Adverse Drug Reactions

On the basis of these studies, should all patients starting warfarin be genotyped This is probably premature since a number of confounding factors need to be studied (Pirmohamed and Park, 2001a). First, the anticoagulant response is partly dependent on R-warfarin, which is metabolized by CYP1A2 and CYP3A4 (Kaminsky and Zhang, 1997). Second, there are a number of pharmaco-dynamic factors, such as vitamin K status and thyroid disease, which alter sensitivity to anticoagulants (Scott, 1989). Third, there are mutations in the clotting factors such as prothrombin that may alter sensitivity to warfarin (Taube et al., 2000). Fourth, there are other methods of dose titration and dose maintenance with warfarin, for example prescribing by computer program (Poller et al., 1998) or home monitoring (Cromheecke et al., 2000), which have been shown to be more effective than conventional prescribing. Finally, the clinical use of warfarin dictates that the genotype of the patient would be required...

Slit Lamp Examination

The anterior segment exam may show conjunctival chemosis or injection in thyroid disease or orbital inflammatory disease. Arterialization of the conjuncti-val vessels might suggest an underlying carotid cavernous fistula. Orbital AVMs may present with findings similar to cavernous sinus AVMs and may require superselective angiography for diagnosis. Anterior uveitis can be seen in patients with systemic inflammatory disorders including sarcoid.14-18

Hongming Zhuang MD PhD Jian Q Yu MD Abass Alavi MD

Numerous reports have demonstrated increased FDG uptake at the sites of infection and inflammation. FDG is applicable to almost any type of infection or inflammation or any anatomic location, including the following abscesses 11-17 , pneumonia 18-20 , tuberculosis 21-25 , Mycobacterium avium-intracellulare infection 26-28 , cryptococcosis 29 , mastitis 30 , enterocolitis 31-33 , infectious mononucleosis 34 , parasitic disease 35 , Clostridium perfringens infection 36 , osteomyelitis 37-42 , infection or loosening following arthrop-lasty 43-45 , fever of unknown origin (FUO) 46-48 , thrombosis 49-51 , amyloidosis 52 , sarcoidosis 53,54 , asthma 55 , bronchitis 56 , encephalitis 57 , costochondritis 58 , radiation pneumonitis 59 , esophagitis 60,61 , pancreatitis 62 , thyroiditis 63-65 , sinusitis 66 , myositis 67 , mediastinitis 68 , gastritis 69 , lobular panniculitis 70 , dental cavity 71 , and inflammation caused by foreign body 72-74 . Despite all of these findings, however,...

Epidemiology And Classification

Although thyroid nodules are extremely common (in countries without iodine deficiency, thyroid nodules are clinically detectable in about 4 to 7 of the general population while this number can rise up to 30 of the population in areas with iodine deficiency) (5), malignant lesions derived from thyroid cells are relatively rare. Less than 1 of all malignant tumors are clinically recognized thyroid carcinomas. However, it is the most common endocrine malignant lesion comprising 90 of all endocrine malignant tumors. It is responsible for more deaths than all the other endocrine cancers combined (6).

Follicular Thyroid Cancer

Follicular thyroid cancer is an epithelial carcinoma showing evidence of follicular cell differentiation but lacking the diagnostic features of papillary carcinoma (11). It tends to be more common in regions with iodine deficiency and in patients older than 50 years. Ten-year survival rates are lower than in PTC ranging from 60 to 70 .

Thyroid abnormalities

In unselected major depression, thyroid hormone levels are usually normal, but there may be abnormalities of the thyrotropin (thyroid-stimulating hormone) response to thyrotropin-releasing hormone. The thyrotropin response is blunted in a significant number of patients, but this effect is poorly understood and has few accepted clinical associations. In contrast, a subgroup of patients may show an enhanced thyrotropin response with normal thyroid hormone levels (referred to as grade II hypothyroidism). These associations and the use of thyroid hormones in treatment suggest that there is more to be learned in this area (see Chapter4. .5.7).

Abnormalities Of Thyroid Hormone Receptors In Thyroid Cancer

Was found in 16 papillary thyroid carcinomas from Polish patients. The TR(3l and TRal protein levels, however, were higher in cancerous tissues than in nearby healthy tissues, an indication of the complexity in the regulation of TR expression in these tumors (36). To understand the nature of TRs in these papillary thyroid carcinomas, cDNAs were cloned concurrently from both the tumor lesions and the healthy thyroids as controls. Sequence analyses indicated that 93.8 and 62.5 of papillary thyroid carcinomas had mutations in and respectively. In contrast, no mutations were found in healthy thyroid controls, and only 11.1 and 22.2 of thyroid adenomas had mutations in TR 3l and TRal, respectively. Functional analysis indicated that these mutated TRs lose their transactivation function and exhibit dominant negative activity (36). carcinomas could be affected by the patient's ethnic origin. Genetic variation between different populations occurs frequently. For example, a wide variation in...

Continuation and maintenance treatment

Choice of mood stabilizer includes an increasingly wide range. Probably lithium is still the drug of first choice, in the absence of major side-effects or patient reluctance. It is usual to recommend doses to achieve blood levels 12 h after the last dose of 0.4 to 0.8 mmol l. Sometimes higher levels may be necessary to prevent recurrences, and to reduce residual symptoms.( 03) After some months of use blood levels are often very stable and only require very occasional monitoring. Advice needs to be given on circumstances which may disturb blood levels (e.g. dehydration, gastrointestinal upset, travel, hot climates). Thyroid function should be monitored every 6 to 12 months, in view of possible insidious onset of hypothyroidism.

Risk Factors For Obesity

Various medical genetic causes of obesity must also be considered. Endocrine conditions associated with weight gain include hypothyroidism, Cushing's syndrome, hypogonadism in the male, polycystic ovary syndrome (PCOS) in the female and growth hormone deficiency (42). Rare genetic causes of obesity include Prader-Willi syndrome, Bardet-Biedl syndrome and Cohen's syndrome. Diabetes can be an obvious consequence of the severe obesity associated with such syndromes.

Pituitarythyroid axis

Thyroid-stimulating hormone stimulates the preferential release of thyroxine (T 4) from the thyroid gland. T4 is then peripherally deiodinated into its active metabolite tri-iodothyronine (T3) or into reverse T3 (rT3) which is thought to be biologically inactive. Both T4 and T3 exert feedback inhibition at the pituitary and hypothalamic level. Critical illness is characterized by a low T 3 or 'sick euthyroid syndrome'. In mild and severe illness T3 production is rapidly decreased by inhibited conversion of T4 to T3. There is then a reciprocal increase in the inactive thyroid metabolite rT 3. With more sustained illness T4 levels may also fall because of reduced T4 binding to its carrier proteins leading to accelerated metabolism. More importantly, thyroid-stimulating hormone secretion is also suppressed for example, the normal night-time surge in thyroid-stimulating hormone is not present in patients with sick euthyroid syndrome and the response of thyroid-stimulating hormone to...

Radioiodine Complications

Acute complications of therapy with I-131 are mostly nonsevere and usually short-lived. The more usual symptoms include sialoadenitis, radiation thyroiditis, neck edema, nausea, and gastritis (95). The salivary glands concentrate iodine and sialoadenitis may occur in about 30 of patients treated with radioiodine (96). It is characterized by pain, tenderness, and swelling of the salivary glands. Some patients suffer from reduced salivary gland function for more than one year after therapy with I-131. The use of lemon juice or lemon candies and abundant water ingestion reduces the incidence and severity of sia-loadenitis and reduces absorbed radiation dose to the salivary glands. Recently, a study indicated that an early start of sucking lemon candy may provoke an increase in salivary gland damage suggesting that lemon candy should not be given until 24 hours after therapy with I-131 (97). The use of amifostine may reduce significantly the damage to salivary glands, mainly when high...

Causes of Overweight and Obesity

The primary care physician must consider genetic syndromes and endocrine conditions as possible explanations for a child's obesity. Prader-Willi syndrome is characterized by a rapid increase in weight from ages 1 to 6, hypotonia and poor feeding in infancy, hypogonadism, and cognitive delay 13 . The majority of children with Cushing syndrome are obese and short in stature 14 , which contrasts with children who are obese from eating excess calories and are commonly taller than their peers. Other medical conditions like hypothyroidism or growth hormone deficiency can cause a child to be obese, which would be suggested by clinical findings like a goiter, short stature, or delayed puberty. After a complete history and physical examination, in the vast majority of obese patients the physician can reassure the parents that their child does not have a genetic disorder or a metabolic syndrome. The one laboratory test all obese patients need is a thyroid-stimulating hormone (TSH) test....

Clinical Utility of Testing

There is no concordance between specific SLC26A4 allele variants and audiogram configuration,42 although some mutations may be associated more frequently with specific temporal bone anomalies. For example, Masmoudi et al. studied two families segregating for L445W and found that while affected persons showed phenotypic variability with respect to thyroid disease, the temporal bone imaging revealed only DVA.44

Cerebral and neurological changes

Thyroid hormones act on protein and nucleic acid synthesis, cerebral lipids, myelinization, and numerous enzymatic activities. In particular, they stimulate synthesis of atherosclerosis, occur in hypothyroidism. Somnolence, lethargy, and coma, sometimes with seizures, are common features of myxedema coma (T chm a.D .D.d Guthrie 1984). These neurological disturbances are made worse by concurrent hyponatremia ( Mariotti efia .i 1995).

Gastrointestinal changes

Constipation is usual in moderate hypothyroidism. Intestinal pseudo-obstruction and paralytic ileus can occur in myxedema coma ( lachman.a.n.d Guthrie 1984). Lack of thyroid hormones induces a slowing in gastric emptying and in the motor activity of the small intestine and colon. Amplitude and frequency of colon muscular

Dermatological changes

Cutaneous changes have been the classic feature of hypothyroidism ever since the first description of myxedema by Ord in 1878. Peripheral vasoconstriction and decreased cutaneous metabolism are expressed as a cold, dry, and pale skin. The accumulation of mucopolysaccharides and proteins in the interstitial spaces of the skin induces thinning of the epidermis and deep wrinkles ( Hair is scarce, with slow growth. Only 40 per cent of hypothyroid patients have

Changes in lipid metabolism

Plasma lipids are often altered in hypothyroidism (lachman.and Guthrie 1984). Hyperglyceridemia is due to increased hepatic output of very-low-density lipoproteins The capacity to counter-regulate hypoglycemia is impaired in hypothyroidism. The risk of severe and prolonged hypoglycemia is high. Insulin clearance is reduced,

Diagnosis of myxedema coma

Diagnosis in a patient with known hypothyroidism, who stopped treatment a long time ago and shows typical clinical features, is easy. It is more difficult when hypothyroidism has not yet been diagnosed. The association of altered mental status, hypothermia, and a precipitating event should lead to tri-iodothyronine, free thyroxine, and cortisol. The diagnosis is positive when the results are in agreement with primary hypothyroidism, i.e. elevated plasma thyroid-stimulating hormone and dramatic reduction of both free tri-iodothyronine and free thyroxine, thus excluding a 'euthyroid sick syndrome' or low

Major Histocompatibility Complex Class II Gene Control of Susceptibility

A strong HLA class II association with autoimmune thyroid disease, including Hashimoto's thyroiditis and Graves' disease, has been more difficult to gain widespread acceptance, despite implications from patient studies, due to the poly-genic nature of the human class II genes as well as ethnic differences. Firm association of autoimmunity with specific HLA class II genes was further made difficult by the now-recognized class II gene influences within a single host, which could jointly affect the extent of susceptibility. Several years ago, we initiated transgenic studies, introducing either H2 or HLA transgenes into mice, in order to determine the influence of a single class II transgene independent of other HLA genes, and in the absence of endogenous H2 class II molecules (reviewed in Kong and David, 2000 Kong et al., 2003). Briefly, for the purpose of this review, we first ascertained that our transgenic techniques were applicable to HLA transgenic studies by using a known...

CD25 Expression on CD4 Regulatory T Cells in Induced Resistance

BALB c background) blocks the development of several autoimmune diseases including thyroiditis, which can arise by the transfer of CD4+CD25- T cells alone (Sakaguchi et al., 1995). In vivo depletion of CD4+CD25+ T cells enabled the induction of autoimmune gastritis in otherwise resistant mice (McHugh and Shevach, 2002). We examined the participation of these cells in dmTg-induced resistance to EAT induction (Morris et al., 2003). After the establishment of tolerance, mice were depleted of CD4+CD25+ T cells with CD25 mAb, their peripheral blood leukocytes verified for depletion, and challenged with mTg and LPS. Depletion of CD4+CD25+ T cells led to the loss of tolerance in most animals, whereas dmTg-pretreated mice given rat IgG remained tolerant. Thus, the CD4+ regulatory T cells mediating EAT tolerance also carry the CD25 marker.

Minor group antigens also may uncommonly contribute to

Hemolytic anemias, transfusions, and trauma associated with hematomas result in increased bilirubin load and are causes of indirect hyperbilirubinemia in any age group. Infants with galactosemia and hypothyroidism may present initially with indirect hyperbilirubinemia in the newborn period. Congenital infections (eg, cytomegalovirus, toxoplasmosis) that cause systemic illness may be associated with hemolysis and indirect hyperbilirubinemia, in addition to hepatitis and direct hyperbiliru-binemia. Indirect hyperbilirubinemia may be exaggerated in the presence of the following risk factors Asian or Native American race, prematurity, polycythemia, male sex, Down syndrome, oxytocin induction, delayed stooling, and having a sibling with a history of neonatal jaundice.

Specific Considerations Related To Radioiodide Treatment

In the healthy thyroid gland, NIS mediates the active accumulation of whereas the mechanisms involved in efflux are poorly understood (see efflux pendrin and AIT below). I organification - i.e., the TPO-mediated iodination of the tyrosine residues on the thyroglobulin molecule - occurs on the colloidal surface of the apical membrane. lodinated thyroglobulin molecules remain in the colloid, surrounded

Correction Of Other Medical Disorders

Treatment of hypothyroidism, acromegaly, and nasal congestion may improve the severity of OSA. OSA is common in patients with hypothyroidism, and it is believed that hypothyroidism predisposes to the development of OSA (50). The mechanism for this association may include weight gain, tongue enlargement, muscle dysfunction, and changes in respiratory drive. In patients with sleep apnea, the prevalence of undiagnosed hypothyroidism has been reported in the range of 3.1 to 11.5 (51,52). Whether all patients with OSA should be screened for hypothyroidism is controversial (53). Nevertheless, treatment of hypothyroid-ism may lead to an improvement of OSA (54), and is likely to improve symptoms of daytime fatigue and promote weight loss (55). Treatment of hypothyroidism masquerading as OSA so called secondary sleep apnea may result in resolution of symptoms (56). Having a low threshold for testing thyroid function in patients with OSA is recommended.

Causes of hypothermia

Hypothermia can be precipitated by alteration of thermoregulatory mechanisms for example, alcoholic intoxication induces peripheral vasodilatation, decreases shivering capacity, depresses central thermoregulatory mechanisms, and impairs judgment. Alcoholics may stay outside for many hours wearing few clothes, either asleep or unconscious, in parks, on river banks, or in snow. Many drugs, such as tricyclic antidepressants, phenothiazines, or barbiturates, can lead to hypothermia either when used at toxic levels for self-poisoning or when administered in normal dose range for therapeutic purpose. Endocrine dysfunction, such as hypothyroidism, hypopituitarism, hypoglycemia, or diabetic ketoacidosis, may also result in hypothermia. Additional risk factors include central nervous system lesions (stroke, hemorrhage, trauma, tumor), spinal cord injuries, Parkinson's disease, Wernicke's encephalopathy, Alzheimer's disease, schizophrenia, anorexia nervosa, agenesis of the corpus callosum, or...

Sellarsuprasellar tumours pituitary adenoma

'Adult GH deficiency syndrome' -weight gain, loss of libido, fatigue Amenorrhoea, sterility, loss of libido Glucocorticoid and androgen deficiency, muscle weakness and fatigue Secondary hypothyroidism -sensitivity to cold, dry skin, physical and mental sluggishness, coarseness of hair Failure of lactation

Non neoplastic orbital lesions

The thyrotoxic patient with bilateral exophthalmos presents no diagnostic difficulty, but dysthyroid exophthalmos, with marked lid oedema, lid retraction and ophthalmoplegia may occur unilaterally without evidence of thyroid disease. Coronal CT scanning establishes the diagnosis by demonstrating enlargement of the extraocular muscles - primarily the medial and inferior recti. MRI shows a similar appearance.

Molecular Markers Of Tumor Recurrence Or Progression

Ditkoff, et al. (66) reported results from 100 individuals including 87 with thyroid cancer, 6 with benign thyroid disease (nontoxic goiters), and 5 normal subjects following total thyroidectomy (except normal subjects). Total RNA was isolated from the macrophage layer of peripheral blood, and, using RT-PCR amplification of thy-roglobulin mRNA, they detected thyroid transcripts in blood from 9 of 9 patients with metastatic thyroid cancer, but from only 7 of 78 patients thought to be free of disease, and no patients having surgery for benign disease or normal control subjects. Detailed clinical information was not included regarding the clinical status of the patients and TSH levels were not reported. However, these investigators clearly demonstrated that thyroglobulin mRNA could be amplified from peripheral blood and that its presence appeared to correlate with stage of disease. The importance of assay methodology has been highlighted in several recent studies. Bojunga, et al. (73)...

Scanning of the Thyroid

Radionuclide imaging of the thyroid is a direct extension of the clinical examination. It is important for the nuclear physician to be familiar with the setting in which the examination is being requested. Patients may be self-medicating with vitamins, kelp or other substances containing iodine and it is recommended to defer the examination for several weeks after discontinuation of these substances (Table 1). Clinical examination of the patient while under the camera allows correlation of palpable features with those of the scan. This ought always to be done by the physician who will report the examination and who should be aware of the presenting complaint, the relevant clinical history and laboratory data. A positive family history will increase the pre-test likelihood for multinodular goitre and Graves's disease. A complaint of pain predisposes toward thyroiditis. A history of radiation exposure with a symptomatic mass increases the probability of a malignancy.

Table 2 Differential diagnosis of thyrotoxicosis

Subacute thyroiditis Silent thyroiditis In Figure 3 the 99mTc-pertechnetate thyroid scans of common thyroid disorders, including a typical patient with Graves' disease, are displayed. On occasion, patients with other forms of chronic thyroid disease may develop TSH receptor antibodies producing a thyrotoxic state. The distinction is not very important except that the latter may be at lower risk of developing eye complications. In these cases, the radionuclide pattern may be somewhat patchy rather than the diffuse homogenous pattern of uptake seen with Graves' disease.

Clinical evaluation of PMS

The differential diagnosis includes hypothyroidism, anemia, perimenopause, drug and alcohol abuse, and affective disorders. Common alternative diagnoses in patients complaining of PMS include affective or personality disorder, menopausal symptoms, eating disorder, and alcohol or other substance abuse. A medical condition such as diabetes or hypothyroidism, is the cause of the symptoms in 8.4 , and 10.6 have symptoms related

Multi Nodular Toxic Goitres

It is less likely than in the case of Graves' disease that patients with multi-nodular toxic goitres will be rendered hypothyroid by a single treatment. The least abnormal tissues are likely to be suppressed by hormone output from the more autonomous nodules and the survivors will resume function after the currently toxic nodules have been destroyed. The delivered radiation dose from any one treatment will vary

Antibody Immunoconjugates

UJ13A (anti-NCAM) was the first antibody to undergo clinical testing for radioimaging and radio-immunotherapy (Lashford et al. 1987). 131I-3F8 (anti-GD2, 6-28 mCi kg) achieved responses in both soft tissue masses and bone marrow (Larson et al. 2000). The use of myeloablative 131I-3F8 (20 mCi kg) to consolidate remission was tested in patients (> 1 year of age) newly diagnosed with stage-4 NB (Cheung et al. 2001a). Extramedullary toxicities were limited to hypothyroidism, which occurred despite aggressive thyroid protection using potassium iodide, liothyro-nine (T3), and potassium perchlorate. 131I-MAb was also tested in RIT of leptomeningeal cancers in children by intraventricular administration (Lashford et al. 1988 Kramer et al. 2000). Estimated radiation doses of 14.9-56 cGy mCi to the cerebrospinal fluid were achieved with 131I-3F8, with less than 2 cGy mCi to blood and other organs outside the CNS (Kramer et al. 2000).

Prevention of mental disorders

Mental disorders with known aetiology this mostly includes those disorders demonstrated to have an organic basis, ranging from the 'historical' general paresis and dementing disorders (e.g. vascular dementia, pellagra, and dementias associated with infectious and parasitic diseases such as malaria and HIV infection) to several forms of mental retardation (Down syndrome, fetal alcohol syndrome, phenylketonuria, and mental retardation due to iodine deficiency).

Mental disorders with known aetiology

As for mental retardation, up to 15 per cent of cases could be prevented by dealing with the causes that lead to it. A recent WHO publication (2) has set detailed guidelines for the prevention of some forms of this condition, namely, Down syndrome, fetal alcohol syndrome, phenylketonuria, and iodine deficiency syndrome. These preventive actions are both efficient and affordable even in very poor regions of the world. Appropriate nutrition, in addition to its major role in health promotion, can prevent at least two other forms of mental retardation, iodine deficiency and phenylketonuria. The world population at risk of mental retardation due to iodine deficiency is approximately 1 billion and it still occurs in large numbers in some regions of the globe. (6) However, it can be very efficiently and cheaply prevented through the addition of iodine to salt, milk, flour, or water, or, in special situations, through injections of an oily solution containing iodine.(7)

Hereditary Breast Ovarian Cancer

One of the more than 50 cancer-related genodermatoses, Cowden's syndrome is characterized by an excess of breast cancer, gastrointestinal and gynecologic malignancies, and thyroid disease, both benign and malignant.64 Skin manifestations include multiple trichilemmomas, oral fibromas and papillomas, and acral, palmar, and plantar keratoses. Germline mutations in PTEN, a protein tyrosine phosphatase with homology to tensin, located on chromosome 10q23, are responsible for this syndrome. Loss of heterozygosity observed in a high proportion of related cancers suggests that PTEN functions as a tumor suppressor gene. Its defined enzymatic function indicates a role in maintenance of the control of cell proliferation.65 Disruption of PTEN appears to occur late in tumorigenesis and may act as a regulatory molecule of cytoskeletal function. Although it accounts for a small fraction of hereditary breast cancer, the characterization of PTEN function will provide valuable insights into signal...

Thyroglossal Duct Cyst and Ectopic Thyroid

Hypothyroidism is a frequent finding in patients with lingual thyroid 105 . Batsakis and collaborators noted a clinical prevalence of lingual thyroid of 1 in 10,000 individuals, but an autopsy prevalence of 1 in 10 10 . Ectopic thyroid is histologically composed of uniform, often small, follicles containing minimal colloid. The mi-crofollicles are usually intercepted by the skeletal muscle of the tongue.

The Diseased And Ageing Heart

Several mechanisms appear to underlie the response of the diabetic heart to ischemia and reperfusion. Reduction in glucose uptake and metabolism increases the sensitivity of the diabetic heart to an episode of hypoxia or mild ischemia (low-flow ischemia). In contrast, decrease in glycolytic product accumulation (lactate and protons) as well as alterations in the regulation of pH (decrease in Na+ H+ exchanger activity) make the diabetic heart less sensitive to an episode of severe ischemia (zero-flow ischemia).205,206 Studies demonstrating increased tolerance of the diabetic heart to ischemia and reperfusion implicate the involvement of cardioprotective intracellular signaling. In fact, ERK phosphorylation was increased at baseline and during ischemia, while inhibition of PKC activation abolished the enhanced tolerance of the diabetic heart to ischemia and reperfusion injury. Persistent translocation of PKCe during ischemia is also observed in the diabetic heart.207 Furthermore,...

Requirement for Iodine

A normal rate of thyroid hormone synthesis depends on an adequate dietary intake of iodine. Iodine is naturally present in water and soil, although some soils contain very low amounts. As a result, seafood is a more reliable source of iodine than crop plants. Approximately 1.6 billion people in more than 100 countries live in areas where natural sources of dietary iodine intake are marginal or insufficient. A minimum of 60 g of elemental iodine is required each day for thyroid hormone synthesis, and at least 100 g day is required to eliminate thyroid follicular cell hyperplasia and thyroid enlargement (i.e., iodine deficiency goiter).

Descriptive epidemiology of severe intellectual impairment IQ

Point prevalence varies between similar birth cohorts (concurrent age groups) in different communities (e.g. 1.62 1000 children born 1951-55 in Salford, United Kingdom, and 7.34 1000 children born in 1957 in Amsterdam). Greater variation is expected in developing countries, (lJ) especially where there is one dominant cause such as iodine deficiency disease, where congenital hypothyroidism can affect more than 10 per cent of village populations. Down syndrome is often the largest aetiological group, especially in communities with traditions of late marriage, large families, and taboos against contraception and or abortion, and where early mortality is low. Mortality and survival vary greatly, generally related to the 'development status' of the community. 3. A similar pattern of temporal variation is common throughout the developed world. Age-specific prevalence was generally low (1.8-4.0 in 1000) for children born in the early 1950s, and high (3.3-5.5 in 1000) for those born in the...

Developing countries17

Rigorous studies are more difficult and good record systems less common in developing countries, so there are few reliable sources for estimating prevalence, but data available suggest differences related to the varying spectrum of organic causes, mortality, and social situations. fy,1.6.) Developing countries are not all the same for example the high infant mortality of most African countries is not shared by China. In some, cretinism due to iodine deficiency disease is an overwhelming cause and can affect over 10 per cent of village populations before salt iodization or similar programmes have much impact. Children with Down syndrome do not generally survive in communities with high infant mortality.

Adverse Effects Of Treatment With Thyroid Hormone

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones.

Euthyroid Multinodular Goiters

Doses of 3.7 to 4.625 MBq (100-125 mCi) per gram of estimated thyroid tissue have been used for the treatment of euthyroid goiters. More than 90 of patients can be expected to demonstrate a decrease in goiter size with an average reduction of 40 at one year (25). Tracheal compression may also improve significantly, both symptomatically and radiographically (26). However, caution should be exercised in patients with significant or impending compression, as RAI may conceivably cause transient swelling owing to inflammation, potentially threatening airway patency. A small percentage of patients may have transient hyperthyroidism, and approximately 4 of patients may develop autoimmune thyroid disease following the treatment of euthyroid goiter with RAI (27). The latter may be attributed to the release of thyroid antigens following radiation-induced tissue necrosis. A significant number of patients may also become hypothyroid following treatment. In one randomized trial, comparing RAI to...

Cancer Risk from Radioactive Iodine Therapy

The possibility of an increased risk of cancer following radioiodine therapy for hyperthyroidism remains controversial despite numerous studies supporting the safety of RAI for this indication. A multicenter retrospective cohort study examined cancer mortality in over 35,000 patients after three treatment modalities for hyperthyroidism (56). The total number of cancer deaths was not increased for this group as a whole. Interestingly, an increased risk of cancer mortality was seen in patients treated exclusively with antithyroid drugs. Radioiodine treatment was not associated with excess total cancer deaths, or to any particular cancer, with the exception of thyroid cancer, where there was a slight increase in thyroid cancer mortality following radioiodine therapy, although the underlying thyroid disease was suggested to have played a role. Another study found that the incidence of thyroid cancer in radioiodine-treated patients over a 27-year period was not significantly different from...

Sarcomeric Myosin Isoforms Determine The Functional Properties Of Atrial And Ventricular Myocardium

During prenatal development of mammalian heart, MyHC-beta is the principal isoform expressed in the ventricles (Chizzonite and Zak, 1984 Chizzonite and Zak, 1984 Lompre et al., 1984), whereas MyHC-alpha is the principal isoform expressed in the atria (Lompre et al., 1981). However, in rodents, shortly after birth, MyHC-beta expression decreases and is replaced by MyHC-alpha to the point that at the age of three weeks, MyHC-alpha is virtually the only isoform expressed in the ventricles. This isoform replacement is attributed to an increase in plasma levels of thyroid hormone (T3) and can be delayed if the animals are made hypothyroid (Morkin, 2000). Further maturation of rodent heart is associated to a re-expression of MyHC-beta, which accounts for 15-20 of the total MHC in adult rat and even more in aged animals. Such an increase in MyHC-beta is generally attributed to the increase in wall mechanical stress as the ventricles enlarge during maturation to adulthood (Swynghedauw, 1999)....

Malnutrition syndromes of childhood

Celiac disease is a genetically determined chronic inflammatory intestinal disease induced by an environmental precipitant, gluten, that often presents without clear GI symptoms. Celiac disease may be characterized by damage to the small intestinal mucosa caused by the gluten fraction of wheat proteins and similar alcohol-soluble proteins (prolamines) of barley and rye in genetically susceptible subjects 101 . Clinical severity varies from silent to severe. FTT is the most frequent presentation in the pediatric age group. Increased frequency of other diseases such as type 1 diabetes or autoimmune thyroiditis, Down's syndrome, Turner's syndrome, or IgA deficiency, is found in family members of celiac patients. In developed countries, the prevalence of celiac disease among children and adults with type 1 diabetes exceeds the prevalence in the general population 101 . Reduced levels of vitamin E have also been reported 102 . Exclusively breastfed children with biopsy-proven celiac...

The Molecular Endocrinology Of Diabetes Mellitus

The most characteristic features of this syndrome are chronic mucocutaneous candidiasis, hypoparathyroidism, Addison's disease, and T1ADM other features include other autoimmune endocrinopathies (such as hypothyroidism or hypogonadism), malabsorption syndromes, pernicious anemia, and alopecia. The gene for this disorder is the autoimmune regulator or AIRE (OMIM 607358), which appears to be a transcription factor. The exact mechanism by which it causes the syndrome is not known (131,132). The second monogenic syndrome is X-linked autoimmu-nity-allergic dysregulation syndrome (XLADD, also called immunodysregulation, polyendocrinopathy, and enteropathy, X-linked or IPEX) (OMIM 304790), a syndrome of multisystem autoimmunity including diabetes and thyroid disease as well as frequent infections, diarrhea, and hemolytic anemia. The disorder is usually fatal. Mutations in the transcription factor forkhead box P3 gene (FOXP3) (OMIM 300292) are causative (133).

Hyperthyroidism in pregnancy

Thyroid function should be assessed in women with hyperemesis gravidarum. Women known to have Graves' disease may decide on definitive treatment of their condition prior to becoming pregnant. If Graves' disease is diagnosed during pregnancy, it is important to use the smallest dose of antithyroid drugs by reviewing regularly to maintain maternal concentrations of free thyroid hormone and thyroid-stimulating hormone within their respective normal ranges. This is to avoid fetal hypothyroidism and goiter. Most recommend that carbimazole should be discontinued 4 weeks before the expected date of delivery to avoid any possibility of fetal hypothyroidism at the time of maximum brain development. If subtotal thyroidectomy is necessary because of poor drug compliance or hypersensitivity, it is most safely performed in the middle trimester. Radio-iodine is contraindicated because it invariably induces fetal hypothyroidism. If antithyroid agents are given postdelivery, breast feeding is not...

Relationship Between Low And Highgrade Maltlymphomas

HASHIMOTO'S THYROIDITIS It is important to note that similar cellular constituents (centrocyte-like and plasma cells) together with lymphoepithelial lesions are encountered in Hashimoto's thyroiditis. Hence, florid cases can be exceptionally difficult to separate from MZBL of MALT-type. It has been suggested that a dense lymphoid infiltrate with fewer intervening reactive lymphoid follicles, broad bands of centrocyte-like or clear cells and large number of lymphoepithelial lesions that diffusely efface the thyroid parenchyma, favour a diagnosis of lymphoma. In the histologically suspicious cases, the demonstration of sheets of B-cells, light chain restriction and heavy chain gene rearrangement are ancillary features that will help in confirming the diagnosis of lymphoma. The clinical picture of sudden or rapid enlargement of the thyroid in a patient previously diagnosed as having Hashimoto's thyroiditis will also be useful. At the end of the day, there are going to be some cases...

The hypothalamicpituitarythyroid axis

It has been recognized for more than a century that adult patients with hypothyroidism exhibit profound disturbances in CNS function, including cognitive impairment and depression. In more recent years, attention has focused on more subtle alterations of the hypothalamic-pituitary-thyroid ( HPT) axis in depressed patients. Hypothyroidism is most frequently subclassified as in four grades as follows. Grade 1 hypothyroidism is classic primary hypothyroidism (increased thyroid-stimulating hormone ( TSH), decreased peripheral thyroid hormone concentrations, and an increased TSH response to thyrotrophin-releasing hormone (TRH)). Grade 2 hypothyroidism is characterized by normal, basal thyroid-hormone concentrations, but an increase in basal TSH concentrations and an exaggerated TSH response to TRH. Grade 3 hypothyroidism can only be detected by a TRH-stimulation test patients have a normal basal thyroid hormone and TSH concentrations, but an exaggerated TSH response to TRH. Grade 4...

Drug Interactions

An adequate dietary intake of iodine is essential to prevent hypothyroidism. In many areas of the world, dietary iodine intake is insufficient and must be supplemented. There is another element in which a dietary intake may be insufficient that is also associated with thyroid hormone metabolism. This element is (B) Many of the effects of elevated thyroid hormones result from an increase in number of p-adrenoceptors. (D) The effects of elevated thyroid hormones are directly antagonized by p-adrenoceptor agonists.

Goals And Expected Outcomes Of Treatment

With adequate doses of radioactivity, an 80 response rate should be expected. A primary goal of treatment is to resolve hyperthyroidism in as short a time as possible. However, with RAI doses calculated to achieve this goal in the majority of patients, a significant number of patients will ultimately become hypothyroid. The incidence of hypothyroidism was first estimated at 20 to 40 of patients one year after RAI therapy (30). With more conservative doses of RAI, the incidence of hypothyroidism may be lower, although, often at the expense of higher rates of persistent hyperthyroidism. Patient preferences, the availability of close follow-up, and potential risks from persistent hyperthyroidism should be considered when deciding between more definitive treatment with higher doses and the use of more conservative doses. Some authorities have maintained that hypothyroidism, which is easily and inexpensively treated with thyroid hormone supplementation, is preferable to persistent...

Developmental Transitions And Developmental Maladies

Aberrant neurologic development is associated with a wide range of physiologic insults. The diverse causes of such problems include various nutritional deficiency disorders, hypothyroidism, fetal alcohol syndrome, treatment of CNS cancers of childhood by radiation, and treatment of even some non-CNS cancers of childhood by chemotherapy. Common to most and perhaps even to all of the physiologic challenges associated with neurologic impairment are problems related to formation or maintenance of myelin. Hypothyroidism Fetal and early postnatal hypothyroidism, usually associated with iodine deficiency, is a major cause of mental retardation, myelination failure and other developmental disorders (e.g., refs. 216 and 217). Children born to mothers with reduced TH levels during early stages of pregnancy perform poorly on later tests of neurological and cognitive function (218-220). In addition, the thyroid status of neonates and children has a significant long-term impact on their behavior,...

Dose For Graves Disease

The amount of RAI to be administered for treating hyperthyroidism related to GD may be selected empirically or determined by a dose calculation based on the assessments of thyroid mass and function (Table 1). Standard treatment usually involves a single administration of RAI. The administration of small amounts of activity (e.g., 2 mCi) at frequent intervals is not recommended, because it allows patients to remain hyperthyroid for longer periods of time, and has not been proven superior at preventing iatrogenic hypothyroidism. Table 1 Calculation of Administered Activities for Treatment of Benign Thyroid Diseases Most recommended administered activities range between 3.7 and 7.4 MBq (100-200 mCi) per gram, corrected for percentage thyroid uptake. Administration of 2.96-4.44 MBq (80-120 mCi) per gram will generally deliver doses of 50100 Gy to the thyroid (9). Lower doses may reduce the incidence of hypothyroid-ism following treatment, but will increase the likelihood that a second...

Metabolic disorders

C Nearly all critically-ill patients have decreased serum levels of T3 and 50 have a decrease in the level of T4 concentration with normal or low thyroid-stimulating hormone (TSH). The reduction in T3 levels results from a decrease in deio-dinase activity that occurs in critical illness. This is reflected in the increase in serum level of T3 that occurs during critical illness. This enzyme is responsible for the degradation reverse of T3, explaining the increase in serum levels of reverse T3 that occurs in critical illness. (Rogers MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition pp. 1290-1297 Wilson D, et al. J Ped, 1982 101 113.)

Experimental Induction Of Thyroid Tumors

Thyroid tumors have been induced in rats by prolonged over-stimulation of the gland with endogenous TSH only. This method involves maintaining the animals in a state of chronic iodine deficiency. The first observations of rats kept in such a state can be traced back to Bircher (1910, 1911). Since then, the method has been perfected by several groups (Hellwig 1935, Bielschowsky 1953, Isler 1959, Al-Saadi 1968 a.o.), but the malignancy of the follicular neoplasms that arise in the rat thyroid as a result of chronic iodine deficiency is questionable. In all cases reported so far, the frequency of carcinomas originating from follicular epithelium is clearly lower in rats kept on a low-iodine diet than in animals treated with goitrogens. In rats, iodine deficiency is a much more effective tumor promoter than is a carcinogen, suggesting that a similar relationship may exist in human populations (Ward & Oshima 1986). In C3H Hey strain-mice, Schaller & Stevenson (1966) used low-iodine...

Congenital rubella syndrome

This is now a rare cause of mental retardation since the introduction of the measles vaccine. Rubella virus belongs to the Togaviridae family of viruses. In children this virus usually causes a non-symptomatic infection (German measles) and in adults may cause a prodrome of low-grade fever, headache, malaise, mild coryza, and conjunctivitis. Maternal infection during the first trimester is usually transmitted to the fetus leading to infection, often causing miscarriages and stillbirths however, up to 20 per cent survive to develop congenital rubella syndrome. Infection beyond 16 weeks gestation is far less likely to cause congenital rubella syndrome. Around 80 per cent of the affected subjects have ocular disorders such as cataracts and microphthalmia leading to poor visual acuity. About 60 per cent have sensorineural hearing deficit, psychomotor retardation, and cardiac abnormalities, and about 40 per cent have mental retardation. This syndrome is also associated with diabetes...

Gene Expression Profiling In Thyroid Cancer

A limited number of studies have reported on DNA microarray studies in thyroid cancer two on follicular tumors, one on papillary carcinoma (PTC) and only one that examined a range of benign and malignant thyroid disease. The numbers of samples analyzed in each study was small to moderate in size. Most of the studies quoted are, however, robust and pass muster for the stringent rules stipulated for reporting of gene expression studies (4). We have used human cDNA microarray constructed in-house by spotting previously PCR-amplified and purified gene-specific samples to study RNA from a range of thyroid tissues. We examined samples from multinodular goitre (MNG), Graves' disease, Hashimoto's thyroiditis, papillary carcinoma, follicular carcinoma and follicular adenoma and compared these to normal perinodular thyroid tissue. Hierarchical cluster analysis (Figure 1) showed clear separation of various clinical pathological entities according to variation in the expression of 1322 genes,...

Factors Influencing Prognosis and Outcome

Other thyroid diseases Family history Tumor variables Histology Other thyroid diseases One study of PTC associated with Graves' disease found that the tumors were more often multifocal with distant metastases (47). Serum from patients with Graves' disease has been shown to stimulate the progression of follicular cells to carcinoma in vitro (48). PTC appears to carry a better prognosis when Hashimoto's thyroiditis or lymphocyte infiltration are associated (49,50). Hashimoto's thyroiditis itself, however, is considered a risk factor for DTC.

Dose For Toxic Nodular Goiter

In addition to GD, thyrotoxicosis can also result from a single hyperfunctioning nodule, or multiple hyperfunctioning nodules (i.e., toxic multinodular goiter). Although antithyroid drugs can ameliorate hyperthyroidism, definitive treatment is more commonly accomplished with RAI or surgery. Less commonly, percutaneous ethanol injection has also been used for large solitary nodules (16,17). Compared with treatment with RAI, hypothyroidism is a more common sequel of surgery (18). The choice of surgery versus radiation for nodular goiters is beyond the scope of this chapter, although surgery should be considered strongly in patients with goiters causing significant airway obstruction or an increased risk of harboring thyroid cancer. Treatment decisions for these patients should be made in consultation with a surgeon with expertise in thyroid surgery. suppressed thyroid tissue may still receive a dose as high as 23 Gy (19). However, hypothyroidism following RAI treatment does seem to...

Potential Pathogenic Roles for AECAs

The spectrum of autoantibodies present in patients with autoimmune diseases provides diagnostic utility and must also in principle provide information about the mechanisms underlying the disease process. In several instances, it is also certain that these autoantibodies play a causal role in pathogenesis (e.g., myasthenia gravis, autoimmune thyroid disease). A pathogenic role for AECAs is less certain, and it may well be that in some diseases AECAs arise as the consequence of vascular damage, which exposes epitopes not usually visible to the immune system, and thus they are simply markers of the extent of vascular pathology. However, there is good evidence that other autoantibodies in systemic vasculitic diseases are pathogenic notably anti-neutrophil cytoplasmic antibodies (ANCAs) and increasing evidence

Injection Snoreplasty

Palatal injection sclerotherapy (injection snoreplasty) was introduced as an inexpensive, minimally invasive office procedure that treats palatal flutter snoring. Essentially, a sclerotherapy agent is injected into the submucosal layer of the soft palate to promote fibrosis and scarring (106). Several different sclerotherapy agents have been employed to stiffen the soft palate. The two most commonly used agents are 3 sodium tetradecyl sulfate (sotradecol) and 50 ethanol (107). The average number of injections required to achieve adequate reduction in snoring was 1.2 injections per patient. Exclusion criteria for this modality include comorbid diseases that interfere with wound healing (uncontrolled diabetes, uncontrolled hypothyroidism, and periodontal disease), marked tonsillar hypertrophy, previous surgical procedures for snoring, and significant OSA. Complete cessation or a significant reduction in snoring was reported by 92 of patients or bed partners. However, the rate of snoring...

Contraindications To Radioactive Iodine Therapy

A patient who is pregnant should not be treated with RAI (7). RAI crosses freely into the placenta, and the fetal thyroid tissue is capable of accumulating iodine after the 12th week of gestation. Administration of RAI during this period may result in severe neonatal hypothyroidism. Fetal and neonatal thyroid irradiation may also increase the risk of developing thyroid cancer later. Retained activity in the maternal bladder may also increase the risk of malignancy by direct radiation exposure to the fetus. RAI has no role for the treatment of hyperthyroid conditions that are self-limited or when thyroid tissue is not hyperfunctioning. These conditions include silent, subacute, and postpartum thyroiditis in addition to factitious thyroid disease.

On Adult Presentations

Hypothyroidism symptoms of fatigue can overlap with those of sleep apnea. Case series have reported improvement or resolution of sleep apnea in selected patients treated with thyroxine alone (84). Nonetheless, the limited evidence available suggests the prevalence of hypothyroidism in sleep apnea patients is no different than that seen in the general population (85) and routine screening in the absence of other signs of hypothyroidism is not cost-effective. Cases have also described lingual thyroids causing airways obstruction at night (86).

Clinical Features of Hemangioma

What Hemangioma The Fall

Hypothyroidism in Hemangioma Huang and colleagues discovered that severe hypothy-roidism can be associated with large hemangiomas 1 . They showed that the likely underlying cause was ectopic expression of type 3 iodothyronine deiodinase (D3) in proliferating hemangiomas. D3 is widely expressed in fetal tissues and some tumors, but after birth, its expression is restricted to placenta and brain. D3 inactivates thyroid hormone and, in the case described by Huang and colleagues, can lead to consumption of therapeutic doses of hormone in a child with a large hemangioma. The impact of hypothyroidism during infancy is severe and irreversible neurological damage in particular can lead to loss of three to five IQ points per month in children under one year of age with untreated hypothyroidism. Hence, the aberrant proliferation of endothelium that characterizes hemangioma can have deleterious systemic effects for a child in addition to the local tissue destruction. The discovery of...

Hypothalamopituitarythyroid HPT axis

Clinical disorders of thyroid function are known to cause alteration in mood. Classically, patients with hypothyroidism frequently report features similar to depression and, while usually more closely linked to feelings of anxiety, depressive reactions are also sometimes seen in hyperthyroid patients. D Subclinical hypothyroidism Given the suggestions of subclinical hypothyroidism in depression, albeit in a minority, it is natural to ask about the effects of thyroid hormone treatment. A recent review found six randomised, controlled trials, and concluded that thyroid hormone may potentiate both the speed and the efficacy of antidepressant medication (Altshuler et al., 2001). Furthermore, there is also evidence that patients resistant to other treatments may respond to such treatment, although there have been no studies linking pre-treatment, subclinical hy-pothyroidism to this response. There is also some evidence that low tri-iodothyronine (T3) levels are prospectively associated...

Biological Basis Of Iodine Accumulation In Thyroid Tissue

The sodium iodide symporter (NIS) is responsible for the specificity of RAI for thyroid tissue. This transmembrane protein transports iodide against an electrochemical gradient via a sodium-dependent active transport mechanism by which two sodium ions are transported along with one iodide ion (4). Synthesis of this protein is regulated by activation at the thyrotropin receptor (5). Following the characterization of the NIS gene in 1996, much research has been directed toward understanding the role of the NIS in autoimmune and malignant thyroid disease. The NIS protein is most abundantly expressed in thyroid tissue, although it is also present in glandular and mucosal tissue, choroid plexus, ciliary body of the eye, and placenta. Normal NIS protein expression is limited to the basolateral membrane in a small percentage of thyroid follicular cells at any one time (6). However, in autoimmune thyroid disease, thyrotropin receptor-mediated activation by stimulating auto-antibodies...

Endocrine 18321 Thyroid Function

Primary hypothyroidism is a common late effect observed in cancer survivors who received head and neck radiation (Kaplan et al. 1983 Halperin et al. 1999). The occurrence of thyroid dysfunction is related, primarily, to the dose of radiotherapy administered but is also influenced by the age and gender of the patient and the time elapsed since the end of treatment (Sklar et al. 2000). Current radiotherapy doses used for local control in high-risk neuroblastoma patients with thoracic or cervical tumors are often in this range (Halperin et al. 1999 Kushner et al. 2001). Patients who received total-body irradiation (TBI) are also at risk for hypothyroidism (Ogilvy-Stuart et al. 1992). The radiation-related risk persists more than 25 years after treatment (Hancock et al. 1991 Sklar et al. 2000). The addition of chemotherapy to radiation therapy does not seem to increase the risk of hypothyroidism (Van Santen et al. 2003). In our cohort, 23 of the patients developed primary hypothyroidism....

Causes of Female Sexual Dysfunction

Hypothyroidism, hyperthyroidism components of the sexual response can cause FSD. Vascular causes of FSD include atherosclerosis, smoking, diabetes, dyslipidemia, peripheral vascular disease, hypertension, renal failure, and perineal or pelvic trauma, such as that seen with bicycle riding. Neurologic diseases associated with FSD may include stroke, multiple sclerosis, spinal cord injury,Alzheimer's disease, Parkinson's disease, pudendal nerve injury, and iatrogenic surgical changes during radical pelvic surgery, CRS, or hysterectomy. Hormonal or endocrinologic causes of FSD include hypogo-nadism, androgen insufficiency, menopausal changes and genital atrophy, hypothyroidism, hyperthyroidism, diabetes, low estrogen levels, pituitary tumor, and hyperpro-lactinemia.Various specific gynecologic causes of FSD have been identified. These include genital atrophy, vulvar dystrophy and cancer, dermatitis, clitoral phimosis and adhesions, Bartholin's duct cysts, episiotomy scars, vestibulitis,...

Drugs And The Thyroid Gland

A decreased amount of T3 and T4 is produced in a condition called hypothyroidism. This is caused by a disorder of the thyroid gland or a secondary lack of TSH secretion. Hyperthyroidism is an increase in circulatory T4 and T3 caused by an overactive thyroid gland or an excessive output of thyroid hormones. Hypothyroidism Primary hypothyroidism is characterized by a decrease in T4 and an increase in TSH levels. Primary hypothyroidism is caused by acute or chronic inflammation of the thyroid gland, radioiodine therapy, excess intake of antithyroid drugs, and surgery. Myexedema is severe hypothyroidism characteristic by lethargy, apathy, memory impairment, emotional changes, slow speech, deep coarse voice, edema In children, hypothyroidism can have a congenital (cretinism) or prepubertal (juvenile hypothyroidism) onset. Hypothyroidism is treated by administering levothyroxine sodium (Levothroid, Synthroid), which increases levels of T3 and T4. Levothyroxine sodium (Levothroid, Synthroid)...

T Cell Regulation and MHC Restriction

In pilot experiments using two EAT-resistant strains, prior depletion of CD4+CD25+ T cells in both BALB c (H2d) mice (Wei et al, 2004) and B10 (H2b) mice (Morris et al., 2004) enabled the animals to respond to immunization with mTg and LPS. However, mononuclear cell infiltration was much less extensive than in susceptible CBA J mice immunized with mTg and LPS with no prior depletion of CD4+CD25+ T cells. These data suggest that traditional resistance in EAT may not be solely the result of an insufficiency to present Tg epitopes in the context of class II molecules, but may represent a reduced capacity to overcome peripheral regulation and generate a thyroiditogenic response. Removal of CD4+CD25+ regulatory T cells lowers the threshold for thyroiditis development. Interestingly, we recently used a novel H2E class II transgenic model, E+B10.Ab0 (H2Ab-Eb+), for EAT that would permit us to examine more precisely the degree of stringency for MHC restriction. Unlike conventional susceptible...


131I-Metaiodobenzylguanidine (MIBG) is a guanethi-dine derivative that is structurally similar to norepi-nephrine, and therefore concentrates in the neurose-cretory granules of catecholamine-secreting cells. Radiolabeled MIBG provides very sensitive and specific visualization of primary and metastatic neuroblastoma by scintigraphy (Shulkin and Shapiro 1998). In an attempt to deliver higher doses of tumor-specific radiotherapy and avoid normal organ toxicity, iodine-131 MIBG therapy has been used in pilot trials since the mid 1980s, with more than 500 children reported in the literature. Initially, it was shown to induce 30-40 response rate in highly refractory relapsed patients, without significant non-hematologic toxicity (Klingebiel et al. 1991 Matthay et al. 1998 Voute et al. 1991). At low and moderate doses, up to 12 mCi kg of 131I-MIBG, the main toxicity has been thrombocytopenia, usually self-limited. Phase-I dose escalation studies showed that higher doses, up to 18 mCi kg,...

Preoperative Evaluation Of Thyroid Nodules

Because germline mutations of the TPO gene that cause functional loss of TPO activity cause of congenital hypothyroidism, loss of heterozygocity (LOH) at the TPO gene locus has been implicated as a cause of the organification defect typical of benign In a study of 73 thyroid specimens from which both FNA and surgically obtained tissue was available, Cheung, et al. (26) evaluated the presence of PTC1-5 by RT-PCR. Only Ret PTC 1, 2 or 3 were detected in the samples Ret PTC translocations were not detected on FNA and surgical samples from 39 benign tissue samples, including 11 follicular adenomas, 25 nodular hyperplasia's and 3 Hashimoto's thyroiditis cases. In contrast, Ret PTC 1, 2, or 3 expression was detected in 17 FNA samples and 21 surgical specimens derived from 33 malignant thyroid tumors. Of importance, this molecular method was more accurate than routine cytopathology in these samples.

Cardiovascular assistance

Hypotension indicates an unfavorable prognosis (Tabje.3) and is sometimes a sign of an irreversible phase of the illness, since hypothyroid patients usually have mild Hypotension can occur as a complication of a silent myocardial infarction. Diagnosis may be difficult because of high levels of muscular enzymes and abnormalities on ECG due to severe hypothyroidism itself (Nicp lpfflnandMlLpPresti 1993). Echocardiography may help to make a definite diagnosis. Caution is needed in treating congestive heart failure. Digitalis, if used, should be given at low dose, since drug metabolism is slowed during hypothyroidism ( NicolofL

Why knowledge of causation is important

For the person with mental retardation a confirmed aetiology is the basis of a correct awareness of his or her own disability the limitations set by the disability and the possibilities for learning and development. The clinical manifestations of some developmental disorders, such as phenylketonuria, galactosaemia, or hypothyroidism can be prevented or arrested by dietary management or hormonal replacement therapy. Knowledge of the prognosis increases awareness of associated disease and disabilities such as sensory impairments, communication disorders, motor and joint problems, epilepsy, and behavioural or psychiatric problems. Thus, aetiology aids the planning of follow-up, rehabilitation, education, and living arrangements. (16) Knowledge of aetiology is particularly important at the time at transition from childhood to adult services, helping to ensure continuity of provision and avoid drop-out.

Changes in drug metabolism

In hypothyroidism, there is a general slowing down of most metabolic processes, particularly those of drugs, whose tolerance is therefore reduced ( Nicoloff and LoPresti 1993). 3. Tranquilizing agents, sedatives, narcotics, and morphine these drugs must be prescribed with caution because of the risk of overdose or severe respiratory depression. Sometimes these drugs convert moderate hypothyroidism into myxedema coma.

Clinical evaluation of urinary incontinence

Duration, characteristics, and severity of the incontinence, precipitating factors and reversible causes should be assessed. Dysuria, urgency, pelvic pain, dyspareunia, constipation, fecal incontinence, pelvic prolapse, or abnormal vaginal discharge should be sought. A history of diabetes, thyroid disease, spinal cord injury, cerebral vascular accidents, urethral sphincter

Clinical evaluation

Physical examination should include a cardiovascular examination as well as evaluation for evidence of hyperlipidemia, hypertension, peripheral vascular disease, congestive heart failure, anemia, and thyroid disease. D. Modifiable risk factors, for coronary heart disease and comorbid factors should be addressed. Risk factors for coronary heart disease include smoking, inappropriate activity level, stress, hyperlipidemia, obesity, hypertension, and diabetes mellitus. Comorbid conditions that could affect myocardial ischemia include hypertension, anemia, thyroid disease, and hypoxemia.


Possible contributors to the patient's sleep complaints. The experienced clinician should be aware of the high prevalence of sleep apnea the relationships between this disorder and age, gender, and ethnicity and the more complex associations including those between OSA and cardiovascular disease, glucose intolerance and insulin resistance, depression, pulmonary disease, and hypothyroidism. A careful evaluation of the patient's social, family, medication, and allergy history is critical for identifying or discounting possible risk factors for sleep apnea. The physical examination for adult patients with suspected OSA should be comprehensive, and should include assessment of blood pressure, indicators of obesity (e.g., BMI, neck circumference), nasal function, pharyngeal, and craniofacial features. Lastly, the examinations of pediatric versus adult patients with suspected OSA are not identical, since the presentation, symptoms, and physical signs associated with childhood OSA are...

Colorectal History

A detailed medical and surgical history is important in the evaluation of any patient. History of metabolic disturbances such as hypothyroidism or hypercalcemia may provide insight into the etiology of constipation. History of inflammatory bowel disease and proctitis will often contribute to a patient's symptoms of incontinence. Diabetes and peripheral neuropathy can also have an important role in incontinence. As mentioned previously, a detailed birth history with particular attention to previous episiotomy, high-birth-weight children, prolonged labor, and the use of forceps for delivery is of paramount importance. Surgical history, with a focus on previous anorectal surgery or bowel resection, will obviously contribute to the evaluation of these patients. Medications can also have a role in a patient's symptoms. Anticholinergic medications, narcotics, and calcium supplements will often contribute to constipation symptoms. Any medications that cause diarrhea will often worsen the...


Polyunsaturated fatty acids of the n-3 and n-6 families are known to suppress hepatic mRNA levels of several lipogenic genes, including FAS.53 With the exception of glucose-6-phosphate dehydrogenase, PUFAs exert their regulatory effects at the level of transcription.53 PUFAs exert dominant negative effects on many of the genes of lipogenesis and are known to override the stimulatory effects of insulin, carbohydrates, and thyroid hormones. Furthermore, the direct effects of PUFAs on the liver do not require extrahepatic factors. 1.11 Regulatory Effects of Thyroid Hormones In addition to changes in the levels of circulating insulin and glucagon, thyroid hormone (T3) is also elevated during refeeding of fasted animals. Thyroid hormone stimulates FAS expression through a mechanism that is independent of insulin. Administration of thyroid hormone to rats for 7 days doubled FAS activity in liver.65 Furthermore, hypothyroidism reduced hepatic FAS activity.66 These effects can be demonstrated...

Medullary Carcinoma

Familial forms of medullary thyroid carcinoma usually result in multicentric disease as well as multicentric C-cell hyperplasia (247). Many definitions of C-cell hyperplasia have been offered, all requiring immunohistochemistry since C cells cannot be reliably recognised with routine histologic stains. Quantitation of C cells as well as geographic mapping throughout the gland must be performed (247,248). C cells are usually limited to the central portion of the junction between the upper and middle thirds of the lateral lobes where they are generally distributed singly rather than in clusters. Increased numbers of C cells (> 7 cells per cluster), complete follicles surrounded by C cells, and distribution of cells beyond this geographic location are indicative of C-cell hyperplasia. The presence of C-cell hyperplasia usually indicates an inherited disorder rather than a sporadic lesion, however, C-cell hyperplasia can also be associated with chronic hypercalcemia, thyroid follicular...


Thyroid nodules are common and their management can be difficult and controversial. Clearly, the pathologist has an important role to play in their evaluation. The use of fine needle aspiration biopsy has significantly improved our ability to identify specific high risk disorders and to facilitate their management in an expeditious and cost-effective manner. Patients who require surgery for further confirmation of the disease process rely upon the pathologist to correctly characterize their nodule and pathologists are actively involved in research to clarify the pathogenesis of thyroid disease. There are other areas of thyroid pathology that have seen uniform advances in our understanding of the pathobiology of disease. Most experts accept tall cell or columnar morphology as predictive of more aggressive variants of papillary carcinoma. The recognition of insular carcinomas as an intermediate category of poorly differentiated carcinoma has been validated by clinical and molecular...


Lymphomas occurring primarily in the thyroid are decidedly uncommon, accounting for about 5 of all thyroid malignancies (7-10). This figures increases to 10 of thyroid malignancies in certain geographic locales where antecedent chronic thyroiditis is common (10, 11). Primary thyroid lymphomas constitute 2.5 to 7 of all extranodal lymphomas (12-14). It is stated that 25 to 100 of thyroid lymphomas arise against a background of thyroiditis, either chronic lymphocytic or Hashimoto's thyroiditis (15-18). This association is so strong that the relative risk of a patient with chronic thyroiditis developing lymphoma of the thyroid is 40 to 80 times greater than the general population (14, 19, 20). The lymphomas evolve after a prolonged period, usually 20 to 30 years after the onset of chronic lymphocytic thyroiditis (14).


Conditions associated with acute gastric retention are summarized in Table 2,. Chronic problems with gastric emptying may become evident when nasogastric feeding and regular gastric aspiration are needed during critical illness (e.g. gastric outlet obstruction from scarring or tumor, diabetic gastroparesis, hypothyroidism, or previous truncal vagotomy). Intolerance to intragastric feeding is particularly common in patients with traumatic brain injury and is independent of the opiates that

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