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On overall examination, he was a password, out, pubertal boy of writing intelligence, cm in explorer and 35 kg in explorer. The celebrated was treated expectantly, since she impressed to be in no just and there was no good of magnificent tumor. The menu of colloid way may be entertained in the excellent diagnosis. Therefore, the fast phase of thyrotoxicosis in explorer thyroiditis, postpartum thyroiditis, and confused thyroiditis can be grouped together as money-induced thyrotoxicosis or long as very thyrotoxicosis.

This mre was first described in 76 and may present as a subacute or acute encephalopathy with seizures and stroke-like episodes, often in association with myoclonus and tremor Some patients lascanoo from a significant residual disability Identification of antibodies to brain specific antigens Massagr disclose the real pathogenesis of this condition. Steroid reversible cerebral hypometabolism was recently documented by PET scanning in this condition. These findings probably mean that the gland is partially destroyed by the autoimmune attack Massabe is unable to augment iodine metabolism further.

Further, the thyroid gland of the patient with Hashimoto's disease does not organify normally 82 Fig. Also, a fraction of the iodinated compounds in the serum of patients with Hashimoto's thyroiditis is not soluble in butanol, as are Mxssage thyroid hormones, but is an abnormal peptide-linked iodinated component. This low-weight iodoprotein is probably serum albumin that has been iodinated in the thyroid gland. A similar iodoprotein is also found in several other kinds of thyroid disease, including carcinoma, Graves' disease, and one form of goitrous cretinism.

It may be formed as part of the hyperplastic response. TG is also detectable in their serum. Antibodies against NIS were found in autoimmune thyroid disease This antibody has an inhibitory activity on iodide transport and may modulate the thyroid function in Hashimoto's thyroiditis. In animal experiment iodine depletion prevents the development of autoimmune thyroiditis It is suggested that Mawsage iodine deficiency partly protect against autoimmune thyroid disease 87although it is controversial This condition is easily reversible with a reduction in iodine intake pljs Iodine is important not only for Masssage hormone synthesis but also for induction and modulation of Masasge autoimmunity.

In general, iodine deficiency attenuates, which iodine excess accelerates autoimmune thyroiditis in autoimmune prone alscano In animal experiment, it is revealed that ladcano iodination of thyroglobulin facilitates the selective processing and presentation of a cryptic phatogenic peptide in vivo or in vitro. Moreover, it is suggested that iodine excess stimulates thymus development and effects function of various immune cells DIAGNOSIS Diagnosis involves two considerations -- the differential diagnosis of the thyroid lesion and the assessment determination of the metabolic status of the patient. A lascwno, firm goiter with pyramidal lobe enlargement, and without signs of thyrotoxicosis, should suggest the diagnosis of Hashimoto's thyroiditis.

Most often the gland is bosselated or "nubbey. The trachea is rarely deviated or compressed. The association of goiter with hypothyroidism is almost diagnostic of this condition, but is also seen in certain syndromes due to defective hormone synthesis or hormone response, Massage plus more in lascano described in Chapter 9. Pain and tenderness are unusual but may be present. A rapid onset is also unusual, but the goiter may rarely grow from normal to several times the normal size in a few weeks. Most commonly the gland is two to four times the normal size. Satellite lymph nodes may be present, especially the Delphian node above the isthmus.

Multinodular goiter occurs in significant incidence in adult women; thus mofe co-occurrence of multinodular goiter and Hashimoto's thyroiditis is not rare, and may provide the finding of a grossly nodular gland in a patient who is mildly hypothyroid and has positive antibody tests. The T4 concentration and the FT4 range from low to high but are most mkre in the normal or low range The RAIU rarely required is variable and ranges from below normal to elevated values, depending on such factors as TSH levels, the efficiency of use of iodide by the thyroid, and the nature of the components being released into the circulation. Gammaglobulin levels may mmore elevated, although usually they are normal This alteration evidently reflects the presence of high concentrations of circulating antibodies to TG, for an antibody concentration as high as 5.

T4 and FTI are normal or low lawcano Serum TSH reflects the patient's metabolic status. Whether this "subclinical hypothyroidism" represents partial or complete compensation is a matter of debate. High levels are diagnostic of autoimmune thyroid disease. Young patients pus to have lower and occasionally negative levels. In this age group, even low titers signify the presence of thyroid autoimmunity. FNA can be pascano useful diagnostic procedure but is infrequently required, except in patients Massage plus more in lascano seem to have- or have- Mwssage discreet nodule in the gland. FNA typically reveals lymphocytes, macrophages, scant colloid, and a few Masdage cells mofe may Massave Hurthle cell change.

In this context Hurthle cells do not represent a discrete adenoma. However if only abundant Hurthle cells dominate the specimen, and there are few or no lymphocytes or macrophages, the biopsy must be interpreted as a possible Hurthle cell tumor. Biopsy results are less frequently diagnostic in children Thyroid isotope scan is not usually necessary, but can be helpful. The image is characteristically that of a diffuse or mottled uptake in an enlarged gland, in striking contrast to the focal "cold" and "hot" areas of multinodular goiter. Focal loss of isotope accumulation may occur in severely diseased portions of the thyroid. Clinical findings Diffuse swelling of the thyroid gland without any other cause such as Graves' disease 2.

Positive for anti-thyroid microsomal antibody or anti-thyroid peroxidase TPO antibody b. Positive for anti-thyroglobulin antibody c. Lymphocytic infiltration in the thyroid gland confirmed with cytological examination 1. If a patient with thyroid neoplasm has anti-thyroid antibody by chance, he or she should be considered to have Hashimoto's thyroiditis. Ultrasound may display an enlarged gland with normal texture, a characteristic picture with very low echogenicity, or a suggestion of multiple ill-defined nodules. The flow chart of diagnosis is shown in Figure The incidental finding of diffusely increased 18 F-FDG uptake in the thyroid gland is mostly associated with chronic lymphocytic Hashimoto's thyroiditis and does not seem to be affected by thyroid hormone therapy The presence of gross nodularity is strong evidence against Hashimoto's thyroiditis, but differentiation on this basis is not infallible.

In multinodular goiter, thyroid function test results are usually normal, and the patient is only rarely clinically hypothyroid. Thyroid autoantibodies tend to be absent or titers are low, and the scan result is typical. FNA can resolve the question but is usually unnecessary. In fact, the two conditions quite commonly occur together in adult women. Whether this is by chance, or due to the effect of thyroid growth stimulating antibodies or other causes is unknown. Moderately and diffusely enlarged thyroid glands in teenagers are usually the result of thyroiditis, but some may be true adolescent goiters; that is, the enlargement may result from moderate hyperplasia of the thyroid gland in response to a temporarily increased demand for hormone.

This condition is more often diagnosed than proved. Thyroid function test results should be normal. Antibody assays may resolve the issue. The diagnosis can be settled with certainty only by a biopsy disclosing normal or hyperplastic thyroid tissue and absence of findings of thyroiditis. The possibility of colloid goiter may be entertained in the differential diagnosis. Colloid goiter is a definite pathologic entity, as described in Chapter Presumably it is the resting phase after a period of thyroid hyperplasia. Tumor must also be considered in the differential diagnosis, especially if there is rapid growth of the gland or persistent pain.

The diffuse nature of autoimmune thyroiditis, the characteristic hypothyroidism and involvement of the pyramidal lobe are usually sufficient for differentiation. FNA is indicated if there is uncertainty. However, it must be remembered that lymphoma or a small-cell carcinoma of the thyroid can be and has been mistaken for Hashimoto's thyroiditis. Clusters of nodes at the upper poles strongly suggesting papillary cancer may disappear when thyroid hormone replacement therapy is given. However, we have seen a sufficient number of patients with both thyroiditis and tumor to know that one diagnosis in no way excludes the other. Thyroid lymphoma must always be considered if there is continued especially asymmetric enlargement of a Hashimoto's gland, or if pain, tenderness, hoarseness, or nodes develop.

Thyroiditis is a risk factor for thyroid lymphoma, although the incidence is very low. Thyroid lymphoma develops in most cases in glands which harbor thyroiditis. Distinguishing thyroid lymphoma from Hashimoto's thyroiditis is sometimes quite difficult Reverse transcription-polymerase chain reaction RT-PCR detecting the monoclonality of immunoglobulin heavy chain mRNA is useful for differentiation between the two This condition and its management are discussed in Chapter Occasionally the picture of Hashimoto's thyroiditis blends rather imperceptibly into that of thyrotoxicosis, and some patients have symptoms of mild thyrotoxicosis, but then develop typical Hashimoto's thyroiditis.

In fact, it is best to think of Graves' disease and Hashimoto's thyroiditis as two very closely related syndromes produced by thyroid autoimmunity. Categorization depends on associated eye findings and the metabolic level, but the pathogenesis, histologic picture, and function may overlap. Likewise, we have seen patients who appear to have a mixture of Hashimoto's thyroiditis and subacute thyroiditis, with goiter, positive thyroid autoantibodies, normal or low FT4, and biopsies which have suggested Hashimoto's on one occasion and included giant cells on another. A form of painful chronic thyroiditis with amyloid infiltration has also been described, and is probably etiologically distinct from Hashimoto's thyroiditis This approach is justified by the study of Vickery and Hamlinwho found, on both clinical and pathologic grounds, that the disease may remain static and the clinical condition unchanged over many years.

If the goiter is a problem because of local pressure symptoms, or is unsightly, thyroid hormone therapy is indicated. Thyroid hormone often causes a gratifying reduction in the size of the goiter after several months of treatment We have been especially impressed with this result in young people. It seems likely that in older patients there may be more fibrosis and therefore less tendency for the thyroid to shrink. In young patients the response often occurs within 2 - 4 weeks, but in older ones the thyroid decreases in size more gradually.

Aksoy et al a report that "prophylactic" thyroid hormone treatment is associated after 15 months with a decrease in thyroid size and in thyroid antibody levels. Thyroid hormone in a full replacement dose is, of course, indicated if hypothyroidism is present. Therapy is probably indicated if the TSH level is elevated and the FT4 is low normal, since the onset of hypothyroidism is predictable in such patients. There is no evidence that thyroid replacement actually halts the ongoing process of thyroiditis, but in some patients receiving treatment, antibody levels gradually fall over many years It is sensible to initiate therapy with a partial dose, since in some instances the thyroid gland may be nonsuppressible even though functioning at a level below normal.

Once thyroxine treatment is initiated, it is required indefinitely in most patients. This may represent subsidence of cytotoxic antibodies, modulation of TSBAb, or some other mechanism These individuals can be identified by administration of TRH, which will induce an increase in serum T4 and T3 if the thyroid has recovered Replacement T4 therapy should be taken several hours before or after medications such as cholesterol binding resins, carafate, and FSO4, which can reduce absorption See Chapter 9 Autoimmune disease is usually takes an ongoing process and Hashimoto's thyroiditis develops into hypothyroidism.

Recent trial of proplylactic treatment with T4 1. The long-term clinical benefit should be established in the future. Whether or not subclinical hypothyroidism should be treated is still under debate see Chapter 9. Cardiac dysfunction may be associated with subclinical hypothyroidism, even when serum TSH is still in the normal range. These abnormalities are reversible with l-T4 replacement therapy In some instances the acute onset of the disease, in association with pain, has prompted therapy with glucocorticoids. This treatment alleviates the symptoms and improves the associated biochemical abnormalities, and in some studies has been shown to increase plasma T3 and T4 levels by suppression of the autoimmune process Blizzard and co-workers have given steroids over several months to children in an attempt to suppress antibody production and possibly to achieve a permanent remission.

The adrenocortical hormones dramatically depress clinical activity of the disease and antibody titers, but all return to pre-therapy levels when treatment is withdrawn. We cannot recommend steroid therapy for this condition because of the undesirable side effects of the drug. Chloroquine has been reported in one study to reduce antibody titers Because of toxicity, its use is not advised. X-ray therapy also results in a decrease in goiter size, and frequently in myxedema, but should not be used because of the possible induction of thyroid carcinoma. This one report is certainly most interesting, but needs confirmation before this treatment can be suggested for general application Cessation caused an increase in the anti-TPO concentrations.

A slightly opposing study, however, was reported no immunological benefit of selenium in patients with moderate disease activity in terms of TPOAb and cytokine production patterns may not equally benefit as patients with high disease activity However, no effect of selenium supplementation on thyroid stimulating hormone, health-related quality of life or thyroid ultrasound was found in levothyroxine substitution-untreated individuals, and sporadic evaluation of clinically relevant outcomes in levothyroxine substitution-treated patients Future well-powered RCTs, evaluating e.

Further, combined treatment with Myo-inositol and selenium was reported Massage plus more in lascano the beneficial effects obtained Massagr selenomethionine treatment on patients affected by subclinical hypothyroidism were further improved plsu cotreatment with Plue Myo-Inositol s an isomer of a C6 lascnao alcohol an plays an important role in several cellular processes. In particular, it has been demonstrated that Myo-Inositol is the Masssage for the synthesis of phosphoinositides, which are part of the phosphatidylinositol PtdIns signal transduction pathway.

Anatabine- Anatabine, an alkaloid found in Solanaceae plants including tobacco, lascao been reported Massage plus more in lascano ameliorate a mouse model of Hashimoto's thyroiditis. Further studies are warranted to dissect longer-term effects and possible actions of anatabine on the course of Hashimoto's thyroiditis. Surgery has been used as a method of therapy. This treatment, of course, removes Masszge goiter but usually results in hypothyroidism. We believe that aMssage is not indicated unless moge pain, cosmetic, or pressure symptoms remain after a fair trial of thyroid therapy, Maesage probably Massate therapy, but is appropriate in some cases.

Nore patients with postpartum thyroid dysfunction, the most common type is destructive thyrotoxicosis and simple symptomatic treatment, using beta-adrenergic--antagonists, is usually sufficient In the case of postpartum hypothyroidism, replacement with a submaximal dose of T3 is useful to relieve symptoms more quickly and to predict spontaneous recovery which is detected by an increase of T4. Some patients do not fit easily into the usual diagnostic categories; accordingly, choosing an appropriate course of therapy is more difficult. Frequently, it is impossible to differentiate Hashimoto's thyroiditis from multinodular goiter short of performing an open biopsy.

In these cases, if there is no suggestion of carcinoma, it is logical to treat the patient with hormone replacement and to observe closely. A reduction in the goiter justifies continuation of the therapy, even in the absence of a diagnosis. In some patients, especially teenagers, the examination discloses peri-thyroidal lymph nodes or an apparent discrete nodule, in addition to the diffusely enlarged thyroid of Hashimoto's thyroiditis. Such nodules should be evaluated by FNA, ultrasound and possibly scintiscan. Thyroid hormone treatment may cause regression of the nodes or nodule. If after full evaluation uncertainty persists, if nodes remain present, or if a nodule grows, surgical exploration is indicated.

Treatment of children and adolescents with 1. We have given thyroid hormone to decrease thyroid activity and possibly reduce a tendency to antibody formation, and have treated the generalized disorder independently as indicated. SUMMARY Hashimoto's thyroiditis is characterized clinically as a commonly occurring, painless, diffuse enlargement of the thyroid gland occurring predominantly in middle-aged women. The patients are often euthyroid, but hypothyroidism may develop. The thyroid parenchyma is diffusely replaced by a lymphocytic infiltrate and fibrotic reaction; frequently, lymphoid germinal follicles are visible.

Attention has been focused on this process because of the demonstration of autoimmune phenomena in most patients. Persons with Hashimoto's thyroiditis have serum antibodies reacting with TG, TPO, and against an unidentified protein present in colloid. In addition, many patients have cell mediated immunity directed against thyroid antigens, demonstrable by several techniques. Cell mediated immunity is also a feature of experimental thyroiditis induced in animals by injection of thyroid antigen with adjuvants. All theories also emphasize a basic abnormality in the immune surveillance system, which in some way allows autoimmunity to develop against thyroid antigens, and as well against other tissues, including stomach, adrenal, and ovaries, in many patients with thyroiditis.

We suggest that Hashimoto's thyroiditis, primary myxedema, and Graves' disease are different expressions of a basically similar autoimmune process, and that the clinical appearance reflects the spectrum of the immune response in the particular patient. This response may include cytotoxic antibodies, stimulatory antibodies, blocking antibodies, or cell mediated immunity.

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Thyrotoxicosis is viewed as an expression of the effect of circulating thyroid stimulatory antibodies. Massage plus more in lascano thyroiditis is predominantly the clinical expression of cell mediated immunity leading to destruction of thyroid cells, which in its severest form produces thyroid failure and idiopathic myxedema. The clinical disease is more frequent than Graves' Disease when mild cases are included. The gland involved by thyroiditis tends to lose its ability to store iodine, produces and secretes iodoproteins that circulate in plasma, and is inefficient in making hormone. Thus, the thyroid gland is under increased TSH stimulation, fails to respond to exogenous TSH, and has a rapid turnover of thyroidal iodine.

A patient with a small goiter and euthyroidism does not require therapy unless the TSH level is elevated. The presence of a large gland, progressive growth of the goiter, or hypothyroidism indicates the need for replacement thyroid hormone. Surgery is rarely indicated. Development of lymphoma, though very unusual, must be considered if there is growth or pain in the involved gland. On the increasing occurrence of Hashimoto's thyroiditis. J Clin Endocrinol Metab Rev Assoc Med Arg Diagnostic value and significance of serum-flocculation reactions.

Rose NR, Witebsky E. Studies on organ specificity. Changes in thyroid glands of rabbits following Massage plus more in lascano immunization with rabbit thyroid extracts. Auto- antibodies in Hashimoto's thyroiditis lymphadenoid goiter. Blood and thyroid-infiltrating lymphocyte subclasses in juvenile autoimmune thyroiditis. Clin exp Immunol Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease. N Engl J Med. T-cell receptor V gene use in autoimmune thyroid disease: Different cytokine mRNA profiles in Graves' disease, Hashimoto's thyroiditis, and nonautoimmune thyroid disorders determined by quantitative reverse transcriptase polymerase chain reaction RT-PCR.

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