Long-term outcome of interferon-alpha-induced thyroid autoimmunity and prognostic influence of thyroid autoantibody pattern at the end of treatment

Thyroid autoimmunity and dysfunction have been widely reported as side effects of interferon-alpha (IFN-alpha) treatment, but the literature lacks data regarding the long-term course of these complications, clinical observation being limited to 6-12 months off therapy. Our study is the first that has aimed to evaluate the natural history of IFN-related thyroid autoimmunity during a 6.2-yr follow-up after the IFN-alpha withdrawal as well as to investigate the potential role of the autoantibody pattern at the end of treatment to predict the long-term outcome. Our study group included 114 patients (79 males, 35 females), mean age 48 yr (range 23-67 yr) with no preexisting thyroid disease, undergoing a 12-month treatment with recombinant IFN-alpha for C virus-related chronic active hepatitis. Thyroid autoimmunity (serum TgAb and TPOAb) and function (serum FT(4), FT(3), TSH) were retrospectively evaluated at the end of IFN therapy, 6 months after IFN withdrawal and after a median period of 6.2 yr (range 5.5-8.4 yr). At the end of treatment, 78 patients were negative for thyroid autoantibodies (Abs-) and all but one of them remained so for the following evaluations. The remaining 36 patients had thyroid autoantibodies (Abs+) at the end of treatment, and they subsequently showed a heterogeneous behavior: 16 patients remained Abs+ for the whole length of the study (persistent thyroiditis); 10 patients became Abs- 6 months off therapy but were again Abs+ 6.2 yr later (remitting/relapsing thyroiditis); 10 patients reverted to autoantibody negativity at different observation times (transient thyroiditis). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroiditis (odds ratio: 0.02, confidence interval (CI) 95%: 0-0.1). On the contrary, the positivity for TgAb and/or TPOAb at high titers at the end of IFN treatment was significantly related to the highest risk of having chronic thyroiditis (odds ratio: 17.3, CI 95%: 3.2-91.7 for TgAb levels > 50 degree percentile; odds ratio: 7.3, CI 95%: 1.5-35.2 for TPOAb levels > 50 degree percentile). None of the patients showed overt thyroid dysfunction throughout the study, whereas a subclinical hypothyroidism was found in 12 patients. In all 12 cases, the functional abnormality was accompanied by the presence of thyroid autoantibodies. Eight of these 12 patients belonged to the group with persistent thyroiditis (P < 0.05). The absence of thyroid autoantibodies at the end of treatment was a protective factor for the successive development of thyroid dysfunction (odds ratio: 0.06, CI 95%: 0.01-0.56). On the contrary, the positivity for both TgAb and TPOAb at the end of IFN therapy was significantly correlated with the highest risk of having subclinical hypothyroidism 6.2 yr. later (odds ratio: 38.7; CI 95%: 6.2-242). Our study demonstrates that in patients undergoing an IFN-alpha therapy for chronic hepatitis C and with no evidence of preexisting thyroid disease: 1) the negativity for thyroid autoantibodies after IFN treatment is a protective factor for the developing thyroid autoimmunity and/or dysfunction in following years; 2) the IFN-alpha-related thyroid autoimmunity is not a complete reversible phenomenon because some patients can develop chronic thyroiditis; 3) high autoantibody levels at the end of IFN therapy are related to the risk of having chronic thyroid autoimmunity; and 4) the coexistence of TgAb and TPOAb at the end of treatment is a predictive factor for the presence of thyroid dysfunction, even if subclinical, many years after IFN withdrawal.     

The effect of treatment with levothyroxine or iodine on thyroid size and thyroid growth stimulating immunoglobulins in endemic goitre patients

OBJECTIVE We assessed the effect of levothyroxine or iodine on thyroid size and on thyroid growth stimulating immunoglobulins in endemic goitre patients. DESIGN Levothyroxine or iodine was given orally in an open randomized prospective study (100 and 200 μ g respectively). PATIENTS Thirty-seven euthyroid patients with diffuse iodine deficiency goitres and thyroid growth stimulating immunoglobulins were studied. MEASUREMENTS Thyroid size, thyroid growth stimulating immunoglobulins (mitosis arrest assay), basal TSH, free T3, free T4, thyroid anti-microsomal antibodies, anti-thyroglobulin antibodies, anti-TSH receptor antibodies and urinary iodine excretion were measured. RESULTS Thyroid size decreased significantly in both groups, in the levothyroxine group more than in the iodine treated group. Thyroid growth stimulating immunoglobulins levels also decreased significantly in both groups. Between groups there was no statistically significant difference. A statistically significant correlation between thyroid growth stimulating immunoglobulins reduction profiles and goitre size reduction could not be established. TSH levels became suppressed in the levothyroxine group while the T4 values rose; in the iodine treated group TSH levels stayed constant as did T4. None of the patients developed thyroid microsomal or thyroglobulin auto-antibodies and/or hyperthyroidism during the treatment. CONCLUSIONS Levothyroxine as well as iodine was effective in reducing thyroid size as well as thyroid growth stimulating immunoglobulins levels in endemic goitre patients. Since in both groups TSH levels were not related to thyroid size reduction, other factors than TSH suppression must be responsible for the observed thyroid size reduction. Iodine itself by virtue of its antiproliferative action on thyrocytes may have had a direct action on the goitre reduction during iodine treatment; however, the levothyroxine dose, containing less iodine, had a similar effect. A complicated picture hence emerges with regard to factors involved in the shrinkage of iodine deficiency goitre during thyroxine or iodine therapy. These findings indicate that TSH and thyroid growth promoting immunoglobulins are not the only influences on the size of endemic goitres, although it cannot be excluded that these two factors contribute to influence the pathogenetic process.     

Anti-bovine thyrotropin autoantibodies in patients with Hashimoto's thyroiditis, subacute thyroiditis, and systemic lupus erythematosus

We report four cases found to have anti-bovine thyrotropin (bTSH) antibodies, two with Hashimoto's thyroiditis and the other two, each with subacute thyroiditis and systemic lupus erythematosus (SLE). The unusually high negative titers of anti-TSH receptor antibodies (Case no. 1, -43.1%; Case no. 2, -34.9%; Case no. 3, -55.2%; Case no. 4, -59.9%) led to the incidental finding of the presence of anti-bovine (bTSH) antibodies in each patient. Case no. 1 was diagnosed to have Hashimoto's thyroiditis and was treated with L-thyroxine (L-T4). With the treatment, serum free T4 (FT4)normalized with a decline in the serum TSH concentration. The other patient diagnosed to have Hashimoto's thyroiditis (Case no. 2) remained euthyroid even without supplemental thyroid hormone therapy and the serum concentrations of FT4 and TSH stayed within the normal range. The third is a case of subacute thyroiditis (Case no. 3) with a typical clinical course of the disease. She had the anti-bTSH antibodies on her first outpatient visit. Serial examination of her sera disclosed the antibody titers to be on the same range over the 28 months after the onset of the symptoms. The fourth is a patient with SLE who had been treated with steroid (alternative day therapy of 40 mg/day prednisolone). Titers of the anti-bTSH antibodies spontaneously declined to the negative level 5 months later. None of the four cases had antibodies against human TSH alpha-subunit of bovine LH and alpha-subunit of bovine FSH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resistance to thyroid hormone associated with autoimmune thyroid disease in a Turkish family

The syndrome of resistance to thyroid hormone (RTH) is characterized by impaired tissue responses to thyroid hormone. Hashimoto's thyroiditis is the most common thyroid autoimmune disease. We present a Turkish family with both RTH and Hashimoto's thyroiditis. RTH was detected through the presence of point mutation in thyroid hormone receptor (TR), and Hashimoto's thyroiditis was diagnosed due to the presence of thyroid autoantibodies. The proposita, her affected mother as well as her unaffected sister have thyroid autoantibodies consistent with Hashimoto's thyroiditis, and a heterozygous point mutation in exon 10 encoding the ligand (3,3',5-L-T3)-binding domain of the TRbeta gene was detected in both the proposita and the mother. The mutation is a replacement of cytosine for guanine in codon 453 (CCT->GCT) producing a missense mutation substituting a normal proline with an alanine (P453A), which reduces the affinity for T3 to 17% of that of the normal TRbeta. Both also have modest elevation of serum TSH levels. In severe RTH, marked elevation of thyroid hormone concentrations in the absence of suppressed TSH supports the laboratory diagnosis of RTH. However, when RTH is mild and associated with thyroiditis, even a modest thyroid gland insufficiency can obliterate the serum T4 and T3 elevations, typical of RTH. This will manifest as elevated serum TSH. Demonstration of TRbeta gene mutation is then necessary to establish the diagnosis. In addition, under these circumstances, treatment with thyroid hormone should be considered.     

Prevalence of thyroid autoimmunity in sporadic idiopathic hypoparathyroidism in comparison to type 1 diabetes and premature ovarian failure

CONTEXT: Thyroid autoimmunity is the most common coexistent endocrinopathy in type 1 diabetes (T1D), Addison's disease, and premature ovarian failure (POF). Although the role of autoimmunity is being investigated in patients with sporadic idiopathic hypoparathyroidism (SIH), there is little information on coexistent thyroid autoimmunity. OBJECTIVE: Our objective was to assess the prevalence of thyroid peroxidase autoantibodies (TPOAb) and thyroid dysfunction in patients with SIH and its comparison with that in T1D, POF, and Hashimoto's thyroiditis (HT) and age- and sex-matched healthy controls (for SIH). DESIGN AND SETTING: We conducted a case control study in a tertiary care setting. PATIENTS AND METHODS: Subjects were consecutive patients with SIH (n = 87), T1D (n = 100), POF (n = 58), and HT (n = 47) and healthy controls (100 females and 64 males). Serum free T3, free T4, TSH, and TPOAb (normal < or = 34 IU/ml) were measured by electrochemiluminescence assay. Subjects with 1) serum TSH at least 5 microU/ml along with TPOAb more than 34 IU/ml; 2) TSH at least 10 microU/ml but normal TPOAb titers; or 3) Graves' disease were considered to have thyroid dysfunction. RESULTS: TPOAb positivity (> 34 IU/ml) in females was 14.6% in SIH, 24.1% in POF, and 42.1% in T1D compared with 76.6% in HT and 9% in healthy controls. The frequencies of TPOAb positivity and thyroid dysfunction in patients with SIH were comparable to those in control and POF groups, but significantly less than in T1D and HT groups. CONCLUSION: The frequencies of TPOAb and thyroid dysfunction were not significantly higher in patients with SIH than in healthy controls, unlike in patients with T1D and POF.     

A population study of the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure

OBJECTIVE: Patients with autoimmune overt hypothyroidism may present with goitrous Hashimoto's disease or autoimmune atrophic thyroiditis. Little is known about the prevalence of subclinical autoimmune hypothyroidism. The aims of this study were to evaluate the association between thyroid autoantibodies in serum and abnormalities in thyroid function and structure, and to study the thyroid volume in subjects with subclinical autoimmune hypothyroidism. DESIGN: A population study including 4649 randomly selected subjects. MEASUREMENTS: Blood tests were used to analyse for thyroid peroxidase autoantibodies (TPO-Ab), thyroglobulin autoantibodies (Tg-Ab), TSH, fT3 and fT4. RESULTS: Thyroid volume was categorized as small (< 6.6 ml) in 4.7%, normal (6.6-14.9 ml) in 60.4% and large (> 14.9 ml) in 34.9% of participants. Thyroid nodules were found in 29.7%. Serum TSH was low (< 0.4 mIU/l) in 4.7%, normal (0.4-3.6) in 91.0% and high (> 3.6) in 4.3%. The prevalence rate of subclinical goitrous Hashimoto's disease was 0.62% and of subclinical autoimmune atrophic thyroiditis 0.24%. There was a strong association between large volume and autoantibodies, but only in subjects with elevated TSH (P < 0.001). An association between thyroid nodules and TPO-Ab in univariate analyses (P < 0.001) was due to confounding by sex and age (multivariate model, P = 0.23). CONCLUSION: We identified a subgroup of the population with subclinical goitrous Hashimoto's disease and a smaller subgroup with subclinical autoimmune atrophic thyroiditis. This relationship between small and large thyroid volume in subclinical disease is opposite to that in overt disease, which may suggest that the period between development of a small volume with circulating autoantibodies and overt hypothyroidism is relatively short.     

Increased thyroid blood flow in the hypoechoic lesions in patients with recurrent, painful Hashimoto's thyroiditis at the time of acute exacerbation

We report two cases with painful Hashimoto's thyroiditis, who developed recurrent fever and painful thyroid. Glucocorticoid treatment was transiently successful but tenderness in the thyroid gland and fever developed when glucocorticoid was tapered. One patient underwent total thyroidectomy uneventfully. As is well known, it is frequently difficult to make differential diagnosis between painful Hashimoto's thyroiditis and subacute thyroiditis particularly at the initial phase. Interestingly, color flow doppler sonography of patient 1 revealed an increased thyroid blood flow in the hypoechoic lesions at the time of acute exacerbation although the serum level of TSH was suppressed. In the other patient, thyroid blood flow was also increased mainly in the hypoechoic lesions when the serum level of TSH was moderately increased, and it disappeared completely after supplementation of prednisolone and L-T4. Since thyroid blood flow in subacute thyroiditis is always decreased, such an increased blood flow in the hypoechoic lesion may be one of clinical characteristics of painful Hashimoto's thyroiditis, and useful for differential diagnosis from subacute thyroiditis.     

Evaluation of thyroid function in patients with isolated adrenocorticotropin deficiency.

Thyroid hormone and thyrotropin (TSH) levels were evaluated before and after adrenal replacement in eight patients (six men and two women, 35-62 years old) with isolated adrenocorticotropin (ACTH) deficiency. Six patients (cases 1-6) showed TSH excess before treatment. Four patients (cases 1-4), who initially had subnormal thyroid hormone levels, showed resolution of biochemical features of primary hypothyroidism after treatment, although TSH excess has persisted in two patients (cases 1 and 2). Case 1 had an extremely high titer of antimicrosomal antibody (MCHA), and cases 2 and 3 showed histologically and cytologically chronic thyroiditis, despite negative results for MCHA and antithyroglobulin antibody, respectively. Two patients (cases 5 and 6), who had had normal thyroid hormone levels and did not show the significant rise in serum T3 in TSH releasing hormone testing, showed TSH normalization without changes in serum thyroid hormone levels after treatment. The other two patients (cases 7 and 8), who initially had normal TSH and thyroid hormone levels, did not show the significant changes in serum TSH and thyroid hormone levels after treatment. The prevalence of chronic thyroiditis coexistence in isolated ACTH deficiency may be higher than predicted. Therefore, TSH excess before adrenal replacement may be attributed to not only direct enhancement of TSH release due to chronic cortisol deficiency but also to thyroid dysfunction due to chronic thyroiditis. It is possible that hypothyroidism due to chronic thyroiditis can be improved only by adrenal supplementation.     

Levothyroxine in euthyroid autoimmune thyroiditis and type 1 diabetes: a randomized, controlled trial

CONTEXT: Patients with type 1 diabetes (T1D) have an increased risk of autoimmune thyroiditis (AIT). OBJECTIVE: Our objective was to determine whether levothyroxine (l-T(4)) treatment prevents the clinical manifestation of AIT in euthyroid subjects with T1D. DESIGN AND SETTING: We conducted a prospective, randomized, open, controlled clinical trial at six tertiary care centers for pediatric endocrinology and diabetes. PATIENTS: Of 611 children and adolescents with T1D, 89 individuals (14.5%) were identified with positive thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), or both. Of these, 30 patients (age, 13.3 +/- 2.1 yr) met the inclusion criteria and were randomized to receive l-T(4) (n = 16 patients) or no treatment (n = 14 patients). INTERVENTION: l-T(4) (1.3 microg/kg daily) was given for 24 months in the treatment group, followed by an additional observation period of 6 months in both groups. MAIN OUTCOME MEASURES: Thyroid gland volume (as determined by ultrasound), serum levels of TSH, thyroid hormones, TPOAb, and TgAb were assessed every 6 months for 30 months. RESULTS: Mean thyroid volume decreased in the treatment group after 24 months (-0.60 sd score) and increased in the observation group (+ 1.11 sd score; P = 0.0218). Serum thyrotropin, free T(4), TPOAb, and TgAb levels were not significantly different in both groups during the entire study period. Hypothyroidism developed in three individuals treated with l-T(4) and in four untreated patients (conversion rate, 9.3% per year). CONCLUSIONS: In this study in euthyroid patients with AIT and T1D, l-T(4) treatment reduced thyroid volume but had no effect on thyroid function and serum autoantibody levels.     

Primary thyroid lymphoma associated with Graves' disease.

We report herein a case of thyroid mucosa-associated lymphoid tissue (MALT) lymphoma in a patient receiving antithyroid drug therapy for Graves' disease. A 75-year-old woman first presented with finger tremor and was diagnosed with Graves' disease on the basis of clinical and laboratory findings. Three years later, she presented with rapid and painless enlargement of the thyroid. Ultrasonography revealed a circumscribed hypoechoic area bilaterally in each lobe of the thyroid, and fine-needle aspiration biopsy showed diffuse monotonous infiltration of small- to medium-sized atypical lymphoid cells. (67)Ga scintigraphy was positive exclusively in the thyroid. After total thyroidectomy, the patient received radiation therapy for treatment of stage IE primary thyroid lymphoma. Results of histological examination, immunohistochemical analysis, and flow cytometric analysis confirmed MALT lymphoma. To our knowledge, there have been few published reports of primary thyroid lymphoma associated with Graves' disease. Our experience with this case, though rare, indicates that an enlarged thyroid in cases of Graves' disease should be examined carefully for primary thyroid lymphoma.     

Selenium supplementation in patients with autoimmune thyroiditis decreases thyroid peroxidase antibodies concentrations

In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells. Selenium-dependent enzymes also have several modifying effects on the immune system. Therefore, even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases. We performed a blinded, placebo-controlled, prospective study in female patients (n = 70; mean age, 47.5 +/- 0.7 yr) with autoimmune thyroiditis and thyroid peroxidase antibodies (TPOAb) and/or Tg antibodies (TgAb) above 350 IU/ml. The primary end point of the study was the change in TPOAb concentrations. Secondary end points were changes in TgAb, TSH, and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation. Patients were randomized into 2 age- and antibody (TPOAb)-matched groups; 36 patients received 200 microg (2.53 micromol) sodium selenite/d, orally, for 3 months, and 34 patients received placebo. All patients were substituted with L-T(4) to maintain TSH within the normal range. TPOAb, TgAb, TSH, and free thyroid hormones were determined by commercial assays. The echogenicity of the thyroid was monitored with high resolution ultrasound. The mean TPOAb concentration decreased significantly to 63.6% (P = 0.013) in the selenium group vs. 88% (P = 0.95) in the placebo group. A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40% reduction in the selenium-treated patients compared with a 10% increase in TPOAb in the placebo group. TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased (P = 0.018), but were unchanged in the selenium group. Nine patients in the selenium-treated group had completely normalized antibody concentrations, in contrast to two patients in the placebo group (by chi(2) test, P = 0.01). Ultrasound of the thyroid showed normalized echogenicity in these patients. The mean TSH, free T(4), and free T(3) levels were unchanged in both groups. We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis, especially in those with high activity. Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated.     

The value of ultrasonography in predicting autoimmune thyroid disease.

Ultrasonography (US) may demonstrate a diffuse reduction in thyroid echogenicity (low-amplitude echoes) in autoimmune thyroid disease (AITD), which includes chronic lymphocytic thyroiditis and Graves' disease, as well as in subacute thyroiditis. The reported occurrence of this finding in AITD varies from 19% to 95%. To assess the validity of diffuse reduction in thyroid echogenicity as a predictor of AITD, 3,077 patients referred for US of the thyroid were examined prospectively with regard to reduced versus normal thyroid echogenicity. The most frequent reasons for referral were goiter, thyroid dysfunction, neck discomfort, and/or difficulty in swallowing. Ultrasonography demonstrated diffuse reduction in thyroid echogenicity in 485 patients. Of these, 452 patients had available records of fine-needle aspiration biopsy (FNAB), and were included in the study. From the remaining patients, with normal thyroid echogenicity, 100 consecutive patients were selected as controls. In 411 of the 452 study patients (90.9%) there was at least one laboratory finding consistent with possible AITD: cytology indicating lymphocytic thyroiditis, 287 of 363 patients (79.1%) with diagnostic specimens; elevated levels of peroxidase antibodies (TPOAb), 225 of 337 (66.8%); elevated thyrotropin (TSH) levels, 290 of 450 (64.4%); or low TSH levels, 79 of 450 (17.6%). The final diagnosis was: chronic autoimmune (Hashimoto's) thyroiditis in 352 patients; Graves' disease in 47 patients; subacute (granulomatous) thyroiditis in 7 patients; toxic nodular goiter in 3 patients; and toxic adenoma in 2 patients. In the remaining 41 patients, those without laboratory results consistent with AITD, the final diagnosis was colloid goiter in 37 and thyroid cancer in 4 patients. In the 100 controls, laboratory results were consistent with possible AITD in 14 patients: elevated TPOAb levels in 5 of 49 patients with retrieved antibody results; lymphocytic thyroiditis in 2 patients; elevated TSH levels in 2 patients; and low TSH levels in 2 patients. In these controls, the final diagnosis was: chronic autoimmune thyroiditis in 7; toxic nodular goiter in 6 patients, and toxic adenoma in 1 patient. The corresponding positive and negative predictive values of reduced thyroid echogenicity as an indicator of AITD were 399 of 452 (88.3% [95% CI, 85% to 91%]), and 93 of 100 (93.0% [95% CI, 88% to 98%]), respectively. Thus, diffuse reduction in thyroid echogenicity was a valid predictor of AITD.     

Effects of prophylactic thyroid hormone replacement in euthyroid Hashimoto's thyroiditis

Hashimoto's thyroiditis is the most frequent autoimmune thyroid disease. L-thyroxine therapy can reduce the incidence and alleviate the symptoms of this disease. The aim of this study was to evaluate the effects of prophylactic L-thyroxine treatment on clinical and laboratory findings of patients who were euthyroid at the time of diagnosis. Thirty-three patients who had diagnosis of euthyroid Hashimoto's thyroiditis were randomized to two groups, one group received prophylactic L-thyroxine treatment and the other was followed-up without treatment. Initial thyroid function tests, autoantibodies, ultrasonography, fine needle aspiration biopsy and peripheral blood lymphocyte subsets were similar in the two study groups. After 15 months of L-thyroxine treatment, there was a significant increase in free T4 and a significant decrease in TSH and anti-thyroglobulin antibody anti-thyroid peroxidase antibody levels. CD8+ cell counts increased in both groups, CD4/CD8 levels decreased significantly because of the increase in CD8+ cell count levels. Though there was no change in cytological findings, ultrasonography showed a decrease in thyroid volume in L-thyroxine receiving patients whereas an increase was detected in patients who were followed without treatment. In conclusion, prophylactic thyroid hormone therapy can be used in patients with Hashimoto's thyroiditis even if they are euthyroid.     

Long-term follow-up of antithyroid peroxidase antibodies in patients with chronic autoimmune thyroiditis (Hashimoto's thyroiditis) treated with levothyroxine

BACKGROUND: A number of studies show that the serum levels of antithyroid peroxidase antibodies (TPO-Ab) in patients with Hashimoto's thyroiditis decline during levothyroxine treatment, but do not provide quantitative data or report the fraction of patients in whom test for TPO-Ab became negative ("normalization percentage"). The objective of the present study was to provide this information. METHODS: This was a retrospective study of TPO-Ab concentrations in 36 women and 2 men (mean age 51 +/- 16 years; range 19-81 years) with Hashimoto's thyroiditis as defined by the following criteria: elevated plasma TPO-Ab and typical hypoechogenicity of the thyroid in high-resolution sonography at first presentation or during follow-up and low pertechnetate uptake in thyroid scintigraphy. When first studied 17 women and 1 man were not yet taking levothyroxine. The remaining 20 patients were receiving levothyroxine. At initial examination 18 patients had serum thyroid-stimulating hormone (TSH) concentrations above normal. Results of up to eight (mean = 5.8) measurements obtained over a mean period of 50 months while patients were receiving levothyroxine were analyzed. In addition, serum TSH, free triiodothyronine (fT3), and free thyroxine (fT4) were measured, and ultrasound of the neck was performed at each follow-up examination. RESULTS: In terms of TPO-Ab levels, 35 of 38 patients (92%) had a decrease, 2 patients had undulating levels, and 1 patient had an inverse hyperbolic increase in her TPO-Ab levels. In the 35 patients in whom there were decreasing TPO-Ab values, the mean of the first value was 4779 IU/mL with an SD of 4099 IU/mL. The mean decrease after 3 months was 8%, and after 1 year it was 45%. Five years after the first value, TPO-Ab levels were 1456 +/- 1219 IU/mL, a decrease of 70%. TPO-Ab levels became negative, < 100 IU/mL, in only six patients, a normalization percentage of 16%. There were no correlations between changes in thyroid volume and changes in TPO-Ab. CONCLUSION: Serum TPO-Ab levels decline in most patients with Hashimoto's thyroiditis who are taking levothyroxine, but after a mean of 50 months, TPO-Ab became negative in only a minority of patients.     

The prevalence of undiagnosed thyroid disorders in a previously iodine-deficient area.

OBJECTIVE: The aim of the present study was to analyze the current status of morphologic and functional thyroid abnormalities in a previously iodine-deficient area. METHODS: The population based Study of Health in Pomerania (SHIP) comprised 4310 participants, aged 20-79 years. Thyroid function (thyrotropin [TSH] free triiodothyronine [FT(3)], and free thyroxine [FT(4)]) and serum autoantibodies to thyroperoxidase (TPOAb) were evaluated from blood samples. Thyroid structure and size were measured by ultrasound. Data from 3941 participants with no known thyroid disorders were analyzed. RESULTS: The median iodine urine excretion was 12.4 microg/dL. The rate of decreased serum TSH levels (<0.3 mIU/L) was 11.3%; 2.2% of participants had suppressed serum TSH levels (<0.1 mIU/L). The prevalence of subclinical hyperthyroidism was 1.8%, the prevalence of overt hyperthyroidism 0.4%. Elevated TSH levels were found in 1.2% of individuals. Subclinical hypothyroidism was observed in 0.5%, overt hypothyroidism in 0.7% of the sample. Elevated TPOAb were detected in 7% of subjects, 4.1% of participants had TPOAb greater than 200 IU/mL. The prevalence of goiter was 35.9%. An inhomogeneous echo pattern was detected in 35.2% and nodules in 20.2% of participants. Diffuse autoimmune thyroiditis was diagnosed in 47 subjects (1.2%). CONCLUSION: There are a number of thyroid disorders in this previously iodine-deficient region. Further studies are required to investigate the change of thyroid disorders during iodine supplementation programs.     

Changes in anti-thyroid hormone and anti-thyroglobulin antibodies during thyroid hormone(s) or prednisolone treatments in 3 cases of Hashimoto's thyroiditis

We have experienced 3 cases of Hashimoto's thyroiditis with anti-thyroid hormone antibodies. Changes in titers of anti-thyroglobulin(Tg) and anti-thyroid hormone antibodies during 6 year (Cases 1 and 2) and 7 year (Case 3) observation periods were examined in each case. Cases 1 (13-year-old) and 2 (10-year-old) are sisters with hypothyroidism whose chief complaint was short stature. They were diagnosed as having Hashimoto's thyroiditis by needle biopsy of the thyroid gland. Presence of anti-thyroid hormone antibodies were found in the sera of both cases (Case 1: anti-thyroxine(T4) antibodies, Case 2: anti-triiodothyronine(T3) antibodies). They were treated with synthetic T4 or combined therapy of T3 and T4, and serial sera obtained during the 6 year treatment period were tested for the titers of anti-Tg and anti-thyroid hormone antibodies. Case 3 (23-year-old female), who was diagnosed as having Hashimoto's thyroiditis associated with systemic lupus erythematosus (SLE) and Sj?gren's syndrome had been treated with prednisolone(PSL) for 8 years. After one year of strating the treatment, she was found to have unusually low serum T3 measured by radioimmunoassay. Further examination revealed the presence of anti-T3 antibodies in her serum. Serial sera obtained during the 7 year observation period were tested for the titers of anti-Tg and anti-T3 antibodies. In cases 1 and 2, replacement therapy with thyroid hormone resulted in the decrease of titers of anti-thyroid hormone antibodies. In addition, increase in serum TSH concentrations was accompanied with increased titers of anti-Tg and anti-thyroid hormone antibodies in all 3 cases. The exact mechanism for it is not clear.(ABSTRACT TRUNCATED AT 250 WORDS)     

甲状腺过氧化物酶抗体检测的临床意义

甲状腺过氧化物酶表达于甲状腺滤泡细胞表面,主要参与甲状腺激素的合成与释放,并与细胞介导的细胞毒效应有关.甲状腺过氧化物酶能诱导机体产生高亲和力的IgG抗体(TPOAb)与甲状腺过氧化物酶特异的T淋巴细胞,分别参与甲状腺的浸润与破坏.TPOAb定量检测最常用的方法为酶联免疫吸附法.与TPOAb相关的疾病包括恶性贫血、结缔组织病、糖尿病、炎症性肠病、情感障碍以及一些妇产科疾病如流产、不孕、体外受精失败、早产、产后甲状腺炎等.正确认识TPOAb检测的指征,如对甲状腺肿以及Graves病或桥本甲状腺炎等自身免疫性甲状腺疾病的诊断和鉴别诊断、预测亚临床甲状腺疾病发生甲状腺功能减退症的风险等具有十分重要的临床意义.     

Inhibition by immunoglobulin G of synthesis of thyroid hormone in thyroid cultures from hypothyroid patients with goitrous Hashimoto's thyroiditis

Recently, thyroid microsomal antigen was identified as thyroid peroxidase, and thyroid microsomal antibody was found to inhibit thyroid peroxidase activity in vitro. We investigated the possibility that anti-microsomal antibody inhibits the iodination of tyrosine, in vivo. Immunoglobulin G with or without anti-microsomal antibody from hypothyroid patients with goitrous Hashimoto's thyroiditis inhibited thyroid hormone synthesis in cultured slices of normal human thyroid tissue. IgGs with anti-microsomal antibody inhibited 125I thyroidal uptake and thyroid hormone synthesis stimulated by TSH more than normal IgG did. However, the same results were obtained with IgGs without anti-microsomal antibody. This effect did not involve anti-microsomal antibody, anti-thyroglobulin antibody, TSH-binding inhibitor immunoglobulin, thyroid stimulation-blocking immunoglobulin, or the cAMP level of the thyroid tissue. The ratio of organic I to inorganic I with stimulation by TSH in slices incubated with IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis or normal IgG was not significantly different, but was significantly higher in slices incubated with methylmercaptoimidazole. Therefore, IgG from hypothyroid patients with goitrous Hashimoto's thyroiditis mainly suppressed 125I thyroidal uptake, rather than inhibiting thyroid peroxidase activity. In addition, this IgG was present in the serum of 11 of the 12 hypothyroid patients with Hashimoto's thyroiditis studied. This IgG may be involved in the mechanism that causes hypothyroidism in some patients with goitrous Hashimoto's disease.     

Recovery of thyroid function with a decreased titre of antimicrosomal antibody in a hypothyroid man with Hashimoto's thyroiditis

A 36 year old man with a diffuse goitre, signs of mild hypothyroidism, strikingly low levels of T4 (0.9 micrograms/dl) and T3 (24 ng/dl), elevated TSH (140 microU/ml) and elevated microsomal haemagglutination antibody (MCHA, 1:409 600), subsequently became non-goitrous and euthyroid with a decreased titre of antimicrosomal antibody without any medication. At the time of surgical biopsy, serum levels of T4 and T3 had risen to the normal range (4.6 micrograms/dl and 73 ng/dl, respectively), serum TSH had decreased to 30 microU/ml and the titre of MCHA to 1:25 600. Thyroid specimens showed Hashimoto's thyroiditis. The activity of thyroid peroxidase (TPO) was normal. The latest examination, 1 year and 3 months after initial evaluation, showed that the patient remained euthyroid with no goitre, that serum thyroid hormones were within the normal range (T4 7.7 micrograms/dl and T3 97 ng/dl), and that TSH was not detectable. The titre of MCHA decreased strikingly to 1:400.     

Should neck pain in a patient with Hashimoto's thyroiditis be underestimated? A case and review of the literature

Hashimoto's Thyroiditis (HT) is an autoimmune disease and the most frequent cause of hypothyroidism. Subacute thyroiditis (SAT) overlapping HT is a rare entity. A 69-year-old female patient with HT and multinodular goiter has been followed on levothyroxine replacement therapy for 7 years. She presented with neck pain radiating to the right ear persisting for 2 months. She was prescribed analgesics and antibiotics by other physicians during that period, which did not work. Her vital signs were stable with no tachycardia or fever. The right lobe of the thyroid gland was tender on palpation. Her TSH level was 3.94 mIU/ml, ESR 23 mm/h, CRP 3.2 mg/l, WBC 4900/μl at presentation. Thyroid ultrasonography revealed a hypoechoic area over the tender lobe. Power Doppler imaging revealed almost no blood flow in that area. She was started on methylprednisolone 32 mg/day. At day 10 of therapy, her symptoms had completely resolved. Ultrasonography repeated showed that the hypoechoic area had disappeared. Glucocorticoid dosage was tapered and stopped. Emergence of subacute thyroiditis in a case with preexisting Hashimoto's thyroiditis is a quite rare condition, but should be kept in mind along with a painful attack of HT in the differential diagnosis.