Thiocyanate in excess develops goiter followed by auto immune thyroid diseases even after effective salt iodization in a rural community of north east India.

PURPOSE: Salt iodization in Manipur of north-east India failed to prevent endemic goiter, therefore an in depth study carried out to evaluate thyroid functions of goitrous subjects in a randomly selected region. METHODS: Goiter survey conducted in children and women of reproductive ages by palpation followed by measurement of urinary iodine, thiocyanate and house-hold salt iodine to evaluate iodine nutritional status and consumption pattern of bamboo-shoots (BS). In all grade-2 goitrous subjects, free thyroxine, triiodothyronine, TSH, TPO and Tg antibodies, thyroid volume and echogenecity by ultrasonography and cytomorphology of thyroid by FNAC studied. RESULTS: Study population was 2486 children and 1506 women, goiter prevalence was 12.59% and 16.27% respectively; median urinary iodine and mean thiocyanate were 166 µg/l and 0.729 ± 0.408 mg/dl while salt iodine was ≥30 ppm. Serum thyroid hormones and TSH profiles of all grade-2 goitrous subjects showed 16.21% were subclinically hypothyroid, 2.16% overt hypothyroid, 4.86% subclinically hyperthyroid and 6.48% overt hyperthyroid, serum TPO- and Tg-antibodies found positive in 41.62%. Ultrasonographic results showed 24% had enlarged thyroid and 86.4% hypoechoic. Cytomorphological studies showed prevalence of colloid goiter (41.08%), lymphocytic thyroiditis (37.83%), Hashimoto's thyroiditis (8.10%), autoimmune thyroiditis (4.32%), sub-acute thyroiditis (2.16%) and 1.62% each papillary, medullary carcinoma, simple diffused hyperplasia and adenomoid nodular goiter. CONCLUSIONS: Grade-2 goitrous individuals in this mild goiter endemic region were affected by hypo- and hyperthyroidism with hypoechoic thyroid and thyroiditis. Thiocyanate that originates from BS even in presence of adequate iodine developed goiter and led goitrous population towards such diseases.

[Interleukin-6 in endemic goiter patients in the south Ural region].

The cytokine and thyroid status was studied in patients with endemic goiter (EG) depending on thyroid function. IL-6 correlated with free T3 levels (a negative relationship) in hyperthyroidism, with IL-2 and IFN-gamma levels in EG patients with euthyroidism, and with IL-1beta, IL-2, IL-8, IL-10, and IFN-gamma in hypothyroidism. The EG patients with high IL-6 levels showed positive relationships to IL-2 and thyroid peroxidase antibodies and a negative relationship to free T3. In these patients, IL-6 acted to stimulate the secretion of antithyroid antibodies, which is a risk of autoimmune thyroiditis.

Involvement of inducible costimulator ligand (ICOSL) expression in thyroid tissue in hyperthyroidism of Graves' disease patients.

BACKGROUND: The role of costimulatory molecules expressed on lymphocytes and thyrocytes in hyperthyroidism has attracted increasing attention and research has shown a close correlation between variant expression of these molecules on lymphocytes and thyrocytes and the development of GD. MATERIALS AND METHODS: [corrected] Thyroid tissues were collected from GD patients during surgery and from Hashimoto disease (HT) and non-toxic goiter (NTG) patients as controls. ICOSL expression on infiltrated B cells and TFC was detected by flow cytometry (FCM), reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). Variation in ICOSL expression on TFC in primary cultures was analyzed in the absence or presence of cytokines using FCM assays. The role of ICOS-ICOSL signaling in proliferation, thyroid hormone production and thyroglobulin (Tg) release was investigated in primary TFC cultures using ICOS gene transfected L929 cells (ICOS-L929 cells) and the blocking ICOSL antibody (11 C4) in MTT assays and radioimmunoassays. RESULTS AND DISCUSSION: ICOSL expression on infiltrated B cells and TFC was detected in GD patient tissue. However, ICOSL expression was only detected on infiltrated B cells in control HT and NTG patient tissue. ICOSL expression on TFC was induced in vitro by the proinflammatory cytokines IFN-γ, IL-6 and TNF-α. Compared with mock transfected L929 (mock-L929) control cells, ICOS-L929 cells promoted significant proliferation of primary cultured TFC, with increased thyroid hormone and Tg production (all P < 0.01). TFC proliferation and production of thyroid hormones and Tg were inhibited significantly in the presence of ICOSL blocking antibody (11 C4) (all P < 0.05). Our observations suggest that ICOS-ICOSL signal plays a direct role in proliferation and differentiation of TFC and may exert important effects in the initiation, maintenance and exaggeration of autoimmune responses in local tissue.

Thyroid autoimmunity role in the evolution of endemic goiter in rural area, Fars, Iran.

BACKGROUND: WHO reports indicate no iodine insufficiency in Iran, however, goiter is still endemic in Fars Province. This study evaluates the role of thyroid autoimmunity in the evolution of endemic goiter. METHODS: A total of 516 permanent residents of Akbarabad County of the Kavar area in Fars Province, Iran were selected by simple random sampling. Patients with thyroid malignancy and dysfunction, and those who consumed drugs affecting thyroid function were excluded. After signing a written consent form and undergoing a thyroid examination, 5 cc of blood were drawn to measure free T3 and T4 (RIA), TSH (IRMA), and anti-thyroid peroxidase (competitive RIA) levels. Moreover, samples of 50 cc morning urine were collected for the measurement of urinary iodine excretion (UIE; chloridric acid digestion). Data were analyzed by SPSS (version 13). P<0.05 was significant. RESULTS: The prevalence of goiter was 38.4% by WHO classification. The prevalence of children with UIE 2-4.9 µg/dL was 5.8%, which indicated sufficient iodine intake. Goiter was more prevalent in females, as well as in patients with positive anti-TPO or higher TSH titers (P<0.01). The prevalence of positive anti-TPO was higher in goiterous patients than healthy persons (P=0.002), which increased with an increase in age, grade of thyromegaly or TSH (P<0.02). Regression analysis showed the odds ratio for diagnosing goiter in females was 2.4 (P<0.001), in those with positive anti-TPO it was 1.87 (P=0.03) and in those with TSH>5.2 mIU/mL the odds ratio was 2.74 (P=0.01). In adolescents compared to children the odds ratio was 0.36 (P=0.01) and the odds ratio in adults to children was 0.33 (P=0.001). CONCLUSION: This study indicates that despite normal UIE, goiter is endemic in Akbarabad County. Some degree of goiter endemicity may be due to thyroid autoimmunity.

The role of thyroid autoantibodies in the etiology of endemic goiter in schoolchildren of Isfahan, Iran.

BACKGROUND: Eleven years after the initiation of universal salt iodization program in Iran, the prevalence of goiter is still high in some areas. AIM: To investigate the role of thyroid autoimmunity in the etiology of residual goiter in schoolchildren of Isfahan, Iran. MATERIAL AND METHODS: In a cross-sectional study, 2331 schoolchildren were selected by multi-stage random cluster sampling. Thyroid size was estimated in each child by inspection and palpation. Urinary iodine concentration (UIC), serum anti-thyroperoxidase antibody (anti-TPO Ab), and anti-thyroglobulin antibody (Anti-Tg Ab) were measured. RESULTS: Overall, 32.9% of children had goiter. The median UIC was 1955.5 microg/dl. There was significant difference in prevalence of positive anti-TPO Ab in goitrous (grade 2) and non-goitrous children (9.7 vs 3.7%, p= 0.02). Goitrous children had higher prevalence of positive anti-Tg Ab than non-goitrous ones (15.1 vs 3.1%, p<0.001). CONCLUSIONS: According to the present study, goiter is still a public health problem in this region. This study suggests that thyroid autoimmunity is among the contributors of goiter persistence after elimination of iodine deficiency in Isfahan.

Thyroid autoantibodies in women with and without thyroid disorders in an iodine-replete area.

To compare the prevalence of positive autoantibodies in patients with thyroid disorders and healthy subjects in an iodine-replete area of the Islamic Republic of Iran, we studied 930 women in a clinic-based study: 698 patients (286 hypothyroid, 140 hyperthyroid, 272 with simple goitre) and 232 healthy women. Serum thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone, and anti-thyroid antibodies were measured. Positive autoantibodies were detected in 75.5% of patients with hypothyroidism, 73.6% of those with hyperthyroidism, 48.9% of those with simple goitre and 35.8% of the control group (P < 0.001). Autoimmunity may have a role in the genesis of common thyroid disorders.

Goiter rate, serum thyrotropin, thyroid autoantibodies and urinary iodine concentration in Tehranian adults before and after national salt iodization.

Goiter rate, serum TSH, antithyroperoxidase (TPOAb), antithyroglobulin (TgAb) antibodies, and urinary iodine concentration (UIC) were evaluated 10-11 yr prior (1983-1984) and 5-6 yr after (1999-2000) national salt iodization in Iran. Pre- and post-iodization groups consisted of 465 and 1426 adults aged > or =20 yr, respectively, selected by random cluster sampling in Tehran province. Total, grade 1 and grade 2 goiter rates were 65.2, 53.1, and 12.1% in 1983-1984 vs 25.2, 15.5, and 9.7% in 1999-2000 (p<0.0001). Median serum TSH was 1.5 mIU/l in 1983-1984 vs 0.8 mIU/l in 1999-2000 (p<0.0001). Median TSH also decreased in 20-29, 30-39, 40-49, 50-59, and > or =60- yr-adults in 1983-1984 vs 1999-2000 (p<0.0001). In 1983-1984, positive TPOAb and positive TgAb were detected in 3.2 and 4%, respectively, using agglutination test. Corresponding values were 12.5 and 16.8% using immunoenzymometric assay in 1999-2000. Overt and subclinical hypothyroidism was present in 0 and 32.8/1000 in 1983-1984 vs 3.5 and 21.7/1000 in 1999-2000, respectively. Overt and subclinical hyperthyroidism was detected in 4.4 and 4.4/1000 in 1983-1984 vs 0.7 and 5.6/1000 in 1999-2000, respectively. Subclinical hypothyroidism in males was significantly more frequent in 1983-1984 vs 1999-2000 (odds ratio 5.02, 95% confidence interval 1.72-14.68; p=0.004). Salt iodization resulted in adequate UIC, decrease in serum TSH and subclinical hypothyroidism in males, and an increase in thyroid autoantibodies without significant change in thyroid abnormalities. Benefits of iodine supplementation far outweigh its hazards in Tehranian adults.

The role of iodine in the evolution of thyroid disease in Greece: from endemic goiter to thyroid autoimmunity.

The thyroid gland is dependent on dietary iodine for the production of thyroid hormones, normal iodine requirement being about 150-200 microg/day. Long-term deficiency in iodine intake is associated with the development of goiter. When the prevalence of goiter in a population rises above 5-10%, the problem is considered endemic. Greece is a country with a recent history of moderate iodine deficiency, endemic goiter being prevalent in the 1960s in inhabitants of mountainous regions. Despite recognition of the problem, an iodine prophylaxis program was never officially implemented. Instead, "silent iodine prophylaxis" took place during the 1980s and 1990s with Greece's improvement in socioeconomic conditions. This resulted in the elimination of iodine deficiency and a parallel decrease in the prevalence of goiter among schoolchildren in formerly iodine deficient areas. However, the transition from iodine deficiency to iodine sufficiency or excess was followed by the emergence of autoimmune thyroiditis, especially among young girls, indicating that exposure to excess iodine may trigger thyroid autoimmunity. Thus, the modification of an environmental factor, ie dietary iodine, over the last 40 years in Greece has been associated with changes in the phenotypic expression of thyroid disease from endemic goiter to goiter associated with autoimmune thyroiditis.

Prevalence of antithyroid microsomal antibody in thyroid patients of endemic goitre area.

The region of greater Mymensingh known for iodine endemicity, recently came under iodine supplementation as a result of mandatory universal iodination of salt program. Autoimmune thyroid diseases (AITD) are among the most common human autoimmune disorders & presence of autoantibodies to the microsomal antigen (AntiMCAb) is a hallmark of disease activity. Both iodine deficiency & iodine supplementation precipitate increase rate of autoimmunity to the thyroid gland. Study was undertaken to determine prevalence of AntiMCAb positive cases among patients with various thyroid diseases. High resolution ultrasound (HRUS), serum thyroid hormone assays & scintiscan were used to classify the thyroid patients into 8 categories. 221 patients were studied during the stipulated period of 3 months. Male patients were 60 & female patients were 161. Age ranged from 11 to 65 years with median age 29.4 years. AntiMCAb test were done with radioimmunoassay (RIA). 126 patients had antimicrosomal antibody (57.01%). All form of hypothyroid (atrophic, goitrous, Hashimoto's) have very high rate of AntiMCAb positive cases. Highest 89.28% were seen in patients showing feature of Hashimoto's thyroiditis or generalized feature of AITD in HRUS with hypothyroidism, followed had 61.29% positive cases, However, antithyroid antibody was found in all form of thyroid disorders. Nodular goiter had 21.73% antiMCAb positive cases. AntiMCAb found positive at the rate of 33.33% in euthyroid patients with HRUS feature of AITD & diffuse euthyroid goiter, 40% in subclinical hypothyroid, 40% in subclinical hyperthyroid. Female rated higher in range of antimicrosomal antibody positivism. 59% of all thyroid patients among female subjects were AntMCAb positive, where as 51.67% male thyroid patients were positive. Highest number of positive cases found in the 30-35 age group. No definite pattern, however, was observed among age distribution. 20 age matched sample from patients unsuspected of thyroid disease shows 10% AntiMCAb positive compared to 73.33% of the same among same age group of thyroid patients. Frank Hashimoto's thyroiditis with positive antiMCAb and hypothyroidism were all detected by HRUS.

[Role of some environmental factors in the development of endemic goiter (a review)]. / Rol' nekotorykh faktorov okruzhaiushchei sredy i razvitii éndemicheskogo zoba (obzor).

The review presents possible causes of endemic goiter since only iodine deficiency fails to explain such a great spread of this disease. Etiological factors of endemic goiter, such as the imbalance of trace elements, the use of contaminated drinking water, the toxic action of chemicals, exposure to ionizing radiation, genetic factors, are discussed. Prevalence rates of endemic goiter in Russia and other countries of the world are presented. The causes of a significant increase in the incidence of this disease are discussed.

[Iodine therapy for iodine deficiency goiter and autoimmune thyroiditis. A prospective study]. / Jodtherapie der Jodmangelstruma und Autoimmunthyreoiditis. Eine prospektive Studie.

PROBLEM: There is epidemiological and clinical evidence that iodine may induce or promote the manifestation of autoimmune thyroiditis. For this reason it is important to know if substitution of alimentary iodine deficiency or iodine treatment of endemic goitre can cause formation of thyroid antibodies. On the other hand the practical importance of this phenomenon should be evaluated. PATIENTS AND METHODS: During a prospective study we examined 209 patients with endemic non-toxic goitre and 53 healthy people. For treatment were used 200 micrograms iodine/d (n = 119), 500 micrograms iodine/d (n = 27), 1.5 mg iodine/week (n = 41), 150 micrograms iodine/d plus 75 to 100 micrograms T4/d (n = 26), 100 micrograms iodine plus 100 micrograms T4/d (n = 24). The observation took 1 year with a 3-month interval for check ups including clinical examination, ultrasound, TSH, T3, fT4, TPO- and thyreoglobuline antibodies and urinary iodine. RESULTS: After 12 months 7.5% of iodine treated persons had produced antibodies, most of them at low levels. In healthy people we found increased antibody-levels in 3.8%, in patients with goitre in 9.0%, in patients with nodular goitres in 11.1%. 500 micrograms iodine caused the most antibody reaction in 14.8%. People treated with 200 micrograms iodine/d showed positive antibody levels in 5%. T4 seems to reduce antibody-reactions. Pathological antibody-levels were not found in patients with combined iodine/T4- and single-T4 therapy. Among the 22 primary pathological antibody levels only 4 increased further (18.2%). Three of them belonged to the group of 5 persons treated with 500 micrograms iodine/d. Primary high antibody values were normalized in 5 patients (22.7%). Hypothyroid disturbances were not found. Ultrasound did not show any alterations, and the reduction of thyroid volumes in antibody-positive patients was not affected. Median urinary iodine excretion during the observation-interval was 5.2 to 7.2 micrograms/dl. CONCLUSIONS: Possible antibody reactions have no clinical importance at all. Individual cases must be observed. Low iodine doses should be preferred. Combined iodine/T4 treatment seems to have an advantage regarding immunological thyroidal reactions.

Elevated anti-galactosyl antibody titers in endemic goiter.

Anti-Gal is a human polyclonal antibody that constitutes approximately 1% of the circulating immunoglobulin G (IgG), interacts specifically with the mammalian carbohydrate alpha-galactosyl epitope. Furthermore, it was found to mimic in vitro thyrotropin (TSH) effects regarding stimulation for cyclic adenosine monophosphate (cAMP) synthesis, 125I uptake, and cellular proliferation on cultured porcine thyrocytes and on Graves' disease thyrocytes, but not on normal human thyrocytes. As immune activation in sporadic and endemic goiters might play a secondary role in regulating thyrocyte proliferation and function, we evaluated anti-Gal titers in endemic goiter. Serum was obtained from 109 Chagas'-negative patients living in an endemic goiter area of Brazil (Grao Mogol, MG) and 160 controls. The patients were divided into 3 groups, according to their goiter size (World Health Organization [WHO] classification): grade 0 (group 1, n = 24), grade I-II (group 2, n = 41), and grade III-IV (group 3, n = 44). Anti-Gal was assessed by a radioimmunological procedure (results expressed as the percentage of bound radioactivity/total activity [%B/T]). The antibody titer was significantly more elevated in group 1 (mean +/- SEM: 9.27%+/-0.80%), in group 2 (mean +/- SEM: 16.17%+/-0.97%), and in group 3 (20.97%+/-1.30%) than in normal controls (6.46%+/-0.33%). Analysis of the male and female data separately for anti-Gal titer did not substantially alter these results. We concluded that the anti-Gal titer is higher in patients with endemic goiter and presented a possible relationship with the size of goiter. Whether these antibodies contribute to the pathogenesis of the disease needs further clarification.

[Endemic goiter in Latium: environmental and genetic factors]. / Gozzo endemico nel Lazio: fattori ambientali e fattori genetici.

Most studies on the pathogenesis of endemic goiter focus above all on iodine deficiency. In some endemic goiter areas (i.e. Nigeria) there is no evidence of iodine deficiency; therefore, we suggest the taking into account of various factors, both environmental and non-environmental. We report the results of two studies carried out in three different areas in Latium: one of them (Cerveteri, RM) could be classified as high prevalence of goiter area, while the two others (Roccasecca dei Volsci, LT and Castel San Pietro Romano, RM) are true endemic goiter areas. The role of environmental factors, radioactivity and electromagnetism, foodstuff, the hydrogeological and chemical composition of natural water and the importance of genetics are here discussed, assuming that the endemic goiter could have a multifactorial pathogenesis.

[Epidemiologic and immunologic parameters in the assessment of endemic goiter in the Orenburg region]. / Epidemiologicheskie i immunologicheskie pokazateli v otsenke zobnoi éndemii v Orenburgskoi oblasti.

Epidemiological investigations were carried out in 2328 children in the districts of the Orenburg district. Iodine deficiency was detected in the children living in the districts having low concentrations in the water and foodstuffs. There was a deviation of immunological parameters from the normal values in the children of the same districts.

[General pathology of trace element deficiency]. / Obshchaia patologiia gipomikroélementozov.

According to the authors' concept, different forms of trace element deficiency show some general rules of development. All of them are followed by a decrease of immune resistance. Trace element deficiency is never isolated, it is always characterized by trace element unbalance and is followed by a considerable disturbance of metabolism (mineral, lipid, carbohydrate and protein) with relevant manifestations. Reduced immune resistance and pluriglandular endocrinopathy create the conditions for various malignancies.

Effects of low level radiation from the Chernobyl accident in a population with iodine deficiency.

UNLABELLED: To determine the effects of low dose radiation from 131I and 137Cs resulting from the Chernobyl disaster on the expression of endemic goiter in children, we studied children in regions with and without evidence of radiocontamination but comparable iodine insufficiency. We included 89 children in the study (radiocontaminated) region (SR) and 116 in the control region (CR) because they were either fetuses, infants, or pre-adolescents at the time of exposure. We evaluated thyroid dimensions by clinical examination and ultrasound; thyroid function by hormonal levels, and thyroglobulin measurement; histology of the thyroid by fine needle aspiration; and thyroid autoimmunity. SR subjects had 5 times the frequency of thyroid enlargement as those from CR, greatest in the younger patients. There were no instances of clinically apparent thyroid dysfunction. Antithyroid microsomal and antithyroglobulin antibodies were present in a markedly greater percentage of SR subjects. Fine needle biopsy demonstrated greater cellular proliferation in samples from SR. CONCLUSIONS: We have demonstrated findings of autoimmune thyroid disease at markedly increased frequency in a population of children with poor iodine nutriture who were exposed to low level radiation, compared to a more iodine deficient population not so exposed. These results suggest that low level radiation may induce thyroid gland changes in children who have inadequate iodine intake nutriture and reinforce the importance of adequate dietary iodine.

Growth stimulating antibodies in endemic goitre: a reappraisal.

OBJECTIVE: Previous studies, using a variety of methods, have reported growth-promoting immunoglobulins (IGs) in a large proportion of patients with endemic goitre. We sought to determine whether thyroid growth-promoting immunoglobulins (TGI) are present in the serum of Indian patients with endemic goitre. DESIGN: IgG was prepared by protein G-Sepharose affinity purification and added to FRTL-5 thyroid cells in the presence of suboptimal concentrations of TSH. PATIENTS: We studied 30 sequential patients with endemic goitre and 16 euthyroid controls without a goitre from the same area. MEASUREMENTS: Two assays for thyroid cell growth were used: 3H-thymidine incorporation, and flow cytometric measurement of the proportion of cells in the S phase and G2/M phase of the cell cycle. RESULTS: Both assays were shown to detect growth produced by TSH and by thyroid stimulating antibodies in IgG preparations from 3 patients with Graves' disease. There was no significant increase in either 3H-thymidine incorporation or the distribution of cells in S or G2/M phase with IgGs from endemic goitre patients, and no difference between the effects of these IgGs and those from the normal subjects. CONCLUSIONS: Thyroid growth-promoting immunoglobulins cannot be detected in Indian patients with endemic goitre.

Prevalence of anti-thyroid peroxidase antibodies in autoimmune and nonautoimmune thyroid disorders in a relatively low-iodine environment.

We evaluated the prevalence of antithyroid peroxidase antibodies (anti-TP0 Ab) in 402 patients with thyroid disease and 30 healthy controls by a commercial radioimmunoassay (RIA) and compared the results with the passive hemagglutination (HA) method. The patients in the study had autoimmune thyroid disorders (AITD) such as Graves' disease and Hashimoto's disease or had nonautoimmune thyroid diseases (NAITD) such as thyroid cancer, congenital goiter, endemic goiter, and nodular goiter. Subjects were recruited from a population with a mild iodine deficiency (Sao Paulo, Brazil). The effect of specific therapy (for either thyrotoxicosis or chronic thyroiditis) on the circulating anti-TPO levels was also investigated. Positive anti-TPO Ab was detected in 89.9% of the patients with AITD as compared with a prevalence of positive tests of only 4.8% in patients with NAITD. Positive microsomal antibody (M Ab) was found in 68.4% of the patients with AITD and in 6.4% of the patients with NAITD. A positive and significant correlation was obtained between M Ab and anti-TPO Ab. A positive anti-TPO test with negative anti-M was found in 14.1% of the patients with AITD but in only 4.3% of the patients with NAITD and normal controls. These results suggest that anti-TPO Ab by RIA is more sensitive and specific than M Ab by HA. In patients with AITD, anti-TPO Ab levels usually decreased after treatment, suggesting that this parameter could be used in the follow-up of these thyroid disorders.

Incidence of thyroid autoantibodies in the endemic goiter.

The aim of our study was to investigate the incidence of thyroid autoantibodies (TA) in the endemic region of the north-eastern Poland. The mean titres of ATMA and TGAb were measured in 1508 randomly chosen persons aged 3 to 68 yrs. ATMA or TGAb were positive in 17% of the population studied. Frequency and mean titres of TA were observed to increase with age. Autoantibodies were more frequently noted in persons with parenchymatous goiter. There was no correlation between the incidence of autoantibodies and goiter enlargement, however, the highest percentage of TGA was noted in people with large thyroid (III). TA were also found in 10% of the subjects without goitre. Our results do not confirm the hypothesis that thyroid autoantibodies play a key role in the pathogenesis of endemic goiter.