Circulating Thyroid Autoantibodies Research Articles

Can Supplementation with Vitamin D Modify Thyroid Autoantibodies (Anti-TPO Ab, Anti-Tg Ab) and Thyroid Profile (T3, T4, TSH) in Hashimoto's Thyroiditis? A Double Blind, Randomized Clinical Trial.

Hashimoto's thyroiditis (HT) is the most prevalent autoimmune disorder characterized by the destruction of thyroid cells caused by leukocytes and antibody-mediated immune processes accompanied by hypothyroidism. In recent years, evidence has emerged pointing to various roles for vitamin D, including, proliferation and differentiation of normal and cancer cells, cardiovascular function, and immunomodulation. Vitamin D deficiency has been especially demonstrated in HT patients. The aim of this study was to investigate the effect of vitamin D on circulating thyroid autoantibodies and thyroid hormones profile (T4, T3, and TSH) in females with HT. Forty-two women with HT disease were enrolled in this randomized clinical trial study and divided into vitamin D and placebo groups. Patients in the vitamin D and placebo groups received 50 000 IU vitamin D and placebo pearls, weekly for 3 months, respectively. The serum levels of 25-hydroxy vitamin D [25(OH) D], Ca++ion, anti-thyroperoxidase antibody (anti-TPO Ab), anti-thyroglobulin antibody (anti-Tg Ab), T4, T3, and TSH were measured at the baseline and at the end of the study using enzyme-linked immunosorbent assays. The results of this study showed a significant reduction of anti-Tg Ab and TSH hormone in the Vitamin D group compared to the start of the study; however, there was a no significant reduction of anti-TPO Ab in the Vitamin D group compared to the placebo group (p=0.08). No significant changes were observed in the serum levels of T3 and T4 hormones. Therefore, vitamin D supplementation can be helpful for alleviation of the disease activity in HT patients; however, further well controlled, large, longitudinal studies are needed to determine whether it can be introduced in clinical practice.

Circulating thyroid autoantibodies are more sensitive than fine needle aspiration in detecting metastatic thyroid cancer

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Sonographic Echo-pattern of the Thyroid Gland among the Non-nodular Goitrous Patients Having Abnormal thyrotropin Level at their First Diagnosis

Objective: This study was done to observe the high resolution sonographic echo-pattern of the thyroid gland among the non-nodular goitrous patients having abnormal thyrotropin (TSH) level at their first diagnosis.Method: This study was conducted at the Institute of Nuclear medicine and Allied Sciences, Rajshahi, Bangladesh during the period between 1st January, 2014 and 31st March, 2015. The goitrous patients are referred at this Institute by the clinicians for radionuclide thyroid scan, HRUS of thyroid gland and thyroid function tests. Under the basis of convenient sampling technique, 62 patients are included as sample. Their age, gender, HRUS echo-patterns of goiter and thyrotropin levels are recorded and analyzed with statistical software IBM SPSS v. 16.Results: Among the total enrolled patients (n=62), 57 (91.9 %) were female and five (8.1 %) were male. Mean (± SD) age was 28 ± 11.85 years (range=8 to 69 years). Regarding thyrotropin level among the sample patients (n=62), 53 (85.5 %) had above normal range and 9 (14.5 %) had below normal range. In relation to sonographic echo-pattern of the non-nodular goitrous patients (n=62), 43 (69.4 %) had hypoechoic feature, 15 (24.2 %) had non-homogenous feature and four (6.5 %) had both hypoechoic and non-homogenous feature. Among the 43 goitrous patients with hypoechoic feature, 38 had thyrotropin above normal range and five had below normal range; among the 15 goitrous patients with non-homogenous feature, 12 had thyrotropin above normal range and three had below normal range and among the four goitrous patients with both hypoechoic and non-homogenous feature, three had thyrotropin above normal range and one had below normal range.Conclusion: The results of this study will be helpful in the relevant prospective studies which will be concerned with developing non-nodular goiter management algorithm, in addition to the role of other parameters like thyroid function tests especially thyrotropin level, circulating thyroid autoantibodies detection and fine needle aspiration biopsy (FNAB) cytology findings.Bangladesh J. Nuclear Med. 18(2): 152-155, July 2015

Is selenium supplementation in autoimmune thyroid diseases justified?

This review provides an appraisal of recent evidence for or against selenium supplementation in patients with autoimmune thyroid diseases, and discusses possible effect mechanisms. Epidemiological data suggest an increased prevalence of autoimmune thyroid diseases under conditions of low dietary selenium intake. Two systematic reviews have evaluated controlled trials among patients with autoimmune thyroiditis and report that selenium supplementation decreases circulating thyroid autoantibodies. The immunomodulatory effects of selenium might involve reducing proinflammatory cytokine release. However, clinically relevant effects of selenium supplementation, including improvement in quality of life, are more elusive. In Graves' disease, some, but not all, trials indicate that adjuvant selenium supplementation enhances the restoration of biochemical euthyroidism, and might benefit patients with mild Graves' orbitopathy. The use of selenium supplementation as adjuvant therapy to standard thyroid medication may be widespread, but a growing body of evidence yields equivocal results. The available evidence from trials does not support routine selenium supplementation in the standard treatment of patients with autoimmune thyroiditis or Graves' disease. However, correction of moderate to severe selenium deficiency may offer benefits in preventing, as well as treating, these disorders. Molecular mechanisms have been proposed, but further studies are needed.

Selenium Supplementation Significantly Reduces Thyroid Autoantibody Levels in Patients with Chronic Autoimmune Thyroiditis: A Systematic Review and Meta-Analysis.

Selenium supplementation may decrease circulating thyroid autoantibodies in patients with chronic autoimmune thyroiditis (AIT), but the available trials are heterogenous. This study expands and critically reappraises the knowledge on this topic. A literature search identified 3366 records. Controlled trials in adults (≥18 years of age) with AIT, comparing selenium with or without levothyroxine (LT4), versus placebo and/or LT4, were eligible. Assessed outcomes were serum thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) autoantibody levels, and immunomodulatory effects. After screening and full-text assessment, 16 controlled trials were included in the systematic review. Random-effects meta-analyses in weighted mean difference (WMD) were performed for 3, 6, and 12 months of supplementation in two different populations: one receiving LT4 therapy and one newly diagnosed and LT4-untreated. Heterogeneity was estimated using I2, and quality of evidence was assessed per outcome, using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines. In LT4-treated populations, the selenium group had significantly lower TPOAb levels after three months (seven studies: WMD = -271 [confidence interval (CI) -366 to -175]; p < 0.0001; I2 = 45.4%), which was consistent at six months (three studies) and 12 months (one study). TgAb decreased at 12 months, but not at three or six months. In LT4-untreated populations, the selenium group showed a decrease in TPOAb levels after three months (three studies: WMD = -512 [CI -626 to -398]; p < 0.0001, I2 = 0.0%), but not after 6 or 12 months. TgAb decreased at 3 months, but not at 6 or 12 months. Quality of evidence was generally assessed as low. Study participants receiving selenium had a significantly higher risk than controls of reporting adverse effects (p = 0.036). Selenium supplementation reduced serum TPOAb levels after 3, 6, and 12 months in an LT4-treated AIT population, and after three months in an untreated AIT population. Whether these effects correlate with clinically relevant measures remains to be demonstrated.

Clinical significance of autoimmune thyroid disease in myasthenia gravis.

We investigated thyroid function and autoimmunity in 74 (61% females) consecutive patients with MG. 30 of these patients were tested twice: the time between the investigations ranging from 1 to 4 years. MG was diagnosed on the basis of typical clinical symptoms, a positive tensilone-test, and/or detectable acetylcholine antibodies and/or repetetive stimulation tests. Eye involvement was present in 86%, concurrent thymomas in 56%. The following parameters were measured in the serum of these patients by commercially available kits: free and total T4, TSH, TSH-Receptor-Antibodies ("TRAB"), antibodies against thyroglobulin (Tg-Ab), against thyroid microsomes (M-Ab) and against acetyl-choline-receptors . An age matched group of 50 patients (54% females) with no known thyroid disease from a cardiological ward and from the neurological outpatient department served as control. There was only 1 MG patient with overt thyroid dysfunction (iodine induced thyrotoxicosis in a patient with autonomous adenoma and no circulating thyroid autoantibodies detected at the second investigation). There were, moreover, 1 euthyroid MG-patient on L-thyroxine therapy with a history of Hashimoto's disease and positive thyroid autoantibodies and 1 other MG-patient with mildly elevated TSH without elevated thyroid antibodies, who has had subtotal thyroidectomy without substitution therapy years before for unknown reasons. Tg-Ab were positive (>360 IU/ml) in 5%, M-Ab were positive (>154 IU/ml) in 15% of the MG patients. The control group had 4% Tg-Ab and 6% M-Ab. TRAB levels were normal in all patients and controls. The relative increase in M-Ab frequency was not statistically significant (x-square test). We conclude from our results, that autoimmune thyroid disease may be associated with MG but that the occurrence of thyroid dysfunction induced by autoimmunity is a very rare phenomenon in MG.

Graves' disease / model of SCID mouse

The severe combined immunodeficient (SCID) mouse constitutes an interesting but not ideal model for the study of human Graves' disease (GD) thyroid tissue. While certainly thyroid tissue survives in the SCID mouse, the lymphocytes do not seem to be able to exert their effects in a long term manner as they do in the human host. Primary thyroid xenografts of GD will not remain hyperfunctional, and antibodies seem to subside after several weeks. GD thyroid tissue which has been removed from its immune environment by passing it through the nude mouse for eight weeks, and then re-xenografted in the SCID mouse, will again manifest lymphocytic infiltration only upon injection of autologous human peripheral blood mononuclear cells which thus reconstitute the lesion to some degree. However, we have not been able to reproduce GD by this procedure. We have been able to show organ-specific homing of the autologous peripheral blood lymphocytes to the GD thyroid tissue and a reappearance of histological lymphocytic infiltration, thyrocyte HLA-DR and ICAM-1 expression, and the reappearance of circulating thyroid autoantibodies after injection of autologous peripheral blood mononuclear cells (PBMC). (No such changes occur when normal thyroid tissue is similarly studied). This can be greatly magnified by deleting the CD8 cells prior to (PBMC) injection and can be prevented by adding a surfeit of CD8 cells instead, signifying that this subpopulation of lymphocytes contains suppressor T lymphocytes. The model affords means of studying various immunomodulators in an in vivo situation. Attempts are being made in various centres to more closely simulate GD but it may be necessary to have other mouse models with fewer natural killer (NK) cells to be able to successfully maintain the lymphocytes and tissue in its original state.

Lithium: Updated Human Knowledge Using an Evidence-Based Approach

Lithium use in mental diseases has changed over the years but remains a cornerstone of treatment in bipolar disorders. In two companion papers, we have reviewed existing (and especially recent) data on lithium efficacy and updated basic knowledge regarding the practical fundamentals of lithium therapy. The present paper reviews safety data on lithium available to date. Gastrointestinal pain or discomfort, diarrhoea, tremor, polyuria, nocturnal urination, weight gain, oedema, flattening of affect and exacerbation of psoriasis are typical complaints of patients receiving long-term lithium therapy. Renal involvement results in a reduced urinary concentrating capacity, expressed as obligate polyuria, with secondary thirst. With long-term therapy, this may result in nephrogenic diabetes insipidus. In addition, glomerular filtration rate falls slightly in about 20% of patients. The view that only a few patients receiving long-term lithium are at increased risk of glomerular impairment and progressive renal insufficiency should be regarded with caution. The risk is increased in case of concomitant diseases or medications. Lithium treatment may inhibit thyroid hormone release and induce goitre. Consequently, the prevalence of both overt and subclinical hypothyroidism is increased, with circulating thyroid auto-antibodies frequently being found. Much less commonly, thyrotoxicosis may also develop in association with lithium therapy. Long-term lithium treatment may also be associated with persistent hyperparathyroidism and hypercalcaemia, as well as with hypermagnesaemia. Overweight of up to 4-10 kg is found in approximately 30% of lithium-treated patients. Most neurological manifestations are benign, for example, the fine postural and/or action tremor present in 4-20% of patients. This is increased by high caffeine consumption and concomitant use of other psychotropic agents. A number of rare, potentially serious neurological adverse effects have been reported, including extrapyramidal symptoms, 'pseudotumour cerebri' or occasionally cerebellar symptoms. Severe neurological sequelae are exceptional. Cognitive disturbances are often mentioned as a lithium-related adverse effect. The few controlled studies do show a statistically significant negative effect of lithium on memory, vigilance, reaction time and tracking. There are frequent reports of mild effects of lithium on cognition at therapeutic serum concentrations. A number of deaths associated with lithium treatment have been reported. The most serious issue is that of non-accidental overdose, i.e. either long-term overdosage or acute overdose on long-term treatment. Progressive renal insufficiency, an exceptional complication of long-term lithium therapy, may also have a fatal outcome. In relation to pregnancy, lithium salts are rated as category D (positive evidence of risk). Therefore, prescription of lithium should be avoided during the first trimester of pregnancy unless the benefit to the mother exceeds the risk to the fetus. Although lithium transfer into breast milk is well established, the long-term fate of babies breast-fed by mothers receiving lithium therapy is unknown. Whether lithium therapy is safe in breast-feeding women is controversial. Although there is no absolute contraindication, it is known that the kidney is particularly sensitive to lithium just after birth. Intoxication in patients on long-term treatment with lithium in the absence of history of acute ingestion is not rare. Contributing factors include change in daily dose, long-term high dosage, kidney disease or drug interaction. In suspected cases, serum concentrations should be obtained early and repeatedly. In addition to supportive measures, haemodialysis is the treatment of choice for severe cases. Thorough knowledge of the limitations and drawbacks of lithium therapy is mandatory for its optimal use, especially at a time when its risk/benefit profile needs to be compared accurately with that of antiepileptic drugs and other mood stabilizing medications.

Clinical features of thyroid autoimmunity are associated with thyroiditis on histology and are not predictive of malignancy in 570 patients with indeterminate nodules on cytology who had a thyroidectomy

The relationship between thyroid autoimmunity and cancer is still uncertain. We approached this issue in 570 consecutive patients submitted to thyroidectomy for an indeterminate nodule on cytology. Thyroid autoimmunity was defined as positivity of circulating thyroid autoantibodies (TAb), autoimmune hypo- or hyperthyroidism, thyroid hypoechogenicity on ultrasound, and lymphocytic infiltration on histology. TAb were found in 122/570 (21.4%), hypoechogenicity in 115/570 (20.1%), and lymphocytic infiltration in 117/570 (20.5%) of patients. The three features of thyroid autoimmunity were highly concordant: hypoechogenicity was observed in 71/448 (15.8%) patients with negative TAb and in 44/122 (36%) with positive TAb (P < 0.0001); lymphocytic infiltration was found in 53/448 (11.8%) patients with negative TAb and in 64/122 (52.4%) with positive TAb (P < 0.0001); hypoechogenicity on ultrasound was observed in 73/453 (16.1%) patients without, and in 42/117 (35.9%) with lymphocytic infiltration (P < 0.0001). None of these parameters was associated with malignancy. TAb were found in 32/135 (23.7%) patients with carcinoma and in 90/435 (20.6%) with a benign lesion (P = NS); hypoechogenicity was observed in 26/135 (19.2%) patients with carcinoma and in 89/435 (20.4%) patients with benign lesions (P = NS); lymphocytic infiltration was present in 28/135 (20.7%) patients with carcinoma and in 89/435 (20.4%) with benign lesions (P = NS). The frequency of cancer in 11 patients with clinically overt thyroid autoimmune disease did not differ from that observed in the whole study group. In this group of patients with indeterminate thyroid nodules at cytology, clinical and pathological criteria of thyroid autoimmunity were strongly concordant and not associated with malignancy.

Lack of association between thyroid autoantibodies and parity in a population study argues against microchimerism as a trigger of thyroid autoimmunity

Thyroid autoimmunity is more common in females than in males. One possible explanation for this female preponderance may be the effect of oestrogens on the immune system. It has also been suggested that foetal microchimerism involving transfer of foetal cells into maternal tissue during pregnancy may play an important role. We investigated the association between the presence of circulating thyroid autoantibodies and previous pregnancy, parity and the use of oral contraceptives (OCs) and hormone replacement therapy (HRT) in a population cohort. We examined 3712 women randomly selected from the general population. Serum was analysed for thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) using assays based on an RIA technique (DYNO test). Data were analysed in logistic regression models to adjust for possible confounders. Women previously treated for thyroid disease or with pregnancy within 1 year prior to the study were excluded from the analyses. In both univariate and multivariate models and whether the presence of TPO-Ab and Tg-Ab was investigated alone or in combination, findings were negative with respect to an association between circulating thyroid antibodies and previous pregnancy, number of pregnancies, parity and previous abortion. There was no association between thyroid autoantibodies and use of OCs. Women aged 60-65 years receiving HRT now or previously had a lower prevalence of Tg-Ab (univariate, P = 0.01; multivariate, P = 0.02). No such association was observed between HRT and TPO-Ab. In this population study there was no association between previous pregnancy, parity and thyroid antibodies, which argues against the role of microchimerism as a trigger of thyroid autoimmunity. Exogenous oestrogens may reduce aspects of autoimmunity.

Thyroid color flow doppler sonography and radioiodine uptake in 55 consecutive patients with amiodarone-induced thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AMT) is a life-threatening condition, the appropriate management of which is achieved by identifying its different subtypes. Type 1 AIT develops in patients with underlying thyroid abnormalities and is believed to be due to increased thyroid hormone synthesis and release; Type 2 AIT occurs in patients with a normal thyroid gland and is an amiodarone-induced destructive process of the thyroid. Management differs in the two forms of AIT, since Type 1 usually responds to combined thionamides and potassium perchlorate therapy, while Type 2 is generally responsive to glucocorticoids. Mixed forms, characterized by coexistence of excess thyroid hormone synthesis and destructive phenomena, may require a combination of the two therapeutic regimens. In this cross-sectional prospective study, 55 consecutive untreated patients, whose AIT was subtyped according to clinical and biochemical criteria, were evaluated to assess the specificity of color flow doppler sonography (CFDS) and thyroidal radioiodine uptake (RAIU) in the differential diagnosis of AIT. Sixteen patients (6 men, 10 women, age 66+/-13 yr), who had diffuse or nodular goiter with or without circulating thyroid autoantibodies, were classified as Type 1 AIT; 39 patients (27 men, 12 women, age 65+/-13 yr) with apparently normal thyroids were classified as Type 2 AIT. All Type 1 patients had normal or increased thyroidal vascularity on CFDS, while Type 2 AIT patients had absent vascularity (p<0.0001). Thirteen Type 1 AIT patients had inappropriately normal or elevated thyroidal 3-h and 24-h RAIU values (range 6-37% and 10-58%, respectively), in spite of elevated values of urinary iodine excretion; the remaining 3 patients (two with nodular goiter, one with a thyroid adenoma) had low 3-h and 24-h RAIU values (range 1.1-3.0% and 0.9-4.0%, respectively). The latter patients, who were unresponsive to the combination of methimazole and potassium perchlorate, became euthyroid after the addition of glucocorticoids. Thirty-eight Type 2 AIT patients had low 3-h and 24-h RAIU values (range 0.4-3.7% and 0.2-3.0%, respectively), but one had inappropriately normal 3-h and 24-h RAIU values (6% and 13%, respectively). In conclusion, CFDS can accurately distinguish between Type 1 and Type 2 AIT, and in general the CFDS pattern is concordant with the thyroid RAIU. However, in 4 out of 55 patients (7%) the thyroid RAIU was discrepant, probably reflecting the coexistence of Type 1 and Type 2 AIT. Thus, assessment of both CFDS and RAIU may provide a more accurate subtyping of AIT and help in selecting the appropriate therapy. Finally, in long standing iodine sufficient areas, such as the United States, where the thyroid RAIU is consistently low irrespective of the etiology of the AIT, CFDS offers a rapid and available method to differentiate between Type 1 and Type 2 AIT.

Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dsfunction in apparently healthy subjects.

In order to establish its usefulness for the diagnosis and follow-up of thyroid autoimmune diseases, thyroid ultrasonography together with free T4 (FT4), free T3 (FT3), TSH, antibodies (Tg Ab) and thyroperoxidase antibodies (TPO Ab) were performed and re-evaluated during a 3-yr follow-up in 482 apparently healthy subjects, living in a borderline iodine-sufficient urban area. Thyroid dysfunction was found in 7 out of 12 (58.3%) subjects with circulating thyroid autoantibodies, who also had thyroid hypoechogenicity (2 had overt and 3 subclinical hypothyroidism at booking; 2 developed subclinical hypothyroidism during the follow-up), and in none of the 12 subjects with normal thyroid echostructure (chi2=7.26, p=0.007). Thyroid dysfunction was found in 4 out of 29 (13.7%) subjects with negative Tg and/or TPO Ab who also had thyroid hypoechogenicity (1 had Graves' disease at booking, 1 developed Graves' disease and 2 subclinical hypothyroidism during the follow-up), and in none of the 429 with normal thyroid echostructure (chi2=82.03, p<0.0001). Although positive TPO and/or Tg Ab were more frequent (24/482, 5%) in subjects with thyroid dysfunction (7/11) than in those who remained euthyroid during the study (17/471, chi2=69.66, p<0.0001), thyroid hypoechogenicity had a higher sensitivity than the positivity of thyroid autoantibody tests (100 vs 63.3%) for diagnosing or predicting thyroid dysfunction. 1) thyroid ultrasonography is a useful tool to detect thyroid autoimmune disease in apparently healthy subjects; 2) present and future thyroid dysfunction is more readily predicted by a hypoechogenic pattern at thyroid ultrasound than by the occurrence of serum thyroid autoantibodies.

WHEN TO TREAT MILD HYPOTHYROIDISM

The availability and wide acceptance of TSH assays for primary assessment of thyroid function has led to the recognition that mild thyroid hormone deficiency is characterized by elevation of the serum TSH concentration despite a normal free thyroxine level. Other conditions can also cause isolated serum TSH elevation, and these conditions can be distinguished from mild thyroid failure usually based-on clinical and circumstantial observations alone. Thyroxine treatment of patients with mild hypothyroidism has been shown in most, but not all, clinical trials to lower atherogenic lipid levels and relieve certain somatic and neuropsychiatric symptoms. Such treatment also prevents the progression to overt hypothyroidism, which is particularly likely in patients who are older, who have circulating thyroid autoantibodies, or who have a serum TSH greater than 10 mU/L. After the optimal thyroxine dose has been defined, long-term monitoring of patients with an annual clinical evaluation and serum TSH measurement is appropriate. The high prevalence of mild hypothyroidism, particularly in older women, and its subtle clinical presentation have led some authorities to recommend a low threshold for case-finding or routine population screening for the disorder.

Circulating thyroid autoantibodies in a sample of Italian octo-nonagenarians: relationship to age, sex, disability, and lipid profile.

Circulating thyroid autoantibodies were assessed in a sample of Italian octo-nonagenarians living in a restricted area (Val Vibrata, Abruzzo), and selected according to the absence or presence of chronic illness and disability. The study groups included: Group A ("Successful aging"), 98 free-living healthy, fully independent, octo-nonagenarians (57 males and 41 females, average age +/-SD 83.9+/-3 years); Group B ("Unsuccessful aging"), 62 highly disabled octo-nonagenarians (24 males and 38 females; average age 86.5+/-3.4 years), and Group C (Controls), 91 randomly selected healthy adult controls (42 males and 49 females; age 53.7+/-16.6 SD years, range 20-70). Serum autoantibodies to thyroglobulin (anti-Tg) and to thyroid peroxidase (anti-TPO) were measured by passive hemagglutination and radioimmunoassays (RIA); serum free thyroxine and thyrotropin by RIA. The prevalence of positive thyroid autoantibody tests was not significantly increased in the elderly groups compared to the controls, with the remarkable exception of anti-Tg detected by RIA which were increased in disabled elderly, compared to free-living elderly and controls. Two/62 disabled elderly had subclinical (1) or mild (1) primary hypothyroidism, and one free-living woman aged 90 years was hyperthyroid (toxic nodular goiter). No correlation was found between serum thyroid autoantibodies, thyroid hormones and TSH and serum lipoprotein fractions. The higher prevalence of thyroid autoantibodies found only in disabled, but not in free-living Italian octo-nonagenarians suggests that thyroid autoimmune phenomena in the elderly may be an expression of age-associated disease rather than related to the aging process in itself.

Independent expression of serological markers of thyroid autoimmunity and hepatitis virus C infection in the general population: results of a community-based study in north-western Sardinia.

To assess the relationship between serological markers of thyroid autoimmunity and chronic hepatitis C, we surveyed the general population of two villages in the region of Sardinia, Italy, where infection with hepatitis viruses is endemic and the prevalence of autoimmune diseases is elevated. A total of 1310 subjects aged 6-88 years (65% of the total resident population) participated in the survey, and 1233 (94%; 444 males and 789 females) agreed to provide a blood sample. Autoantibodies to thyroid peroxidase (anti-TPO) were measured by radioimmunoassay; antibodies to HCV (anti-HCV) by a third generation enzyme immunoassay and borderline positive results confirmed by recombinant immunoblot assay. For both anti-HCV and anti-TPO the age- and gender-standardized prevalence rates (SPR) were calculated and the significance of the association between the two antibodies tested by Yates corrected chi2 test. The overall SPR for anti-HCV was 50.7x10(-3) (86/1,233), similar between men [49.1x10(-3) (22/444)] and women [52.3x10(-3) (64/789)]. The overall SPR for anti-TPO was 136.9x10(-3) (204/1,233), and that among women [201x10(-3) (174/789)] was almost 3-fold that among men [71.6x10(-3) (30/444)]. A concurrent anti-HCV and anti-TPO positivity was found in a small minority of subjects [8/1,233 (0.65%)], all women aged 57-81 years. The SPR for the two concurrent events was 3.3x10(-3), which was not significantly different (Yates corrected chi2 test = 0.65) from that expected under the assumption of unrelated events. To explore whether HCV infection is a risk factor for anti-TPO positivity, we designed a case-control study with anti-TPO positive subjects as the cases, and anti-TPO negative subjects as the controls. The age- and gender-adjusted odd ratio (OR) was 0.4 (95% CI 0.2,0.7), indicating a negative association. In conclusion, no evidence for epidemiological association of circulating thyroid autoantibodies and antibodies to HCV was found. Our findings do not therefore support a pathogenetic link between HCV infection and thyroid autoimmunity.

Thyroid autoantibodies are not associated with recurrent pregnancy loss

Objective: Approximately 1% of all women have recurrent pregnancy loss, defined as ≥3 spontaneous losses of pregnancy; however, a cause is determined in only 50% of cases. Recent studies have associated the presence of thyroid autoantibodies during the first trimester of pregnancy with spontaneous abortion in the current pregnancy among women without a history of recurrent abortion. The objective of this study was to determine whether circulating thyroid autoantibodies were associated with recurrent pregnancy loss. Study Design: Sera from 74 nonpregnant women with a history of recurrent pregnancy loss and from 75 healthy, fertile control subjects of similar gravidity were tested for thyroglobulin and thyroid peroxidase antibodies by means of radioimmunoassay kits. All women had a third-generation thyroid-stimulating hormone assay performed. Samples were obtained ≥6 months after a pregnancy. Results: Twenty-two of the women with a history of recurrent pregnancy loss (29.3%) and twenty-eight of the control subjects (37%) had positive results for either one or both of the thyroid autoantibodies ( P > .05). Mean thyroid-stimulating hormone levels and the proportion of women with abnormal thyroid-stimulating hormone values did not differ between the 2 groups. Conclusion: Women with a history of recurrent pregnancy loss are no more likely than are fertile control subjects to have circulating thyroid autoantibodies. Testing for antithyroid antibodies is not clinically useful in the evaluation of patients with a history of recurrent pregnancy loss. (Am J Obstet Gynecol 1998;179:1583-6.)

Prevalence of thyroid autoantibodies in children and adolescents from Belarus exposed to the Chernobyl radioactive fallout

The long-term effects of ionising radiation, including radioiodine, on thyroid function are not well known. We compared thyroid immunity and function in two groups of children from Belarus, one of whom was exposed to the radioactive fallout of Chernobyl. We measured serum free thyroxine 4 (free T4), free T3, and thyrotropin hormone (TSH) and the prevalence of thyroid autoantibodies (antithyroglobulin and antithyroperoxidase), in 287 children or adolescents living in Hoiniki (average caesium contamination of 5.4 Ci/km2). We also studied 208 children and adolescents living in Braslav (average contamination <0.1 Ci/km2), who were age 12 years or less at the time of the Chernobyl accident. The prevalence of antithyroglobulin or antithyroperoxidase, or both, was significantly higher (p=0.0001) in individuals living in Hoiniki (56 [19.5%] of 287) than in those living in Braslav (eight [3.8%] of 208). In both villages, no sex differences were found in the antibody prevalence before age 13 years. Thereafter, a significantly higher prevalence of thyroid autoantibodies was found in girls from Hoiniki. The increase in the prevalence of circulating antibodies in the contaminated group was already apparent in individuals who, at the time of the accident, were in utero or newborn (15.7%), and was even more pronounced in children of 9 years or more (35.1%). No major alterations of serum FT-4, FT-3, or TSH were found. 6-8 years after the Chernobyl accident, a significant increase in thyroid autoimmunity was found in children exposed to radioactive fallout. Pubertal age in girls is a risk factor for increased prevalence of thyroid autoimmunity. The autoimmune phenomena are limited to an increased prevalence of circulating thyroid autoantibodies without evidence of significant thyroid dysfunction. The future development of clinically relevant thyroid autoimmune diseases, especially hypothyroidism, is a possibility.

Enhanced susceptibility to amiodarone-induced hypothyroidism in patients with thyroid autoimmune disease.

The iodine-rich antiarrhythmic drug, amiodarone, can induce both thyrotoxicosis and hypothyroidism, the former being more frequent in iodine-deficient areas, the latter in iodine-sufficient areas. In this study we evaluated prospectively thyroid function in amiodarone-treated patients with positive or negative baseline thyroid autoantibody test results who resided in a moderately iodine-deficient area of Italy. Two groups of patients received long-term amiodarone treatment: Group 1 included 13 patients with negative thyroid autoantibody test results. Group 2 consisted of seven patients with positive thyroid autoantibody test results and thyroid ultrasound patterns compatible with Hashimoto's thyroiditis. The control group (group 3) included 16 untreated euthyroid patients with Hashimoto's thyroiditis. All subjects resided in a mildly iodine-deficient area of Italy (Southern Sardinia) and had low urinary iodine values. Patients in groups 1 and 2 had markedly elevated urinary iodine excretion during treatment. The follow-up period ranged from 6 to 29 months in group 1, from 4 to 9 months in group 2, and from 12 to 55 months in group 3. Two (15%) of 13 patients in group 1 with nodular goiter developed thyrotoxicosis. No patient in this group developed circulating thyroid autoantibodies. Five (71%) of seven patients in group 2 became hypothyroid after 4 to 9 months of amiodarone treatment associated with a rise in serum thyroid autoantibody levels. No patient in group 3 became hypothyroid. (1) Amiodarone administration can cause both thyrotoxicosis and hypothyroidism. (2) Hypothyroidism is far more frequent in patients with preexisting thyroid autoimmune disease. (3) Amiodarone can modify the natural history of Hashimoto's thyroiditis. (4) Circulating thyroid autoantibodies do not appear in amiodarone-treated patients who have negative test results prior to therapy.

The role of complement in the pathogenesis of postpartum thyroiditis.

Postpartum thyroiditis (PPT) affects half of the 10% of women who have elevated circulating thyroid autoantibodies during the postpartum year. Because of the similarities between PPT and Hashimoto's thyroiditis, the pathogenic role of complement in PPT has been investigated. Complement fixation by thyroid peroxidase antibodies (TPO Abs) (expressed as log reciprocal titer) in serum from euthyroid TPO Ab-positive women (n = 29) was 0.91 at 1 month postpartum and increased to 1.45 by 12 months postpartum; complement C3 activation, measured by enzyme-linked immunosorbent assay, in a similar group of women (n = 75) was 0.05 at delivery and increased to 0.33 by 6 months postpartum. In women with PPT, there was greater TPO Ab-related complement activation during the postpartum year; complement fixation increased from 1.00 at 1 month postpartum to 1.48 at 4 months postpartum (P < 0.005) (n = 25), and C3 activation increased from 0.11 at delivery to 0.63 at 6 months postpartum (P < 0.005) (n = 73). Bioactive TPO Ab (TPO Ab x C3 index) was significantly higher in PPT women (55 kilo international units of activity (kIU)/L at 6 months postpartum) (Hashimoto range, 30-108 kIU/L) compared with euthyroid TPO Ab-positive women (< 9 kIU/L at all time points; P < 0.005). Serum samples from TPO Ab-negative control women showed no interaction with complement in either assay at any time during the postpartum year (complement fixation < 0.7; complement C3 activation index < 0.01). This detailed examination of the role of complement in the pathogenesis of PPT shows that TPO Ab-driven complement fixation is a marker for thyroid dysfunction in TPO Ab-positive women. The levels of bioactive TPO Ab in PPT fall within the range seen in Hashimoto's thyroiditis, suggesting similarities in their pathology.

Serum thyreoglobulin: an early indicator of autoimmune post‐partum thyroiditis

The aim of this study was to assess whether autoimmune thyroid damage in post-partum thyroiditis was accompanied by a significant rise in the concentration of thyroglobulin in the serum and whether its measurement could be useful in the prediction of the risk and severity of an episode of post-partum thyroid dysfunction. Fifty-one women, who had taken part in a larger survey of post-partum thyroiditis, were selected at random for this study. Fourteen women without elevated circulating thyroid autoantibodies and 21 with raised thyroid autoantibodies remained euthyroid throughout the post-partum year. A third group of 14 women had raised thyroid autoantibody levels and showed one or more episodes of thyroid dysfunction during the course of the first year post partum. Thyroid autoantibodies were measured by ELISA, free T3 and free T4 by the Amerlex M method and TSH by an immunoradiometric method. Serum thyroglobulin was measured by a method free from interference by circulating endogenous thyroglobulin autoantibodies. Thyroid ultrasonography was performed using a General Electric RT3600 scanner operating at 7.5 MHz. Fourteen control women had a mean serum thyroglobulin concentration of 3.3 micrograms/l (SD 4.4; range < 1-12 micrograms/l; 95% confidence interval up to 6.0 micrograms/l). Twenty-one thyroid autoantibody positive euthyroid women had a mean serum thyroglobulin level of 5.8 micrograms/l (SD 6.2; range < 1-36 micrograms/l) which was not significantly different from that seen in the control group. Sixteen thyroid autoantibody positive women who showed one or more episodes of thyroid dysfunction during the post-partum period had a mean serum thyroglobulin of 31 micrograms/l (SD 24.8; range up to 88 micrograms/l) and this was significantly elevated compared with both the control and antibody positive groups (P < 0.001). Serum thyroglobulin concentrations at 3 months post partum correlated with the degree of post-partum hypothyroidism (as indicated by the maximum TSH and the minimum free thyroxine concentrations post partum) and, in those cases where thyroid ultrasound examinations were performed, with the degree of lymphocytic infiltration of the thyroid gland. The data presented in this paper confirm the destructive nature of post-partum thyroiditis and indicate that the measurement of serum thyroglobulin concentration could assist in the identification of those women at risk of post-partum thyroiditis.