Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization.

OBJECTIVE: Rheumatoid arthritis (RA) and thyroid dysfunction are frequently observed in the same patient. However, whether they co-occur or exhibit a causal relationship remains uncertain. We aimed to systematically investigate the causal relationship between RA and thyroid function using a large sample and advanced methods. METHODS: Bidirectional two-sample Mendelian randomization (MR) analysis was performed based on RA and six thyroid function trait data sets from the European population. The robustness of the results was demonstrated using multiple MR methods and a series of sensitivity analyses. Multivariable MR using Bayesian model averaging (MR-BMA) was performed to adjust for possible competing risk factors. A sensitivity data set, which included data from patients with seropositive RA and controls, was used to repeat the analyses. Furthermore, enrichment analysis was employed to discover the underlying mechanism between RA and thyroid functions. RESULTS: A significantly positive causal effect was identified for RA on autoimmune thyroid disease (AITD) as well as for AITD on RA (P < 0.001). Further sensitivity analyses showed consistent causal estimates from a variety of MR methods. After removing the outliers, MR-BMA results showed that RA and AITD were independent risk factors in their bidirectional causality, even in the presence of other competing risk factors (adjusted P < 0.05). Enrichment analysis showed immune cell activation and immune response play crucial roles in them. CONCLUSION: Our results illustrate the significant bidirectional causal effect of RA and AITD, which holds even in multiple competing risk factors. Clinical screening for thyroid dysfunction in patients with RA deserves further attention, and vice versa.

Assessment of Visual and Brainstem Auditory Evoked Potentials in Patients with Hashimoto's Thyroiditis.

BACKGROUND: The present study was aimed to evaluate parameters of visual and brainstem auditory evoked potentials (VEP, BAEP) in euthyreotic Hashimoto's thyroiditis (HT) patients without central nervous system involvement. METHODS: 100 HT patients (92 women, 8 men), mean age 46.9 years, and 50 healthy controls. They underwent a neurological examination, thyroid hormone levels, thyroid autoantibody titers, and brain imaging. Latencies and amplitudes of the N75, P100, and N145 component of VEP and the I-V components of BAEP were analyzed. RESULTS: The neurological examination revealed in 31 patients signs of increased neurovegetative excitability. Brain resonance imaging showed no abnormalities in HT patients. The mean P100, relative P100, and N145 VEP latencies were significantly longer, and P100 amplitude significantly higher in HT patients than the controls. HT patients also had a longer mean wave BAEP V latency and mean wave III-V and I-V interpeak latencies, and significantly lower mean wave I and V amplitudes. Abnormal VEP and BAEP were recorded in 34% of the patients. There were no statistically significant correlations between the mean VEP parameters and thyroid profile and the applied dose of L-thyroxine. There was a relationship between the level of TSH and the wave BAEP III-V interpeak latency. CONCLUSIONS: There were changes in the brain's bioelectrical activity in one-third of the patients with HT without nervous system involvement. The increased amplitude of the VEP may indicate increased cerebral cortex activity. Disorders of the brain's bioelectrical activity in the course of HT may be associated with an autoimmune process.

Uncertainty quantification of bioassay functions for the internal dosimetry of radioiodine.

Bioassay functions, which are provided by the International Commission on Radiological Protection, are used to estimate the intake activity of radionuclides; however, they include considerable uncertainties in terms of the internal dosimetry for a particular individual. During a practical internal dose assessment, the uncertainty in the bioassay function is generally not introduced because of the difficulty in quantification. Therefore, to clarify the existence of uncertainty in the bioassay function and provide dosimetrists with an insight into this uncertainty, this study attempted to quantify the uncertainty in the thyroid retention function used for radioiodine exposure. The uncertainty was quantified using a probabilistic estimation of the thyroid retention function through the propagation of the distribution of biokinetic parameters by the Monte Carlo simulation technique. The uncertainties in the thyroid retention function, expressed in terms of the scattering factor, were in the ranges of 1.55-1.60 and 1.40-1.50 for within 24 h and after 24 h, respectively. In addition, the thyroid retention function within 24 h was compared with actual measurement data to confirm the uncertainty due to the use of first-order kinetics in the biokinetic model calculation. Significantly higher thyroid uptakes (by a factor of 1.9) were observed in the actual measurements. This study indicates that consideration of the uncertainty in the thyroid retention function can avoid a significant over- and under-estimation of the internal dose, particularly when a high dose is predicted.

Hyperthyroidism association with SLE, lessons from real-life data--A case-control study.

BACKGROUND: Despite the frequently encountered association between thyroid disease and systemic lupus erythematosus (SLE) is well known, it is of surprise that only several reports compromised of small population size support this observation. OBJECTIVES: To investigate the association of comorbid SLE and hyperthyroidism. METHODS: Using the database of the largest health maintenance organization (HMO) in Israel, the Clalit Health Services, we searched for the co-existence of SLE and hyperthyroidism. Patients with SLE were compared with age- and sex-matched controls regarding the prevalence of hyperthyroidism in a case-control study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. RESULTS: The study included 5018 patients with SLE and 25,090 age- and sex- matched controls. The prevalence of hyperthyroidism in patients with SLE was increased compared with the prevalence in controls (2.59% and 0.91%, respectively, p < 0.001). In a multivariate analysis, SLE was associated with hyperthyroidism (odds ratio 2.52, 95% confidence interval 2.028-3.137). CONCLUSIONS: Patients with SLE have a greater prevalence of hyperthyroidism than matched controls. Therefore, physicians treating patients with SLE should be aware of this possibility of this thyroid dysfunction.

Local versus international recommended TSH references in the assessment of thyroid function during pregnancy.

The aim of this study was to compare the prevalence of subclinical and overt hypothyroidism based on local population-specific reference intervals versus arbitrary cutoffs that are not specific for the population studied or the assay used, during pregnancy in an area of iodine sufficiency. We tested a total of 203 pregnant women in the first trimester of pregnancy, and followed their status in the second and third trimesters. Serum samples from women were assayed for levels of total T4 and T3, FT4I, TSH, TPOAb, and TgAb. Of the 203 women based on our national trimester specific reference ranges of serum TSH and FT4I, 153, 157, and 157 were euthyroid in 3 consecutive trimesters of pregnancy. Accordingly, a total of 23, 12, and 13 had subclinical hypothyroidism in the first, second, and third trimester, respectively. Overt hypothyroidism was detected in 4, 5, and 1 women in the first, second, and third trimesters of pregnancy, respectively. The prevalence of subclinical hypothyroidism was 49, 31, and 34 in each of the trimesters respectively, when TSH>2.5 mIU/l was considered for definition of hypothyroidism in the first trimester, and over 3 mIU/l in the second and third trimesters. Our results showed that using arbitrary cutoff values for TSH instead of population-specific reference intervals may inappropriately increase the rate of subclinical hypothyroidism.

Cytologic, flow cytometry, and molecular assessment of lymphoid infiltrate in fine-needle cytology samples of Hashimoto thyroiditis.

BACKGROUND: The thyroidal lymphoid infiltrate (TLI) in Hashimoto thyroiditis (HT) represents the substrate from which thyroid lymphoma may arise. The objective of the current study was to classify the TLI in HT by comparing the cytologic features with flow cytometry (FC) data and evaluating the kappa/lambda light chain ratio and its molecular assessment. METHODS: Fine-needle aspiration cytology (FNAC) was performed in 34 patients with HT with nodular or diffuse palpable enlargement of the gland. Two or 3 passes were performed to prepare traditional smears, FC, and immunophenotyping, and RNAlater suspensions for molecular assessment. FC was performed using the following antibodies: CD3, CD5, CD4, CD8, CD10, CD19, and kappa and lambda light chains. In 4 cases, high molecular weight DNA was extracted and used for polymerase chain reaction (PCR) to amplify the variable diversity joining region of the heavy chain immunoglobulin (Ig) genes (IgH). Statistical analysis was performed to evaluate possible associations between clinical ultrasound presentation, cytologic pattern, and TLI phenotype. Light chain expression was evaluated as the percentage of the expressing cells (20%) and as the kappa/lambda ratio. RESULTS: Smears were classified as "lymphocytic," "lymph node-like," or "mixed." FC demonstrated T cells (CD3 positive [+], CD5+) in all cases, and T cells and B cell (CD19+, CD10+/-) lymphocytes in 22 cases. Light chains were expressed in 30 cases (in <20% of the gated cells in 13 cases and in >20% of the gated cells in 17 cases). Five cases demonstrated small kappa/lambda ratio imbalances and PCR analysis demonstrated diffuse bands in the gel and Gaussian curves at the heteroduplex. Statistical analysis indicated significant associations between the "lymphocytic" pattern and T-cell phenotype and between the "lymph node-like" pattern and B-cell phenotype. A significant association also was observed between light chain restriction and low light chain expression (P < .005). CONCLUSIONS: The cytologic pattern of TLI in HT is quite representative of the clinical presentation and phenotypic cell type. Small light chain imbalances are not sustained by heavy chain Ig gene (IgH) rearrangements. FNA coupled with FC may contribute to making the distinction between florid TLI and non-Hodgkin lymphoma.

Maternal thyroid autoantibodies during the third trimester and hearing deficits in children: an epidemiologic assessment.

Elevated maternal thyroid autoantibodies during pregnancy are linked to infertility, miscarriage, and neurodevelopmental deficits such as in cognitive function. It has not been established whether autoantibodies to thyroid peroxidase are associated with sensorineural hearing loss (SNHL). The authors tested stored third-trimester maternal serum specimens of 1,736 children for thyroid peroxidase autoantibodies (TPOaAb) by using an enzyme-linked immunosorbent assay technique. The children participated at the Baltimore, Maryland, site of the Collaborative Perinatal Project, which enrolled pregnant women in 1959-1965. An audiology examination was administered to the children at 8 years of age and was used to identify cases of SNHL. Compared with 4.3% of the other children, 22.7% of the children whose mothers had elevated TPOaAb (> or =62.5 IU/ml) had SNHL. The difference was significant after controlling for maternal race, age, and hypothyroidism (exact prevalence odds ratio = 7.5, 95% confidence interval: 2.4, 23.3). When a lower cutoff of TPOaAb > or =31.25 IU/ml was used, there continued to be an association with SNHL (exact prevalence odds ratio = 5.7, 95% confidence interval: 2.1, 15.6). The direction and magnitude of the association were similar when an alternative case definition of SNHL was used. These data suggest that antenatal exposure to maternal TPOaAb during the third trimester of pregnancy is associated with impaired auditory development.

Serological evidence of thyroid autoimmunity among schoolchildren in two different socioeconomic environments.

CONTEXT: The mechanisms leading to thyroid autoimmunity are largely unknown. OBJECTIVE: Our objective was to assess the role of environment in the development of thyroid autoimmunity. DESIGN: Prevalence of thyroid autoantibodies in two neighboring populations living in completely different socioeconomic circumstances (Russian Karelia and Finland) was studied. SETTING: We studied two population-based cohorts partly sharing the same ancestry. PATIENTS OR OTHER PARTICIPANTS: A total of 532 schoolchildren from Russian Karelia and 532 schoolchildren in Finland matched for age, gender, and season of the blood sampling were included. INTERVENTIONS: There were no interventions. MAIN OUTCOME MEASURES: The prevalence of thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TGAb) and HLA-DQ alleles was measured. RESULTS: The prevalence of TPOAb was significantly lower in Russian Karelian than in Finnish children (0.4 vs. 2.6%, P=0.006). A similar difference was observed for TGAb (0.6 vs. 3.4%, P=0.002). Finnish girls tested positive for both TPOAb (4.3 vs. 0.4%, P=0.01) and TGAb (5.3 vs. 0.9%, P=0.01) more frequently than Finnish boys. Seven of the 23 tested subjects with signs of thyroid autoimmunity (30%) had increased serum TSH concentrations as a sign of subclinical hypothyroidism. The frequency of HLA genotypes did not differ between the two countries or between autoantibody-positive and -negative subjects. CONCLUSIONS: The prevalence of thyroid autoimmunity is lower in Russian Karelia than in Finland. This difference was not related to ethnic background or HLA-DQ alleles. The results support the idea that the Russian Karelian environment, which is characterized by inferior prosperity and standard of hygiene, may provide protection against thyroid autoimmunity.

Hashimoto's encephalopathy : epidemiology, pathogenesis and management.

Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world. The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal.Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and nonparaneoplastic limbic encephalitis. In the context of the typical clinical picture, high titres of antithyroid antibodies, in particular antithyroid peroxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population. Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immunomodulation, such as intravenous immune-globulin and plasma exchange, may also be effective. Despite the link to autoimmune thyroid disease, the aetiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic, but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process, but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.

[National external quality assessment in auto-immunity: auto-antibodies against thyroid constituents]. / Contrôle national de qualité en auto-immunité: anticorps anti-thyroïdiens.

The French Health Products Safety Agency organized in 2005, for the scheme of the national external quality assessment, a survey on antibodies against thyroid constituents which included for the first time the quantitative assay. The purpose of this survey was to assess the quality of the different methods of these assays. The overall qualitative results are satisfactory. However, this survey pointed out a lower performance for immunodot which appeared to have been misused. Concerning the titer of antibodies, results show a broad dispersion between reagents. This confirms the lack of a real standardisation despite of the existence of the international MRC standards.

Autoantibody testing in children with newly diagnosed type 1 diabetes mellitus.

OBJECTIVES: To determine the role of autoantibody tests for autoimmune diseases in children with newly diagnosed type 1 diabetes mellitus. DATA SOURCES: MEDLINE, EMBASE and the Cochrane Library. Citation lists of included studies were scanned and relevant professional and patient websites reviewed. Laboratories and manufacturers were contacted to identify ongoing or unpublished research. REVIEW METHODS: Following scoping searches on thyroid and coeliac autoantibodies, a systematic review of autoantibody tests for diagnosis of coeliac disease was carried out. Studies were included where cohorts of untreated patients with unknown disease status were included, all patients had undergone the reference test (biopsy) and antibody tests, and sensitivity and specificity were reported or calculable. Selected studies were then evaluated against a quality checklist. Summary statistics of diagnostic accuracy, i.e. sensitivity, specificity, positive and negative likelihood ratios and diagnostic odds ratios, were calculated for all studies. A decision analytic model was developed to evaluate the cost utility of screening for coeliac disease at diagnosis of diabetes. RESULTS: All antibody tests for diagnosis of coeliac disease showed reasonably good diagnostic test accuracy. Studies reported variable measures of test accuracy, which may be due to aspects of study quality, differences in the tests and their execution in the laboratories, different populations and reference standards. The decision analytic model indicated screening for coeliac disease at diagnosis of diabetes was cost-effective. Sensitivity analyses exploring variations in the cost and disutility of gluten-free diet, the utilities attached to treated and untreated coeliac disease and the decrease in life expectancy associated with treated and untreated coeliac disease did substantially affect the cost-effectiveness of the screening strategies considered. CONCLUSIONS: In terms of test accuracy in testing for coeliac disease, immunoglobulin A (IgA) anti-endomysium is the most accurate test. If an enzyme-linked immunoassay test was required, which may be more suitable for screening purposes as it can be semi-automated, testing for IgA tissue transglutaminase is likely to be most accurate. The decision analytic model shows that the most accurate tests combined with confirmatory biopsy are the most cost-effective, whilst combinations of tests add little or no further value. There is limited information regarding test accuracy in screening populations with diabetes, and there is some uncertainty over whether the test characteristics would remain the same. Further research is required regarding the role of screening in silent coeliac disease and regarding long-term outcomes and complications of untreated coeliac disease.

[Histochemical assessment of immunoreactivity of thyroid peroxidase and its correlation with biochemical activity]. / Valutazione istochimica della immunoreattività della perossidasi tiroidea e sua correlazione con l'attività biochimica.

BACKGROUND: Peroxidase content has been recently evaluated in normal thyroid and in different thyroid disorders by biochemical, histochemical, ultrastructural and immunocytochemical methods Nevertheless immunocytochemical detection of thyroid peroxidase in thyroid samples conventionally processed for histology hes never been done using a commercially available antibody, neither its correlation with the biochemical activity on adjacent samples. METHODS: In this study we have analyzed normal thyroid tissue (3 patients), follicular adenoma (2 patients) and multinodular goiter (2 patients) conventionally processed for histology and stiined by immunocytochemistry (Avidin Biotin System) using a polyclonal (rabbit) antibody for horseradish peroxidase (Serotec). Biochemical assay was performed on adjacent samples according to Hosoya method. RESULTS: Normal thyroid showed peroxidase immunoresectivity in the majority of follicular celis; neoplastic cells of adenomas were variably stained. Biochemical assay showed positive correlation with ICC ranging from 20.4 mg/mg/prot a in multinodular goiter to 42.12 in normal thyroid, up to 122 of follicular adenoma. CONCLUSIONS: Peroxidase content in the thyroid gland may be of clinical interest in several thyroid diseases, and in this study we have demonstrated that thyroid peroxidase can be detected by ICC in routinely processed thyroid samples using a commercially available antibody.

Assessment of thyroid function in two hundred patients with beta-thalassemia major.

Despite improved hematologic care, multiendocrine dysfunction is a common complication of homozygous transfusion-dependent beta-thalassemia. In this study our goal was to estimate the prevalence of thyroid dysfunction in a large homogenous group of thalassemic patients. Two hundred patients with beta-thalassemia major (100 males and 100 females; mean age, 23.2 +/- 6.7 years; age range 11-43 years), regularly transfused and desferioxamine chelated, were randomly selected from a pool of approximately 800 patients with beta-thalassemia followed in our department. Thyroid function and iron-load status were evaluated by measurements of free thyroxine (FT4), free triiodothyronine (FT3), thyrotropin (TSH), and serum ferritin levels. Of the subgroup of patients who proved to have normal thyroid hormone values, 26 (12 males, 14 females; mean age, 23.6 +/- 6.8 years; age range, 15-36 years) were randomly selected and underwent a standard TRH stimulation test. Thyroid dysfunction was defined as follows: overt hypothyroidism: low FT4 and/or FT3, increased TSH levels; subclinical hypothyroidism: normal FT4, FT3, increased TSH levels; exaggerated TSH response: normal FT4, FT3, normal basal TSH, deltaTSH > or = 21 microIU/mL (TSH levels measured prior and 30 minutes after intravenous TRH administration). Normal thyroid hormone values were found in 167 (83.5%) of the 200 patients studied. Eight (4%) of the remaining patients had overt hypothyroidisim, and 25 (12.5%) had subclinical hypothyroidism. Exaggerated TSH response to TRH was revealed in 7 of the 26 patients with normal hormone values tested (26.9%). Antithyroglobulin and anti-thyroid peroxidase (TPO) antibody titers were negative in 191 patients (95.5%). Mean ferritin levels in hypothyroid and euthyroid patients were 2707.66 +/- 1990.5 mg/L and 2902.9 +/- 1997.3 mg/L, respectively, (p = 0.61), indicating no correlation between ferritin levels and thyroid functional status. Mean ferritin levels in the patients who responded normally to TRH stimulation and in those who overresponded, were 2,586 +/- 1791 mg/L and 3,228 +/- 2473 mg/L, respectively (p = 0.46; NS). Thyroid failure is a rather rare endocrine complication in patients with beta-thalassemic from Greece. In our series, no case of central hypothyroidism was observed. No correlation was found between thyroid functional status and ferritin plasma levels. Approximately 1 of 5 beta-thalassemic patients with normal thyroid hormone values showed an exaggerated TSH response to TRH test. It is to be investigated how many of these patients will establish overt or subclinical hypothyroidism in the future.

[Assessment of the influence of the Chernobyl nuclear disaster on incidence of thyroid diseases among children in Poland. Preliminary results]. / Ocena wplywu awarii jadrowej w czarnobylu na wystepowanie chorób tarczycy u dzieci w polsce. Wyniki wstepne.

It was attempted to assess the incidence of thyroid diseases in Polish children born between 1980-1986, who at the time of the Chernobyl nuclear disaster were 0-6 years old, or whose mothers were in the third trimester of pregnancy. 3071 children have been examined, 1772 girls and 1299 boys. The following were assessed in each child: the health status, the developmental level, the thyroid ultrasound examination, and the level of TSH, FT4, antithyroid antibodies ATM and ATGL in the blood serum. Disorders in thyroid morphology (abnormal echogenicity) have been found in 462 children (15%), almost twice as much in girls than in boys. Goiter has been recognized in 4.6% of all children, an abnormal echogenity in 5.4% and focal changes in 4.8%. 3.9% of children have been found to have a high level of ATM antibodies, and 8.7%--a high level of ATGL antibodies. Among 6 children, who had thyroidectomy, 2 children have been diagnosed to have ca papillary and 4 children--adenoma.

Immunohistochemical assessment of peroxidase-like immunoreactivity in the thyroid gland and its correlation with biochemical assay.

BACKGROUND: Peroxidase content has been recently evaluated in normal thyroid and in different thyroid disorders by biochemical, histochemical, ultrastructural and immunocytochemical methods. Nevertheless immunocytochemical detection of thyroid peroxidase in thyroid samples conventionally processed for histology has never been done using a commercially available antibody, neither its correlation with the biochemical activity on adjacent samples. METHODS: In this study we have analyzed normal thyroid tissue (3 patients), follicular adenoma (2 patients) and multinodular goiter (2 patients) conventionally processed for histology and stained by immunocytochemistry (Avidin Biotin System) using a polyclonal (rabbit) antibody for horseradish peroxidase (Serotec). Biochemical assay was performed on adjacent samples according to Hosoya method. RESULTS: Normal thyroid showed peroxidase immunoreactivity in the majority of follicular cells; neoplastic cells of adenomas were variably stained. Biochemical assay showed positive correlation with ICC ranging from 20.4 micrograms/mg/prot a in multinodular goiter to 42.12 in normal thyroid, up to 122 of follicular adenoma. CONCLUSIONS: Peroxidase content in the thyroid gland may be of clinical interest in several thyroid diseases, and in this study we have demonstrated that thyroid peroxidase can be detected by ICC in routinely processed thyroid samples using a commercially available antibody.

[Clinico-ultrasonographic assessment of the thyroid volume and function in chronic enteritis and colitis: preliminary data]. / Valutazione clinico-ecografica del volume e della funzione tiroidea nelle enteriti e coliti croniche: dati preliminari.

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) and ulcerative colitis (UC) have frequent extraintestinal (hepatobiliary, cutaneous, ocular, articular, urinary) complications. On the contrary, no data are available about possible thyroid involvement. We studied thyroid morphology and function in 39 patients affected with active IBD (13 UC; 26 CD) before (all) and 45 and 90 days after onset of therapy (21/39), and in 55 normal control subjects. Every time, the following exams were performed: thyroid US (parenchymal assessment, thyroid volume calculation), hormone and immunologic assays (T3, T4, FT3, FT4, TSH; antithyroglobulin and antithyroid microsomal/peroxidase antibodies). A statistically significant increase in thyroid volume was found in IBD (mean: 22.1 ml) compared to control subjects (mean: 15.6 ml), more frequently in CD (18/26 patients; 69.2%) than in UC (2/13 patients; 15.4%). Parenchymal structure was inhomogeneous in the two groups of patients (88.4% CD; 15.4% UC) more frequently than in control subjects (12.7%). Hormone assays demonstrated increased FT4 values in UC (9/13 patients; 69.2%) and decreased T4 values in CD (14/26 patients; 53.8%). IBD patients increased frequency of antithyroglobulin and antithyroid microsomal/peroxidase antibodies. Such abnormalities subsided only partially after therapy. Our data suggest that in IBD there is a frequent thyroid involvement with morphological, hormone, and immunologic abnormalities.

Experience with immunoglobulins in thyroid autoimmunity.

The physiopathology of Graves' ophthalmopathy is poorly understood. Therefore, the best treatment of Graves' ophthalmopathy is still a matter of debate. Steroids, X-ray therapy, surgery and more recently cyclosporine, plasma exchange and somatostatine analogs have been tried. There is no doubt that we are dealing with an autoimmune process. The use of immunoglobulins has been shown to be safe and efficient.

Assessment of antibody dependent cell cytotoxicity in autoimmune thyroid disease using porcine thyroid cells.

Antibody Dependent Cell Cytotoxicity (ADCC) appears to be involved in Autoimmune Thyroid Disease (AITD). Homologous system may trigger non-specific reactions which might obscure specific ADCC. Heterologous target cells may be useful for studying ADCC, provided relevant antigen(s) are expressed. We therefore tested the capacity of porcine thyroid cells to elicit ADCC reaction in the presence of sera from various patients with AITD. Porcine thyroid cells were used in a 4-hr chromium release assay in the presence of 1/10 heat inactivated human sera and human peripheral blood lymphocytes at a 30:1 effector-target ratio. There was a significant correlation (r = 0.64; P < 0.01) between ADCC activities tested on human or porcine thyroid cells. Serum or IgG effects on porcine thyroid ADCC were dose-dependent between 1/10 to 1/10,000 dilutions. Non-thyroid cell systems were unaffected by thyroid cytotoxic sera. Porcine thyrocyte susceptibility to ADCC peaked at the fourth day of culture and was enhanced by addition of TSH or TSH and methimazole in the culture medium. Using this heterologous system, we demonstrated ADCC activity in a significant proportion of patients with thyroiditis (14/19), Graves' opthalmopathy (19/44) or of mothers of children with congenital hypothyroidism (14/39) and in the children themselves (15/39). Discrepancies observed in some sera between ADCC activity and antithyroperoxidase antibody suggest that thyroperoxidase is not the only antigen involved in ADCC. These results indicate that porcine thyroid cells appear suitable for ADCC assay in patients with AITD. Also this system should be helpful to characterize the antigen-antibody involved.