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PubMedDate not supplied

Auto-immunity in certain thyroid diseases.

In the years 1971-74, 88 patients were admitted to the Department of Otorhinolaryngology of the Finsen Institute because of thyroid disease. In 37 of these patients, who had also been tested for antibodies against the thyroid, the diagnosis was confirmed histologically. The existence of circulating antibodies against thyroid tissue was found to reflect the degree of lymphocyte infiltration in the thyroid gland, and is thus of significance in the evaluation of the patients' prognosis and potential risk at surgery.

Autoantibodies↗
PubMed1996

Autoantibody against Na+/I- symporter in the sera of patients with autoimmune thyroid disease.

Using recombinant rat Na+/I- symporter (NaIS) protein, we have immunochemically searched for the autoantibody in the sera from patients with autoimmune thyroid disease. We found that 22 out of 26 sera (84%) from patients with Graves' disease and 3 out of 20 sera (15%) from patients with Hashimoto's thyroiditis recognized it. By Western blot, these IgGs reacted with 80 kDa protein in FRTL-5 cell membrane, which co-migrated with the band stained by rabbit antibody toward NaIS. These results indicate that autoantibody against NaIS, newly identified antibody, frequently exists in patients with autoimmune thyroid disease, especially in Graves' disease.

Animals↗
PubMed1991

Contemporary approach to thyroid disease emphasizing use of high-sensitivity thyrotropin assays.

Capabilities of new high-sensitivity immunoradiometric assays for thyroid-stimulating hormone (TSH-IRMA) to distinguish among hypothyroid, euthyroid, and hyperthyroid subjects and patient groups with low TSH for nonthyroidal causes suggested an algorithmic approach (directed TSH) to the evaluation of patients with suspected thyroid disease. Utilizing the algorithm, a TSH-IRMA result outside normal limits (0.5 to 5.0 mU/L) generates follow-up tests on the same sample. The interpretation of thyroid function tests (TSH-IRMA, thyroxine, resin uptake, free thyroxine index) and associated studies in the context of different clinical settings is reviewed. The approach is a cost-effective and efficient utilization of laboratory services.

Algorithms↗
PubMed2001

Differential regulation of Fas-mediated apoptosis in both thyrocyte and lymphocyte cellular compartments correlates with opposite phenotypic manifestations of autoimmune thyroid disease.

Several mechanisms are probably involved in determining the evolution of autoimmune thyroid disease (AITD) towards either hypothyroidism and the clinical syndrome known as Hashimoto's thyroiditis (HT) or toward hyperthyroidism and the symptoms of Graves' disease (GD). To gain further insight into such mechanisms we performed an exhaustive comparative analysis of the expression of key molecules regulating cell death (Fas, Fas ligand [FasL], Bcl-2) and apoptosis in both thyrocytes and thyroid infiltrating lymphocytes (TILs) from patients with either GD or HT. GD thyrocytes expressed less Fas/FasL than HT thyrocytes, whereas GD TILs had higher levels of Fas/FasL than HT TILs. GD thyrocytes expressed increased levels of the antiapoptotic molecule Bcl-2 compared to the low levels detected in HT thyrocytes. The opposite pattern was observed in GD (low Bcl-2) and HT (high Bcl-2) TILs. The patterns of apoptosis observed were consistent with the regulation of Fas, FasL, and Bcl-2 described above. Our findings suggest that in GD thyroid the regulation of Fas/FasL/Bcl2 favors apoptosis of infiltrating lymphocytes, possibly limiting their autoreactive potential and impairing their ability to mediate tissue damage. Moreover, the reduced levels of Fas/FasL and increased levels of Bcl-2 should favor thyrocyte survival and favor the thyrocyte hypertrophy associated with immunoglobulins stimulating the thyrotropin (TSH) receptor. In contrast, the regulation of Fas/FasL/Bcl2 expression in HT promotes thyrocyte apoptosis, tissue damage, and a gradual reduction in thyrocyte numbers leading to hypothyroidism. These findings help define key molecular mechanisms contributing to the clinical outcome of thyroid autoimmunity.

Adult↗
PubMed1992

Thyrotropin receptor antibodies: advances and importance of detection techniques in thyroid diseases.

The study of autoimmune thyroid disorders (AITD) has greatly contributed to our knowledge of autoimmunity. Graves' disease and Hashimoto's thyroiditis represent two ends of the range of autoimmune responses seen in AITD. Autoantibodies reactive to cytoplasmic antigens are associated with cell damage, and thyrotropin (TSH)-receptor antibodies (TRAb) influence the function and growth of the gland and play a major role in pathogenesis. The heterogeneous nature of TRAb is well accepted. Besides their long-known thyroid stimulating activity, TRAb can act as blocking antibodies or growth-promoting antibodies and, thus, cause hypothyroidism (primary myxedema) or endemic and sporadic goiters, respectively. Advanced methodologies for detection of these antibodies with the TSH-receptor assay and thyroid cell bioassay allow various activities to be measured. Current data using these assays confirm the presence of heterogeneity of functional activities of TRAb(s) in vivo. The activity of predominating antibody may relate to clinical presentation. This indicates a need for paired determinations of both TSH-binding inhibitory immunoglobulin (TBII) and thyroid-stimulating immunoglobulin (TSI) for accurate clinical correlations. Cloning the TSH-receptor gene has clarified its structure and function. The future identification of its epitopes will further delineate the clinical role of these antibodies and may allow development of new diagnostic and therapeutic approaches.

Animals↗
PubMed2004

Estimation of thyroid radiation doses for the hanford thyroid disease study: results and implications for statistical power of the epidemiological analyses.

Residents of eastern Washington, northeastern Oregon, and western Idaho were exposed to I released into the atmosphere from operations at the Hanford Nuclear Site from 1944 through 1972, especially in the late 1940's and early 1950's. This paper describes the estimated doses to the thyroid glands of the 3,440 evaluable participants in the Hanford Thyroid Disease Study, which investigated whether thyroid morbidity was increased in people exposed to radioactive iodine from Hanford during 1944-1957. The participants were born during 1940-1946 to mothers living in Benton, Franklin, Walla Walla, Adams, Okanogan, Ferry, or Stevens Counties in Washington State. Whenever possible someone with direct knowledge of the participant's early life (preferably the participant's mother) was interviewed about the participant's individual dose-determining characteristics (residence history, sources and quantities of food, milk, and milk products consumed, production and processing techniques for home-grown food and milk products). Default information was used if no interview respondent was available. Thyroid doses were estimated using the computer program Calculation of Individual Doses from Environmental Radionuclides (CIDER) developed by the Hanford Environmental Dose Reconstruction Project. CIDER provided 100 sets of doses to represent uncertainty of the estimates. These sets were not generated independently for each participant, but reflected the effects of uncertainties in characteristics shared by participants. Estimated doses (medians of each participant's 100 realizations) ranged from 0.0029 mGy to 2823 mGy, with mean and median of 174 and 97 mGy, respectively. The distribution of estimated doses provided the Hanford Thyroid Disease Study with sufficient statistical power to test for dose-response relationships between thyroid outcomes and exposure to Hanford's I.

Adolescent↗
PubMed2006

Incidental thyroid carcinoma in a large series of consecutive patients operated on for benign thyroid disease.

BACKGROUND: The diagnosis of incidental thyroid carcinoma (ITC) in patients operated on for a benign disease is frequent. This study aims to determine both its clinical effect and the possibility of identifying this class of patients preoperatively. METHODS: A total of 998 consecutive patients (697 women and 301 men; mean age, 49.5 years) undergoing surgery for benign thyroid pathology in a single institution were studied. The mean time between first diagnosis of thyroid disease and operation was 9.0 years (range, 0-50 years). All patients underwent at least one ultrasonography before surgery, and 678 patients underwent fine-needle aspiration cytology. Patients with undetermined cytology or follicular nodules were excluded from the study. RESULTS: Histology revealed an ITC in 104 patients (10.4%): 99 had a papillary carcinoma. Mean and median diameters of ITC were 1.4 and 0.7 cm, respectively (range, 0.1-7.5 cm). In 43 patients, the tumour size was greater than 1 cm, whereas it exceeded 2 cm in 25 patients. Tumours were multicentric in 19.8% of the patients and occurred in 8.2% of patients with nodular toxic goiter, 8.7% of patients with toxic diffuse goiter and 13.8% of patients with multinodular goiter. DISCUSSION: The results confirm the high frequency of ITC. ITC was more frequent in euthyroid patients than in thyrotoxic patients (P < 0.03). Sex, age, thyroid volume and interval between diagnosis and surgery did not significantly influence its incidence. The majority of ITC was represented by microcarcinomas, but in approximately 25% of patients, the tumour size was greater than 2 cm. The role played by FNAC in excluding malignancies proved to be fairly inconclusive.

Adolescent↗
PubMed1996

Lack of increased serum interleukin-6 and soluble IL-6 receptor concentrations in patients with thyroid diseases following recombinant human interferon alpha therapy.

BACKGROUND: Serum interleukin-6 (IL-6) concentrations are frequently elevated in inflammatory thyroid diseases, such as subacute thyroiditis and amiodarone induced thyroiditis. We and others have recently observed that recombinant interferon-alpha (rIFN-alpha) therapy for chronic, active viral hepatitis and malignant disorders may induce thyroid dysfunction, including thyrotoxicosis secondary to thyroiditis. Serum IL-6 and its soluble receptor (sIL-6R) have been measured for the first time in patients with chronic active hepatitis receiving rIFN-alpha therapy. METHODS: Studies were carried out in 37 patients treated with rIFN-alpha for chronic, active viral hepatitis. Thyroid function tests and serum IL-6 and sIL-6R were measured before and during rIFN-alpha therapy. RESULTS: Six patients developed inflammatory or destructive thyrotoxicosis confirmed by elevated serum free T4 or free T3 concentrations, suppressed serum thyroid-stimulating hormone (TSH) values, and a low thyroid radioactive iodine uptake. Serum IL-6 and sIL-6R concentrations were not elevated in these patients with rIFN-alpha-induced thyroiditis. CONCLUSIONS: These results suggest that serum IL-6 concentrations are not useful in differentiating between inflammatory thyrotoxicosis and hyperthyroidism induced by rIFN-alpha therapy as is the case in amiodarone-induced thyrotoxicosis. It is possible that rIFN-alpha therapy could be associated with an inhibitory effect of rIFN-alpha on the release of IL-6 from damaged thyroid cells and not on the basal secretion of IL-6.

Antigens, CD↗
PubMed1992

Use of recombinant epitopes to study the heterogeneous nature of the autoantibodies against thyroid peroxidase in autoimmune thyroid disease.

Microsomal antigen is often recognized by the sera from patients with autoimmune thyroid disease (AITD). Human thyroid peroxidase (hTPO) is the main component of this antigen. In a previous study, we expressed hTPO cDNA as fusion proteins in prokaryotic vector; we thereby defined seven antigenic peptides by using two rabbit polyclonal anti-hTPO antibodies. In the present study we used the seven epitopes and three widened peptides to define the reactivity pattern of 61 sera from patients with AITD. Thirty-eight of them reacted against at least one of the seven hTPO-restricted epitopes; 14 were negative against the seven determinants but recognized one or two of the extended peptides. Thus, the antibody response against hTPO appeared to be highly heterogeneous in AITD patient sera. Moreover, we demonstrated that the immunodetection of the hTPO on Western blotting with deoxycholate solubilized microsomes can be perfectly correlated with the recognition of one of the epitopes in the region 554-735.

Autoantibodies↗
PubMed1999

[Fine-needle aspiration biopsy in the diagnosis of nodular thyroid disease in children].

BACKGROUND: Fine-needle aspiration biopsy (FNAB) is a standard diagnostic procedure for adult patients with thyroid nodules. However, it is still controversial whether in pediatric patients thyroid nodules should be aspirated or excised. The aim of the study was to determine the usefulness of FNAB in clinical evaluation and follow up of children with nodular thyroid disease. MATERIAL AND METHODS: The study group comprised 36 children (33 girls and 3 boys) aged from 10 to 18 years (mean age 13.6 years) with nodular goiter. All children were in euthyreosis and their goiter size ranged from IAo to IIIo according to WHO criteria. In all the patients FNAB was performed and in 13 it was repeated after 4-8 months. RESULTS: Cytology of the first FNAB in 25 (69.5%) children showed colloid nodules, in 3 (8.3%)--carcinoma papillare, in 3 (8.3%)--neoplasma folliculare (NF), in 4 (11.1%)--Hashimoto thyroiditis and in 1 (2.8%)--thyroiditis granulosa de Quervaine. In one girl, in whom colloid nodule was cytologically diagnosed, FNAB was repeated after 4 months because of the nodule growth and change in the USG structure revealed papillary carcinoma. In one boy NF diagnosed in first biopsy was not confirmed in the second one (patient's parents refused the consecutive biopsy). All children with malignant or suspicious cytology and three with goiter size IIIo were operated and postoperative histopathological examination was performed. All colloid nodules were confirmed histopathologically, but in one patient with a large colloid goiter follicular adenoma was found. In two children with NF in cytology--follicular adenoma was found and in three patients with papillary carcinoma in FNAB--the diagnosis was confirmed. In all children in whom thyroid nodules did not expand in the volume, did not change their structure or regressed on USG, repeated FNAB confirmed the first diagnosis. CONCLUSIONS: 1. FNAB is useful in diagnosis and management of nodular thyroid disease in children. 2. Cytology of repeated biopsies of the nodules that decreased or did not increase in size confirms the primary diagnosis. 3. All children with thyroid nodules have to be carefully followed-up, and in case of nodule growth and/or change of the USG picture, repeated FNAB is necessary.

English Abstract↗
PubMed1993

Improved measurement of anti-thyroglobulin IgG in urine of patients with autoimmune thyroid diseases by sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay.

Previously, antithyroglobulin IgG was assayed in dialyzed urine from patients with autoimmune thyroid diseases by a sensitive enzyme immunoassay (immune complex transfer enzyme immunoassay), and most of the assay results were useful as a diagnostic aid for autoimmune thyroid diseases. However, dialysis of urine was laborious and time-consuming, and some results were less reliable due to low levels of anti-thyroglobulin IgG in urine. This paper describes some improvements of the assay. Useful assay results could be obtained for most of urine samples without dialysis, although some interfering substance(s) was suggested to be present in some urine samples before dialysis. Accurate assay results with no interference could be obtained after gel filtration by only two min centrifugation in place of dialysis. More reliable assay results for urine samples containing low levels of antithyroglobulin IgG were obtained after concentration using a molecular sieve.

Animals↗
PubMed2001

The management of thyroid disease by GPs.

BACKGROUND: Good medical practice depends on a collaborative relationship between a GP and a targeted specialist. OBJECTIVE: The aim of the present study was to assess knowledge and management by GPs of common endocrine disorders such as thyroid diseases. METHODS: We submitted to all the GPs (622) of the Province of Lecce an anonymous questionnaire with 11 questions which aimed to evaluate methods of approach to (questions 1 and 2) and knowledge about (questions 3-11) thyroid diseases. RESULTS: (i) Most GPs (72.1%) evaluate thyroid function on the basis of a clinical suspicion and perform preliminary investigations before referring the patient to a specialist. (ii) The ratio between right and wrong answers was significantly higher for four questions, significantly lower for one question and distributed by chance for four questions. (iii) The degree of knowledge strictly corresponds to the GP's attitude to patient's management. CONCLUSIONS: For a thyropathic patient to be diagnosed rapidly and treated efficiently, it is necessary to disseminate knowledge of standardized protocols to ensure a better utilization by both the GP and the endocrinologist of their respective competences.

Chi-Square Distribution↗
PubMed1986

Activated (Ia+) T-lymphocytes and their subsets in autoimmune thyroid diseases: analysis by dual laser flow microfluorocytometry.

Peripheral blood lymphocytes of patients with autoimmune thyroid diseases were studied using monoclonal antibodies reacting with cell surface antigens of activated T-cells (Ia+T), as well as their helper-inducer (Ia+TH/I) and suppressor-cytotoxic (Ia+TS/C) subsets, using two-color dye labeling and dual laser activated cell sorter analyses. Compared to normal subjects, hyperthyroid Graves' disease patients had significantly higher percent Ia+T values in association with an increase in percent Ia+TH/I as well as a reduction in percent Ia+TS/C; whereas patients with hypothyroid Hashimoto's thyroiditis as well as those with postpartum thyroiditis studied in the hyperthyroid phase also had a significant but lesser increase in percent Ia+T-cells, but their percent Ia+TH/I subset was significantly decreased, whereas the percent Ia+TS/C subset was increased; and patients with toxic nodular goiter or factitious hyperthyroidism (nonimmunogenic causes of hyperthyroidism) had a significant increase in percent Ia+T-cells without a significant difference in their Ia+T subsets or their ratios in comparison to controls. These studies demonstrated the feasibility of detecting Ia+T-cells and their subset characteristics using two-color dye labeling and dual laser flow microfluorocytometric methodology. In both the active and treated phases of Graves' disease, Hashimoto's thyroiditis, and postpartum thyroiditis, the percent Ia+T-cells was increased compared to normal subjects, with the highest values occurring in hyperthyroid Graves' disease. Furthermore, patients with hyperthyroid Graves' disease had the opposite changes in percent Ia+TH/I and Ia+TS/C subsets as compared to patients with either untreated hypothyroid Hashimoto's disease or the hyperthyroid phase of postpartum thyroiditis, suggesting that the pathogenic mechanisms involved in Hashimoto's disease and the destructive hyperthyroidism of painless thyroiditis are similar, and that they are both distinctly different from that of hyperthyroid Graves' disease.

Adult↗
PubMed1997

[Gene expression of thyrotropin receptor, thyroid peroxidase and thyroglobulin in autoimmune thyroid disease].

To investigate the expression of thyrotropin (TSH) receptor gene in autoimmune thyroid disease and the relationship with expression of thyroid peroxidase (TPO) and thyroglobulin (TG) genes, we examined TSH receptor, TPO and TG gene expression levels in 10 human thyroid tissues by Northern blot analysis, including 7 Graves disease (GD), 2 Hashimoto disease (HT), and 1 normal thyroid tissue. The expression levels of TSH-R gene and TG/TPO gene were different between GD group and HT group. In GD group, TSH-R gene expression was closely correlated to the expression of TPO gene (r = 0.882; P < 0.01) and TG gene (r = 0.723; P < 0.05). The gene expression levels in GD were higher than those in HT and control. In HT group, TPO, TG gene expression levels were relatively lower while TSH-R gene expression levels were still in normal range. The difference in gene expression is possibly related to the types of autoimmune antibodies and various dripping rates.

Adult↗