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PubMed1989

Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6.

Cytokine production was studied in thyroid tissue from patients with Graves' disease, Hashimoto's thyroiditis and non-toxic goitre. The expression of interferon gamma, tumour necrosis factor alpha and beta, interleukin-1 alpha and beta, interleukin-6 and platelet-derived growth factor A chain was assessed by slot-blot analysis of the respective mRNA in freshly isolated tissue samples. All seven cytokines were detected in patients of all groups. Although the respective mRNA levels were, in general, higher in thyroid autoimmune disorders, this appeared to relate to the degree of the lymphocytic infiltration of the thyroid gland at the time of surgery. Purified thyroid follicular cells expressed high levels of interleukin-1 alpha and interleukin-6 mRNA and when established in primary culture, purified thyroid follicular cells from Graves' disease as well as non-toxic goitre produced interleukin-1 alpha and interleukin-6 bioactivity spontaneously. In the case of interleukin-1 this could be further augmented by addition of lipopolysaccharide to the thyroid follicular cell cultures. These results demonstrate that the lymphocytic infiltrate found in autoimmune and non-autoimmune thyroid disorders is associated with cytokine production. Additionally we have shown that intrathyroidal cytokine production is not restricted to thyroid-infiltrating mononuclear cells, but may also involve thyroid follicular cells both in vivo and in vitro. The cytokines produced by thyroid follicular cells may have an important role in stimulating autoantigen specific T cells in vivo as both interleukin-1 and interleukin-6 facilitate T cell activation.

Adult↗
PubMedDate not supplied

History of thyroid diseases and subsequent thyroid cancer risk.

A history of benign thyroid diseases has been associated with the risk of thyroid cancer. We have analyzed this issue using data from a case-control study conducted in northern Italy between 1986 and 1992 on 399 incident, histologically confirmed thyroid cancer cases and 617 controls admitted to the hospital for acute, nonneoplastic, non-hormone-related diseases. The overall multivariate relative risk (RR) estimates were 2.8 [95% confidence interval (CI), 0.6-12.4] for previous episodes of thyroiditis, 27.1 (95% CI, 6.5-111.9) for adenoma, 8.2 (95% CI, 3.5-19.1) for goiter, 3.8 (95% CI, 1.4-10.9) for hyperthyroidism, and 1.5 (95% CI, 0.4-5.1) for hypothyroidism when all histotypes were analyzed. The RR for any thyroid disease was 7.7 (95% CI, 4.6-12.8). A family history of thyroid disease was significantly related to thyroid cancer with an RR of 1.6. The RR for having resided in endemic goiter areas was 1.3 for < 20 years of residence and 1.6 for 20 or more years. These associations were somewhat stronger when only papillary, follicular, and mixed papillary/follicular cancers were considered. Analyses of data in separate strata of sex and age suggested that several benign conditions play a more important role in females and in subjects younger than 50 years. Results were similar to the overall ones when papillary and follicular carcinomas were considered separately. The population-attributable risk for any previous thyroid disease was approximately 20% in this Italian population. These results confirm that history of thyroid disease is a relevant indicator of subsequent thyroid cancer risk also in areas at relatively low prevalence of goiter and other thyroid diseases.

Adenocarcinoma, Follicular↗
PubMed1993

Rapidly progressive thyroid failure in Graves' disease after painful attack in the thyroid gland.

We studied a new type of Graves' disease: rapidly progressive thyroid failure after painful attack in the thyroid gland. Four women with the mean (+/- SD) age of 51 +/- 3.2 years had newly diagnosed hyperthyroid Graves' disease. A severe painful episode developed in the thyroid glands of two patients and permanent hypothyroidism occurred spontaneously within 2 or 3 months thereafter. Two to three episodes of pain developed in the thyroid glands of the other two patients during antithyroid drug therapy. There was a transient rise in serum thyrotropin level after each painful episode and permanent hypothyroidism developed 6 to 8 months after the initial painful attack. The clinical picture is characterized by moderate to severe pain in the thyroid gland with tenderness. Patients responded to steroid or anti-inflammatory therapy. During painful attack, increased or normal thyroid radioiodine uptake, elevated levels of C-reactive protein, and an elevated erythrocyte sedimentation rate were found, but there was no cytological evidence of subacute thyroiditis. After painful attack, serum thyroid stimulation antibody began to decrease in three of the patients while thyroid stimulation blocking antibody developed in one patient. This is a rapid and self-destructive process of the Graves' thyroid gland, which appears to be associated with painful attack in the thyroid gland.

Autoantibodies↗
PubMed1993

[Management of the cold thyroid nodule and thyroid malignancy].

The evaluation and management especially of cold thyroid nodules remains an area of controversy. The past decade has witnessed two important advances. The increased availability of fine-needle aspiration of thyroid nodules has altered the clinician's approach to this disease, and provides for the single most precise method for selecting appropriate patients for surgery. The introduction of high-resolution thyroid ultrasonography provides for anatomic definition that is clearly superior to thyroid scintigraphy. However, radionuclide imaging remains critical for determining the functional status of abnormal thyroid tissue. This review attempts to provide a practical approach to the evaluation and management of the thyroid nodule. Only rare data exists concerning the therapeutic approach of cold thyroid nodules and non-toxic nodular goitre. There seems to be a size-reducing effect by thyroxin-treatment, but no data are reported from iodine deficient areas. Concerning the treatment of differentiated thyroid carcinoma total thyroidectomy combined with eradication of remaining thyroid tissue with iodine 131 is usually preferred. In case of smaller or occult carcinoma various modes of uni- or bilateral subtotal resection are used. Chemotherapy is of little use in treating differentiated thyroid carcinoma and remains as a last possibility if usual approaches are no longer effective. To control local-invasive growth of anaplastic thyroid carcinoma combined treatment with mitoxantrone and hyperfractionated irradiation seems to be a successful approach.

Biopsy, Needle↗
PubMed2000

Comparing thyroid ultrasonography to thyroid function in long-term survivors of childhood lymphoma.

BACKGROUND: We studied the value of thyroid ultrasonography as a follow-up tool in survivors of childhood lymphomas and correlated morphologic abnormalities with thyroid function tests. PROCEDURE: A prospective follow-up study of 45 long-term survivors of histology-proved childhood lymphomas was performed. Mean age at diagnosis was 9.1 years (range 2.1-16.4 years) and mean follow-up duration 10.9 years (range 3.9-22.2 years). RESULTS: Among the 26 survivors of Hodgkin disease (HD) who received mantle field irradiation, 14 (54%) had abnormal ultrasonograms. Elevated thyroid-stimulating hormone (TSH) concentrations were found in 14 (54%), and 6 of them (42%) had normal thyroid functions. Six of twelve patients with normal ultrasonograms had abnormal thyroid function, and 5 of 11 patients with normal function had abnormal sonograms. Among the 19 non-HD survivors who did not receive radiotherapy, 18 (95%) had both normal sonograms and normal function. Thus thyroid gland abnormalities were detected in 54% of HD survivors after mantle field irradiation. No correlation between the abnormalities detected on ultrasonography and serum levels of TSH and thyroid hormones were found. CONCLUSIONS: Both ultrasound and thyroid function tests independently provide clinically useful information; the former examines gland morphologogy and the latter evaluates hormonal changes associated with thyroid disease. The high frequency of thyroid abnormalities detected by ultrasonography suggests that periodic thyroid ultrasonography is advisable in the follow-up of patients treated with mantle irradiation to screen for morphologic changes that may presage malignant transformation.

Adolescent↗
PubMed2001

Lysophosphatidic acid, a novel lipid growth factor for human thyroid cells: over-expression of the high-affinity receptor edg4 in differentiated thyroid cancer.

Lysophosphatidic acid (LPA) is a small lipid mediator with pleiotropic biological activities, e.g., the regulation of cellular proliferation and various aspects of cellular physiology. Signal transduction is achieved by binding to 2 high-affinity receptors, EDG2 and EDG4, and a group of low-affinity receptors, EDG1-7, all belonging to the superfamily of G protein-coupled receptors. We examined the growth-regulatory effects of LPA in primary cultures of 8 goiters and 1 papillary thyroid cancer. We further assessed mRNA expression of high-affinity receptors EDG2 and EDG4 in 14 normal thyroids, 29 papillary thyroid cancers, 7 follicular thyroid cancers and 13 goiters by quantitative RT-PCR. We also identified mRNA expression of phospholipase A(2) and LPA acyltransferase in fresh thyroid tissues derived from various sources. At concentrations of 10, 50 and 150 microM, LPA induced a 2-fold rise of proliferation (p < 0.001) and acted as strongly as thyrotropin. The combination of LPA and TSH produced significant synergistic effects compared with each substance alone (p < 0.05). Normal thyroid, goiter and papillary or follicular thyroid cancer expressed 2 high-affinity cognate LPA receptors, EDG2 and EDG4. EDG4 receptor mRNA expression was increased 3-fold in differentiated thyroid cancer (p < 0.01), both papillary (p < 0.01) and follicular (p < 0.05), compared to normal thyroid or goiter. Overall expression of EDG2 receptor was unchanged in malignancy; however, increased EDG2 expression in individual samples correlated with lymphonodular metastasis (p = 0.01). Thus, lipid mediators are a novel class of factors involved in the control of proliferation in the human thyroid. Altered mRNA expression of the high-affinity LPA receptor EDG4 suggests a role in the pathogenesis of differentiated thyroid cancer.

Acyltransferases↗
PubMed1989

Autologous CD8-positive cells suppress T cell proliferation in response to thyroid antigens in Hashimoto's thyroiditis.

To assess whether there is a defect in thyroid antigen-specific suppressor cells in Hashimoto's thyroiditis (HT) and whether such cells actively prevent thyroid autoreactivity in control subjects, T cell proliferation was measured before and after removal of CD8-positive cells from the lymphocyte population. CD8 depletion significantly increased the proliferation of HT lymphocytes to soluble thyroglobulin and to thyroid microsomal antigen immunoblotted onto nitrocellulose; some of these cultures also reacted with an unidentified thyroid antigen, mol wt approx 16 kDa. However, CD8 depletion did not permit normal lymphocytes to respond to thyroid antigens. Peripheral blood CD8 cells were also found to suppress proliferation of a thyroid T cell line, derived from a patient with HT, in response to autologous, Ia-positive thyroid follicular cells. These results do not support the existence of a defect in antigen-specific suppressor cells in HT, nor the active suppression of thyroid autoreactivity by such cells in normal subjects. The data suggest that there may be an imbalance in T cell helper and suppressor influences in thyroiditis, but in some patients a new balance is achieved, so that T cell sensitization to thyroid autoantigens can only be identified by removal of CD8-positive cells.

Adult↗
PubMed1989

Thyroid autoantigens and their relevance in the pathogenesis of thyroid autoimmunity.

Humoral and cellular immune responses are both involved in autoimmune disorders of the thyroid gland. In the last five years, new substantial data have been obtained on the nature and the expression of thyroid cell surface autoantigens and on the demonstration of the functional heterogeneity of autoantibodies to the thyroid stimulating hormone (TSH) receptor. In the present report, attention will be mainly focused on recent studies carried out in our laboratory. The main autoantigens so far identified include the 'microsomal' antigen, thyroglobulin and the TSH receptor. For many years the 'microsomal' antigen (M) was considered a poorly characterized constituent of the cytoplasm of the thyroid cell. In the last five years, several lines of evidence were provided indicating that M is also well represented on the surface of the follicular cell and is identical to thyroid peroxidase (TPO). The use of anti-TPO monoclonal antibodies, presently available, have confirmed this antigenic identity. Microsomal (anti-TPO) antibodies are very useful markers of autoimmune thyroid disorders and are generally present in Hashimoto's thyroiditis, idiopathic myxedema and Graves' disease. TSH receptor antibodies (TRAb) are present in the sera of patients with Graves' disease. TRAb are able to stimulate thyroid adenylate cyclase and also to mimic TSH in its thyroid growth stimulation. Thus, these antibodies may have a pathogenetic role in goiter formation and in thyroid hyperfunction in Graves' disease. TRAb were also shown to inhibit both TSH binding to its receptor and TSH-stimulated adenylate cyclase activity. Recently TRAb, which inhibited TSH-stimulated adenylate cyclase activity, were found in idiopathic myxedema patients and may be responsible for impairment of thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantigens↗
PubMed2000

Differential nuclear and cytoplasmic expression of PTEN in normal thyroid tissue, and benign and malignant epithelial thyroid tumors.

Germline mutations in PTEN (MMAC1/TEP1) are found in patients with Cowden syndrome, a familial cancer syndrome which is characterized by a high risk of breast and thyroid neoplasia. Although somatic intragenic PTEN mutations have rarely been found in benign and malignant sporadic thyroid tumors, loss of heterozygosity (LOH) has been reported in up to one fourth of follicular thyroid adenomas (FAs) and carcinomas. In this study, we examined PTEN expression in 139 sporadic nonmedullary thyroid tumors (55 FA, 27 follicular thyroid carcinomas, 35 papillary thyroid carcinomas, and 22 undifferentiated thyroid carcinomas) using immunohistochemistry and correlated this to the results of LOH studies. Normal follicular thyroid cells showed a strong to moderate nuclear or nuclear membrane signal although the cytoplasmic staining was less strong. In FAs the neoplastic nuclei had less intense PTEN staining, although the cytoplasmic PTEN-staining intensity did not differ significantly from that observed in normal follicular cells. In thyroid carcinomas as a group, nuclear PTEN immunostaining was mostly weak in comparison with normal thyroid follicular cells and FAs. The cytoplasmic staining was more intense than the nuclear staining in 35 to 49% of carcinomas, depending on the histological type. Among 81 informative tumors assessed for LOH, there seemed to be an associative trend between decreased nuclear and cytoplasmic staining and 10q23 LOH (P = 0.003, P = 0.008, respectively). These data support a role for PTEN in the pathogenesis of follicular thyroid tumors.

Cell Nucleus↗
PubMed1984

Evidence that thyroid-stimulating antibody is produced in the thyroid gland.

The hyperthyroidism in Graves' disease results from the action of thyroid-stimulating antibodies (TSAb). The thyroid gland in Graves' disease shows diffuse lymphocytic infiltration, and after removal of the gland antibody titres usually decline and patients go into remission. It is postulated that the lymphocytes in the thyroid may be an important site of TSAb production. 10 patients with Graves' disease and 8 patients with other thyroid disorders were studied. Blood was taken during operation, but before thyroid mobilisation, from the thyroid vein and simultaneously from a peripheral vein. In patients with Graves' disease the concentration of TSAb activity in the thyroid vein was much greater than that in the peripheral vein. TSAb was not detected in either peripheral vein or thyroid vein samples in the other patients. The increase in TSAb concentration in the thyroid vein indicates production of antibodies by lymphocytes within the thyroid and could explain why removal of the thyroid results in disappearance of TSAb from the circulation.

Adult↗
PubMed1998

Expression of alpha- and beta-subunits and activity of Na+K+ ATPase in pig thyroid cells in primary culture: modulation by thyrotropin and thyroid hormones.

Na+ K+ ATPase located at the basolateral pole of thyroid epithelial cells, contributes to thyroid hormone synthesis by generating the driving force for the uptake of the substrate, iodide. We have investigated whether the expression of the alpha- and beta-subunits and activity of Na+ K+ ATPase were subjected to variations in response, (a) to TSH, that controls the expression of differentiation in thyroid cells and (b) to thyroid hormones as potential autocrine factors. Studies were carried out on pig thyroid cells cultured (a) without TSH to obtain thyroid cell monolayers (TCM) in basal state or (b) with TSH in the form of cell monolayers (TCM-T) or as reconstituted thyroid follicles (RTF). Iodide uptake activity, thyroperoxidase protein and thyroglobulin mRNA taken as parameters of thyroid cell differentiation were 6 to 25-fold higher in RTF and TCM-T than in TCM. Western blot analyses of Na+ K+ ATPase subunits revealed that the alpha-subunit (105 kDa) content of TCM-T and RTF was similar but 8-fold higher than that of TCM. In contrast, the beta-subunit (50 kDa) content of TCM-T and RTF was only about twice that of TCM. Similar relative variations were observed at the mRNA level for both alpha- and beta-subunits. Na+ K+ ATPase activity was only 40% higher in RTF and TCM-T than in TCM. A 48 h treatment of RTF by either T4 or T3 (1-100 nM) induced a 3-fold increase of the alpha-subunit but did neither alter the beta-subunit nor the Na+ K+ ATPase activity. In conclusion, Na+ K+ ATPase activity and the level of expression of its beta-subunit, known to control the assembly and targetting of alpha-beta oligomers and thus the amount of functional sodium pump at the plasma membrane, are only moderately altered when thyroid cells undergo major changes in their differentiation status. Our data show that the expression of the alpha-subunit of Na+ K+ ATPase by thyroid cells is up-regulated by TSH and thyroid hormones.

Animals↗
PubMed1998

Coexistent thyroiditis is associated with lower tumour stage in thyroid carcinoma.

BACKGROUND: Microsatellite instability (MSI) is a new mechanism described in carcinogenesis of several tumours and seems to predispose for cancer in some chronic inflammatory diseases. As thyroiditis is thought to be both the cause and the consequence of thyroid carcinoma, it was the aim of this retrospective study to investigate the epidemiology and the influence of a coexistent thyroiditis on prognosis and clinicopathological parameters in an iodine-deficient area. METHODS: The grade of lymphocytic infiltration (LI) of 153 thyroid carcinomas was determined in paraffin-embedded tissues: G0 = no LI, G1 = peritumoral LI, G2 = peritumoral LI with follicle, G3 = diffuse LI. A non-radioactive PCR-based screening method was used for detection of MSI. RESULTS: Twenty-seven (17.7%) out of 153 carcinomas were accompanied by thyroiditis (G1, 16; G2, 5; G3, 6). Ten cases fulfilled the criteria necessary for diagnosing Hashimoto's thyroiditis. Nine out of 10 (90%) Hashimoto's cases and 16 out of 17 (94%) other thyroiditis cases were associated with a significantly (chi2 < 0.01) lower pT stage (pT1, pT2) than cases without thyroiditis. No statistical association was found by comparing multifocality or sclerosing variants with the grade of lymphocytic infiltration. MSI was detected neither in patients with severe inflammation nor in the absence of thyroiditis. CONCLUSIONS: MSI does not seem to play a role in the pathogenesis of thyroid carcinoma. Coexistent thyroiditis is associated with a lower pT stage and thus could be an indicator of a better prognosis.

Adult↗
PubMed1996

Effect of L-thyroxine administration on antithyroid antibody levels, lipid profile, and thyroid volume in patients with Hashimoto's thyroiditis.

The changes in the serum thyroid autoantibodies, antithyroglobulin (TgAb) and antithyroid-peroxidase (TPOAb), lipid profile, and thyroid volume following L-thyroxine (L-T4) therapy is still a controversial matter. We studied 23 patients with goiter due to Hashimoto's thyroiditis; 10 had clinical hypothyroidism (CH) and 13 had subclinical hypothyroidism (SH). Both groups received L-T4 (2.0 to 2.5 micrograms/kg/day) for a median period of 6 months. Serum concentration of TgAb (normal value: < 200 mUI/mL) and TPOAb (normal value: < 150 mUI/mL) were measured by a sensitive IRMA using 125I protein-A. Thyroid volume was determined by ultrasound (normal value: 8-14 mL). At the end of the observation period the median serum TSH concentration decreased significantly in both groups (42.9 to 0.55 in CH and 2.4 to 0.74 mU/L in SH patients) and serum FT4I levels increased only in the CH group (0.87 to 2.1; p < 0.05). Serum TgAb concentration did not change in SH patients (72 to 218 mUI/mL) but declined in CH patients (364.5 to 75 mU/mL; p < 0.05). TPOAb levels also fell in the CH group (871 to 194 mUI/mL; p < 0.05) and no significant change was noted in SH patients (260 to 116 mUI/mL). Further, a significant correlation was obtained between TSH and either TPOAb concentration (rs = 0.569, p < 0.01) or thyroid volume (rs = 0.488, p < 0.05) in the CH group but not in SH patients (rs = 0.232, NS). LDL-cholesterol was higher in the CH (159.4 mg/dL) compared with the SH group (116 mg/dL). Moreover, only in the CH patients was there a significant fall in total cholesterol (224.5 to 165.5 mg/dL, p < 0.05) and in LDL-cholesterol (159.4 to 104.3 mg/dL, p < 0.05) values. The thyroid volume decreased in all patients with CH and in 77% (10/13) of SH patients and a significant median in the thyroid volume decrease was found (39.7% of initial volume in the CH group and 80.9% in SH patients; p < 0.01). The influence of L-T4 on both thyroid autoantibody levels and thyroid volume might be explained by reduction of antigenic substance through a decreased stimulation of thyroid tissue by circulating TSH as was seen in CH but not in SH patients. The benefits of the administration of L-T4 replacement therapy in SH patients due to Hashimoto's thyroiditis remain to be clarified.

Adolescent↗
PubMed2005

Controversial ectopic thyroid: a case report of thyroid tissue in the axilla and benign total thyroidectomy.

A 43-year-old woman presented with a mass in her left axilla, which was surgically excised. Histologically, the tissue was a reactive lymph node with adjacent thyroid follicular tissue. The differential diagnosis included benign ectopic thyroid versus metastatic well-differentiated follicular-derived thyroid carcinoma. Because of the possibility of carcinoma, the patient underwent a diagnostic total thyroidectomy. The thyroid was grossly normal with no histologic evidence of malignancy. Post-operatively, the patient underwent a whole body 131I scan. Aside from an expected residual uptake in the thyroid bed region, there was no extrathyroidal uptake to suggest additional ectopic thyroid tissue or metastatic disease. At the time of this scan, her thyrotropin (TSH) was 92.8 microU/mL, thyroglobulin was less than 0.3 ng/mL, and thyroglobulin antibody was less than 3 IU/mL. Abnormalities in the embryologic development and migration of the thyroid gland can result in ectopic thyroid tissue. The most frequent locations are along the midline from the base of the tongue to the mediastinum. Only rare case reports exist of ectopic thyroid in other locations, including the chest (heart, trachea), abdomen (liver, gallbladder, pancreas), and pelvis (vagina). This case represents the first description of thyroid tissue in the axilla with a histologically benign thyroid gland.

Adult↗
PubMed2004

Estimating individual thyroid doses for a case-control study of childhood thyroid cancer in Bryansk Oblast, Russia.

Following the Chernobyl accident, radioactive fission products, including (131)I and (137)Cs, were deposited in Bryansk Oblast in Russia. Intakes of radioiodines, mainly (131)I in milk, were the principal sources of radiation doses to thyroids of residents of the contaminated areas, but those radionuclides decayed before detailed contamination surveys could be performed. As a result, (137)Cs deposition density is the primary measure of the contamination due to the accident and there are relatively few measurements of the ratio of (131)I to (137)Cs in vegetation or soil samples from this area. Although many measurements of radiation emitted from the necks of residents were performed and used to estimate thyroidal (131)I activities and thyroid doses, such data are not available for all subjects. The semi-empirical model was selected to provide a dose calculation method to be applied uniformly to cases and controls in the study. The model was developed using dose estimates from direct measurements of (131)I in adult thyroids, and relates settlement average thyroid doses to (137)Cs contamination levels and ratios of (131)I to (137)Cs. This model is useful for areas where thyroid monitoring was not performed and can be used to estimate doses to exposed individuals. For application to children in this study, adjustment factors are used to address differences in age-dependent intake rates and thyroid dosimetry. Other individual dietary factors and sources (private/public) of milk consumed are reflected in the dose estimates. Countermeasures that reduced thyroid dose, such as cessation of milk consumption and intake of stable iodine, are also considered for each subject. The necessary personal information of subjects was obtained by interview, most frequently of their mothers, using a questionnaire developed for the study. Uncertainties in thyroid dose, estimated using Monte Carlo techniques, are presented for reference conditions. Thyroid dose estimates for individual children made using the semi-empirical model and questionnaire data compare reasonably well with dose estimates made for 19 children whose thyroid burdens of (131)I were measured from May to June 1986.

Animals↗
PubMed1979

Evidence for thyroid antigen-reactive T lymphocytes infiltrating the thyroid gland in Graves' disease.

We have investigated the relative distribution and some in vitro functions of thyroid-infiltrating immunocompetent cells obtained at fine-needle aspiration biopsy in twelve patients with Graves' disease and thirteen patients with Hashimoto's thyroiditis. In both disorders the predominant (57--59%) thyroid-infiltrating cell was a small lymphocyte. Significant numbers of plasma cells (10%) were seen only in Hashimoto's thyroiditis. Mononuclear phagocytes (monocytes plus macrophages) were present in similar numbers (12--18%) in both disorders. In both Graves' and Hashimoto's disease there was a relative reduction of (thymus-dependent) lymphocytes in the thyroid gland as compared to the blood. Blood and thyroid-infiltrating T lymphocytes were tested for in vitro cell-mediated immunity (CMI) to thyroid antigen in the leucocyte migration inhibition test (LMT). CMI was readily demonstrated in the blood of most patients with Graves' and Hashimoto's disease. When the thyroid-infiltrating lymphocytes were tested for CMI in the LMT, only the infiltrating cells from patients with Graves' disease displayed CMI, whereas the thyroid-infiltrating lymphocytes in Hashimoto's disease were negative. Fractionation of the immunocompetent cells demonstrated that the thyroid antigen-induced LMT response of blood and thyroid-infiltrating lymphocytes in Graves' disease is a T lymphocyte-dependent phenomenon.

Adolescent↗
PubMed1981

Thyroxine and triiodothyronine levels in thyroid vein blood and in thyroid tissue of patients with autonomous adenomas.

Thyroxine (T4) and triiodothyronine (T3) concentrations were measured in peripheral and thyroid vein blood and in nodular and extranodular thyroid tissue from twenty-four patients with autonomous thyroid nodules (AFTN); fifteen of these patients showed clinical signs of hyperthyroidism and nine were euthyroid. Thirteen patients with solitary non-functioning thyroid adenomas who were clinically euthyroid, served as controls; samples of thyroid vein blood and normal thyroid tissue being obtained from the contralateral lobe. T4 (189.4 +/- 27.2 nmol/l) and T3 (7.05 +/- 2.03 nmol/l) concentrations were significantly higher in the thyroid vein blood of patients with AFTN compared with controls (T4 = 119 +/- 9.1 nmol/l, P less than 0.05; T3 = 2.3 +/- 0.21 nmol/l, P less than 0.01) whereas peripheral levels in the two groups were similar. The T3 concentrations (10.56 +/- 4.12 nmol/g wet tissue) in autonomously-functioning thyroid nodular tissue were significantly higher than those of extranodular (1.9 +/- 0.62 nmol/g wet tissue, P less than 0.01) and normal thyroid tissue (2.63 +/- 0.43 nmol/g wet tissue, P less than 0.05). The T4 levels were not different in the tissues examined. The concentrations of T4 and T3 in thyroid vein blood did not show any significant correlation with the hormone levels in thyroid tissue.

Adenoma↗
PubMed2005

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

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

Adolescent↗