scholarly journals Increased levels of serum interleukin-12 in Graves' disease

1999 ◽  
pp. 111-116 ◽  
Author(s):  
M Tamaru ◽  
B Matsuura ◽  
M Onji
Keyword(s):  
Thyroid Hormone ◽  
Hashimoto’S Thyroiditis ◽  
Normal Subjects ◽  
Free Thyroxine ◽  
Hashimoto's Thyroiditis ◽  
Interleukin 12 ◽  
Graves Disease ◽  
Prolonged Stimulation ◽  
Hyperthyroid State

We investigated serum total interleukin-12 (IL-12) levels in patients with Graves' disease and Hashimoto's thyroiditis. The serum IL-12 levels in Graves' disease were significantly increased in the hyperthyroid state, and were decreased during treatment with methimazole or propylthiouracil in accordance with the decline of free tri-iodothyronine (T(3)) levels, free thyroxine levels and thyroid-binding inhibiting immunoglobulin (TBII) levels. When T(3) was administered orally to normal subjects, serum IL-12 levels were slightly increased. These results suggest that IL-12 might be increased due to prolonged stimulation with thyroid hormone, and thyroid hormone by itself might be a self-perpetuating factor of Graves' disease via increased IL-12 production.

scholarly journals Dendritic cells produce interleukin-12 in hyperthyroid mice

1999 ◽  
pp. 625-629 ◽  
Author(s):  
M Tamura ◽  
B Matsuura ◽  
S Miyauchi ◽  
M Onji
Keyword(s):  
Dendritic Cells ◽  
Thyroid Hormone ◽  
Mouse Model ◽  
Thyroid Hormones ◽  
Normal Subjects ◽  
Interleukin 12 ◽  
Graves Disease ◽  
Hyperthyroid State ◽  
Thyroid Glands

We previously reported that serum interleukin-12 (IL-12) levels were significantly increased in patients with hyperthyroid Graves' disease and in normal subjects after administration of thyroid hormone. In the present study, we investigated which cells produce IL-12 and the interactions between IL-12 and thyroid hormones, using a hyperthyroid mouse model. Thyroid hormones induced IL-12 production, and IL-12 was mainly produced by dendritic cells outside the thyroid glands in a hyperthyroid state.

Cellular and antibody mediated cytotoxicity in autoimmune thyroid disease

1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S133-S138 ◽  
Author(s):  
Ulrich Bogner ◽  
Jack R. Wall ◽  
Horst Schleusener
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Nk Cell ◽  
Cell Activity ◽  
Antithyroid Drug ◽  
Normal Subjects ◽  
Hashimoto's Thyroiditis ◽  
Target Cells ◽  
Graves Disease ◽  
Nk Cell Activity ◽  
Specific Lysis

Abstract. Antibody-dependent cell-mediated cytotoxicity (ADCC) and natural killer (NK) cell-mediated cytotoxicity was measured in patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) using a cytotoxicity assay against thyroid target cells. In the ADCC assay, mean ± sd specific lysis produced by sera from patients with HT was 21.7 ± 10% compared t 6.2 ± 3.9% from normal subjects. In the NK assay, cytotoxicity was significantly increased using lymphocytes from HT patients as effector cells. At effector: target (E:T) cell ratios of 50:1 and 25:1, mean specific lysis ± sd was 18.3 ± 14.3% and 14 ± 11.6%, respectively, compared to 3.7 ±2.1 and 3.1 ± 2.1, respectively, for normals. In Graves' disease, 9 of 19 patients had elevated cytotoxicity, whereas no significant changes of ADCC could be found either, as determined in thyrotoxic patients, after 6 months and at the end of a one-year antithyroid drug treatment. Eight of 19 patients showed normal cytotoxicity (mean % specific lysis 2.5 ± 3.1% compared to 2 ± 2.9% in normal controls) and low titres of microsomal antibodies (Mab), 3 patients had significantly increased cytotoxicity (mean specific lysis 27.6 ± 10%) in the presence of high titres of Mab, whereas 8 patients evidenced high values for cytoxicity (mean specific lysis 24.5 ± 14.1%) but low titres of Mab. NK cell activity, determined in euthyroid Graves' disease patients either under antithyroid drug therapy or in remission, was not significantly different than that of normal subjects at all E:T cell ratios. In conclusion, we demonstrated increased ADCC and NK cell activity in Hashimoto's thyroiditis but normal NK cell activity in euthyroid Graves' disease. Like in HT, ADCC is associated with titres of Mab in sera of Graves' disease patients but was also detectable in Mab-negative sera, which led us to suggest that a hitherto unknown cytotoxic antibody exists which is not measurable by passive haemagglutination for Mab.

scholarly journals Thyroid vascularity and blood flow are not dependent on serum thyroid hormone levels: studies in vivo by color flow doppler sonography

1999 ◽  
pp. 452-456 ◽  
Author(s):  
F Bogazzi ◽  
L Bartalena ◽  
S Brogioni ◽  
A Burelli ◽  
L Manetti ◽  
...  
Keyword(s):  
Blood Flow ◽  
Hashimoto’S Thyroiditis ◽  
Normal Subjects ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Toxic Adenoma ◽  
Color Flow ◽  
Color Flow Doppler Sonography ◽  
Hypothyroid Patients

OBJECTIVE: Thyroid blood flow is greatly enhanced in untreated Graves' disease, but it is not known whether it is due to thyroid hormone excess or to thyroid hyperstimulation by TSH-receptor antibody. To address this issue in vivo patients with different thyroid disorders were submitted to color flow doppler sonography (CFDS). SUBJECTS AND METHODS: We investigated 24 normal subjects, and 78 patients with untreated hyperthyroidism (49 with Graves' hyperthyroidism, 24 with toxic adenoma, and 5 patients with TSH-secreting pituitary adenoma (TSHoma)), 19 patients with thyrotoxicosis (7 with thyrotoxicosis factitia, and 12 with subacute thyroiditis), 37 euthyroid patients with goitrous Hashimoto's thyroiditis, and 21 untreated hypothyroid patients with Hashimoto's thyroiditis. RESULTS: Normal subjects had CFDS pattern 0 (absent or minimal intraparenchimal spots) and mean intraparenchimal peak systolic velocity (PSV) of 4.8+/-1.2cm/s. Patients with spontaneous hyperthyroidism due to Graves' disease, TSHoma, and toxic adenoma had significantly increased PSV (P<0.0001, P=0.0004, P<0.0001 respectively vs controls) and CFDS pattern. Patients with Graves' disease had CFDS pattern II (mild increase of color flow doppler signal) in 10 (20%) and pattern III (marked increase) in 39 cases (80%). Mean PSV was 15+/-3cm/s. Patients with toxic adenoma had CFDS pattern I (presence of parenchymal blood flow with patchy uneven distribution) in 2 (8%), pattern II in 16 (70%) and pattern III in 5 (22%). Mean PSV was 11+/-2.4cm/s. Patients with TSHoma showed CFDS pattern I in one case (20%) and pattern II in 4 (80%). Mean PSV was 14.8+/-4.2cm/s. Patients with thyrotoxicosis had normal PSV (4.2+/-1. 1cm/s in subacute thyroiditis, 4+/-0.8cm/s in thyrotoxicosis factitia, P=not significant vs controls) and CFDS pattern 0. Untreated euthyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern 0, and mean PSV (4.3+/-0.9cm/s; P=not significant vs controls). Untreated hypothyroid patients with goitrous Hashimoto's thyroiditis had CFDS pattern I in 14 cases (67%), pattern II in 4 (19%) and pattern 0 in 3 (14%) and mean PSV (5.6+/-1. 4cm/s) was higher than that of controls (P=0.026). CONCLUSIONS: An increase in both intrathyroidal vascularity and blood velocity was observed in patients with spontaneous hyperthyroidism but not in thyrotoxicosis due to either ingestion of thyroid hormones or to a thyroidal destructive process. The slightly increased vascularity and blood velocity observed in patients with hypothyroid Hashimoto's thyroiditis suggests that thyroid stimulation by either TSH-receptor antibody or TSH is responsible for the increased thyroid blood flow.

Assessment of thyroid growth stimulating activity of immunoglobulins from patients with autoimmune thyroid diseases by cytokinesis arrest assay

1997 ◽  
Vol 136 (5) ◽  
pp. 499-507 ◽  
Author(s):  
Shinichi Miyamoto ◽  
Kanji Kasagi ◽  
Mohammad Sayeedul Alam ◽  
Takashi Misaki ◽  
Yasuhiro Iida ◽  
...  
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Normal Subjects ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Autoimmune Thyroid Diseases ◽  
Thyroid Cells ◽  
Autoimmune Thyroid

Abstract Objective: To develop a novel bioassay for the assessment of thyroid cell growth stimulating activity using cytochalasin B (CB) and to test immunoglobulins (IgGs) from patients with autoimmune thyroid diseases. Design: The assay is based on the principle that growing cells during incubation with CB show an increased number of nuclei in a cell (N/C index), since CB. at appropriate concentrations, is known to inhibit cytoplasmic cleavage without affecting nuclear mitosis. The N/C index represents potential DNA production while cells are incubated with CB. Methods: FRTL-5 thyroid cells were incubated with various thyroid stimulators in TSH-free medium containing 2 mg/l CB for 3 days. After the incubation, the cells were harvested in trypsin/EDTA to obtain single cell suspension, fixed, dropped onto a glass slide, stained and observed under a microscope to determine the N/C index. Results: Bovine TSH at 10−3–1·0 U/l, forskolin at 1×10−7–10−5 mol/l, cholera toxin at 10×10−5–10−3 mg/l, or (Bu)2cAMP at 1× 10−5–10−3 mol/l increased the N/C index up to approximately 2·0 in a dose-dependent manner. IgGs not only from 27 patients with untreated goitrous Graves' disease but also from 14 patients with goitrous Hashimoto's thyroiditis elicited an increase in the N/C index, which exceeded the mean+2s.d. of the values for 17 normal subjects (mean ± s.d., 1·063 ±0.014). Four patients with primary myxedema displayed a normal N/C index. In Graves' disease, the N/C index did not correlate significantly with thyroid stimulating antibodies (TSAb) activities but did correlate significantly with estimated goiter size (P<0·05). IgGs containing blocking-type TSH-receptor antibodies inhibited the TSH- or Graves' IgG-stimulated increase in N/C index almost completely, but did not influence the stimulatory effect of IgG from two patients with Hashimoto's thyroiditis. Conclusions: We have developed a sensitive and simple assay for thyroid growth stimulating activity by using CB, and found that all tested patients with goitrous Graves' disease and goitrous Hashimoto's thyroiditis have thyroid growth stimulating immunoglobulins whose activity does not correlate with TSAb. European Journal of Endocrinology 136 499–507

Impact of the serum thyroglobulin concentration on the diagnostics of benign and malignant thyroid diseases

2000 ◽  
Vol 39 (05) ◽  
pp. 133-138 ◽  
Author(s):  
W. Dembowski ◽  
H.-J. Schroth ◽  
K. Klinger ◽  
Th. Rink
Keyword(s):  
Hashimoto’S Thyroiditis ◽  
Thyroid Volume ◽  
Nodular Goiter ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Normal Range ◽  
Serum Thyroglobulin ◽  
Diffuse Goiter ◽  
Hyperthyroid Patients

Summary Aim of this study is to evaluate new and controversially discussed indications for determining the thyroglobulin (Tg) level in different thyroid diseases to support routine diagnostics. Methods: The following groups were included: 250 healthy subjects without goiter, 50 persons with diffuse goiter, 161 patients with multinodular goiter devoid of functional disorder (108 of them underwent surgery, in 17 cases carcinomas were detected), 60 hyperthyroid patients with autonomously functioning nodular goiter, 150 patients with Hashimoto’s thyroiditis and 30 hyperthyroid patients with Graves’ disease. Results: The upper limit of the normal range of the Tg level was calculated as 30 ng Tg/ml. The evaluation of the collective with diffuse goiter showed that the figure of the Tg level can be expected in a similar magnitude as the thyroid volume in milliliters. Nodular tissue led to far higher Tg values then presumed when considering the respective thyroid volume, with a rather high variance. A formula for a rough prediction of the Tg levels in nodular goiters is described. In ten out of 17 cases with thyroid carcinoma, the Tg was lower than estimated with thyroid and nodular volumes, but two patients showed a Tg exceeding 1000 ng/ml. The collective with functional autonomy had a significantly higher average Tg level than a matched euthyroid group being under suppressive levothyroxine substitution. However, due to the high variance of the Tg values, the autonomy could not consistently be predicted with the Tg level in individual cases. The patients with Hashimoto’s thyroiditis showed slightly decreased Tg levels. In Graves’ disease, a significantly higher average Tg level was observed compared with a matched group with diffuse goiter, but 47% of all Tg values were still in the normal range (< 30 ng/ml). Conclusion: Elevated Tg levels indicate a high probability of thyroid diseases, such as malignancy, autonomy or Graves’ disease. However, as low Tg concentrations cannot exclude the respective disorder, a routine Tg determination seems not to be justified in benign thyroid diseases.

A sensitive method for assaying thyroid stimulating immunoglobulins of Graves' disease: use of the guanyl nucleotide-amplified thyroid adenylate cyclase assay

1983 ◽  
Vol 103 (3) ◽  
pp. 345-351 ◽  
Author(s):  
E. Macchia ◽  
P. Carayon ◽  
G. F. Fenzi ◽  
S. Lissitzky ◽  
A. Pinchera
Keyword(s):  
Adenylate Cyclase ◽  
Hashimoto’S Thyroiditis ◽  
Plasma Membranes ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Tissue Preparation ◽  
Thyroid Cells ◽  
Significant Stimulation ◽  
Adenylate Cyclase Stimulation ◽  
Sensitive Method

Abstract. The purpose of this study was to develop and validate a sensitive method for evaluating adenylate cyclase stimulation by thyroid-stimulating antibodies (TSAb), based on the measurement of thyroid membrane adenylate cyclase activity in the presence of a non-hydrolyzable GTP analogue, guanyl-5'-yl imidodiphosphate (Gpp(NH)p). The addition of Gpp(NH)p (10−5 m) produced a 10-fold increase of the sensitivity of the system for both TSH and TSAb. Immunoglobulin G preparations from sera of 30 patients with Graves' disease were tested for the adenylate cyclase stimulation either in the presence or in the absence of Gpp(NH)p: a significant stimulation was observed in 27/30 patients when the GTP analogue was added to the system, while only 20/30 patients were positive in the absence of the nucleotide. The advantage of Gpp(NH)p addition was also evident in a large series which included 57 patients with Graves' disease, 15 with Hashimoto's thyroiditis or primary myxoedema and 22 normal subjects. In fact, 88% of patients with Graves' disease resulted positive, while no significant stimulation was elicited by Hashimoto's thyroiditis, primary myxoedema and by normal immunoglobulins. The sensitivity achieved in our system which employs thyroid plasma membranes was similar to that obtained by other investigators with the use of thyroid slices or thyroid cells in primary culture. Furthermore, methods based on thyroid plasma membranes are supposed to have a better reproducibility, since the same tissue preparation, if appropriately stored, may be used in several different tests.

scholarly journals Defect of a subpopulation of natural killer immune cells in Graves’ disease and Hashimoto’s thyroiditis: normalizing effect of dehydroepiandrosterone sulfate

2005 ◽  
Vol 152 (5) ◽  
pp. 703-712 ◽  
Author(s):  
Sebastiano Bruno Solerte ◽  
Sara Precerutti ◽  
Carmine Gazzaruso ◽  
Eleonora Locatelli ◽  
Mauro Zamboni ◽  
...  
Keyword(s):  
Nk Cells ◽  
Hashimoto’S Thyroiditis ◽  
Nk Cell ◽  
Secretory Activity ◽  
Thyroid Diseases ◽  
Hashimoto's Thyroiditis ◽  
Graves Disease ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Tnf Α

Background: The study of the natural killer (NK) immune compartment could provide important findings to help in the understanding of some of the pathogenetic mechanisms related to autoimmune thyroid diseases (Graves’ disease (GD) and Hashimoto’s thyroiditis (HT)). Within this context, it was suggested that alterations in NK cell cytotoxicity (NKCC) and NK production of cytokines might occur in subjects with GD and HT, whereas the normalization of NK functions could potentially contribute to the prevention of the onset or the progression of both diseases. Objective: Due to the hypothesis of alterations in NK in autoimmune thyroid diseases, we were interested to evaluate NKCC in GD and HT patients and to modulate NK function and secretory activity with cytokines and dehydroepiandrosterone sulfate (DHEAS) in an attempt to normalize NK cell defect. Design: We studied 13 patients with recent onset Graves’ disease, 11 patients with Hashimoto’s thyroiditis at first diagnosis and 15 age-matched healthy subjects. Methods: NK cells were concentrated at a density of 7.75 × 106 cells/ml by negative immunomagnetic cell separation and validated by FACScan as CD16 + /CD56 + cells. NK cells were incubated with interleukin-2 (IL-2) and interferon-β (IFN-β) and co-incubated with DHEAS at different molar concentrations for measuring NKCC and the secretory pattern of tumor necrosis factor-α (TNF-α) from NK cells. Results: Lower spontaneous, IL-2- and IFN-β-modulated NKCC was demonstrated in GD and HT patients compared with healthy subjects (P < 0.001). A decrease in spontaneous and IL-2-modulated TNF-α release from NK cells was also found in both groups of patients (P < 0.001). The co-incubation of NK cells with IL-2/IFN-β + DHEAS at different molar concentrations (from 10−8 to 10−5 M/ml/NK cells) promptly normalized NKCC and TNF-α secretion in GD and HT patients. Conclusions: A functional defect of a subpopulation of NK immune cells, involving both NKCC and the secretory activity, was demonstrated in newly-diagnosed GD and HT patients. This defect can be reversed by a dose-dependent treatment with DHEAS. The impairment of NK cell activity in autoimmune thyroid diseases could potentially determine a critical expansion of T/B-cell immune compartments leading to the generation of autoantibodies and to the pathogenesis of thyroid autoimmunity.

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