Thyrostatic drugs act through modulation of thyroid cell activity to induce remissions in Graves' disease

1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S305-S311 ◽  
Author(s):  
Robert Volpé ◽  
Anders Karlsson ◽  
Rolf Jansson ◽  
Per Anders Dahlberg
Keyword(s):  
Immune System ◽  
Antigen Presentation ◽  
Thyroid Function ◽  
Cell Activity ◽  
Interferon Γ ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Thyroid Cell ◽  
Thyroid Autoantibodies ◽  
Organ Specific

Abstract. It has been proposed elsewhere that antithyroid drugs (ATD) bring about remissions in Graves' disease (GD) by directly suppressing the immune system. The decline in thyroid stimulating antibody (TSAb) and other thyroid autoantibodies, and the reduction in intra-thyroidal lymphocytes has been attributed to this effect, which has been considered to be via interference with oxidative reactions within the antigen-presenting cell. However, if ATD exert an immunosuppressive effect, one might expect that this would be a pharmacological action, paralleling the overall pharmacological effect of normalizing thyroid function. Moreover, there is evidence that in Hashimoto's thyroiditis (HT) thyroid autoantibodies do not decline as a result of such treatment. We propose herein that ATD act through modulation of thyroid cell activity, which in turn has an effect on the immune system so as to induce immunological remissions in GD. It has been shown that hyperthyroidism itself has a deleterious effect on generalized suppressor T (Ts) lymphocyte function which is additive to the organ-specific defect in Ts function. Normalization of thyroid function tends to normalize non-specific Ts function; suppression of the thyroid-specific helper T cell (Th) population is thus brought about, in that subset of patients who do not have a severe organ specific Ts defect. This results in a reduction of interferon γ production, as well as reduced Th stimulation of B lymphocytes to produce TSAb. The combined reduction of TSAb and interferon γ will then reduce thyroid antigen and HLA-DR expression, i.e. antigen presentation by the thyroid cell, as well as a further reduction in thyroid hormone production. The latter will further reduce Ts inhibition, reducing Th activity; reduced antigen presentation will also reduce Th activity. This beneficial cycle will then lead to remissions, except in those patients with a more severe organ specific Ts defect.

Graves' disease and radioiodine therapy

2008 ◽  
Vol 47 (04) ◽  
pp. 153-166 ◽  
Author(s):  
I. Weber ◽  
W. Eschner ◽  
F. Sudbrock ◽  
M. Schmidt ◽  
M. Dietlein ◽  
...  
Keyword(s):  
Success Rate ◽  
Thyroid Function ◽  
Therapeutic Dose ◽  
Radioiodine Therapy ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Inclusion Criteria ◽  
End Point ◽  
Point Measure ◽  
The Impact

SummaryAim: This study was performed to analyse the impact of the choice of antithyroid drugs (ATD) on the outcome of ablative radioiodine therapy (RIT) in patients with Graves' disease. Patients, material, methods: A total of 571 consecutive patients were observed for 12 months after RIT between July 2001 and June 2004. Inclusion criteria were the confirmed diagnosis of Graves' disease, compensation of hyperthyroidism and withdrawal of ATD two days before preliminary radioiodine-testing and RIT. The intended dose of 250 Gy was calculated from the results of the radioiodine test and the therapeutically achieved dose was measured by serial uptake measurements. The end-point measure was thyroid function 12 months after RIT; success was defined as elimination of hyperthyroidism. The pretreatment ATD was retrospectively correlated with the results achieved. Results: Relief from hyperthyroidism was achieved in 96 % of patients. 472 patients were treated with carbimazole or methimazole (CMI) and 61 with propylthiouracil (PTU). 38 patients had no thyrostatic drugs (ND) prior to RIT. The success rate was equal in all groups (CMI 451/472; PTU 61/61; ND 37/38; p=0.22). Conclusion: Thyrostatic treatment with PTU achieves excellent results in ablative RIT, using an accurate dosimetric approach with an achieved post-therapeutic dose of more than 200 Gy.

scholarly journals Differential Interactions between Th1/Th2, Th1/Th3, and Th2/Th3 Cytokines in the Regulation of Thyroperoxidase and Dual Oxidase Expression, and of Thyroglobulin Secretion in Thyrocytes in Vitro

Endocrinology ◽  
2008 ◽  
Vol 149 (4) ◽  
pp. 1534-1542 ◽  
Author(s):  
Sylvie Poncin ◽  
Benoit Lengelé ◽  
Ides M. Colin ◽  
Anne-Catherine Gérard
Keyword(s):  
Thyroid Function ◽  
Interferon Γ ◽  
Thyroid Cell ◽  
Dual Oxidase ◽  
Th1 Cytokine ◽  
Glandular Atrophy ◽  
Rat Thyroid ◽  
Th1 Cytokines ◽  
The Impact

Hypothyroidism, together with glandular atrophy, is the usual outcome of destructive autoimmune thyroiditis. The impairment in the thyroid function results either from cell destruction or from Th1 cytokine-induced alteration in hormonogenesis. Here, we investigated the impact of the local immune context on the thyroid function. We used two rat thyroid cell lines (PCCL3 and FRTL-5) and human thyrocytes incubated with IL-1α/interferon (IFN) γ together with IL-4, a Th2 cytokine, or with TGF-β, or IL-10, two Th3 cytokines. We first observed that IL-4 totally blocked IL-1α/interferon γ-induced alteration in dual oxidase and thyroperoxidase expression, and in thyroglobulin secretion. By contrast, TGF-β and IL-10 had no such effect. They rather repressed thyrocyte function as do Th1 cytokines. In addition, IL-4 blocked IL-10-induced repression of thyrocyte function, but not that induced by TGF-β. In conclusion, Th1 cytokine- and IL-10-induced local inhibitory actions on thyroid function can be totally overturned by Th2 cytokines. These data provide new clues about the influence of the immune context on thyrocyte function.

Different aetiologies in post-partum thyroiditis?

1983 ◽  
Vol 104 (2) ◽  
pp. 195-200 ◽  
Author(s):  
Per Anders Dahlberg ◽  
Rolf Jansson
Keyword(s):  
Thyroid Function ◽  
Autoimmune Thyroiditis ◽  
Thyroid Dysfunction ◽  
Post Partum ◽  
Lymphocytic Infiltration ◽  
Graves Disease ◽  
Thyroid Autoantibodies ◽  
Radioiodine Uptake ◽  
Thyroid Cytology

Abstract. During a 4 year period 19 women with post-partum onset of thyroid dysfunction have been seen in our clinic. Five women had high radioiodine uptake thyrotoxicosis (Graves' disease). Twelve women had hypothyroid symptoms starting within 3–6 months of delivery. All of these women had thyroid microsomal and/or cytoplasmic autoantibodies and thyroid lymphocytic infiltration suggesting aggravation of pre-existing subclinical autoimmune thyroiditis (Hashimoto's disease). At follow-up thyroid function gradually improved in all but signs of persistent thyroid hypofunction remained in seven. Thus women developing symptomatic postpartum hypothyroidism should be followed regularly and when thyroxine treatment is commenced in the post-partum period, it has to be continued indefinitely in many cases. Two women presented with transient low radioiodine uptake thyrotoxicosis and a small painless goitre. Thyroid cytology revealed thyroiditis but they had no thyroid autoantibodies. When followed after a succeeding delivery none of these women developed post-partum thyroid dysfunction in contrast to women in the autoimmune group. Probably the aetiology of thyroid dysfunction in these 2 women was different.

scholarly journals An Interleukin (IL)-10/IL-12 Immunoregulatory Circuit Controls Susceptibility to Autoimmune Disease

1998 ◽  
Vol 187 (4) ◽  
pp. 537-546 ◽  
Author(s):  
Benjamin M. Segal ◽  
Bonnie K. Dwyer ◽  
Ethan M. Shevach
Keyword(s):  
Immune System ◽  
Autoimmune Disease ◽  
Innate Immune System ◽  
Demyelinating Disease ◽  
Critical Role ◽  
Interferon Γ ◽  
Innate Immune ◽  
Th Cell ◽  
Organ Specific ◽  
Cytokine Networks

Cells of the innate immune system secrete cytokines early in immune responses that guide maturing T helper (Th) cells along appropriate lineages. This study investigates the role of cytokine networks, bridging the innate and acquired immune systems, in the pathogenesis of an organ specific autoimmune disease. Experimental allergic encephalomyelitis (EAE), a demyelinating disease of the central nervous system, is widely used as an animal model for multiple sclerosis. We demonstrate that interleukin (IL)-12 is essential for the generation of the autoreactive Th1 cells that induce EAE, both in the presence and absence of interferon γ. The disease-promoting effects of IL-12 are antagonized by IL-10 produced by an antigen nonspecific CD4+ T cell which, in turn, is regulated by the endogenous production of IL-12. This unique immunoregulatory circuit appears to play a critical role in controlling Th cell differentiation and provides a mechanism by which microbial triggers of the innate immune system can modulate autoimmune disease.

Effect of glucocorticoids and oestrogen on interleukin-6 production by human thyrocytes from patients with Graves' disease and toxic multinodular goitre and from HTori3 cells

1997 ◽  
pp. 429-432 ◽  
Author(s):  
TH Jones ◽  
RL Kennedy ◽  
SK Justice ◽  
R Davies
Keyword(s):  
Interleukin 6 ◽  
Interleukin 1 ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Thyroid Cell ◽  
Multinodular Goitre ◽  
Necrosis Factor Alpha ◽  
Serum Free ◽  
Thyroid Cell Culture ◽  
Serum Free Conditions

Interleukin-6 (IL-6) is a cytokine released by thyrocytes and is involved in disease processes such as autoimmune thyroid disease. The secretion of IL-6 can be stimulated by interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF), serum, TSH and agents which increase intracellular cyclic AMP levels. Antithyroid drugs such as methimazole inhibit IL-6 production by thyrocytes but the effects of glucocorticoids and oestrogen have not been investigated. The effects of dexamethasone and 17 beta-oestradiol on IL-1-, TNF-, TSH-, forskolin- and phorbol 12-myristate 13-acetate (PMA)-stimulated IL-6 release in serum-free conditions were studied in human thyrocytes derived from patients with Graves' disease and toxic multinodular goitres, and in the immortalised human thyrocyte cell line, HTori3. Dexamethasone inhibited IL-6 production under stimulated conditions. In serum-free conditions, no basal release of IL-6 was assayable. In all but one of the primary thyroid cultures, TSH did not stimulate IL-6 release above the lower detectable limit of the assay. In Graves' and multinodular goitre thyrocytes, inhibition of IL-1 (100 U/ml)-stimulated IL-6 release by dexamethasone (100 nmol/l) was 62.51% +/- 10.43 (S.E.M.), and in HTori3 cells it was 78.35% +/- 3.9. The degree of IL-1 stimulation of IL-6 release and inhibition by dexamethasone was not significantly different in thyrocytes derived from either Graves' or multinodular glands. 17 beta-Oestradiol had no effect on IL-1-stimulated IL-6 release in either primary thyroid cell culture or in HTori3 cells.

scholarly journals Differences in the Treatment Response to Antithyroid Drugs versus Electroconvulsive Therapy in a Case of Recurrent Catatonia due to Graves’ Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Takahiro Saito ◽  
Rie Saito ◽  
Hiroshi Suwa ◽  
Fumiatsu Yakushiji ◽  
Kenji Takezawa ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Treatment Response ◽  
Thyroid Function ◽  
Electroconvulsive Therapy ◽  
Physical Symptoms ◽  
First Episode ◽  
Antithyroid Drugs ◽  
Graves Disease

We reported a case which presented recurrent episodes of catatonia as a result of Graves’ disease with hyperthyroidism. The patient showed different treatment response in each episodes; in the first episode, psychiatric and physical symptoms were resolved by a combination of antithyroid and anxiolytic therapies, while in the second episode, the combination therapy did not ameliorate her symptoms and ECT was indicated. We postulated that decreased CSF level of TTR and the resulting susceptibility to the derangement of peripheral thyroid function might be involved in this different treatment response.

scholarly journals Myopathy Associated with Treatment of Graves’ Disease

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1016
Author(s):  
Yoon-Kyung Ji ◽  
Shin-Hee Kim
Keyword(s):  
Creatine Kinase ◽  
Adverse Reaction ◽  
Thyroid Function ◽  
Serum Creatine Kinase ◽  
Free Thyroxine ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Pediatric Case ◽  
Antithyroid Treatment

Here, we report a case of an increase in serum creatine kinase (CK) concentration in an 11-year-old girl being treated for Graves’ disease with antithyroid drugs (ATDs). The patient complained of myalgia two weeks after methimazole treatment. Triiodothyronine (T3) and free thyroxine (FT4) levels were normal, but the serum CK level was significantly elevated. After switching to propylthiouracil, the serum CK level decreased to normal, and the myalgia was resolved. The development of myopathy during the treatment of hyperthyroidism may be considered as an adverse reaction of MMI. In this report, we present a rare pediatric case, along with a discussion on the possible causes of myopathy that occurred during the treatment of Graves’ disease. A careful follow-up (serum CK levels and thyroid function) and treatment reassessment should always be considered after antithyroid treatment.

scholarly journals Management of Graves’ Disease during Pregnancy: The Key Role of Fetal Thyroid Gland Monitoring

2005 ◽  
Vol 90 (11) ◽  
pp. 6093-6098 ◽  
Author(s):  
Dominique Luton ◽  
Isabelle Le Gac ◽  
Edith Vuillard ◽  
Mireille Castanet ◽  
Jean Guibourdenche ◽  
...  
Keyword(s):  
Thyroid Gland ◽  
Thyroid Function ◽  
Thyroid Dysfunction ◽  
Tsh Receptor ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
Test Results ◽  
Bone Maturation ◽  
Normal Test ◽  
Fetal Thyroid

Abstract Background: Fetuses from mothers with Graves’ disease may experience hypothyroidism or hyperthyroidism due to transplacental transfer of antithyroid drugs (ATD) or anti-TSH receptor antibodies, respectively. Little is known about the fetal consequences. Early diagnosis is essential to successful management. We investigated a new approach to the fetal diagnosis of thyroid dysfunction and validated the usefulness of fetal thyroid ultrasonograms. Methods: Seventy-two mothers with past or present Graves’ disease and their fetuses were monitored monthly from 22 wk gestation. Fetal thyroid size and Doppler signals, and fetal bone maturation were determined on ultrasonograms, and thyroid function was evaluated at birth. Thyroid function and ATD dosage were monitored in the mothers. Results: The 31 fetuses whose mothers were anti-TSH receptor antibody negative and took no ATDs during late pregnancy had normal test results. Of the 41 other fetuses, 30 had normal test results at 32 wk, 29 were euthyroid at birth, and one had moderate hypothyroidism on cord blood tests. In the remaining 11 fetuses, goiter was visualized by ultrasonography at 32 wk, and fetal thyroid dysfunction was diagnosed and treated; there was one death, in a late referral, and 10 good outcomes with normal or slightly altered thyroid function at birth. The sensitivity and specificity of fetal thyroid ultrasound at 32 wk for the diagnosis of clinically relevant fetal thyroid dysfunction were 92 and 100%, respectively. Conclusion: In pregnant women with past or current Graves’ disease, ultrasonography of the fetal thyroid gland by an experienced ultrasonographer is an excellent diagnostic tool. This tool in conjunction with close teamwork among internists, endocrinologists, obstetricians, echographists, and pediatricians can ensure normal fetal thyroid function.

T lymphocyte subpopulations in Graves' disease: relationship with clinical conditions

1983 ◽  
Vol 102 (2) ◽  
pp. 213-219 ◽  
Author(s):  
M. Bagnasco ◽  
G. W. Canonica ◽  
S. Ferrini ◽  
P. Biassoni ◽  
G. Melioli ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Radioiodine Therapy ◽  
Cell Activity ◽  
Suppressor Cell ◽  
Lymphocyte Subpopulations ◽  
Antithyroid Drugs ◽  
Graves Disease ◽  
T Lymphocyte Subpopulations ◽  
Clinical Conditions

Abstract. T lymphocytes were franctionated according to their receptors for IgG (TG) or IgM (TM) and scored in 37 patients with Graves' disease (17 hyperthyroid and untreated, 10 euthyroid on antithyroid drugs, 10 in long-term remission after radioiodine therapy). TG percentages were very low both in untreated and in drugtreated patients. By contrast, normal TG levels were observed in patients in long-term remission. These data are consistent with the hypothesis of a defective suppressor cell activity in Graves' disease.

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