Effects of Antithyroid Therapy on the Long-Acting Thyroid Stimulator and the Antithyroglobulin Antibodies<sup>1</sup>

Pinchera, Aldo; Liberti, Paul A.; Martino, Enio; Fenzi, Gianfranco; Grasso, Lucia; Rovis, L; Baschieri, L; Doria, Gino

doi:10.1210/jcem-29-2-231

Cited by 110 publications

(34 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…01 versus IFNgCTNFa- thyrodectomy (Antonelli et al 2006b) or after treatment with 131 I (Antonelli et al 2007). Treatment with thionamidein AITDs, in addition to its effect on hormone synthesis, is accompanied by a gradual remission of the autoimmune aberration in the majority of patients (Pinchera et al 1969, Mc Gregor et al 1980, Laurberg 2006. A recent report describes a reduction in CXCL10 circulating levels in hyperthyroid patients with GD under MMI therapy (Antonelli et al 2006c).…”

Section: Discussionmentioning

confidence: 99%

Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes

Crescioli

Cosmi²,

Borgogni

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

CXC chemokine ligand 10 (CXCL10) plays a pivotal role in the self-perpetuation of the inflammatory processes in patients with autoimmune thyroid disease. Treatment with methimazole (MMI) reduces serum CXCL10 in patients with Graves' disease. In isolated human thyrocytes, tumor necrosis factor (TNF)a demonstrates a potent synergistic effect on interferon (IFN)g-induced CXCL10 secretion. We investigated the mechanism underlying the synergism between IFNg and TNFa and the effect of MMI on CXCL10 secretion in human thyrocytes. A peroxisome proliferatoractivated receptor g agonist, rosiglitazone (RGZ), a known inhibitor of T helper 1 (Th1)-mediated responses, was also studied for comparison. Experiments were carried out in human thyrocytes isolated from internodular parenchyma of thyroid tissues derived from patients who had undergone surgery for multinodular goiter. ELISA was used to measure CXCL10 levels in culture supernatant. Flow cytometry was used to assess IFNg membrane receptor expression. Specific mRNA analysis was performed by Taqman real-time PCR. Immunofluorescence was performed to detect nuclear translocation of nuclear factor-kB (NF-kB). In human thyrocytes, the synergistic effect of TNFa with IFNg on CXCL10 secretion is due to the upregulation of IFNg receptor expression. MMI decreased cytokine-induced CXCL10 secretion by reducing TNFa-induced upregulation of the IFNg receptor. RGZ decreased the cytokine-induced CXCL10 secretion by impairing NF-kB translocation, without affecting IFNg receptor. MMI and RGZ targeted thyrocytes with the same pharmacological potency, likely acting throughout different mechanisms. Targeting T helper 1-mediated autoimmune thyroid disease with drugs that impair different intracellular pathways could be a novel pharmacological tool.

show abstract

Section: Discussionmentioning

confidence: 99%

Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes

Crescioli

Cosmi²,

Borgogni

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…There remains controversy about the effects of thyroid antibodies on the outcome following RAI treatment (2,9,15,19). Since RAI treatment triggers a humoral (28) and possibly a cell-mediated autoimmune response within the thyroid gland, it is quite likely that the coexisting chronic thyroiditis represented by the presence of thyroid autoantibodies (29) contributes to the progressive development of hypothyroidism. Our study supports this concept and demonstrates the prognostic significance of the presence of thyroid antibodies on the development of hypothyroidism following RAI therapy.…”

Section: Factors Regression Coefficient (B )mentioning

confidence: 99%

Objective estimates of the probability of developing hypothyroidism following radioactive iodine treatment of thyrotoxicosis

Ahmad

Young

2002

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Several risk factors have been shown individually to influence the outcome following radioactive iodine (RAI) therapy in the treatment of hyperthyroidism. However, no attempt has been made to determine their independent prognostic values that could be used in a regression model to provide objective estimates of the probability of developing hypothyroidism. Study design and methods: We audited records of all hyperthyroid patients treated with first dose RAI between 1980 and 1996. Patients were aetiologically categorized into Graves' disease, solitary toxic nodule and toxic multinodular goiter. Following RAI, outcome was categorized as hypothyroidism, euthyroidism and persistent hyperthyroidism. Multiple logistic regression analysis was used to identify significant risk factors, their prognostic values and probability estimates of developing hypothyroidism in the presence of one or more of these factors. Results: The cumulative incidence of hypothyroidism was 55.8% at 1 year and 86.1% at 10 years. Graves' disease (odds ratio: 4.29), presence of thyroid autoantibodies (odds ratio: 3.51), no antithyroid treatment given prior to RAI (odds ratio: 2.50), non-palpable goiter (odds ratio: 2.48) and high RAI dose (odds ratio: 1.90), were identified as significant independent risk factors. We then developed a predictive table that provides objective estimates of developing hypothyroidism. In the absence of all risk factors we can predict an 11.9% probability of developing hypothyroidism; this increases linearly to a 96.4% probability in the presence of all factors. Conclusions: These objective estimates would help in understanding the relative contributions of the known risk factors, and to predict the probability of developing hypothyroidism following RAI treatment. This would not only help patients make an informed consent for a treatment that would lead to life-long replacement therapy but may also prove useful in calculating the RAI dose that may reduce or delay the onset of developing hypothyroidism.

show abstract

“…In addition to such a variation, it is well established that the therapy of hyperthyroidism may influence disease activity (6). During prolonged follow-up, TRAb tend to disappear from serum after all types of therapy for hyperthyroidism (8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study

Laurberg

Wallin²,

Tallstedt³

et al. 2008

European Journal of Endocrinology

359

231

View full text Add to dashboard Cite

Introduction: Autoimmunity against the TSH receptor is a key pathogenic element in Graves' disease. The autoimmune aberration may be modified by therapy of the hyperthyroidism. Objective: To compare the effects of the common types of therapy for Graves' hyperthyroidism on TSHreceptor autoimmunity. Methods: Patients with newly diagnosed Graves' hyperthyroidism aged 20-55 years were randomized to medical therapy, thyroid surgery, or radioiodine therapy (radioiodine was only given to patients R35 years of age). L-thyroxine (L-T 4 ) was added to therapy as appropriate to keep patients euthyroid. Anti-thyroid drugs were withdrawn after 18 months of therapy. TSH-receptor antibodies (TRAb) in serum were measured before and for 5 years after the initiation of therapy. Results: Medical therapy (nZ48) and surgery (nZ47) were followed by a gradual decrease in TRAb in serum, with the disappearance of TRAb in 70-80% of the patients after 18 months. Radioiodine therapy (nZ36) led to a 1-year long worsening of autoimmunity against the TSH receptor, and the number of patients entering remission of TSH-receptor autoimmunity with the disappearance of TRAb from serum during the following years was considerably lower than with the other types of therapy. Conclusion: The majority of patients with Graves' disease gradually enter remission of TSH-receptor autoimmunity during medical or after surgical therapy, with no difference between the types of therapy. Remission of TSH-receptor autoimmunity after radioiodine therapy is less common.

show abstract

Effects of Antithyroid Therapy on the Long-Acting Thyroid Stimulator and the Antithyroglobulin Antibodies¹

Cited by 110 publications

References 14 publications

Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes

Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes

Objective estimates of the probability of developing hypothyroidism following radioactive iodine treatment of thyrotoxicosis

TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study

Contact Info

Product

Resources

About

Effects of Antithyroid Therapy on the Long-Acting Thyroid Stimulator and the Antithyroglobulin Antibodies1

Cited by 110 publications

References 14 publications

Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes

Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes

Objective estimates of the probability of developing hypothyroidism following radioactive iodine treatment of thyrotoxicosis

TSH-receptor autoimmunity in Graves' disease after therapy with anti-thyroid drugs, surgery, or radioiodine: a 5-year prospective randomized study

Contact Info

Product

Resources

About

Effects of Antithyroid Therapy on the Long-Acting Thyroid Stimulator and the Antithyroglobulin Antibodies¹