Antithyroid Drug Treatment Research Articles

MON-621 A Second Course of Antithyroid Drug Therapy Is Effective in Patients with Relapsed Graves' Disease

Background: Antithyroid drugs (ATDs) are preferred as a first-line treatment for Graves’ disease (GD). However, around 50-60% of patients relapse following treatment withdrawal. Radioactive iodine (RAI) or thyroidectomy is recommended for these patients, however, repeat ATD therapy is a further option, dependent upon patient choice. The long-term efficacy of ATD in relapsed GD has not been robustly established. Methods: We conducted a retrospective study to assess the prognosis after a second course of ATD and investigate the clinical predictors for remission. Consecutive ATD-treated GD patients with at least three years of follow-up who attended our endocrine service since 2004 were identified and medical records analysed. Remission was defined as maintaining a euthyroid status for at least one year after ATD withdrawal. Results: 219 patients underwent an initial course of ATD therapy. A total of 129 patients (59%) relapsed upon treatment withdrawal after a mean time of 2.0 ± 2.7 years (range 0-15 years). Seventy-two (58%) patients (70% female, age at diagnosis 43.7 ± 15.0 years) opted for a second course of ATD. Eight patients were lost to follow-up. During 6.1 years (range 1.5-11.7 years) median follow-up, 24 patients (38%) achieved remission, 29 patients (45%) relapsed and 17% (n=11) continued ATD treatment. Male gender (RR=1.88, CI 1.21-2.91) and presence of a large goitre (RR=2.07, CI 1.42-3.02) were independent risk factors for relapse. A higher free T4 level at the time of relapse (mean fT4 36.2 ± 20.7 pmol/L vs. 29.6 ± 14.3 pmol/L) was also suggestive of increased risk of relapse following second ATD therapy (p=0.05). Age, smoking status and orbitopathy did not show significant association. Conclusion: A second course of ATD therapy results in a satisfying long-term remission rate (38%) in GD patients. The best outcomes are in females presenting with lower fT4 level on relapse in the absence of a large goitre.

Quality of Life Is Worse at 6-10 Years after Radioactive Iodine Treatment of Graves’ Disease as Compared with Antithyroid Drugs or Surgery

Quality of Life Is Worse at 6-10 Years after Radioactive Iodine Treatment of Graves’ Disease as Compared with Antithyroid Drugs or Surgery

Primary Cilium in the Human Thyrocyte: Changes in Frequency and Length in Relation to the Functional Pathology of the Thyroid Gland.

Primary cilia (PC) are conserved structures in the adult thyroid gland of different mammals. It was recently described that in humans, PC are usually present as a single copy per follicular cell emerging from the follicular cell apex into the follicular lumen. To understand the role developed by PC in thyroid hormonogenesis better, their changes in different human functional thyroid diseases (diffuse toxic hyperplasia/Graves' disease [GD] and nodular hyperplasia [NH]/nodular goiter), in comparison to normal thyroid tissue, were investigated using immunofluorescence, morphometry, and electron microscopy analyses. Significantly decreased ciliary frequencies were found in both NH (51.16 ± 11.69%) and GD (44.43 ± 23.70%) compared to normal thyroid tissue (76.09 ± 7.31%). Similarly, PC lengths were also significantly decreased in both NH (2.02 ± 0.35 μm) and GD (2.4 ± 0.48 μm) compared to normal glands (3.93 ± 0.90 μm). Moreover, in GD patients, hyperactive-follicle foci always showed diminished ciliary frequency and length compared to any other thyroid follicle pattern, independent of their thyroid status. Finally, in GD, the percentage of thyrocytes exhibiting PC in the "normal-appearance areas" was significantly lower in correspondence with the subsistence of signs of thyroid biosynthetic hyperactivity after long-term antithyroid drug treatment. The results suggest a direct relationship between ciliogenesis and both follicle activity and tissue heterogeneity in the functional pathology of the thyroid gland.

Factors suggesting relapse of Grave's disease after first radioiodine therapy. Analysis of 607 cases.

Despite the effectiveness of radioiodine therapy (RIT), a few patients are refractory and show relapse, warranting repeated RIT (RRIT). The purpose of this study is to explore the risk factors for RRIT. We retrospectively analyzed 607 cases treated with iodine-131 (131I) between January 2013 and June 2016. Patients were categorized into two groups: RRIT (n=76) or non-RRIT (n=531). Univariate analysis and a final multivariate model were used to determine the risk factors for RRIT. P<0.05 indicated significance. After a mean 314.5MBq dose of 131I, 76 patients underwent secondary therapy. In the univariate analysis, the differences in terms of age, gender, family history of hyperthyroidism, course of disease, 24-hour 131I uptake, curve shape of 131I uptake, dose of 131I, thyroid peroxidase antibody, and thyrotrophin receptor antibody were not statistically significant (P>0.05). Anti-thyroid drug (ATD) treatment history, thyroid mass and dose of 131I were statistically significant (P values: 0.001, <0.001 and <0.001, respectively). Binary logistic analysis of factors that lead to repeated RIT showed a higher probability of ATD treatment history [OR=2.919, 95%CI (1.424, 5.982), P=0.003] and thyroid mass [OR=1.042, 95%CI(1.031, 1.052), P<0.001] associated with RRIT. Patients treated with ATD before radioiodine treatment and with larger thyroid mass are at a higher risk for repeated radioiodine treatment.

Novel Association between Flavin-Containing Monooxygenase 3 Gene Polymorphism and Antithyroid Drug-Induced Agranulocytosis in the Han Population

Some effective antithyroid drugs (ATDs) have been widely used for patients with Graves’ disease (GD) but are associated with ATD-induced agranulocytosis. We selected 29 ATD-induced agranulocytosis patients, 44 ATD-induced neutropenia patients, and 140 GD controls among the Chinese Han population who were recruited at the First Affiliated Hospital of Xi’an Jiao Tong University. We assessed their response to ATDs treatment by performing genotyping for a candidate gene association study of samples from patients receiving treatment. Human flavin-containing monooxygenase 3 (FMO3), which is the major hepatic enzyme involved in the production of N-oxide of trimethylamine, catalyzes the oxygenation of a variety of drug compounds. Six single SNP, genotype, haplotype (HAP), and association analyses of the FMO3 gene with ATD-induced agranulocytosis/neutropenia under different models (i.e., additive, dominant, and recessive models) were performed. Rs1736557, which caused an amino acid variation V257M, showed a strong association between ATD-induced agranulocytosis and GD controls after Bonferroni correction (p = 0.011, OR 2.301, 95% CI 1.201–4.409). The presence of HAP 3 (HAP3) in the FMO3 gene HAP was statistically associated with ATD-induced agranulocytosis (p = 0.038, permutation p value). Our findings indicate that genetic variations in the FMO3 gene are associated with the response to ATDs maintenance treatment in ATD-induced agranulocytosis patients of ­Chinese Han population.

Follicular cell lineage in persistent ultimobranchial remnants of mammals.

It has been a subject of much debate whether thyroid follicular cells originate from the ultimobranchial body, in addition to median thyroid primordium. Ultimobranchial remnants are detected in normal dogs, rats, mice, cattle, bison and humans and also in mutant mice such as Eya1 homozygotes, Hox3 paralogs homozygotes, Nkx2.1 heterozygotes and FRS2α2F/2F. Besides C cells, follicular cell lineages immunoreactive for thyroglobulin are located within these ultimobranchial remnants. In dogs, the C cell complexes, i.e., large cell clusters consisting of C cells and undifferentiated cells, are present together with parathyroid IV and thymus IV in or close to the thyroid lobe. In addition, follicular cells in various stages of differentiation, including follicular cell groups and primitive and minute follicles storing colloid, are intermingled with C cells in some complexes. This review elaborates the transcription factors and signaling molecules involved in folliculogenesis and it is supposed why the follicular cells in the ultimobranchial remnants are sustained in immature stages. Pax8, a transcription factor crucial for the development of follicular cells, is expressed in the fourth pharyngeal pouch and the ultimobranchial body in human embryos. Pax8 expression is also detected in the ultimobranchial remnants of Eya1 and Hes1 null mutant mice. To determine whether the C cells and follicular cells in the ultimobranchial remnants consist of dual lineage cells or are derived from the common precursor, the changes of undifferentiated cells in dog C cell complexes are examined after chronically induced hypercalcemia or antithyroid drug treatment.

Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy

BackgroundGraves' disease (GD) is an autoimmune thyroid disorder caused by antibodies stimulating the thyrotropin (TSH) receptor. TSH receptor antibody (TRAb) measurement is useful for predicting GD relapse after antithyroid drug (ATD) treatment. However, the association of other thyroid autoantibodies with GD relapse remains obscure.MethodsThis retrospective study enrolled patients with GD who were initially treated with ATD. TRAb, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) were measured at the initial diagnosis and at the time of ATD discontinuation.ResultsA total of 55 patients were enrolled. The mean age was 49.7 years, and 39 patients (70.9%) were female. Antibody positivity at diagnosis was 90.9%, 69.1%, and 61.9% for TRAb, TPOAb, TgAb, respectively. Median ATD treatment period was 15.1 months. At the time of ATD withdrawal, TRAb titers decreased uniformly overall. Conversely, TPOAb and TgAb showed various changes. After withdrawal of ATD, 19 patients (34.5%) experienced relapse. No clinical features or laboratory results were significantly related to relapse in the overall patient group. However, in the TPOAb positive group at diagnosis, increasing titer of TPOAb or TgAb after ATD treatment was significantly and independently related to relapse free survival (TPOAb: hazard ratio [HR], 17.99; 95% confidence interval [CI], 1.66 to 195.43; P=0.02) (TgAb: HR, 5.73; 95% CI, 1.21 to 27.26; P=0.03).ConclusionChanges in TPOAb or TgAb titers during treatment might be useful for predicting relapse after ATD treatment in patients with positive TPOAb at diagnosis.

99mTc-pertechnetate thyroid scintigraphy predicts clinical outcomes in personalized radioiodine treatment for Graves’ disease

ObjectiveThe aim of this study was, first, to ascertain the efficacy of radioiodine therapy (RIT) for Graves’ disease (GD) based on a calculated-dose regime and, second, to determine the value of 99mTc-pertechnetate thyroid scintigraphy in predicting the clinical outcomes of RIT. MethodsOne hundred and thirty nine consecutive GD patients who underwent RIT using a calculated-dose method in our hospital from January 2015 to September 2015 were retrospectively evaluated. Radioiodine dose was calculated based on the Marinelli's formula. 99mTc-pertechnetate uptake, age, gender, thyroid mass, duration of the disease, previous antithyroid drugs treatment, serum levels of TSH, FT3 and FT4, a positive rate of TPOAb and Anti-TRAb, radioiodine dose and follow-up were evaluated as potential interference factors for RIT success. ResultsOne hundred and eight (77.7%) GD patients including 71 (51.1%) euthyroid and 37 (26.6%) hypothyroid were successful, but 31 (22.3%) remained hyperthyroid (treatment failure). Significant differences were found between the treatment success group and the failure group in 99mTc-pertechnetate uptake (p<0.0001), the duration of disease (p=0.0140) and positive rate of Anti-TRAb (p=0.0103). 99mTc-pertechnetate uptake is an independent risk factor for predicting treatment failure (p=0.0394). Using a cut-off value of 18.4%, 99mTc-pertechnetate uptake could predict treatment failure with a sensitivity of 84.3%, and a specificity of 80.6%. ConclusionOur study has shown that a calculated radioiodine dose is effective in treating GD patients with a consequent low rate of hypothyroid. A 99mTc-pertechnetate uptake above 18.4% is a significant predictor of treatment failure and these patients should receive a higher radioiodine dose in this scenario.

Antithyroid drug treatment for Graves' disease: baseline predictive models of relapse after treatment for a patient-tailored management.

Antithyroid drugs (ATDs) are first-line treatment for Graves' hyperthyroidism worldwide, but relapses are frequent. The reliability of individual risk factors to predict at baseline subsequent relapse is poor. Predictive scores grouping single risk factors might help to select the best treatment (pharmacological vs. ablative). To assess the predictivity of a recently developed score (Clinical Severity Score, CSS) and to compare it with another score (GREAT score). A retrospective observational, single-center study was conducted of 387 consecutive, newly diagnosed Graves' patients, who completed an 18-24months ATD course and were followed for at least 2years. Hyperthyroidism relapsed in 185 patients (48%). At diagnosis and before treatment, the relapse group had higher serum TSH-receptor antibody and free thyroxine levels and larger goiters than the remission group, with no differences in Graves' orbitopathy prevalence and severity. In the multivariate analyses, only large goiter size was significantly associated with an increased recurrence hazard ratio. Using CSS, the risk of relapse increased from 36% in the mild category and 49% in the moderate category to 59% in the severe category, with quite a good area under the curve (AUC) (0.60; 95% CI: 0.55; 0.66). GREAT score showed an increase in relapse from 34% for class I (mild) and 49% for class II (moderate) to 64% for class III (severe) (AUC, 0.63; CI: 0.58; 0.68). Both CSS and GREAT score are useful, although imperfect, tools to predict at baseline relapse of hyperthyroidism after treatment. In real life they may help the clinician to tailor a treatment for newly diagnosed Graves' hyperthyroidism.

Deficiency of type 2 iodothyronine deiodinase reduces necroptosis activity and oxidative stress responses in retinas of Leber congenital amaurosis model mice.

Thyroid hormone (TH) signaling has been shown to regulate cone photoreceptor viability. Suppression of TH signaling with antithyroid drug treatment or by targeting iodothyronine deiodinases and TH receptors preserves cones in mouse models of retinal degeneration, including the Leber congenital amaurosis Rpe65-deficient mice. This work investigates the cellular mechanisms underlying how suppressing TH signaling preserves cones in Rpe65-deficient mice, using mice deficient in type 2 iodothyronine deiodinase (Dio2), the enzyme that converts the prohormone thyroxine to the active hormone triiodothyronine (T3). Deficiency of Dio2 improved cone survival and function in Rpe65-/- and Rpe65-deficiency on a cone dominant background ( Rpe65-/-/ Nrl-/-) mice. Analysis of cell death pathways revealed that receptor-interacting serine/threonine-protein kinase (RIPK)/necroptosis activity was increased in Rpe65-/-/ Nrl-/- retinas, and Dio2 deficiency reversed the alterations. Cell-stress analysis showed that the cellular oxidative stress responses were increased in Rpe65-/-/ Nrl-/- retinas, and Dio2 deficiency abolished the elevations. Similarly, antithyroid drug treatment resulted in reduced RIPK/necroptosis activity and oxidative stress responses in Rpe65-/-/ Nrl-/- retinas. Moreover, treatment with T3 significantly induced RIPK/necroptosis activity and oxidative stress responses in the retina. This work shows that suppression of TH signaling reduces cellular RIPK/necroptosis activity and oxidative stress responses in degenerating retinas, suggesting a mechanism underlying the observed cone preservation.-Yang, F., Ma, H., Butler, M. R., Ding, X.-Q. Deficiency of type 2 iodothyronine deiodinase reduces necroptosis activity and oxidative stress responses in retinas of Leber congenital amaurosis model mice.

Alemtuzumab-Induced Thyroid Dysfunction Exhibits Distinctive Clinical and Immunological Features

ContextAlemtuzumab, a highly effective treatment for multiple sclerosis (MS), predisposes to Graves disease (GD), with a reportedly indolent course.ObjectiveTo determine the type, frequency, and course of thyroid dysfunction (TD) in a cohort of alemtuzumab-treated patients with MS in the United Kingdom.DesignCase records of alemtuzumab-treated patients who developed TD were reviewed.ResultsA total of 41.1% (102 out of 248; 80 female and 22 male) of patients developed TD, principally GD (71.6%). Median onset was 17 months (range 2 to 107) following the last dose, with the majority (89%) within 3 years. Follow-up data (range 6 to 251 months) were available in 71 case subjects, of whom 52 (73.2%) developed GD: 10 of these (19.2%) had fluctuating TD. All 52 patients with GD commenced antithyroid drugs (ATDs): 3 required radioiodine (RAI) due to ATD side effects, and drug therapy is ongoing in 2; of those who completed a course, 16 are in remission, 1 developed spontaneous hypothyroidism, and 30 (64%) required definitive or long-term treatment (RAI, n = 17; thyroidectomy, n = 5; and long-term ATDs, n = 8). Three cases of thyroiditis and 16 cases of hypothyroidism were documented: 5 with antithyroid peroxidase antibody positivity only, 10 with positive TSH receptor antibody (TRAb), and 1 of uncertain etiology. Bioassay confirmed both stimulating and blocking TRAb in a subset of fluctuating GD cases.ConclusionsContrary to published literature, we recorded frequent occurrence of GD that required definitive or prolonged ATD treatment. Furthermore, fluctuating thyroid status in GD and unexpectedly high frequency of TRAb-positive hypothyroidism suggested changing activity of TRAb in this clinical context; we have documented the existence of both blocking and stimulating TRAb in these patients.

A Validated Tool Can Predict Risk or Nonrisk of Graves’ Orbitopathy During Antithyroid Drug Treatment of Hyperthyroid Graves’ Disease

A Validated Tool Can Predict Risk or Nonrisk of Graves’ Orbitopathy During Antithyroid Drug Treatment of Hyperthyroid Graves’ Disease

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves' disease.

Antithyroid drugs are generally selected as the first-line treatment for Graves’ Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 47 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves’ disease than in control subjects (P<0.005) and were significantly reduced after medical treatment for Graves’ disease. High serum s(P)RR levels were associated with resistance to antithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves’ disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves’ disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss.

Hepatotoxicity in hyperthyroid patient after consecutive methimazole and propylthiouracil therapies

SummaryMethimazole (MMI) and propylthiouracil (PTU) are widely used antithyroid drugs (ATD) that have been approved for the treatment of hyperthyroidism. Hepatotoxicity may be induced by these drugs, though they exert dissimilar incidence rates of hepatotoxicity and, possibly, with different underlying pathogenic mechanisms. We report the case of a 55-year-old woman with no relevant medical history diagnosed with hyperthyroidism due to Graves’ disease, who developed two episodes of acute hepatitis concurrent with the consecutive administration of two different ATDs, first MMI and then PTU. Given the impossibility of administering ATDs, it was decided to perform a total thyroidectomy because the patient was found to be euthyroid at that point. Pathological anatomy showed diffuse hyperplasia and a papillary thyroid microcarcinoma of 2 mm in diameter. Subsequent clinical check-ups were normal. This case suggests the importance of regular monitoring of liver function for hyperthyroid patients. Due to the potential severity of this side effect, it is recommended to determine baseline liver function prior to initiation of treatment.Learning points:We present a rare case of two acute hepatitis episodes concurrent with two different consecutive ATD therapies.Our results highlight the relevance of a liver function monitoring during the treatment with MMI or PTU.A baseline assessment of the liver function before starting an ATD treatment should be recommendable.

Fluctuating thyroid function in an infant born to mother with Graves' disease: To treat or not to treat

Graves' disease (GD) in pregnancy is common, and management is often challenging during pregnancy and postpartum. Antithyroid drugs (ATDs) cross the placenta and inhibit fetal thyroid hormone production, whereas anti-thyrotropin receptor antibody (TRAb) cross the placenta and stimulate thyroid hormone production and last longer than ATDs in neonate's circulation (3–12 weeks vs. 7–10 days). The resultant clinical presentation, therefore, depends on the age of the child and the balance between the opposing effect of ATD and TRAb. We present a case of an infant born to a mother with active GD, on ATD treatment who presented with diagnostic and therapeutic dilemma. We performed masterly inactivity as his thyrotropin levels sequentially changed from elevated at birth to suppressed at 1 month age to stable after 3 months onward. Knowledge of natural history and pathogenesis of alteration of thyroid function test in an infant born to mothers of GD on carbimazole are essential for appropriate management.

Elevated Serum IL-17 Expression at Cessation Associated with Graves' Disease Relapse.

Background Antithyroid drug (ATD) treatment occupies the cornerstone therapeutic modality of Graves' disease (GD) with a high relapse rate after discontinuation. This study aimed to assess potential risk factors for GD relapse especially serum interleukin-17 (IL-17) expression. Methods Consecutive newly diagnosed GD patients who were scheduled to undergo ATD therapy from May 2011 to May 2014 were prospectively enrolled. Risk factors for GD relapse were analyzed by univariate and multivariate Cox proportional hazard analyses. The association between serum IL-17 expression at cessation and GD relapse was analyzed with relapse-free survival (RFS) by the Kaplan–Meier survival analysis and log-rank test. Results Of the 117 patients, 72 (61.5%) maintained a remission for 12 months after ATD withdrawal and 45 (38.5%) demonstrated GD relapse. The final multivariate Cox analysis indicated elevated IL-17 expression at cessation to be an independent risk factor for GD relapse within 12 months after ATD withdrawal (HR: 3.04, 95% CI: 1.14–7.67, p = 0.021). Patients with higher expressions of IL-17 (≥median value) at cessation demonstrated a significantly higher RFS than those with lower levels by the Kaplan–Meier analysis and log-rank test (p = 0.028). Conclusions This present study indicated elevated serum IL-17 expression at cessation to be a predictor for GD relapse within 12 months.

Does Antithyroid Drug Treatment Improve Outcomes in Wild-Type Offspring of Mothers with Thyroid Hormone Resistance?

Does Antithyroid Drug Treatment Improve Outcomes in Wild-Type Offspring of Mothers with Thyroid Hormone Resistance?

Preoperative management in patients with Graves' disease.

Graves' disease is the most frequent cause of hyperthyroidism in iodine-sufficient geographical areas and is characterized by the presence in patients' serum of autoantibodies directed against the thyrotropin receptor (TRAb) that cause overproduction and release of thyroid hormones. Clinical presentation results from both hyperthyroidism and underlying autoimmunity. The diagnosis is based on characteristic clinical features and biochemical abnormalities. If serum thyrotropin (TSH) is low, serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations should be measured to distinguish between subclinical (with normal circulating thyroid hormones) and overt hyperthyroidism (with increased circulating thyroid hormones). Graves' disease is treated with any of three effective and relatively safe initial treatment options: antithyroid drugs (ATDs), radioactive iodine ablation (RAIU), and surgery. Total thyroidectomy is favored in several clinical situations, such as intolerance, ineffectiveness or recurrence after ATD treatment, radioiodine therapy contraindicated, documented or suspected thyroid malignancy, one or more large thyroid nodules, coexisting moderate-to-severe active Graves' orbitopathy, women planning a pregnancy within 6 months. Whenever surgery is selected as treatment, selection of an expert high-volume thyroid surgeons is fundamental and careful preoperative management is essential to optimize surgical outcomes. Pretreatment with ATDs in order to promptly achieve the euthyroid state is recommended to avoid the risk of precipitating thyroid storm during surgery. For the majority of patients, euthyroidism is achieved after few weeks of ATD treatment. Beta-blockers, such as propranolol, are often added effectively to control hyperthyroid symptoms. Saturated solution of potassium iodide (SSKI) or potassium iodine (Lugol's solution), given for a short period prior to surgery, in order to reduce both thyroid hormone release and thyroid gland vascularity, is beneficial to decrease intra-operative blood loss.

Predictive Value of Gene Polymorphisms on Recurrence after the Withdrawal of Antithyroid Drugs in Patients with Graves' Disease.

Graves’ disease (GD) is one of the most common endocrine diseases. Antithyroid drugs (ATDs) treatment is frequently used as the first-choice therapy for GD patients in most countries due to the superiority in safety and tolerance. However, GD patients treated with ATD have a relatively high recurrence rate after drug withdrawal, which is a main limitation for ATD treatment. It is of great importance to identify some predictors of the higher recurrence risk for GD patients, which may facilitate an appropriate therapeutic approach for a given patient at the time of GD diagnosis. The genetic factor was widely believed to be an important pathogenesis for GD. Increasing studies were conducted to investigate the relationship between gene polymorphisms and the recurrence risk in GD patients. In this article, we updated the current literatures to highlight the predictive value of gene polymorphisms on recurrence risk in GD patients after ATD withdrawal. Some gene polymorphisms, such as CTLA4 rs231775, human leukocyte antigen polymorphisms (DRB1*03, DQA1*05, and DQB1*02) might be associated with the high recurrence risk in GD patients. Further prospective studies on patients of different ethnicities, especially studies with large sample sizes, and long-term follow-up, should be conducted to confirm the predictive roles of gene polymorphism.

Long-Term Antithyroid Drug Treatment: A Systematic Review and Meta-Analysis.

Several studies have reported inconsistent findings on the advantages and disadvantages of long-term treatment with antithyroid drugs (ATD). A systematic review and meta-analysis was undertaken to clarify the numerous aspects of long-term treatment with ATD. Medline and the Cochrane Library for trials published between 1950 and May 2016 were systematically searched. Studies containing data for long-term (>24 months) ATD treatment were included. Summary estimates of pooled prevalence, odds ratio, and weighted mean difference were calculated with a random effects model. Of 587 related articles found, six fulfilled the inclusion criteria. Long-term ATD treatment induced a remission rate of 57% [confidence interval (CI) 45-68%], a rate that was higher in adults than in non-adults (61% vs. 53%). The rate of complications was 19.1% [CI 9.6-30.9%], of which only 1.5% were major complications. The annual remission rate for each year of treatment was 16% [CI 10-27%], which was higher in adults than non-adults (19% vs. 14%). However, it should be noted that this is not a true linear correlation, but a positive relationship can be suggested between time and remission rate. Meta-regression revealed that smoking had a significant lowering effect on remission rate. Long-term ATD treatment is effective and safe, especially in adults, indicating that it should be considered as an alternative treatment for Graves' disease.