Correlation between CTLA-4 and CD40 gene polymorphisms and their interaction in graves' disease in a Chinese Han population.

BACKGROUND: Single-nucleotide polymorphism (SNP) haplotype and SNP-SNP interactions of CTLA-4 and CD40 genes, with susceptibility to Graves' disease (GD), were explored in a Chinese Han population. METHODS: SNP were genotyped by high resolution melting (HRM). Use the method of Pearson χ2 test and Logistic regression for the association between single SNP and Graves' disease. Using the method of χ2 test and Multifactor Dimensionality Reduction (MDR) to analysis the haplotype frequency distribution, the interaction of SNPs respectively. RESULTS: Genotypic and allelic frequencies of SNP rs231775, rs3087243 and rs1883832 were statistically different between controls and GD (p < 0.05). Mutant allelic frequency of G rs231775 was higher, and A and T allelic frequencies of rs3087243 and rs1883832 were lower in GD than in controls (P < 0.05). In CTLA-4 rs1024161, rs5742909, rs231775, rs231777, rs231779, rs3087243 and rs11571319 showed D' < 50% and r2 < 0.3 among each SNP. We identified six commonly found haplotypes; TCGCTGC was associated with the highest GD risk (OR = 2.565) and TCACTAC the lowest (OR = 0.096). MDR analysis indicated interactions among the rs231775 GG, rs231779 TT and rs3087243 GG genotypes in CTLA-4 might increase GD risk by 2.53-fold (OR = 2.53). CONCLUSION: CTLA-4 and CD40 were associated with GD incidence in a Chinese Han population. The TCGCTGC and TCACTAC haplotypes in the CTLA-4 gene, were risk and protective factors for Graves'disease respectively. Interactions among the SNPs of rs231775, rs231779 and rs3087243 significantly increase the susceptibility to GD.

Association between the functional PTPN22 G788A (R263Q) polymorphism and susceptibility to autoimmune diseases: A meta-analysis.

This study explored whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) G788A (R263Q) polymorphism is associated with susceptibility to autoimmune diseases. A meta-analysis was conducted using 23 comparative studies with a total of 16,719 patients and 17,783 controls. The meta-analysis showed an association between the A allele of the PTPN22 G788A polymorphism and decreased risk of autoimmune diseases in all subjects (p < 0.001). Analysis after stratification by ethnicity indicated that the PTPN22 788A allele was significantly associated with autoimmune diseases in Europeans (p < 0.001) but not in Latin Americans. Meta-analysis by autoimmune disease type showed a significant negative association between the PTPN22 788A allele and systemic lupus erythematous (SLE) (p = 001), rheumatoid arthritis (RA) (p = 0.008), ulcerative colitis (UC) (p = 0.016), but not Crohn's disease (CD). A single study for each showed no association between the PTPN22 788A allele and systemic sclerosis, giant cell arteritis, Henoch-schonlein purpura, uveitis, and Grave's disease. This meta-analysis demonstrates that the PTPN22 G788A polymorphism confers protection against SLE, RA, and UC, supporting evidence of association of the PTPN22 gene with a subgroup of autoimmune diseases.

Genetic study of early-onset Graves' disease in the Chinese Han population.

Graves' disease (GD) is a complex autoimmune disorder in which genetic and environmental factors are both involved in the pathogenesis. Early-onset patients have a shorter exposure time to environmental factors and are, therefore, good models to help understand the genetic architecture of GD. Based on previous studies of early-onset GD, 11 single nucleotide polymorphisms (SNPs) and their related SNPs (R2 > .6), SNPs located within a ±1-Mb region of the FOXP3 gene, and 20 validated GD-risk SNPs were selected and screened for genotyping in 3735 GD and 4893 control patients to investigate whether early-onset GD is a subtype of GD with distinct susceptibility genes. Ultimately, we did not confirm the reported genetic markers of early-onset GD in our Chinese Han population but found that a GD-risk SNP located in the human leukocyte antigen class I region-rs4947296-was more strongly correlated with early-onset GD than non-early-onset GD. In addition, heterogeneity analysis of GD patients suggests that it may be more reasonable to define early-onset GD as an onset age ≤20 years.

Treatment of Swedish Patients with Graves' Hyperthyroidism Is Associated with Changes in Acylcarnitine Levels.

BACKGROUND: Hyperthyroidism is associated with alterations in metabolism that are currently only partially understood. The objective of the study was to investigate changes in metabolism associated with reinstatement of euthyroidism in Swedish patients. METHODS: Eighty metabolites in plasma were profiled from 10 subjects with Graves' disease (GD) at baseline and after 9 and 15 months of treatment to reinstate euthyroidism. Thyroid parameters, thyrotropin (TSH), TSH receptor antibodies, free triiodothyronine, and free thyroxine were followed. Main findings were validated in plasma from 20 subjects with GD at baseline and at three, six, and nine months. The study was conducted at the endocrinology clinic in Malmö, Sweden. RESULTS: Euthyroidism was reinstated at three months, and thyroid status did not change further during the 15-month follow-up. This was paralleled by altered levels of 9/19 detected acylcarnitines (p < 0.05 after adjustment for multiple testing). Levels of short-chain acylcarnitines were decreased, intermediate-chain acylcarnitines elevated, and long-chain acylcarnitines unaltered. CONCLUSIONS: GD and treatment of the disease is associated with pronounced acyl chain length-dependent alterations in acylcarnitine levels. These changes may be impacted by ethnicity and or dietary differences.

Association of Interleukin 10 Gene Polymorphisms with Autoimmune Thyroid Disease: Meta-Analysis.

The aim of this study was to perform a meta-analysis of eligible studies and to derive a precise estimate of the association between interleukin 10 (IL10) polymorphisms and susceptibility to autoimmune thyroid disease (AITD). Meta-analyses were conducted on the associations between AITD and the -1082 G/A (rs1800896), -819 C/T (rs1800871) and -592 C/A (rs1800872) polymorphisms in IL10, and the haplotype of these polymorphisms and AITD. A total of 2903 AITD patients and 3060 controls in 10 eligible studies were included in the meta-analysis. This meta-analysis showed significant associations between IL10 at the -1082 G allele and overall AITD (OR: 1.44, 95% CI 1.13-1.82, P = 0.003), but no association between the IL10 -592 C allele and the -819 C allele and AITD. Subgroup studies demonstrated significant associations between the -1082 G allele and susceptibility to Graves' disease. Ethnicity-specific meta-analysis revealed significant associations between the -1082 G allele and AITD susceptibility in Asian populations; however, in Middle Eastern populations, no association was evident. Meta-analysis of the IL10 haplotype revealed an association between the ATA haplotype and AITD (OR: 1.17, 95% CI 1.00-1.36, P = 0.04). Meta-analysis demonstrates that the IL10 polymorphisms are associated with susceptibility to AITD.

Physiological and Metabolic Changes During the Transition from Hyperthyroidism to Euthyroidism in Graves' Disease.

BACKGROUND: The serum metabolomic profile and its relationship to physiological changes during hyperthyroidism and restoration to euthyroidism are not known. This study aimed to examine the physiological, adipokine, and metabolomic changes that occur when subjects with Graves' disease transition from hyperthyroidism to euthyroidism with medical treatment. METHODS: Chinese women between 21 and 50 years of age and with newly diagnosed Graves' disease attending the endocrine outpatient clinics in a single institution were recruited between July 2012 and September 2014. All subjects were treated with thioamides to achieve euthyroidism. Clinical parameters (body weight, body composition via bioelectrical impedance analysis, resting energy expenditure and respiratory quotient via indirect calorimetry, and reported total energy intake via 24 h food diary), biochemical parameters (thyroid hormones, lipid profile, fasting insulin and glucose levels), serum leptin, adiponectin, and metabolomics profiles were measured during hyperthyroidism and repeated in early euthyroidism. RESULTS: Twenty four Chinese women with an average age of 36.3 ± 8.6 years were included in the study. The average duration of treatment that was required to reach euthyroidism for these subjects was 38 ± 16.3 weeks. There was a significant increase in body weight (52.6 ± 9.0 kg to 55.3 ± 9.4 kg; p < 0.001) and fat mass (14.3 ± 6.9 kg to 16.8 ± 6.5 kg; p = 0.005). There was a reduction in resting energy expenditure corrected for weight (28.7 ± 4.0 kcal/kg to 21.5 ± 4.1 kcal/kg; p < 0.001) and an increase in respiratory quotient (0.76 to 0.81; p = 0.037). Resting energy expenditure increased significantly with increasing free triiodothyronine levels (p = 0.007). Significant increases in total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol were noted. There was no significant change in leptin levels, but adiponectin levels increased significantly (p = 0.018). Significant reductions in fasting C2, medium-chain, long-chain, and total acylcarnitines were observed, but no changes in the fat-free mass, branched chain amino acid levels, or insulin sensitivity during recovery from hyperthyroidism were noted. CONCLUSIONS: Serum metabolomics profile changes complemented the physiological changes observed during the transition from hyperthyroidism to euthyroidism. This study provides a comprehensive and integrated view of the changes in fuel metabolism and energy balance that occur following the treatment of hyperthyroidism.

Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study.

Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21-1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.

Genetic association of Fc receptor-like glycoprotein with susceptibility to Graves' disease in a Chinese Han population.

BACKGROUND: Graves' disease (GD) is recognized as a most frequent form of autoimmune thyroid disease, but the etiology underlying GD still remains unclear. Among the thyroid-specific and immune-modulating genes involved in susceptibility to GD, FCRL3 polymorphisms have been demonstrated to be associated with GD in independent studies. However, considering the limited sample size and statistical power of previous studies, there is no study analyzing this relationship systematically. Therefore, this investigation was aimed to perform a case-control study in a Chinese population and a meta-analysis including relevant studies was carried out to confirm a potential correlation between SNPs investigated and risk of GD. METHODS AND MATERIALS: Seven single nucleotide polymorphisms (SNPs) were selected in this case-control study involved with 671 GD patients and 706 controls. Later, a meta-analysis including seven case-control studies related to GD susceptibility and FCRL3 polymorphisms was carried out. T-test and chi-square test were utilized to find if difference in clinical variables existed between case and control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the association between GD susceptibility and FCRL3 polymorphisms. RESULTS: Three polymorphisms, namely, FCRL3_3C, FCRL3_5C and FCRL3_6A, were significantly associated with increased risk of GD in terms of a Chinese Han population in both dominant model [OR=1.33 (95% CI: 1.04-1.69), OR=1.34 (95% CI: 1.05-1.70) and OR=1.36 (95% CI: 1.07-1.75), respectively] and allelic model [OR=1.27 (95% CI: 1.10-1.48), OR=1.28 (95% CI: 1.11-1.49) and OR=1.23 (95% CI: 1.06-1.43), respectively]. Further meta-analyses indicated that the effects of FCRL3_3C, FCRL3_5C and FCRL3_6A on susceptibility to GD varied between Asians and Caucasians. CONCLUSIONS: This case-control analysis demonstrated that FCRL3_3, FCRL3_5 and FCRL3_6 polymorphisms were associated with significantly elevated risk of GD in a Chinese population. Furthermore, the following meta-analysis confirmed that FCRL3_3, FCRL3_5 and FCRL3_6 polymorphisms could increase susceptibility to GD only in Asians, rather than in Caucasians.

Redistribution of body composition in patients with Graves' disease after iodine-131 treatment.

OBJECTIVE: The objective of this study was to investigate body composition redistribution at 3 months after radioactive iodine therapy (RAI). METHODS: Eighty patients with Graves' disease (GD) for RAI and 18 volunteers were recruited. All patients underwent thyroid status test and dual-energy x-ray absorptiometry at baseline and 3 months after RAI. According to the second thyroid status test, patients were divided into the following groups: A, with aggravated hyperthyroidism; B-1, with improved hyperthyroidism; B-2, with euthyroidism; and B-3, with hypothyroidism. RESULTS: Total lean mass (LM) but fat mass (FM) and bone mineral content (BMC) of whole GD patients after RAI recovered to be not different with controls. Compared with baseline, in group A, FM in the left leg increased, and LM in left arm, right arm, trunk and total LM decreased (P<0.05). In B-2, FM in the head increased, and LM in the head, right arm, trunk and total LM increased (P<0.05). In B-3, FM in the right leg and total body fat percentage decreased, but FM in the head, android-to-gynoid fat ratio and body mass index increased (P<0.05); LM of all sites, weight and total mass increased (P<0.05); BMC in lumbar spine and left leg, and total BMC decreased (P<0.05). Body composition of unmentioned sites was retained after RAI in each group (P>0.05). CONCLUSIONS: Replenishment of LM gets priority rather than FM and BMC during the first 3 months after RAI, and the increase in LM starts from the upper body; head is the regional site in which FM recovery occurs first.

Relationship between the IL-4 gene promoter -590C/T (rs2243250) polymorphism and susceptibility to autoimmune diseases: a meta-analysis.

OBJECTIVE: Studies investigating the association between interleukin (IL)-4 gene promoter -590C/T (rs2243250) polymorphism and autoimmune diseases report conflicting results. To derive a more precise estimation of the relationship, a meta-analysis was performed. METHODS: A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association. RESULTS: A total of 6001 cases and 6788 controls from 24 studies were analysed. Significant association of the C allele of IL-4 rs2243250 polymorphism with rheumatoid arthritis (RA) was detected (odds ratio (OR) = 0.696, 95% confidence interval (CI) = 0.601-0.807). Stratification by ethnicity indicated an association between the IL-4 rs2243250 polymorphism and RA in Caucasians. Furthermore, the overall ORs of the associations between the C allele and multiple scleorosis (MS) were 1.340 (95% CI = 1.102-1.630). However, we failed to reveal any association between IL-4 rs2243250 polymorphism and systemic lupus erythematosus (SLE), type 1 diabetes (T1D) or Graves' disease (GD). CONCLUSIONS: The present study suggests that the IL-4 rs2243250 polymorphism might be associated with genetic susceptibility to autoimmune diseases, including RA and MS.

Association of Toll-like receptor 7 and 8 gene polymorphisms with Graves' disease in Chinese Cantonese population.

Graves' disease (GD) is a common polygenic multifactorial autoimmune disease. Toll-like receptors (TLRs) play critical roles in the activation of innate and adaptive immune responses. This study investigated the association of TLR7 and TLR8 gene polymorphisms with susceptibility of GD. Five single nucleotide polymorphisms (SNPs), namely, rs179019, rs179010 and rs3853839 in TLR7 and rs3764880 and rs5744088 in TLR8, were evaluated in 332 GD patients and 351 controls using High-Resolution Melting analysis. After adjusting for age, SNP rs179010 was found to decrease the risk of GD in females (OR(T vs C) = 0.64, P = 0.004). In the additive model, the risk of GD decreased significantly as the number of T alleles increased in females [odds ratio (OR) = 0.67 (0.50-0.90), P = 0.007]. The multivariate logistic regression analysis confirmed the independent contribution of rs179010 to the protective effect against GD. This study indicates that rs179010 in TLR7 may be associated with the decreased susceptibility to GD in Chinese Cantonese.

Association of TLR4 and TLR5 gene polymorphisms with Graves' disease in Chinese Cantonese population.

Graves' disease (GD) is postulated to be caused by the combined effects of susceptibility genes and environmental triggers. Toll like receptors (TLRs) play a role in the activation of innate and adaptive immune responses in mammalians. The aim of this study was to evaluate the potential association of TLR4 and TLR5 gene polymorphisms with GD in Chinese Cantonese population. Four single nucleotide polymorphisms (SNPs), rs11536889 and rs7873784 in TLR4, rs2072493 and rs5744174 in TLR5, were evaluated in 332 GD patients and 351 unrelated controls from Chinese Cantonese population. The minor allele C of TLR5 rs5744174 decreased the risk to GD in females (ORC vs. T=0.63; p=0.003; ptrend=0.003). Under a dominant model, rs5744174 conferred a protective effect in all cases (ORCC/CT vs. TT=0.65; p=0.009) or female subset (ORCC/CT vs. TT=0.57; p=0.002). Under a co-dominant model, rs5744174 also conferred a protective effect in all cases (ORTC vs. TT=0.64; p=0.008) and females (ORTC vs. TT=0.57; p=0.002). The haplotype A-C of TLR5 (rs2072493-rs5744174) decreased the risk of GD in females (OR=0.62; p=0.002). The other three SNPs were not found associated with GD. This study provided evidence that polymorphisms in TLR5 might be associated with decreased susceptibility of GD in females.

The association of SCGB3A2 polymorphisms with the risk of Graves' disease: a meta-analysis.

The aim of this study is to assess the association of the SCGB3A2 -112G>A promoter polymorphism with Graves' disease(GD) using a meta-analysis. Relevant studies were identified using PubMed and EMBASE electronic databases. A meta-analysis of relevant studies was performed. This meta-analysis included four case-control studies, containing 6,913 GD cases (Caucasian 3904, Han 3009) and 7,185 controls(Caucasian 4155, Han 3030). The combined results showed a significant difference in genotype distribution (-112A/G) between GD and control populations (A vs. G P = 1.53 × 10(-7); GG vs. AA+AG P = 6.78 × 10(-9)). Meta-analysis was performed using a fixed-effects model. Under the dominant model (GG/AA + GA), the AA and GA genotypes were significantly associated with GD (pooled OR = 1.24, 95 % CI 1.12-1.37). When the two European studies are combined, the AA and GA genotypes were also significantly associated with GD (pooled OR = 1.29, 95 % CI 1.20-1.39). This meta-analysis suggests that SCGB3A2 polymorphism at positions -112G>A was associated with GD both in Chinese and Caucasian population.

Genetic heterogeneity of susceptibility gene in different ethnic populations: refining association study of PTPN22 for Graves' disease in a Chinese Han population.

In our previous studies, we presumed subtypes of Graves' disease (GD) may be caused by different major susceptibility genes or different variants of a single susceptibility gene. However, more evidence is needed to support this hypothesis. Single-nucleotide polymorphism (SNP) rs2476601 in PTPN22 is the susceptibility loci of GD in the European population. However, this polymorphism has not been found in Asian populations. Here, we investigate whether PTPN22 is the susceptibility gene for GD in Chinese population and further determine the susceptibility variant of PTPN22 in GD. We conducted an imputation analysis based on the results of our genome-wide association study (GWAS) in 1,536 GD patients and 1,516 control subjects. Imputation revealed that 255 common SNPs on a linkage disequilibrium (LD) block containing PTPN22 were associated with GD (P<0.05). Nine tagSNPs that captured the 255 common variants were selected to be further genotyped in a large cohort including 4,368 GD patients and 4,350 matched controls. There was no significant difference between the nine tagSNPs (P>0.05) in either the genotype distribution or allelic frequencies between patients and controls in the replication study. Although the combined analysis exhibited a weak association signal (P(combined) = 0.003263 for rs3811021), the false positive report probability (FPRP) analysis indicated it was most likely a false positive finding. Our study did not support an association of common SNPs in PTPN22 LD block with GD in Chinese Han population. This suggests that GD in different ethnic population is probably caused by distinct susceptibility genes.

The replication of the association of the rs6832151 within chromosomal band 4p14 with Graves' disease in a Polish Caucasian population.

Recently Chu et al. conducted a genome-wide association study in a Chinese Han population and identified two novel Graves' disease (GD) susceptibility loci within 4p14 (rs6832151) and 6q27 (rs9355610). Our purpose was to replicate these associations in a Polish Caucasian population. We analyzed rs6832151 and rs9355610 genotypes in a case-control study based on 560 GD patients and 1475 unrelated controls using TaqMan assays. Our study had the power of 0.8 and 0.6 to detect the effects originally reported for rs6832151 and rs9355610, respectively. We found an association between GD and the rs6832151 G allele (odds ratio OR = 1.27, P = 0.002). Analysis of model of inheritance suggested that the dominant model should be preferred (P(fit) = 0.938, OR = 1.39, P = 0.001). For rs9355610 a formally significant effect was observed assuming a recessive model (OR = 1.24, P = 0.028), whereas analysis of allele distribution showed a trend for association (OR = 1.14,95%, P = 0.082). Our findings are the first to show that rs6832151 and possibly rs9355610 contribute to GD pathogenesis also in Caucasians.

Are Maori women at increased risk of cardiac complications of Graves disease?

We present a case series of three women of New Zealand Maori ethnicity, who presented to the emergency department of a Brisbane hospital (Brisbane, Australia) with symptomatic cardiac complications of Graves disease requiring hospital admission. We raise the question as to whether individuals of Maori ethnicity are genetically susceptible to cardiac complications of thyrotoxicosis.

[Thyrotoxic hypokaliemic periodic paralysis revealing Graves' disease in a male Caucasian]. / Paralysie périodique thyréotoxique hypokaliémique révélatrice d'une maladie de Basedow chez un caucasien.

OBJECTIVES: Hypokaliemic thyrotoxic periodic paralysis (TPP) is an uncommon complication of hyperthyroidism. Mostly described among Asian patients, it is rare in other ethnic groups, in particular in Caucasian people. CASE REPORT: We present the case of a Caucasian male admitted to our unit after several paretic episodes. Tachycardia, goiter and mild proptosis led to the diagnosis of Graves' disease. CONCLUSION: Rare in the Caucasian population, TPP involves dysfunction of the NA-K-ATPase pump. Beta-blockers should be associated with medical or surgical treatment of hyperthyroidism.

CD40 C/T(-1) and CTLA-4 A/G(49) SNPs are associated with autoimmune thyroid diseases in the Chinese population.

This study was to investigate whether the common polymorphisms of CD40 and CTLA4 genes confer susceptibility to AITD in the Chinese population. A set of unrelated subjects including 303 GD patients, 208 HT patients, and 215 matched healthy controls were recruited. SNPs were genotyped by the method of PCR-RFLP. (1) As for CD40 C/T(-1) SNP, only a significant difference was found in allele frequencies between GD and control groups (P = 0.033). (2) On the part of CTLA-4 A/G(49) SNP, significant differences were found in genotype and allele frequencies between GD and control groups (P = 7.0 × 10(-5) and P = 0.002, respectively), and similar results were found between HT and control groups (P = 0.015 and P = 0.003, respectively). (3) The logistic regression analysis showed there was no interaction between CD40 and CTLA4 genotypes (P = 0.262). These results indicate that both CTLA-4 A/G(49) and CD40 C/T(-1) SNPs are associated with genetic susceptibility of GD, and CTLA-4 A/G(49) is also associated with HT.

Prediction of late (24-hour) radioactive iodine uptake using early (3-hour) uptake values in Japanese patients with Graves' disease.

Measurement of 24-hour radioactive iodine uptake (RAIU), which is commonly used to calculate the dose of radioiodine (RI) therapy, cannot be accomplished in a single day. The purpose of this study was to predict 24-hour RAIU from 3-hour RAIU in Japanese patients with Graves' disease, and to investigate other factors that could be used to predict 24-hour RAIU. A total of 66 Japanese patients (14 men and 52 women; age, 17-83 years) with Graves' disease who had undergone both 3-hour and 24-hour ¹²³I RAIU measurements between January 2006 and September 2011 were included in this study. Stepwise multiple regression analyses were performed in order to identify factors that could be used to predict 24-hour RAIU. The investigated factors were gender, age, thyroid volume, TSH, free thyroxine (FT4), free triiodothyronine (FT3), serum creatinine, second generation assay TSH receptor antibody (TRAb2), antithyroid drugs discontinuation period (ADP), iodine restriction period and 3-hour RAIU. The ADP was converted to an ordinal scale ADP score (ADPS) for multiple regression analyses. Multiple regression analyses showed that 3-hour RAIU (P < 0.001), FT3 (P < 0.001) and ADPS (P < 0.001) were statistically significant predictive factors of 24-hour RAIU. The relationship between 24-hour RAIU (LU) and 3-hour RAIU (EU), FT3 and ADPS was: LU = 11.5 + 29.1 × log10 EU + 23.0 × log10 FT3 - 2.7 × ADPS (r = 0.82, P < 0.001). The present results indicate that prediction of LU from EU, FT3 and ADPS is feasible in Japanese patients with Graves' disease.