Associations between gut microbiota and thyroidal function status in Chinese patients with Graves' disease.

OBJECTIVE: The imbalance of gut microbiota has been linked to manifold endocrine diseases, but the association with Graves' disease (GD) is still unclear. The purpose of this study was to investigate the correlation between human gut microbiota and clinical characteristics and thyroidal functional status of GD. METHODS: 14 healthy volunteers (CG) and 15 patients with primary GD (HG) were recruited as subjects. 16SrDNA high-throughput sequencing was performed on IlluminaMiSeq platform to analyze the characteristics of gut microbiota in patients with GD. Among them, the thyroid function of 13 patients basically recovered after treatment with anti-thyroid drugs (oral administration of Methimazole for 3-5 months). The fecal samples of patients after treatment (TG) were sequenced again, to further explore and investigate the potential relationship between dysbacteriosis and GD. RESULTS: In terms of alpha diversity index, the observed OTUs, Simpson and Shannon indices of gut microbiota in patients with GD were significantly lower than those in healthy volunteers (P < 0.05).The difference of bacteria species was mainly reflected in the genus level, in which the relative abundance of Lactobacillus, Veillonella and Streptococcus increased significantly in GD. After the improvement of thyroid function, a significant reduction at the genus level were Blautia, Corynebacter, Ruminococcus and Streptococcus, while Phascolarctobacterium increased significantly (P < 0.05). According to Spearman correlation analysis, the correlation between the level of thyrotropin receptor antibody (TRAb) and the relative abundance of Lactobacillus and Ruminococcus was positive, while Synergistetes and Phascolarctobacterium showed a negative correlation with TRAb. Besides, there were highly significant negative correlation between Synergistetes and clinical variables of TRAb, TPOAb and TGAb (P < 0.05, R < - 0.6). CONCLUSIONS: This study revealed that functional status and TRAb level in GD were associated with composition and biological function in the gut microbiota, with Synergistetes and Phascolarctobacterium protecting the thyroid probably, while Ruminococcus and Lactobacillus may be novel biomarkers of GD.

Comparative assessment of gut microbial composition and function in patients with Graves' disease and Graves' orbitopathy.

BACKGROUND: A previous study indicated that gut microbiota changed notably in Graves' orbitopathy (GO) patients as compared to controls. However, the characteristics of intestinal bacteria in Graves' disease (GD) and GO are unclear. OBJECTIVE: The present study aimed to identify specific intestinal bacteria of GD and GO, respectively. METHODS: The gut microbial communities of the fecal samples of 30 GD patients without GO, 33 GO subjects, and 32 healthy subjects were analyzed and compared by 16S rRNA gene sequencing. RESULTS: At the phylum level, the proportion of Deinococcus-Thermus and Chloroflexi was decreased significantly in GO patients as compared to GD. At the genus level, the proportion of Subdoligranulum and Bilophila was increased while that of Blautia, Anaerostipes, Dorea, Butyricicoccus, Romboutsia, Fusicatenibacter, unidentified_ Lachnospiraceae, unidentified_Clostridiales, Collineslla, Intestinibacter, and Phascolarctobacterium was decreased in the GO group as compared to the GD group. Random forest analysis was used for the identification of specific intestinal microbiota, and Deinococcus-Thermus, Cyanobacteria and Chloroflexi were ranked in the top ten according to their contributions to sample classification. Moreover, compared to the control, there were multiple gut bacterial enrichment metabolic pathways in GO and GD patients, including nucleotide metabolism, enzyme family, and energy metabolism. Compared to GO, the only enrichment metabolic pathway found in GD was the viral protein family. CONCLUSIONS: This study highlighted the significant differences in the intestinal microbiota and predictive functions of GD with GO, thereby providing new insights into the role of the gut bacteria that might contribute to the development of GO in GD patients.

The microbiota and autoimmunity: Their role in thyroid autoimmune diseases.

Since the 1970s, the role of infectious diseases in the pathogenesis of Graves' disease (GD) has been an object of intensive research. The last decade has witnessed many studies on Yersinia enterocolitica, Helicobacter pylori and other bacterial organisms and their potential impact on GD. Retrospective, prospective and molecular binding studies have been performed with contrary outcomes. Until now it is not clear whether bacterial infections can trigger autoimmune thyroid disease. Common risk factors for GD (gender, smoking, stress, and pregnancy) reveal profound changes in the bacterial communities of the gut compared to that of healthy controls but a pathogenetic link between GD and dysbiosis has not yet been fully elucidated. Conventional bacterial culture, in vitro models, next generation and high-throughput DNA sequencing are applicable methods to assess the impact of bacteria in disease onset and development. Further studies on the involvement of bacteria in GD are needed and may contribute to the understanding of pathogenetic processes. This review will examine available evidence on the subject.

Gut microbiome in the Graves' disease: Comparison before and after anti-thyroid drug treatment.

While several studies have proposed a connection between the gut microbiome and the pathogenesis of Graves's disease (GD), there has been a lack of reports on alteration in microbiome following using anti-thyroid drug treatment (ATD) to treat GD. Stool samples were collected from newly diagnosed GD patients provided at baseline and after 6 months of ATD treatment. The analysis focused on investigating the association between the changes in the gut microbiome and parameter including thyroid function, thyroid-related antibodies, and the symptom used to assess hyperthyroidism before and after treatment. A healthy control (HC) group consisting of data from 230 healthy subjects (110 males and 120 females) sourced from the open EMBL Nucleotide Sequence Database was included. Twenty-nine GD patients (14 males and 15 females) were enrolled. The analysis revealed a significant reduction of alpha diversity in GD patients. However, after ATD treatment, alpha diversity exhibited a significant increase, restored to levels comparable to the HC levels. Additionally, GD patients displayed lower levels of Firmicutes and higher levels of Bacteroidota. Following treatment, there was an increased in Firmicutes and a decrease in Bacteroidota, resembling levels found in the HC levels. The symptoms of hyperthyroidism were negatively associated with Firmicutes and positively associated with Bacteroidota. GD had significantly lower levels of Roseburia, Lachnospiraceaea, Sutterella, Escherichia-shigella, Parasuterella, Akkermansia, and Phascolarctobacterium compared to HC (all p < 0.05). Post-treatment, Subdoligranulum increased (p = 0.010), while Veillonella and Christensenellaceaea R-7 group decreased (p = 0.023, p = 0.029, respectively). Anaerostipes showed a significant association with both higher smoking pack years and TSHR-Ab levels, with greater abundantce observed in smokers among GD (p = 0.16). Although reduced ratio of Firmicutes/Bacteroidetes was evident in GD, this ratio recovered after treatment. This study postulates the involvement of the gut microbiome in the pathogenesis of GD, suggesting potential restoration after treatment.

Use of bidirectional Mendelian randomization to unveil the association of Helicobacter pylori infection and autoimmune thyroid diseases.

Previous observational studies found associations between Helicobacter pylori infection and autoimmune thyroid diseases (AITDs), but the causal nature of this association is still uncertain. We investigated the causal effect of six crucial antibodies against H. pylori on AITDs using a bidirectional Mendelian randomization (MR). We found that anti-H. pylori outer membrane protein (OMP) significantly increased the risk of hyperthyroidism and Graves' disease (GD). In addition, our reverse MR analysis indicated that hyperthyroidism could increase the levels of cytotoxin-associated gene A and OMP antibodies. We also observed causal roles of GD on anti-H. pylori OMP. Our analyses indicate the mutual effects of H. pylori infection and AITDs, suggesting the existence of a gut-thyroid axis. These results also provide evidence of the bidirectional causal association between anti-H. pylori OMP with hyperthyroidism and GD, resulting in a vicious circle.

Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis.

Background: Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID. Methods: We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD. Results: The meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto's thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves' disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like Bifidobacterium and Lactobacillus were decreased in the AITD group, and harmful microbiota like Bacteroides fragilis was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as Bacteroidetes, Bacteroides, and Lachnospiraceae was increased compared with the controls. Conclusions: This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels. Systematic Review Registration: PROSPERO, identifier CRD42021251557.

Elevated Levels of Circulating Biomarkers Related to Leaky Gut Syndrome and Bacterial Translocation Are Associated With Graves' Disease.

Background: A growing number of studies have found dysbiosis of the intestinal microbiota in patients with Graves' disease (GD). The intestinal epithelial barrier serves as the first line of defense, protecting the immune system from excessive stimulation of microbiota and toxins. Most autoimmune diseases are associated with a gut barrier dysfunction (leaky gut) which allows bacterial translocation. However, to date, potential correlations between intestinal barrier dysfunction and GD have not been explored. Methods: Serum lipopolysaccharide (LPS), intestinal fatty acid-binding protein (I-FABP), zonulin, D-lactate, and diamine oxidase (DAO) were measured to assess barrier integrity in 91 patients with GD (61 initial GD and 30 euthyroid GD) and 44 healthy controls. The quality of life (QOL) of patients with GD was assessed using the thyroid-specific patient-reported outcome (ThyPRO-39) questionnaire. Results: The serum levels of LPS, I-FABP, zonulin, and D-lactate were significantly higher in patients with initial GD than in healthy controls. Logistic regression analysis revealed that zonulin and D-lactate were independently associated with risk for GD and circulating zonulin could effectively distinguish patients with initial GD from healthy controls. Correlation analyses showed that I-FABP, LPS, and D-lactate were positively associated with FT4 and negatively associated with TSH. In addition, circulating LPS, zonulin, and D-lactate levels were all independent predictors of TRAb levels. Moreover, higher circulating LPS levels in patients with GD were associated with more severe hyperthyroidism (higher concentrations of FT3, FT4, and TRAb and lower TSH concentrations) and worse scores of hyperthyroid and eye symptoms. Conclusion: Patients with initial GD show a disrupted intestinal barrier, characterized by elevated levels of leaky gut biomarkers. Increased intestinal permeability and bacterial translocation were associated with TRAb levels and hyperthyroidism in GD. Further research is required to elucidate the underlying mechanisms.

Gut Microbiota May Play a Significant Role in the Pathogenesis of Graves' Disease.

Background: Gut microbiota are considered to be intrinsic regulators of thyroid autoimmunity. We designed a cross-sectional study to examine the makeup and metabolic function of microbiota in Graves' disease (GD) patients, with the ultimate aim of offering new perspectives on the diagnosis and treatment of GD. Methods: The 16S ribosomal RNA (rRNA) V3-V4 DNA regions of microbiota were obtained from fecal samples collected from 45 GD patients and 59 controls. Microbial differences between the two groups were subsequently analyzed based on high-throughput sequencing. Results: Compared with controls, GD patients had reduced alpha diversity (p < 0.05). At the phylum level, GD patients had a significantly lower proportion of Firmicutes (p = 0.008) and a significantly higher proportion of Bacteroidetes (p = 0.002) compared with the controls. At the genus level, GD patients had greater numbers of Bacteroides and Lactobacillus, although fewer Blautia, [Eubacterium]_hallii_group, Anaerostipes, Collinsella, Dorea, unclassified_f_Peptostreptococcaceae, and [Ruminococcus]_torques_group than controls (all p < 0.05). Subgroup analysis of GD patients revealed that Lactobacillus may play a key role in the pathogenesis of autoimmune thyroid diseases. Nine distinct genera showed significant correlations with certain thyroid function tests. Functional prediction revealed that Blautia may be an important microbe in certain metabolic pathways that occur in the hyperthyroid state. In addition, linear discriminant analysis (LDA) and effect size (LEfSe) analysis showed that there were significant differences in the levels of 18 genera between GD patients and controls (LDA >3.0, all p < 0.05). A diagnostic model using the top nine genera had an area under the curve of 0.8109 [confidence interval: 0.7274-0.8945]. Conclusions: Intestinal microbiota are different in GD patients. The microbiota we identified offer an alternative noninvasive diagnostic methodology for GD. Microbiota may also play a role in thyroid autoimmunity, and future research is needed to further elucidate the role.

Identification of a correlation between Helicobacter pylori infection and Graves' disease.

BACKGROUND: Viral and bacterial antigens have been suspected to be able to mimic the antigenic profile of the thyroid cell membrane and to play an important role in the onset of the autoimmune diseases, such as Graves' disease and Hashimoto thyroiditis. The Helicobacter pylori infection is worldwide diffused and is present in the developed countries up to 50% of the population. The presence of the cytotoxin-associated gene A antigens identifies the most virulent strains of the bacterium. Previous studies have demonstrated the possible correlation between the Helicobacter pylori and Hashimoto's thyroiditis but these results are controversial. AIMS: We studied the prevalence rate of this bacterium in the Graves' disease and two selected subgroups such as the hyperthyroid patients, at the first time of diagnosis, and the euthyroid methimazole-treated patients. MATERIALS AND METHODS: We analyzed Helicobacter pylori in fresh stool samples with an enzyme immunoassay method and the presence of cytotoxin-associated gene A antigens with a serological test. RESULTS: Our results show that a significative increased rate of prevalence is present in Graves' patients, when the disease is ongoing, with an overall prevalence of the strains expressing the cytotoxin-associated gene A antigens compared to the control group. CONCLUSIONS: The association between the Helicobacter pylori and Graves' disease suggests a possible role of this bacterium in the onset and/or the maintenance of the disease.

Microorganisms associated to thyroid autoimmunity.

Autoimmune thyroid diseases are a group of diseases characterized by a dysfunction of the immune system concerning the thyroid gland, associated with hypothyroidism or hyperthyroidism. The thyroid gland autoimmunity has been recognized as multifactorial. It has been reported that microorganisms may play a role on the pathogenesis of Hashimoto's thyroiditis and Graves´ disease. These could explain the high incidence of the autoimmune thyroid diseases. Helicobacter Pylori (H. pylori) and Hepatitis C virus (HCV) are the microorganisms in which the association with autoimmune thyroid diseases is clearer. The pathophysiologic mechanisms are still not well defined. For H. pylori, molecular mimicry has been the most accepted mechanism. It has been proposed Hepatitis C virus as the trigger of the thyroid autoimmunity by exacerbating the production of thyroid auto-antibodies, while some mention that the real factor that triggers the thyroid autoimmunity is the treatment with Interferon alpha (IFN-alpha) by upregulating MHC class I and inducing ligation of CD40+ cells to thyrocytes. Other microorganisms such as Toxoplasma gondii, Human Immunodeficiency virus, Herpes virus and others have reported information about their association with thyroid autoimmune diseases There are no proposals on how these last microorganisms induce thyroid autoimmunity. There is still a lack of evidence on this topic. Further research must be done to determine the interaction of these microorganisms and the best way to manage these patients.

Intestinal microbiota changes in Graves' disease: a prospective clinical study.

Graves' disease (GD) occurs due to an autoimmune dysfunction of thyroid gland cells, leading to manifestations consistent with hyperthyroidism. Various studies have confirmed the link between autoimmune conditions and changes in the composition of intestinal microbial organisms. However, few studies have assessed the relationship between the GD and the changes in intestinal microbiota. Therefore, the present study aimed to investigate changes in intestinal flora that may occur in the setting of GD. Thirty-nine patients with GD and 17 healthy controls were enrolled for fecal sample collection. 16S rRNA sequencing was used to analyze the diversity and composition of the intestinal microbiota. High-throughput sequencing of 16S rRNA genes of intestinal flora was performed on Illumina Hiseq2500 platform. Comparing to healthy individuals, the number of Bacilli, Lactobacillales, Prevotella, Megamonas and Veillonella strains were increased, whereas the number of Ruminococcus, Rikenellaceae and Alistipes strains were decreased among patients with GD. Furthermore, patients with GD showed a decrease in intestinal microbial diversity. Therefore, it indicates that the diversity of microbial strains is significantly reduced in GD patients, and patients with GD will undergo significant changes in intestinal microbiota, by comparing the intestinal flora of GD and healthy controls. These conclusions are expected to provide a preliminary reference for further researches on the interaction mechanism between intestinal flora and GD.

The Human Microbiota in Endocrinology: Implications for Pathophysiology, Treatment, and Prognosis in Thyroid Diseases.

The human microbiota is an integral component in the maintenance of health and of the immune system. Microbiome-wide association studies have found numerous diseases associated to dysbiosis. Studies are needed to move beyond correlations and begin to address causation. Autoimmune thyroid diseases (ATD) are one of the most common organ-specific autoimmune disorders with an increasing prevalence, higher than 5% worldwide. Most frequent manifestations of ATD are Hashimoto's thyroiditis and Graves' disease. The exact etiology of ATD remains unknown. Until now it is not clear whether bacterial infections can trigger ATD or modulate the efficacy of treatment and prognosis. The aim of our review is to characterize the microbiota and in ATD and to evaluate the impact of dysbiosis on treatment and prognosis. Moreover, variation of gut microbiome has been associated with thyroid cancer and benign nodules. Here we will characterize the microbioma in benign thyroid nodules, and papillary thyroid cancer to evaluate their implications in the pathophysiology and progression.

Molecular Alteration Analysis of Human Gut Microbial Composition in Graves' disease Patients.

The gut microbial association with host co-existence is critical for body homeostasis and pathogenicity. Graves' disease (GD) is an autoimmune disease manifested with hyperthyroidism and ophthalmopathy. However, we hypothesized that gut bacteria could affect an important role in GD pathogenicity. The current study aim was to characterize and investigate the intestinal bacterial composition of GD qualitatively and quantitatively. 27 GD and 11 healthy controls were enrolled for fecal sample collection. The PCR-DGGE of 16S rRNA gene by targeting V3 region and Real-time PCR for Lactobacillus, Bifidobacterium, Bacteroides vulgatus and Clostridium leptum, were performed. High-throughput sequencing of 16S rRNA gene with the V3+V4 site was perormed on Hiseq2500 platform on randomly 20 selected samples. The relative analysis of richness indices and diversity illustrated lesser diversification of intestinal bacteria in GD patients in contrast to controls. The data statistics shows the alteration in phyla of GD as compared to control. At the family taxonomic level, the relative abundance of Prevotellaceae and Pasteurellaceae were significantly higher in patients, while Enterobacteriaceae, Veillonellaceae, and Rikenellaceae were significantly lower in the diseased group as compared to control. At the genus level, a significant raised in genera count of the diseased group were Prevotella_9 and Haemophilus, while significantly decreased in the genera of the GD group were Alistipes and Faecalibacterium. The modulation in intestinal bacterial composition was checked at species level particularly H. parainfluenza abundance was raised in GD. The outcomes of the current study are aligned with the proposed hypothesis of gut microbial dysbiosis in GD. Statistically, alpha indices and differential abundance analyses of each intestinal bacterial community were significantly changed in GD. Therefore, the current study may provide a new insight into the GD pathogenesis and, in turn, explore its contribution in possible treatments.

Absence of foamy virus DNA in Graves' disease.

A report on the high prevalence of foamy virus DNA in lymphocytes from French patients with Graves' disease prompted us to investigate a similar cohort of 41 German patients. Using PCR amplification and Southern blot hybridization, we detected foamy virus DNA only in lymphocytes of two accidentally infected humans and five naturally infected monkeys, as well as in DNA samples from four Graves' disease patients investigated in the French study. However, we failed to detect foamy virus DNA in peripheral blood lymphocytes from any of the 41 Graves' disease patients of the German cohort. Thus, a causative role of foamy viruses in this thyroid disease is highly improbable.

Lack of evidence for the presence of human immunodeficiency virus type 1-related sequences in patients with Graves' disease.

The pathogenesis of human autoimmune diseases, including Graves' disease, remains to be elucidated. Recently, Ciampolillo et al. proposed that human immunodeficiency virus type 1 (HIV-1)-related retroviruses were involved in Graves' disease. Using Southern blot analysis, they found specific integration of exogenous sequences homologous to HIV-1 gag region in genome DNA of thyrocytes and peripheral blood lymphocytes (PBL) of patients with Graves' disease. In order to test their hypothesis, we examined the presence or the absence of HIV-1 gag-related sequences in Japanese Graves' patients using the polymerase chain reaction (PCR) in addition to Southern blotting. Sets of primer pairs used in PCR were designed to cover the whole span of the HIV-1 gag region. Hybridization was performed in both relaxed and stringent conditions. Our results showed that neither Southern blot hybridization nor PCR gave positive signals in any of the samples examined from Graves' patients. This suggests that HIV-1 or its closely associated viruses are unlikely to be involved in the pathogenesis of Graves' disease in Japan.

A major role for non-major histocompatibility complex genes but not for microorganisms in a novel murine model of Graves' hyperthyroidism.

The etiology of Graves' disease is multifactorial. We investigated the role of genetic and environmental factors on the susceptibility to Graves' hyperthyroidism using a new murine model. Intramuscular injection of recombinant adenovirus expressing the thyrotropin receptor (AdCMVTSHR) induces Graves'-like hyperthyroidism (thyrotropin receptor [TSHR] antibodies, elevated thyroxine, and diffuse goiter) in more than 50% of female BALB/c mice. The relative contributions of major histocompatibility complex (MHC) and non-MHC genes on the susceptibility to hyperthyroidism were studied by immunizing BALB/c (H-2d), BALB.K (H-2k), and DBA/2J (H-2d) mice with AdCMVTSHR. Hyperthyroidism developed in approximately 50% of BALB/c and BALB.K mice but only 5% of DBA/2J mice, indicating a major role for non-MHC genes in disease development. The effect of environmental microorganisms was evaluated by comparing disease incidence in BALB/c mice maintained in pathogen-free conditions versus those in nonsterile, conventional housing, as well as by coadministering microorganism components (Escherichia coli lipopolysaccharide or yeast zymosan A) as adjuvants with AdCMVTSHR. Neither type of exposure to environmental pathogens influenced disease induction. In conclusion, non-MHC genes, but not infectious organisms, play a major role in the etiology of this novel murine model of Graves' disease.

The infection by Helicobacter pylori strains expressing CagA is highly prevalent in women with autoimmune thyroid disorders.

UNLABELLED: H. pylori infection is putatively associated with extra-digestive disorders and may also play a role in the development of autoimmune thyroid diseases (ATD). It was recently found that monoclonal antibodies to an H. pylori strain with cagA-positivity reacted with follicular cells of the thyroid gland, and that an H. pylori organism possessing the cag pathogenicity island carried a gene encoding for an endogenous peroxidase. The aims of this study was (1); To ascertain whether the infection by strains endowed with an increased inflammatory potential (those expressing CagA) could further enhance the risk of developing ATD (2); To verify the possible existence of an immune cross-reactivity between autoantibodies to peroxidase and thyroglobulin and H. pylori antigens (3). To establish whether thyroid colloid antigens could cross-react with an anti-H. pylori serum. The study was partly designed retrospectively. We examined 41 consecutive women with ATD, and, as a control, 33 consecutive age- and socio-economic class-matched women without autoimmune thyroid disorders, living in the same area as patients, occurred at the same institution in the same period (six months). Both patients and controls were examined serologically for H. pylori infection and CagA status by Western blotting. Some serum samples were absorbed with H. pylori to determine whether the antibody levels decreased. Colloid proteins were resolved electrophoretically and matched with a hyperimmune serum raised in rabbits against a CagA-positive H. pylori. Thirty-two patients (78.0%) tested seropositive for H. pylori infection, vs. 16 controls (48.4%) (P = 0.008, OR = 3.78, RR = 1.61). The prevalence of anti-CagA antibodies was 71.8% in infected patients, and 50% in infected controls (P = 0.161, n.s.). The overall prevalence of infection by CagA-positive H. pylori was significantly higher in patients with ATD (23/41, or 56.0%) than that in controls (8/33, or 24.2%) (P = 0.006, OR = 3.99, RR = 2.31). The other tests gave negative or inexplicable results. IN CONCLUSION: CagA-positive H. pylori infection increases the risk of ATD development.

Pseudomonas aeruginosa ecthyma gangrenosum in a woman with recurrent Graves' disease.

A 35-year-old woman with postoperative recurrent Graves' disease presented with a 5-day history of a red swelling on the right cheek associated with 4 days of remittent hyperpyrexia. Investigations revealed fever, a gangrenous ulcer on the right cheek, submandibular lymphadenopathy, and thyroid gland enlargement. Her white blood cell count, immunoglobulins, and lymphocyte subsets were unremarkable. Thyroid function tests showed low thyroid-stimulating hormone, high free thyroxine, and elevated radioactive iodine uptake. Repeated pus cultures grew Pseudomonas aeruginosa, but blood cultures were negative. An ill-demarcated erythematous plaque occurred on the right leg on hospital day 3. She was treated with intravenous antibiotics with topical gentamicin, recombinant bovine basic fibroblast growth factor, and radioiodine therapy with anti-thyroid drugs. The ulcer healed leaving a depressed scar at 35 days after discharge. This patient may represent the first case of P. aeruginosa ecthyma gangrenosum and cellulitis in postoperative recurrent Graves' disease.