Comparison of Surgical Outcomes of Transoral Versus Open Thyroidectomy for Graves Disease.

INTRODUCTION: The transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a safe alternative to thyroidectomy for thyroid goiter and provides the benefit of being scarless. However, the data on the use of TOETVA in patients with Graves disease are limited. This retrospective study compared the outcomes of Graves disease patients who underwent TOETVA versus those who underwent open thyroidectomy (OT). MATERIALS AND METHODS: Patients with Graves disease who received TOETVA or OT for bilateral total thyroidectomy between September 2017 and October 2022 were included. Patient demographics and surgical outcomes, including operation time, blood loss, length of stay, and complications, were compared. RESULTS: There were 15 patients in each group. The mean age in the TOETVA group was 35.80±8.13 years, which was significantly younger than that in the OT group, which was 51.53±14.22 years. Females predominated in both groups. The other demographic characteristics were similar in both groups. The operation time and intraoperative blood loss were also comparable. The postoperative stay and complications, including hypoparathyroidism, recurrent laryngeal nerve injury, surgical site infection, postoperative hemorrhage, and recurrence of hyperthyroidism, were not different between the 2 groups. There were 11 patients in the TOETVA group and 10 in the OT group who had thyroglobulin levels <0.1 ng/dL, indicating the completeness of total thyroidectomy in the 2 groups. There was no conversion of TOETVA to an open procedure. CONCLUSIONS: For carefully selected Graves patients, TOETVA offers a safe, scarless, and feasible alternative to conventional open thyroidectomy.

Pediatric thyroid surgery: Retrospective analysis on the first 25 pediatric thyroidectomies performed in a reference center for adult thyroid diseases.

Introduction: Pediatric thyroid carcinoma represents about 4-5% of all pediatric carcinoma with an incidence of 0.5 cases/100,000, compared to 2-10/100000 cases in the adult population. The aim of this study is to present the experience of a reference adult endocrine surgery unit in charge of the treatment of pediatric thyroid diseases. Materials and methods: From January 2019 to September 2022, 25 patients, aged 5-17, underwent thyroid surgery. We analysed indications for surgery, use of intraoperative nerve monitoring (IONM), definitive histological examination, postoperative outcomes and risk factors related. Results: Surgical indication was performed for Graves' disease (27%) and for nodular pathology (73%): of these, four were malignant lesions (TIR4/TIR5), eight with indeterminate characteristics (TIR3A/TIR3B) and four characterized as benign (TIR1/TIR2). Total thyroidectomy (TT) was performed in 76% of cases, three of which were prophylactic for the activation of the RET gene mutation in MEN 2A. IONM was used in eight cases (32%), all patients aged 11 years or less. FNA's accuracy was 100% for lesions typified as benign and malignant (TIR1/TIR2 and TIR4/TIR5). The overall malignancy rate achieved was 40% and in the final histological examination 75% of the TIR 3B lesions were malignant. Six patients (24%) developed hypoparathyroidism in the first postoperative day, with normalization of calcium values within thirty days in 5 patients. Conclusions: Pediatric thyroid nodules are rare and distinguished from adult thyroid disease by a worse prognosis and higher malignancy rates. Our work reports a much higher malignancy rate among indeterminate TIR 3B lesions than observed in the adult population and the three patients who underwent prophylactic total thyroidectomy for activating RET gene mutation had all a definitive histological diagnosis of medullary carcinoma. Post-surgical hypoparathyroidism is a common finding in these patients: in most cases the condition is transient and it benefits from supportive therapy. Intraoperative finding of a thinner recurrent laryngeal nerve in younger patients makes nerve isolation more difficult than in adult surgery: IONM is recommended in patients under 12. Pediatric thyroid surgery is challenging, we sustain it requires referral thyroid Centers for thyroid disease with highly skilled general endocrine surgeons.

Familial Risk of Graves Disease Among First-Degree Relatives and Interaction With Smoking: A Population-Based Study.

CONTEXT: Population-based studies on the familial aggregation of Graves disease (GD) are scarce and gene-environment interactions are not well-studied. OBJECTIVE: We evaluated the familial aggregation of GD and assessed interactions between family history and smoking. METHODS: Using the National Health Insurance database, which includes information on familial relationships and lifestyle risk factors, we identified 5 524 403 individuals with first-degree relatives (FDRs). Familial risk was calculated using hazard ratios (HRs), comparing the risk of individuals with and without affected FDRs. Interactions between smoking and family history were assessed on an additive scale using relative excess risk due to interaction (RERI). RESULTS: The HR among individuals with affected FDRs was 3.39 (95% CI, 3.30-3.48) compared with those without affected FDR, and among individuals with affected twin, brother, sister, father, and mother, the HRs were 36.53 (23.85-53.54), 5.26 (4.89-5.66), 4.12 (3.88-4.38), 3.34 (3.16-3.54), and 2.63 (2.53-2.74), respectively. Individuals with both a positive family history and smoking had an increased risk of disease (HR 4.68) with statistically significant interaction (RERI 0.94; 95% CI, 0.74-1.19). Heavy smokers with a positive family history showed a nearly 6-fold increased risk, which was higher than moderate smoking, suggesting a dose-response interaction pattern. Current smoking also showed a statistically significant interaction with family history (RERI 0.52; 95% CI, 0.22-0.82), while this was not observed for former smoking. CONCLUSION: A gene-environment interaction can be suggested between smoking and GD-associated genetic factors, which diminishes after smoking cessation. Smokers with a positive family history should be considered a high-risk group and smoking cessation should be advised.

Combination of treatments with transoral endoscopic thyroidectomy vestibular approach (TOETVA) for Graves' disease.

Although the success rates of non-surgical treatments for Graves' disease such as antithyroid medication and radioiodine ablation were good, there were still failure of treatments or intolerance for some patients. Traditional thyroid surgery could treat these patients but result in unaesthetic neck scars. Herein, we report the preliminary results of our combination of treatments with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease. A retrospective review of patients who underwent the transoral endoscopic thyroidectomy vestibular approach for the treatment of different sizes of goiters between January 2019 and December 2020 was performed. The demographic and clinical data of patients were collected. All patients were followed up for > 12 months. Each patient's goiter size was determined using four grades-from 0 to 3. In total, 14 female patients receiving the combination treatment with > 1 year of follow-up and a median (range) age of 35 (20-48) years at surgery were included. There were two, three, four, and five patients with grade 0, 1, 2, and 3 goiters, respectively. The median (range) intraoperative blood loss was higher in grade 3 patients (100 [20-850] mL) than in grade 2 patients (20 [10-200] mL) and grade 1 and 0 patients (both < 10 mL) (p = 0.033). All patients had normal-looking necks with a euthyroid or hypothyroid status within 1 year. There were no complications, including re-operation for bleeding, hypoparathyroidism, vocal cord palsy, or infections. The designed combination treatment with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease provides optimal cosmetic results with a high success rate.

TSAb Modulates Microglia M1 Polarization via Activation of the TSHR-Mediated NF-κB Signaling Pathway.

INTRODUCTION: Thyrotropin receptor-stimulating antibody (TSAb) is a pathogenic antibody in the serum of patients with Graves' disease. The binding of TSAb to thyroid-stimulating hormone receptor (TSHR) in non-thyroid tissue may be associated with the occurrence and development of Graves' disease-related complications. However, only few studies have been conducted on the effects of TSAb on the brain, and the pathogenesis of acute hyperthyroidism myopathy (ATM) is unclear. Therefore, this study aimed to explore the effect of TSAb on the polarization of BV-2 cells in the brain and its possible mechanism and provide a basic experimental basis for ATM. METHODS: BV-2 cells were treated with different concentrations of TSAb. The relative survival rate of BV-2 cells was determined using the CCK-8 assay; the migration ability of BV-2 cells was detected using the Transwell migration assay; and the expression levels of M1/M2 polarization markers (CD86, inducible nitric oxide synthase [iNOS], CD206, and arginase 1 [Arg-1]), TSHR, tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) protein in BV-2 cells were measured using WB. RESULTS: Compared with the negative control group, the proliferative activity of BV-2 cells was significantly increased in the 20, 50, and 100 ng/mL TSAb groups, and the migration ability of BV-2 cells was significantly enhanced in the 50 and 100 ng/mL TSAb groups. The expression levels of M1 polarization markers (CD86 and iNOS), TSHR, TNF-α, and NF-κB protein in BV-2 cells treated with 50 and 100 ng/mL TSAb for 24 h were significantly upregulated, whereas those of M2 polarization markers (CD206 and Arg-1) significantly decreased. CONCLUSIONS: TSAb can induce abnormal activation of microglia, polarize to the M1 phenotype, and promote the inflammatory cascade reaction, in which TSHR plays a key role in NF-κB activation and proinflammatory cytokine release.

Hipertiroidismo por enfermedad de Graves posterior a vacuna contra SARS-CoV-2: reporte de 2 casos / Graves' disease hyperthyroidism following SARS-CoV-2 vaccination: a two cases report

Luego del inicio de las campañas de vacunación masiva contra la infección por COVID-19, se han publicado una serie de reportes que muestran la posible asociación entre la vacuna y alteraciones de la función tiroidea. Desde entonces, múltiples teorías han intentado explicar este hallazgo, en su mayoría de índole autoinmune. Dentro de estas destaca el síndrome autoinmune-autoinflamatorio secundario a adyuvantes (ASIA), que podría generar desórdenes tiroideos de novo o exacerbar los ya existentes. Presentamos dos casos de enfermedad de Graves Basedow posterior al uso de Coronavac. Ambas pacientes presentaron características similares a las descritas en la literatura y cumplen con los criterios de ASIA. No obstante, los beneficios de las vacunas superan los posibles riesgos asociados.

After the beginning of COVID-19 vaccination campaigns, a number of reports have shown the potential association between vaccines and thyroid disfunction. Since then several theories have tried to explain this finding, mostly autoinmmune. One of them is the autoimmune/inflammatory syndrome induced by adjuvants, that could trigger or exacerbate thyroid disease. We present two cases of Graves' disease post Coronavac vaccination. Both pacients share similar features than cases published previously and meet criteria for ASIA syndrome. Nevertheless, the benefts of vaccination largely outweigh any adverse events associated.

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.

Thyroid complications of SARS and coronavirus disease 2019 (COVID-19).

We have reviewed the available literature on thyroid diseases and coronavirus disease 2019 (COVID-19), and data from the previous coronavirus pandemic, the severe acute respiratory syndrome (SARS) epidemic. We learned that both SARS and COVID-19 patients had thyroid abnormalities. In the limited number of SARS cases, where it was examined, decreased serum T3, T4 and TSH levels were detected. In a study of survivors of SARS approximately 7% of the patients had hypothyroidism. In the previous evaluation evidence was found that pituitary function was also affected in SARS. Others suggested a hypothalamic-pituitary-adrenal axis dysfunction. One result published recently indicates that a primary injury to the thyroid gland itself may play a key role in the pathogenesis of thyroid disorders in COVID-19 patients, too. Subacute thyroiditis, autoimmune thyroiditis and an atypical form of thyroiditis are complications of COVID-19. Thyroid hormone dysfunction affects the outcome by increasing mortality in critical illnesses like acute respiratory distress syndrome, which is a leading complication in COVID-19. Angiotensin-converting enzyme 2 is a membrane-bound enzyme, which is also expressed in the thyroid gland and the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) uses it for docking, entering as well as replication. Based on the available results obtained in the SARS-CoV-2 pandemic, beside others, we suggest that it is necessary to monitor thyroid hormones in COVID-19.

Gene polymorphisms of pro-inflammatory cytokines may affect the risk of Graves' disease: a meta-analysis.

PURPOSE: Gene polymorphisms of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) may influence the risk of Graves' disease, but the results of so far published studies remain inconclusive. Therefore, the authors conducted this meta-analysis to assess relationships between TNF-α/IL-1/IL-6 polymorphisms and the risk of Graves' disease by pooling the findings of all relevant studies. METHODS: A comprehensive literature searching of Pubmed, Embase, Web of Science and CNKI was conducted by the authors, and twenty-eight studies were found to be eligible for pooled analyses. RESULTS: The pooled meta-analyses results showed that genotypic frequencies of TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects differed significantly. Moreover, we found that genotypic frequencies of TNF-α rs1800629 and IL-6 rs1800795 polymorphisms among patients with Graves' disease and control subjects in Caucasians differed significantly, and genotypic frequencies of IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms among patients with Graves' disease and control subjects in Asians also differed significantly. Nevertheless, we did not detect such genotypic frequencies differences for TNF-α rs361525 and IL-1B rs1143627 polymorphisms. CONCLUSIONS: This meta-analysis suggests that TNF-α rs1800629, IL-1A rs1800587, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in overall population. Moreover, TNF-α rs1800629 and IL-6 rs1800795 polymorphisms may influence the risk of Graves' disease in Caucasians, while IL-1A rs1800587, IL-1B rs16944, IL-6 rs1800795 and IL-6 rs1800796 polymorphisms may influence the risk of Graves' disease in Asians.

Graves' disease: Epidemiology, genetic and environmental risk factors and viruses.

Graves' disease (GD) is the most common cause of hyperthyroidism in developed Countries. It is more common between 30 and 60 years; 5-10 times more frequent in women. The genetic predisposition accounts for 79% of the risk for GD, while environmental factors for 21%. About 70% of genes associated with autoimmune thyroid disorders (AITD) are implicated in T-cell function. Among GD endogenous factors, estrogens, X-inactivation and microchimerism are important. Among environmental risk factors, smoking, iodine excess, selenium and vitamin D deficiency, and the occupational exposure to Agent Orange have been associated with GD. Many studies showed that HCV is associated with thyroid autoimmunity and hypothyroidism, in patients with chronic HCV hepatitis (CHC); a significant link has been shown also between HCV-related mixed cryoglobulinemia and risk for GD. Moreover, IFN-α-treated CHC patients develop GD more frequently. Novel studies are needed about possible risk factors to reduce the occurence of GD in West Countries.

An improved mouse model of Graves disease by once immunization with Ad-TSHR289.

The novel Graves disease (GD) model was established in BALB/c mice with recombinant adenovirus expressing the full-length human TSHR (Ad-TSHR289) by three times immunizations for nearly three months. Reducing the frequency of immunizations may shorten the modeling time to improve the efficiency of the study. In this study, female BALB/c mice were immunized one time with an adenovirus expressing the autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). At the 3, 6, 12, 17 weeks after the immunization, mice were sacrificed. The blood was collected and thyroids were removed. T3, T4, TRAB and thyroid weight/body weight (TW/BW) were tested. Compared with the Normal control (NC) group, the incidence of hyperthyroidism at 3, 6, 12 and 17 weeks after immunization were about 66.67%, 100%, 100%, and 100%. Meanwhile, the incidences of goiter were nearly 50%, 83.33%, 100% and 100% at the same stages. Therefore, modeling rates of GD were about 50%, 83.33%, 100%, 100% at 3, 6, 12 and 17 weeks after immunization. T3 in serum continues to increase from 3 weeks to 17 weeks after immunization. Serum TRAb reached to peak at 6 weeks and remained from 12 weeks after immunization, while T4 and TW/BW had kept steady from 6 weeks. There are positive correlations between T3, T4 and TRAb, TRAb and TW/BW, as well as T3, T4 and TW/BW. GD model can be constructed by primary immunization with Ad-TSHR289, which could be detected at 3 weeks and at least until the 17 weeks after primary immunization. It would improve the efficiency of GD research.

Does the Epstein-Barr Virus Play a Role in the Pathogenesis of Graves' Disease?

Graves' disease (GD) it the most common chronic organ-specific thyroid disorder without a fully recognized etiology. The pathogenesis of the disease accounts for an interaction between genetic, environmental, and immunological factors. The most important environmental factors include viral and bacterial infections. The Epstein-Barr virus (EBV) is one of the most common latent human viruses. Literature has suggested its role in the development of certain allergic and autoimmune diseases. EBV also exhibits oncogenic properties. The aim of the study was to analyze and compare the presence of EBV DNA in peripheral blood mononuclear cells (PBMCs) in patients with newly recognized GD and to find a correlation between EBV infection and the clinical picture of GD. The study included 39 untreated patients with newly diagnosed GD and a control group of 20 healthy volunteers who were gender and age matched. EBV DNA was detected with reverse transcription polymerase chain reaction (RT PCR) assay. The studies showed a significantly higher incidence of EBV copies in PBMCs among GD patients compared to the control group. Whereas, no significant correlations were found between the incidence of EBV copies and the evaluated clinical parameters. Our results suggest a probable role of EBV in GD development. EBV infection does not affect the clinical picture of Graves' disease.

Dihydrotestosterone regulates oxidative stress and immunosuppressive cytokines in a female BALB/c mouse model of Graves' disease.

Background: Graves' disease (GD) is an autoimmune disease that affects more women than men. In our previous study, a potent bioactive androgen, 5α-dihydrotestosterone (DHT) showed a protective effect against GD in female BALB/c mice. Evidence indicates that abnormal oxidative stress and immunosuppressive cytokines (TGF-ß, IL-35) play critical roles in the pathogenesis and development of GD. The purpose of this research is to measure these cytokines and oxidative stress markers to explore potential protective mechanisms of DHT in a BALB/c mouse model of GD. Methods: GD was induced in female BALB/c mice by intramuscular injection of an adenovirus expressing the A-subunit of the TSH receptor (Ad-TSHR289). DHT or a matching placebo was injected every 3 days. Mice were sacrificed four weeks after the third virus immunization to obtain blood, thyroid and spleen for further analysis. Results: Thyroid hormones were significantly reduced in DHT treated GD mice. In addition, DHT attenuated thyroid oxidative injuries in GD mice, as shown by decreased total antioxidation capability (TAOC), superoxide dismutase (SOD) and the level of malondialdehyde (MDA). The levels of immunosuppressive cytokines (TGF-ß, IL-35) in DHT group were significant higher compared with the GD group. Conclusions: The results demonstrated that DHT could reduce the severity of GD in female BALB/c mice by regulating oxidative stress. The upregulation of immunosuppressive cytokines might be another important protective mechanism.

Possible participation of colloid antigen 2 and abhormone (IgG with hormone activity) for the etiology of Graves' disease.

The theory that antibody (Ab) directed against the TSH receptor (TSHR) (TSHRAb) is the causal factor of Graves' disease seems unlikely. Corticosteroids have not had a curative effect on the hyperthyroidism of Graves' disease despite their effectiveness for other autoimmune diseases. Two kinds of TSHRAb, thyroid-stimulating Ab (TSAb) and thyroid-blocking Ab (TBAb), are known as causal factors of hyperthyroidism and hypothyroidism, respectively. Previously, we reported that TSAb may be thyroid stimulating animal IgG-like hormone and TBAb may be the precursor of TSAb. In this paper we suggested that TBAb (precursor) converts to TSAb (active form) via the action of the protease, colloid antigen 2 (CA2). We speculate that the conversion of TBAb to TSAb is controlled by two factors: the protease and an anti-protease Ab. When anti-protease Ab levels are high, the patient exhibits hypothyroidism due to the increase in TBAb levels caused by neutralization of the protease. When anti-protease Ab levels are negative, the patient's hypothyroidism disappeared by the negative serum TBAb due to increased protease. An immunoglobulin G (IgG) with enzyme activity is known as an abzyme, which may be an undeveloped form. IgG with hormone activity may be likewise called an abhormone, which could also be an undeveloped form. The tumor marker CEA is a known member of the IgG supergene family. Many ancestral versions of proteins may have been produced as an IgG form. Possible participation of colloid antigen 2 and abhormone for the etiology of Graves' disease is suggested.

Thyrotrophin receptor antibody concentration and activity, several years after treatment for Graves' disease.

OBJECTIVE: TSH receptor antibodies (TRAb) are responsible for autoimmune hyperthyroid disease (Graves' disease; GD) with TRAb levels tending to decrease following treatment. Measurement of TRAb activity during follow-up could prove valuable to better understand treatment effectiveness. STUDY DESIGN: TRAb concentration and stimulating (TSAb) and blocking (TSBAb) activity of patient serum were assessed following different treatment modalities and follow-up length. METHODS: Sixty-six subjects were recruited following treatment with carbimazole (n = 26), radioiodine (n = 27) or surgery (n = 13). TRAb, TPOAb, TgAb and GADAb were measured at a follow-up visit as well as bioassays of TSAb and TSBAb activity. RESULTS: Forty-five per cent of all patients remained TRAb-positive for more than one year and 23% for more than 5 years after diagnosis, irrespective of treatment method. Overall, TRAb concentration fell from a median (IQR) of 6.25 (3.9-12.7) to 0.65 (0.38-3.2) U/L. Surgery conferred the largest fall in TRAb concentration from 11.4 (6.7-29) to 0.58 (0.4-1.4) U/L. Seventy per cent of TRAb-positive patients were positive for TSAb, and one patient (3%) was positive for TSBAb. TRAb and TSAb correlated well (r = 0.83). In addition, 38/66 patients were TgAb-positive, 47/66 were TPOAb-positive and 6/66 were GADAb-positive at follow-up. CONCLUSIONS: TRAb levels generally decreased after treatment but persisted for over 5 years in some patients. TRAb activity was predominantly stimulatory, with only one patient demonstrating TSBAb. A large proportion of patients were TgAb/TPOAb-positive at follow-up. All treatment modalities reduced TRAb concentrations; however, surgery was most effective.

[New perspectives for the diagnosis and prognosis of Graves' disease]. / Nouvelles perspectives pour le diagnostic et pronostic de la maladie de Basedow.

Graves' thyroiditis is a frequent disease. It has a considerable impact on patient's life quality and health expenses. Thus, it is important to optimize the treatment and follow up. The identification of new factors predisposing to the disease and factors that may help to predict the severity or recurrence of the disease or the occurrence of graves' orbitopathy could optimize the management. Genetic predisposition has a major role in the development of Graves' disease. The new genes in addition to those already known to be involved in Graves' disease are under study. However, genetic predisposition alone cannot explain the occurrence of the disease. MicroRNAs are non-genetic factors that are significantly associated with different severities or relapses of Graves' disease as well as with the occurrence of graves' orbitopathy. These genetic and epigenetic factors together with known environmental factors can be used to predict the risk of relapse of Graves' disease or of the occurrence of orbital orbitopathy. This will lead to new promising therapeutic targets.

Graves' disease following allogenic hematopoietic stem cell transplantation for severe aplastic anemia: case report and literature review.

BACKGROUND: Similar autoimmune processes (defective T-cell function) take place during the pathogenesis of aplastic anemia (AA) and Graves' disease (GD). Antithyroid drugs used for the management of GD may induce AA and GD may occur following treatment of severe aplastic anemia (SAA). CASE PRESENTATION: Clinical and laboratory investigations were performed for an 11-year-and-2-month-old girl who was referred for bilateral exophthalmus and abnormal thyroid function tests. She had been diagnosed as having severe acquired AA at the age of 8 years and had been treated with allogenic hematopoietic stem cell transplantation from her healthy human leukocyte antigen-matched sibling donor. Clinical examination revealed a weight of 32.6 kg (-0.88 standard deviation [SD] score); height, 145.7 cm (-0.14 SD score); body mass index 15.5 kg/m2 (-1.01 SD score); heart rate, 110/min; blood pressure, 128/74 mmHg; bilateral exophthalmos and an enlarged thyroid gland. The laboratory workup showed hemoglobin of 11.1 g/dL; white blood cells, 7500/mL; platelets, 172,000/mL; free thyroxine (FT4), 4.80 ng/dL (normal, 0.5-1.51); free triiodothyronine (FT3), 17.7 pg/mL (normal, 2.5-3.9); thyrotropin (TSH), 0.015 mIU/mL (normal, 0.38-5.3); antithyroglobulin peroxidase (TPO) antibody, 61.7 IU/mL (normal, 0-9); antithyroglobulin (TG) antibody, <0.9 IU/mL (normal, 0-4) and thyrotropin (TSH) receptor antibodies 14 U/L (normal, 0-1). Doppler ultrasonography showed diffuse enlargement of the thyroid gland and increased vascularity. She was treated with methimazole (0.6 mg/kg/day). L-thyroxine treatment was also needed (50 µg/day). Thrombocytopenia developed during follow-up. A thyroidectomy was performed for definitive treatment at the 14th month of treatment. CONCLUSIONS: The association of hyperthyroidism and AA in the pediatric age group is rare. The long-term use of antithyroid drugs and radioactive iodine should be avoided due to their hematologic toxic side effects.

Recurrence of Graves' disease in ectopic thyroid tissue.

A 40-year-old woman with a history of Graves' disease status postorbital decompression for severe ophthalmopathy underwent total thyroidectomy by a high volume thyroid surgeon in July 2013 with a benign final pathology. Eight months later, she presented with a mass on the right anterior neck that showed minimal growth over time. Her thyroid stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were consistently elevated and increasing. She underwent removal of the neck mass in September 2016. Final pathology showed benign thyroid tissue with diffuse hyperplasia and lymphoid follicles, consistent with Graves' disease. We present an unusual recurrence of Graves' disease post-total thyroidectomy that recurred secondary to ectopic thyroid tissue in the right upper anterior neck deep to the strap muscles.