A 51-year-old Caucasian male developed Graves’ thyrotoxicosis following long-standing treatment for hypothyroidism. After a short period of treatment with carbimazole, he developed agranulocytosis and required total thyroidectomy. In this relevant case report, we review several pathogenetic mechanisms that explain the transformation of autoimmune hypothyroidism into Graves’ disease and the possible approaches to the management of agranulocytosis secondary to antithyroid medications. Further studies are required to determine the best way to manage severe thyrotoxicosis when agranulocytosis develops due to antithyroid medications.
Hypothyroidism ; Antithyroid Agents ; Carbimazole ; Agranulocytosis

Objective: The study aims to develop and validate the Filipino version of Thyroid-disease specific quality of life Patient Reported Outcome (ThyPROph) questionnaire, and to conduct a pilot study comparing the quality of life of patients with Graves’ disease at University of Santo Tomas Hospital (USTH) after receiving radioactive iodine ablation (RAI) or anti-thyroid drug (ATD) using the validated ThyPROph. Methodology: This study has 2 phases. Phase 1 is the development and validation of the ThyPROph with prior translation and pretesting to Graves’ disease patients. Phase 2 is the pilot study involving 58 euthyroid patients with Graves’ disease recruited to answer the validated ThyPROph. All of the participants completed the ThyPROph. A cross sectional comparative design was used to compare health-related quality of life (HRQoL) under two modes of treatment for Graves’ disease: RAI and ATD. Likewise, correlation of the domains with the demographics was determined using Pearson correlation coefficient and Spearman rank signed test. Results: For the phase 1 study, internal consistency exists across all domains of ThyPROph with Cronbach’s alpha of 0.839. Overall, discriminant validity falls within range of 0.028-0.606 and convergent validity showed moderate correlations. Phase 2 study showed that there is a significant difference in the domains “goiter symptoms” (p=0.0209), “emotional susceptibility” (p=0.0067) and “impaired daily life” (p=0.0463). The HRQoL is significantly better in the RAI group based on these three domains. Statistically significant correlations exist between goiter grade and goiter symptoms domain (p=0.0001), gender and impaired daily life domain (p=0.016), cosmetic complaints domain with age (p=0.002), marital status (p=0.046), and disease duration (p=0.005). Limitations: Results are not powered to achieve the primary objective because complications of Graves’ disease were excluded. The reliability of the domains is reduced. A prospective randomized study is more ideal. Conclusion Quality of life of patients with Graves’ disease as assessed by ThyPROph is significantly better with RAI compared to ATD. RAI therapy can be considered as the better treatment option in our setting especially for patients who have noticeable goiters with symptoms attributable to their goiters, and those with emotional instability.
Graves Disease ; Quality of Life ; Antithyroid Agents

Antithyroid drugs are the most common treatment modality for Graves' disease and are used for the treatment of relapsed Graves' disease in Korea. Agranulocytosis is a rare and severe complication of antithyroid drug therapy, and most cases occur within 3 month after drug treatment. Agranulocytosis can develop in patients who have relapsed Graves' disease and undergo a second course of antithyroid drugs with a prior uneventful course of drug therapy. We report a case of antithyroid drug-induced agranulocytosis in a relapsed Graves' disease patient who had undergone prior uneventful antithyroid drug therapy. We also present a review of the relevant literature.
Agranulocytosis ; Antithyroid Agents ; Graves Disease ; Humans ; Korea ; Recurrence

Among the three treatment modalities of Graves' disease which include antithyroid drug (ATD), radioactive iodine and surgery, the ATD is most commonly preferred in Korea due to ease of use and definite curative effects on the thyrotoxic symptoms. However, several uncertainties about ATD remain: for example, the mechanism of actions on immune modulation, differences in the effects of drugs among individuals and associated factors in the view of remission. In recent years, long-term ATD treatment has been confirmed as an effective and safe therapy modality in adults, and several treatment guidelines have been released which accept long-term ATD therapy as an acceptable alternative to ablative therapy in Graves' patients. In this review, we summarize the recent progress in understanding the clinical role of ATD and emerging new antithyroid drugs focusing on immunomodulation.
Adult ; Antithyroid Agents ; Graves Disease ; Humans ; Immunomodulation ; Iodine ; Korea

Antithyroid drugs (ATD) has been widely used to treat Graves' disease. However agranulocytosis, a serious fatal complication of ATD treatment, occurs in about 0.5 percent. The symptoms may mimic viral infections (fever, sore throat), and the potentially life-threatening pyogenic infections can go unrecognized initially. The median duration of drug exposure before the onset of acute agranulocytosis is within 30 days in most cases. We report a case of agranulocytosis with secondary soft tissue infection and abscess occuring after increasing the dose of methimazole in a woman who had taken methimazole for more than 10 years. We administered broad-spectrum antibiotics and aspirated the soft tissue abscess. A review of the medical literature regarding agranulocytosis in the setting of ATDs is presented.
Abscess ; Agranulocytosis ; Anti-Bacterial Agents ; Antithyroid Agents ; Female ; Graves Disease ; Humans ; Hydrazines ; Methimazole ; Soft Tissue Infections

BACKGROUND: Propylthiouracil (PIV) and methimazole (MMI) were widely used for the treatment of hyperthyroidism. Hepatic injury caused by these agents is a rare but serious complication. This study is to investigate the clinical features of hepatotoxicity from antithyroid drugs. METHODS: We reviewed 17 cases of hepatic injury during treatment with antithyroid drugs in patients with hyperthyroidism. Included were 6 cases we experienced and 11 cases reported in Korean literature from 1986 to 1999. We analyzed the clinical features of hepatic injury. RESULTS: Of 17 cases of hepatic injury, 12 were PTU cases and 5 MMI cases. The mean age of PTU cases was 40 years with 6/12 patients over 40 years old and 2/5 MMI cases were over 40 years old. The dose of PTU was 300 mg/d or more in 10/12 cases (83%) and the dose of MMI was 30 mg/d in 3/5 cases (60%). The hepatic injury occurred within 3 months in 8/12 PTU cases (67%) and within 2 months in 4/5 MMI cases (80%). The duration of hepatic injury tended to be longer in MMI cases than in PTV cases (median; 80 vs 41 days, p=0.102). In PTU cases, the duration of hepatic injury was correlated with the duration of drug use before hepatic injury (p<0.05). All of 8 biopsied cases who took PTU had predominantly hepatocellular necrosis. Two biopsied cases who took MMI had cholestatic jaundice and nonspecific abnormality, respectively. Biochemical findings of all MMI cases were compatible with cholestatic jaundice. As to the treatment of hyperthyroidism after hepatic injury, 4/12 PTU cases were treated with RAI therapy, 5 with MMI and one with surgery, and treatment was unknown in two. On the other hand 3/5 MMI cases interestingly entered into spontaneous remission after hepatic injury and 2/5 had RAI therapy. Hepatic dysfunction recurred in each one whom treatment by changing to MMI or PTU was tried on. CONCLUSION: Most of hepatic injury during treatment with antithyroid drugs developed within two to three months of drug use. The hepatic injury related to PTU was mainly cytotoxic whereas that related to MMI was cholestatic. Since there is a cross-reaction between PTU and MMI in hepatotoxicity, RAI therapy or operation shoud be considered as an alternative treatment of hyperthyroidism after hepatic injury.
Adult ; Antithyroid Agents* ; Hand ; Humans ; Hyperthyroidism* ; Jaundice, Obstructive ; Methimazole ; Necrosis ; Propylthiouracil ; Remission, Spontaneous

OBJECTIVE: Since Graves' disease (GD) is resistant to antithyroid drugs (ATDs), an accurate quantitative thyroid function measurement is required for the prediction of early responses to ATD. Quantitative parameters derived from the novel technology, single-photon emission computed tomography/computed tomography (SPECT/CT), were investigated for the prediction of achievement of euthyroidism after methimazole (MMI) treatment in GD. MATERIALS AND METHODS: A total of 36 GD patients (10 males, 26 females; mean age, 45.3 ± 13.8 years) were enrolled for this study, from April 2015 to January 2016. They underwent quantitative thyroid SPECT/CT 20 minutes post-injection of (99m)Tc-pertechnetate (5 mCi). Association between the time to biochemical euthyroidism after MMI treatment and %uptake, standardized uptake value (SUV), functional thyroid mass (SUVmean × thyroid volume) from the SPECT/CT, and clinical/biochemical variables, were investigated. RESULTS: GD patients had a significantly greater %uptake (6.9 ± 6.4%) than historical control euthyroid patients (n = 20, 0.8 ± 0.5%, p < 0.001) from the same quantitative SPECT/CT protocol. Euthyroidism was achieved in 14 patients at 156 ± 62 days post-MMI treatment, but 22 patients had still not achieved euthyroidism by the last follow-up time-point (208 ± 80 days). In the univariate Cox regression analysis, the initial MMI dose (p = 0.014), %uptake (p = 0.015), and functional thyroid mass (p = 0.016) were significant predictors of euthyroidism in response to MMI treatment. However, only %uptake remained significant in a multivariate Cox regression analysis (p = 0.034). A %uptake cutoff of 5.0% dichotomized the faster responding versus the slower responding GD patients (p = 0.006). CONCLUSION: A novel parameter of thyroid %uptake from quantitative SPECT/CT is a predictive indicator of an early response to MMI in GD patients.
Antithyroid Agents ; Female ; Follow-Up Studies ; Graves Disease* ; Humans ; Male ; Methimazole* ; Thyroid Gland

BACKGROUND: Graves' disease is an organ specific autoimmune disease. Three kinds of therapeutic modalities(antithyroid drugs, ablation with radioactive iodine and subtotal thyroidectomy) are frequently performed for the management of this disease. The most popular therapeutic policy for the disease in Korea is antithyroid treatment. We analysed and compared the remission rates of all three modalities for Graves' disease, and evaluated the antithyroid modality to determine the correct duration of treatment. SUBJECTS AND METHODS: The medical records of 205 patients with Graves' disease were reviewed. For the evaluation of the antithyroid modality medical treatment, antithyroid drugs were administered for more than 1 year. The prognostic factors associated with remission were analysed by means of an ROC curve. RESULTS: 1) Of the 205 patients, proportions that received medical therapy, subtotal thyroidectomy and radioiodine therapy were 83.0, 14.1 and 2.9%, respectively. 2) The remission rates of the medical therapy, surgery and radioiodine therapy were 60.0, 96.5 and 83.0%, respectively. 3) The remission rate of the medical therapy was associated with the duration of medication and TBII activity. The determined proper duration for the antithyroid treatment was 26 months from the ROC curve analysis. CONCLUSION: The above results suggest that the proper duration of antithyroid treatment for Graves' disease is 26 months, after which time the subtotal thyroidectomy or radioiodine therapy should be considered if the disease has not remitted.
Antithyroid Agents ; Autoimmune Diseases ; Graves Disease* ; Humans ; Iodine ; Korea ; Medical Records ; ROC Curve ; Thyroidectomy

Vasculitis is a rare complication of antithyroid drugs. Recently it was reported in association with ANCA. In most cases, the ANCA was specific for myeloperoxidase. The glomerulonephritis was key clinical manifestation in majority of cases. When antithyroid drugs were discontinued, clinical disease generally improved and ANCA titers were tended to fall. We experienced a 44 year old woman who presented with gross hematuria and generalized edema, after she had been treated with prophylthiouracil for 6 week for thyrotoxicosis. Renal biopsy was done, which showed mesangial proliferative glomerulonephritis. Indirect immunoflurorescence staining showed highly positive perinuclear pattern of ANCA in her serum. Prophylthiouracil associated ANCA positive glomerulonephritis was suspected. After cessation of prophylthiouracil and administration of prednisolone, renal function recovered gradually and ANCA titers were reduced. We hereby report a case of prophylthiouracil associated ANCA positive glomerulonephritis with a brief review of literature.
Adult ; Antibodies, Antineutrophil Cytoplasmic* ; Antithyroid Agents ; Biopsy ; Edema ; Female ; Glomerulonephritis* ; Hematuria ; Humans ; Peroxidase ; Prednisolone ; Thyrotoxicosis ; Vasculitis

Graves' disease (GD) accounts for 10%-15% of thyroid disorders in children and adolescents. The use of antithyroid drugs as the initial treatment option in GD is well accepted. An average two years remission is achieved in about 30% of children treated with antithyroid drugs. However, the optimal treatment duration and the predictive marker of remission after antithyroid drug therapy are still controversial. Additionally, 131I therapy and surgery are considered the option for treatment in children and adolescents with GD. We review the treatment options for pediatric GD and the possible determinants of remission and relapse on antithyroid drug treatment in children and adolescents.
Adolescent* ; Antithyroid Agents ; Child* ; Drug Therapy ; Graves Disease* ; Humans ; Hyperthyroidism ; Recurrence ; Thyroid Gland