Endocrinology and Metabolism

Original Articles

Thyroid
Efficacy and Safety of Long-Term Methimazole versus Radioactive Iodine in the Treatment of Toxic Multinodular Goiter: Fereidoun Azizi, Navid Saadat, Mir Alireza Takyar, Hengameh Abdi, Ladan Mehran, Atieh Amouzegar; Endocrinol Metab. 2022;37(6):861-869. Published online November 23, 2022; DOI: https://doi.org/10.3803/EnM.2022.1476

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Background
This study compared the degree of sustained control of hyperthyroidism in patients with toxic multinodular goiter (TMNG) treated with long-term methimazole (LT-MMI) or radioactive iodine (RAI).
Methods
In this clinical trial, 130 untreated patients with TMNG were randomized to either LT-MMI or RAI treatment. Both groups were followed for 108 to 148 months, with median follow-up durations of 120 and 132 months in the LT-MMI and RAI groups, respectively. Both groups of patients were followed every 1 to 3 months in the first year and every 6 months thereafter.
Results
After excluding patients in whom the treatment modality was changed and those who were lost to follow-up, 53 patients in the LT-MMI group and 54 in the RAI group completed the study. At the end of the study period, 50 (96%) and 25 (46%) patients were euthyroid, and two (4%) and 25 (46%) were hypothyroid in LT-MMI and RAI groups, respectively. In the RAI group, four (8%) patients had subclinical hyperthyroidism. The mean time to euthyroidism was 4.3±1.3 months in LT-MMI patients and 16.3± 15.0 months in RAI recipients (P<0.001). Patients treated with LT-MMI spent 95.8%±5.9% of the 12-year study period in a euthyroid state, whereas this proportion was 72.4%±14.8% in the RAI-treated patients (P<0.001). No major treatment-related adverse events were observed in either group.
Conclusion
In patients with TMNG, LT-MMI therapy is superior to RAI treatment, as shown by the earlier achievement of euthyroidism and the longer duration of sustained normal serum thyrotropin.

Citations

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Control rate of hyperthyroidism and its associated factors after prolonged use of anti-thyroid drugs in a hospital setting, Northwest Ethiopia
Seyoum Mengesha, Abilo Tadesse, Biruk Mulat Worku, Kifle Alamrew, Tesfaye Yesuf, Yonas Gedamu
Medicine.2024; 103(23): e38201. CrossRef
Approach to the Patient Considering Long-term Antithyroid Drug Therapy for Graves’ Disease
Fereidoun Azizi, Ladan Mehran, Hengameh Abdi, Atieh Amouzegar
The Journal of Clinical Endocrinology & Metabolism.2024; 109(10): e1881. CrossRef
Mechanism of Huatan Sanjie Fang in improving goiter in Graves' disease mice based on the Hippo signaling pathway
Huimin Yuan, Wenxin Ma, Yifei Song, Hang Wang, Shuxin Yan, Silan Hao, Xiaoyun Zhu, Yang Tang
Journal of Traditional Chinese Medical Sciences.2023; 10(3): 289. CrossRef

The Effect of Methimazole on the Thyroglobulin Synthesis in Cultured Porcine Thyroid Cells.: Eun Jig Lee, Hyun Chul Lee, Kap Bum Huh, Kyung Rae Kim, Sung Kil Lim, Kyung Mi Lee; J Korean Endocr Soc. 1994;9(4):332-336. Published online November 6, 2019

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Abstract PDF: The thioureylene drugs, propylthiouracil and methylmercaptoimidazol(MMI), exert their antithyroid effect primarily through inhibition of thyroid peroxidase-catalyzed iodination of thyroglobulin. Recently the interest about the effect to the thyroglobulin synthesis of these drugs have been increasing. So we studied the MMI effect to the thyroglobulin synthesis in cultured porcine thyroid cells. Porcine thyroid cells were isolated by sequential trypsinization in the presence of EGTA, seeded at high density(1X10^6 cells/cm^2) and cultured. One week later, MMI was added in different concentrations(0, 0.2, 1, 5mM) with TSH only or with 4H(b-TSH, Insulin, Transferrin, Hydrocortisone) or without hormone. Medias were collected after 24 hours and compared the amount of thyroglobulin secreted. And also pulse-labeling were performed with S^35 cysteine/methionine(1-2uCi/well) for 30, 60, 90min at the same conditions.There was no significant change in the amount of the secreted thyroglobulin by MMI, and there was no significant change in the pulse-labeled interacellular thyroglobulin by MMI. And also there was no significant change in the secretion of TSH-stimulated thyroglobulin by MMI. So we conclude that MMI has no effect on the thyroglobulin synthesis in cultured porcine thyroid cells and also MMI has no effect on the TSH-stimulated thyroglobulin synthesis in cultured porcine thyroid cell.

Free Thyroxine, Anti-Thyroid Stimulating Hormone Receptor Antibody Titers, and Absence of Goiter Were Associated with Responsiveness to Methimazole in Patients with New Onset Graves' Disease: Hoon Sung Choi, Won Sang Yoo; Endocrinol Metab. 2017;32(2):281-287. Published online June 23, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.281

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Background

Anti-thyroid drug therapy is considered a treatment of choice for Graves' disease; however, treatment response varies among individuals. Although several studies have reported risk factors for relapse after initial treatment, few have assessed responsiveness during the early treatment period. Our study aimed to identify the clinical characteristics for responsiveness to methimazole.

Methods

We included 99 patients diagnosed with Graves' disease for the first time. Drug responsiveness was defined as the correlation coefficients between decreasing rates of free thyroxine level per month and methimazole exposure dose. According to their responsiveness to treatment, the patients were classified into rapid or slow responder groups, and age, sex, free thyroxine level, and thyrotropin binding inhibiting immunoglobulin (TBII) titers were compared between groups.

Results

The mean patient age was 44.0±13.5 years and 40 patients were male (40%). The mean TBII titer was 36.6±74.4 IU/L, and the mean free thyroxine concentration was 48.9±21.9 pmol/L. The rapid responder group showed higher TBII titer and free thyroxine level at diagnosis, while age, sex, smoking, and presence of goiter did not differ between the two groups. Logistic regression analyses revealed that high level of serum thyroxine, high titer of TBII, and absence of goiter were significantly associated with a rapid response, while age, sex, and smoking were not significant factors for the prediction of responsiveness.

Conclusion

In patients with new onset Graves' disease, high level of free thyroxine, high titer of TBII, and absence of goiter were associated with rapid responsiveness to methimazole treatment.

Citations

Citations to this article as recorded by

Enhanced predictive validity of integrative models for refractory hyperthyroidism considering baseline and early therapy characteristics: a prospective cohort study
Xinpan Wang, Tiantian Li, Yue Li, Qiuyi Wang, Yun Cai, Zhixiao Wang, Yun Shi, Tao Yang, Xuqin Zheng
Journal of Translational Medicine.2024;[Epub] CrossRef
Analysis of Related Factors in Refractory Graves’ Disease
鑫王
Advances in Clinical Medicine.2023; 13(08): 13439. CrossRef
Clinical efficacy of thyroid-stimulating immunoglobulin detection for diagnosing Graves’ disease and predictors of responsiveness to methimazole
KunY Liu, Yu Fu, TianT Li, SunQ Liu, DouD Chen, ChengC Zhao, Yun Shi, Yun Cai, Tao Yang, XuQ Zheng
Clinical Biochemistry.2021; 97: 34. CrossRef
Changes in Thyroid Peroxidase and Thyroglobulin Antibodies Might Be Associated with Graves' Disease Relapse after Antithyroid Drug Therapy
Yun Mi Choi, Mi Kyung Kwak, Sang Mo Hong, Eun-Gyoung Hong
Endocrinology and Metabolism.2019; 34(3): 268. CrossRef
When should antithyroid drug therapy to reduce the relapse rate of hyperthyroidism in Graves’ disease be discontinued?
Suyeon Park, Eyun Song, Hye-Seon Oh, Mijin Kim, Min Ji Jeon, Won Gu Kim, Tae Yong Kim, Young Kee Shong, Doo Man Kim, Won Bae Kim
Endocrine.2019; 65(2): 348. CrossRef

Case Reports

Thyroid
Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease: Eun Roh, Ye An Kim, Eu Jeong Ku, Jae Hyun Bae, Hye Mi Kim, Young Min Cho, Young Joo Park, Kyong Soo Park, Seong Yeon Kim, Soo Heon Kwak; Endocrinol Metab. 2013;28(1):55-60. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.55

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We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

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A Case of Methimazole-Induced Insulin Autoimmune Syndrome and Literature Review
东昕王
Advances in Clinical Medicine.2024; 14(10): 19. CrossRef
HLA Alleles Associate with Insulin Autoimmune Syndrome
Dan Yao, Jiefeng Jiang, Qianyun Zhou, Caiyun Feng, Jianping Chu, Zhiyan Chen, Jie Yang, Jinying Xia, Yujia Chen
Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 3463. CrossRef
Insulin Autoimmune Syndrome: A Systematic Review
MingXu Lin, YuHua Chen, Jie Ning, Tatsuya Kin
International Journal of Endocrinology.2023; 2023: 1. CrossRef
Safety of Antithyroid Drugs in Avoiding Hyperglycemia or Hypoglycemia in Patients With Graves’ Disease and Type 2 Diabetes Mellitus: A Literature Review
Yu-Shan Hsieh
Cureus.2023;[Epub] CrossRef
Case report: hypoglycemia secondary to methimazole-induced insulin autoimmune syndrome in young Taiwanese woman with Graves’ disease
Hsuan-Yu Wu, I-Hua Chen, Mei-Yueh Lee
Medicine.2022; 101(25): e29337. CrossRef
Analysis of the clinical characteristics of insulin autoimmune syndrome induced by methimazole
Linli Sun, Weijin Fang, Dan Yi, Wei Sun, Chunjiang Wang
Journal of Clinical Pharmacy and Therapeutics.2021; 46(2): 470. CrossRef
Preoperative plasmapheresis experience in Graves’ disease patients with anti-thyroid drug-induced hepatotoxicity
Tugce Apaydın, Onur Elbasan, Dilek Gogas Yavuz
Transfusion and Apheresis Science.2020; 59(5): 102826. CrossRef
Glycemic variation in uncontrolled Graves’ disease patients with normal glucose metabolism: Assessment by continuous glucose monitoring
Gu Gao, Feng-fei Li, Yun Hu, Reng-na Yan, Bing-li Liu, Xiao-mei Liu, Xiao-fei Su, Jian-hua Ma, Gang Hu
Endocrine.2019; 64(2): 265. CrossRef
Insulin autoimmune syndrome induced by exogenous insulin injection: a four-case series
Yimin Shen, Xiaoxiao Song, Yuezhong Ren
BMC Endocrine Disorders.2019;[Epub] CrossRef
Assessment and Management of Anti-Insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome
David Church, Luís Cardoso, Richard G Kay, Claire L Williams, Bernard Freudenthal, Catriona Clarke, Julie Harris, Myuri Moorthy, Efthmia Karra, Fiona M Gribble, Frank Reimann, Keith Burling, Alistair J K Williams, Alia Munir, T Hugh Jones, Dagmar Führer,
The Journal of Clinical Endocrinology & Metabolism.2018; 103(10): 3845. CrossRef
MANAGEMENT OF ENDOCRINE DISEASE: Pathogenesis and management of hypoglycemia
Nana Esi Kittah, Adrian Vella
European Journal of Endocrinology.2017; 177(1): R37. CrossRef
Insulin autoimmune syndrome during the administration of clopidogrel
Eijiro Yamada, Shuichi Okada, Tsugumichi Saito, Aya Osaki, Atushi Ozawa, Masanobu Yamada
Journal of Diabetes.2016; 8(4): 588. CrossRef
Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog
Chih-Ting Su, Yi-Chun Lin
Endocrinology, Diabetes & Metabolism Case Reports.2016;[Epub] CrossRef
Anti-tuberculosis Treatment-Induced Insulin Autoimmune Syndrome
Jung Suk Han, Han Ju Moon, Jin Seo Kim, Hong Il Kim, Cheol Hyeon Kim, Min Joo Kim
The Ewha Medical Journal.2016; 39(4): 122. CrossRef
2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis
Douglas S. Ross, Henry B. Burch, David S. Cooper, M. Carol Greenlee, Peter Laurberg, Ana Luiza Maia, Scott A. Rivkees, Mary Samuels, Julie Ann Sosa, Marius N. Stan, Martin A. Walter
Thyroid.2016; 26(10): 1343. CrossRef
Insulin Autoimmune Syndrome in a Patient with Hashimoto's Thyroiditis
In Wook Song, Eugene Han, Nan Hee Cho, Ho Chan Cho
Journal of Korean Thyroid Association.2014; 7(2): 180. CrossRef
Brief Review of Articles in 'Endocrinology and Metabolism' in 2013
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Endocrinology and Metabolism.2014; 29(3): 251. CrossRef

A Case of Neutropenic Enterocolitis Complicating Methimazole-induced Agranulocytosis.: Sang Hyun Park, In Sung Cho, Hyun Jin Kim, Soo Jung Gong, Nae You Kim, Jung Ae Lee; J Korean Endocr Soc. 2007;22(4):282-286. Published online August 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.4.282

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Abstract PDF: Agranulocytosis is a rare complication of antithyroid drug therapy. Neutropenic enterocolitis is characterized by neutropenia plus cecal and ascending colon inflammation, and this is the most feared side effect of agranulocytosis. This is a rare complication of chemotherapy for treating hematological malignancies and less commonly, of the medication used for treating other diseases (e.g., hyperthyroidism). The mortality rate varies from 50 to 100%, with most deaths being due to bowel perforation and sepsis. Therefore, early recognition and proper medical management of neutropenic enterocolitis is important. Recently, early recognition and progress in the management have probably reduced the mortality of this malady, yet there have been no prospective randomized trials or high-quality retrospective studies on the treatment of neutropenic enterocolitis. Therefore, standardized recommendations concerning the indications for surgery cannot be made, but most of these patients are probably not candidates for surgical intervention. Non-surgical management may be a reasonable initial approach for those patients presenting without significant complications such as peritonitis, perforation or bleeding. We report here on a case that was treated with successful medical management for neutropenic enterocolitis that occurred when administering methimazole therapy as an antithyroid drug.

A Case of Methimazole-induced Pancytopenia: Successful Treatment with Recombinant Human Granulocyte Colony-stimulating Factor.: Joo Hyoung Lee, Jihyun Lee, Sang Hun Sung, Sung Hwa Bae, Sang Gyung Kim, Hoon Kyu Oh; J Korean Endocr Soc. 2006;21(6):548-551. Published online December 1, 2006; DOI: https://doi.org/10.3803/jkes.2006.21.6.548

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Abstract PDF

Methimazole has remained the cornerstone for the treatment of hyperthyroidism since 1940's and it is a well-tolerated antithyroid drug. Pancytopenia is one of the major side effects of methimazole, but its occurrence is very rare. There have been some case reports about methimazole-induced pancytopenia that was treated with recombinant human granulocyte colony-stimulating factor (G-CSF), but its usefulness is still controversial. We present here a case of a 50-year-old female who had been treated with methimazole for hyperthyroidism and she subsequently presented pancytopenia. G-CSF was given for 10 days and she successfully recovered from the pancytopenia.

Citations

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A Case of Graves' Disease with Pancytopenia
Jong Ho Shin, Hyun Jin Kim, Si Bum Kim, Dong Pil Kim, Bong Suk Ko, Dong Soon Kim, Ji Myung Kim, Soo Jung Gong, Jung-Ae Lee
Journal of Korean Endocrine Society.2009; 24(4): 272. CrossRef

A case of Methimazole-Induced Cholestatic Jaundice With Agranulocytosis.: Sang Gu Kang, Jong Oh Bae, Eun Young Lee, Seong Min Lim, Sang Kun Cho, Ji Hye Kim, Sun Kyung Song; J Korean Endocr Soc. 2005;20(5):519-523. Published online October 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.5.519

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Abstract PDF

Methimazole is a widely used and generally well-tolerated antithyroid agent. Adverse reactions occur in 1~5% of patients taking methimazole medication, but these are most commonly transient, benign leukopenia and a skin rash. Severe cholestatic jaundice, combined with agranulocytosis, has been known as a rare complication. Herein, a case of methimazole induced cholestatic jaundice, with agranulocytosis, is reported.

Citations

Citations to this article as recorded by

A Case Report of Methimazole-Induced Acute Liver Failure Successfully Treated with Liver Transplantation
Sung Jin Jeon, Tae Yong Kim, Seung-Hoon Lee, Jong Sik Kang, Gwang Hyeon Choi, Seung-Gyu Lee, Hee Sang Hwang
Korean Journal of Medicine.2012; 83(3): 363. CrossRef
A Case of Methimazole-induced Pancytopenia: Successful Treatment with Recombinant Human Granulocyte Colony-stimulating Factor
Joo Hyoung Lee, Jihyun Lee, Sang Hun Sung, Sung Hwa Bae, Sang Gyung Kim, Hoon Kyu Oh
Journal of Korean Endocrine Society.2006; 21(6): 548. CrossRef

Original Article

Hepatic Injury during Treatment with Antithyroid Drugs in Patients with Hyperthyroidism.: Ki Young Lee, Yun Jeong Lee, Soon Hong Hong, Sung Kwoen Jung, Hwa Eun Lee, Chan Jong Seo, Yon Sil Jung, Sung Kwang Lee, Hong Kyu Kim, Hye Young Park, Moon Ho Kang; J Korean Endocr Soc. 2000;15(4-5):554-560. Published online January 1, 2001

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Abstract PDF: 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.

Case Reports

A Case of Methimazole-Induced Cholestatic Jaundice with Steroid Therapy.: Wan Sup Kim, Jae Han Kim, Byung Ok Yoon, Young Min Kim, Sang Hun Song, Myoung Jin Oh, Heon Gyen Hwang, Chul Hee Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; J Korean Endocr Soc. 1999;14(3):592-598. Published online January 1, 2001

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Abstract PDF: Cholestatic jaundice caused by imidazole derivatives is a rare complication of antithyroid drug therapy. We present a case of cholestatic jaundice with systemic hypersensitivity reaction, which developed in a 27-year old male one day after exposure to methimazole. The patient showed clinical improvement and gradual resolution of jaundice after the discontinuation of methimazole and treatment with prednisolone. Histologic findings of liver revealed bile pigment, predominantly in centrilobular area, and infiltration of chronic inflammatory cells in a few portal area without evidence of degeneration or necrosis of hepatocytes. Methimazole could be presumed as etiologic agent from clear chronological relationship and the lack of other causative factors. We report this unusual case with review of literature.

A Case of Methimazole Induced Agranulocytosis Complicated with Deep Neck Abscess.: Kwan Woo Lee, Sung Kyu Lee, Yun Suk Chung, Hyun Man Kim, Yoon Jung Kim, Eun Kyung Hong, Bong Nam Chae, Jin Ho Lee, Chang Young Ha, Joon Sung Park; J Korean Endocr Soc. 1998;13(4):617-621. Published online January 1, 2001

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Abstract PDF: The thiourea derivatives, propylthiouracil and methimazole are in widespread use for the treatment of hyperthyroidism. The untoward side effects of these drugs are not infrequent and agranulocytosis is the most serious side effect them. We observed one case of methimazole induced agranulocytosis complicated by deep neck abscess. A 54-year-old woman was admitted because of fever, chilling and sore throat for 1 week. The symptom was developed after receiving methimazole 30mg daily day due to hyperthyroidism during last 3 months. Physical examination revealed hyperemic, enlarged tonsils and tender swelling of the right lower neck The peripheral blood total leukoeyte count was 1,500/mm' (absolute neutrophil count, ANC 9) and a peripheral blood smear revealed few neutrophil. The patient was administered G-CSF 2 mg/kg daily, and on the fifth day of hospitalization, fever subsided and ANC increased to 3,431. On the 11th day, fever developed again and the tenderness and swelling in both lower neck area were aggrevated. Computed tomography of the neck was performed, and revealed a large deep neck abscess. After pus aspiration and antibiotics therapy, the neck abscess was disappeared.

Ensulin Autoimmune Syndrome in a Patient with Methimazole-Treated Graves' Disease: A Case report.: Joong Kyu Lim, Yong An Woo, Sung Jin Kang, Sung Sik Yoo, Kun Young Hong, Soon Ho Kim; J Korean Endocr Soc. 1998;13(4):612-616. Published online January 1, 2001

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Abstract PDF: Insulin autoimmune syndrome (IAS) includes fasting or reactive hypoglycemia, hyperinsulinemia and the presence of insulin-binding antibodies in patients who have never been exposed to exogenous insulin. This report concems a 29-year-old male patient with Graves disease who had history of having taken methimazole for two months, without any consequence, 6 months previously. However, when methimazole was administered again for three weeks, the patient suffered hypoglycemia during the next fourth week. He denied history of diabetes mellitus (DM), of taking any oral hypoglycemic agent or of having received insulin injection. Laboratory data showed total serum insulin level > 300 pu/mL, C-peptide reactivity (CPR) 8.0ng/mL and insulin antibody 89%. After stopping methimazole, he was treated with radioiodine (131I). There was no episode of hypoglycemic attack during 8 months of follow-up.

A Case of Methimazole Induced Agranulocytosis Treated with Granulocyte Colony Stimulating Factor ( G-CSF ).: Kwan Woo Lee, Yoon Sok Chung, Hyeon Man Kim, So Yeon Choi, Min Kyung Song, Hyun Soo Kim, Hee Sun Jeon; J Korean Endocr Soc. 1997;12(1):68-74. Published online January 1, 2001

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Abstract PDF: A 31-year-old woman admitted because of fever, chilling and sore throat for 4 days. The symptom was developed after receiving methimazole 20mg per day and carteolol 10mg per day due to Graves disease during last 4 weeks. Physical examination revealed hyperemic enlarged tonsils with whitish plaque. The peripheral blood total neutrophil count was 1,400/mm3 (absolute neutrophil count, ANC 36) and a peripheral blood smear revealed rare neutrophil with lymphocytosis. On the first day of hospitalization, the patient was severely ill with ANC 0, it was decided to administer G-CSF 2ug/kg daily. On the fifth day of hospitalization, ANC in peripheral blood count was persistently zero and bone marrow aspiration and biopsy were performed, which revealed hypocellularity and myeloid hypoplasia. G-CSF given daily for 7days, it was discontinued when the ANC reached 1,539/mm3. The availability of G-CSF may help to shorten the course of agranulocytosis and to reduce its mortality rate.

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