methimazole and Agranulocytosis

Thionamides, such as methimazole and propylthiouracil, are used for the management of hyperthyroidism. Agranulocytosis is a rare adverse effect of thionamides and elderly patients are especially vulnerable. Here we discuss a case of an 80-year-old woman who developed agranulocytosis and pneumonia approximately 4 weeks after starting low dose methimazole therapy. Despite aggressive treatment with broad-spectrum antibiotics and granulocyte colony stimulating factor, she developed multiorgan failure and died. Our goals are to identify risk factors common to elderly patients and hopefully improve outcomes in this population when prescribed thionamides.

Topics: Age Factors; Aged, 80 and over; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Fatal Outcome; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Methimazole; Propylthiouracil; Risk Factors

Propylthiouracil (PTU), methimazole (MMI) and carbimazole are indicated for the treatment of hyperthyroidism in adult and pediatric patients. The aim of this review is to present all the relevant information regarding the use of antithyroid drugs (ATD) in pediatric thyrotoxic cases, the pediatric toxicology of ATD and the warning which has recently been issued for PTU by the FDA.. Epidemiology, diagnosis and treatment of pediatric thyrotoxicosis are all presented in this article. The authors also extensively discuss the details regarding the pharmacology, bioactivation, biodisposition, bioavailability and pharmacokinetic properties of the two main ATD (MMI and PTU).. The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Topics: Agranulocytosis; Animals; Antithyroid Agents; Carbimazole; Child; Child, Preschool; Evidence-Based Medicine; Female; Graves Disease; Humans; Hyperthyroidism; Liver Failure; Methimazole; Pregnancy; Propylthiouracil; Randomized Controlled Trials as Topic; Thyrotoxicosis; Vasculitis

Drug-induced agranulocytosis is believed to be an extremely rare adverse drug reaction. It can be caused by various drugs, but it is mostly described in patients taking antithyroid drugs, antipsychotics and antibiotics. Four cases of patients treated for drug-induced agranulocytosis from January 2006 to March 2007 were described. In two cases agranulocytosis appeared in the course of therapy with methimazole. In one patient agranulocytosis was caused by perazine and by promazine or olanzapine in the last one. In all of the cases the leading symptom was fever, three of our patients had changes of mouth mucosa. All patients were treated with betalactam antibiotics. Granulocyte colony-stimulating factor (G-CSF) was not used in anyone. The recovery of white blood cell count and granulocyte count in all of the patients was detected in the first ten days of hospitalization.

Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; Antipsychotic Agents; Antithyroid Agents; Benzodiazepines; beta-Lactams; Female; Humans; Male; Methimazole; Middle Aged; Olanzapine; Perazine; Promazine

Topics: Agranulocytosis; Algorithms; Antithyroid Agents; Female; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Gland; Thyrotoxicosis; Thyroxine; Triiodothyronine

Topics: Aged; Agranulocytosis; Antithyroid Agents; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Methimazole; Neutrophils

A 48-year-old woman who was treated for thyrotoxicosis with methimazole developed agranulocytosis. The methimazole was stopped and treatment with subcutaneous granulocyte colony-stimulating factor (G-CSF) was initiated. Administration of the drug for 8 days did not effectively shorten the recovery period compared with the average reported in the literature without the drug, and may have triggered additional iatrogenic complications. A search of the literature yielded 15 instances of severe antithyroid-drug-induced granulocytopenia (ATDIA) (granulocyte count of less than 0.1 x 10(9)/L) treated with G-CSF. Of the 16 patients, including the 1 reported here, only 3 displayed significant shortening of the agranulocytic period after treatment. We conclude that routine therapeutic application of G-CSF in afebrile severe ATDIG is not justified, and in some cases may generate a cascade of iatrogenic adverse events.

Topics: Aged; Agranulocytosis; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Humans; Methimazole; Thyrotoxicosis; Time Factors

Thyroid hormone preparations, especially thyroxine, are widely used either at replacement doses to correct hypothyroidism or at suppressive doses to abolish thyrotropin (thyroid-stimulating hormone) secretion in patients with differentiated thyroid carcinoma after total thyroidectomy or with diffuse/ nodular nontoxic goitre. In order to suppress thyrotropin secretion, it is necessary to administer slightly supraphysiological doses of thyroxine. Possible adverse effects of this therapy include cardiovascular changes (shortening of systolic time intervals, increased frequency of atrial premature beats and, possibly, left ventricular hypertrophy) and bone changes (reduced bone density and bone mass), but the risk of these adverse effects can be minimised by carefully monitoring serum free thyroxine and free liothyronine (triiodothyronine) measurements and adjusting the dosage accordingly. Thionamides [thiamazole (methimazole), carbimazole, propylthiouracil] are the most widely used antithyroid drugs. They are given for long periods of time and cause adverse effects in 3 to 5% of patients. In most cases, adverse effects are minor and transient (e.g. skin rash, itching, mild leucopenia). The most dangerous effect is agranulocytosis, which occurs in 0.1 to 0.5% of patients. This life-threatening condition can now be effectively treated by granulocyte colony-stimulating factor administration. Other major adverse effects (aplastic anaemia, thrombocytopenia, lupus erythematosus-like syndrome, vasculitis) are exceedingly rare.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone and Bones; Carbimazole; Cardiovascular System; Child; Collagen Diseases; Humans; Leukopenia; Liver; Methimazole; Propylthiouracil; Skin; Thyroid Hormones; Thyroxine

The frequency, predisposing factors and course of agranulocytosis (granulocytes < 250/microliter) secondary to antithyroid drugs were studied in a cohort of 1256 continuously treated outpatients with hyperthyroidism during the 15 year period from 1973 to 1987. Two cases of agranulocytosis were detected; the frequency was 0.18% (95%-confidence intervals, 0.0-0.44%). This prevalence appears to be lower than reported in previous studies (up to 1.8%). For other adverse drug reactions, there was a clear-cut relationship to initial thionamide dose and to the body mass index; most reactions occurred during the first weeks of treatment. In addition, eight patients referred for thionamide drug- induced agranulocytosis were studied, and the following results obtained: Methimazole dose in patients with agranulocytosis was almost twice as in other patients (63.3 +/- 19.7 vs 34.3 +/- 29.7 mg daily) suggesting that this complication was related to dose. The interval between start of antithyroid drug treatment and first symptoms of agranulocytosis was 33 days (median; range, 23-55 days); hence, prolonged treatment beyond this period would appear relatively safe. Withdrawal of the causative agent and treatment of infection led to recovery of leukocyte counts within 15 days (median; range, 5-31 days). Two fatal outcomes were seen in referred patients. In one severely hyperthyroid patient with methimazole-induced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the most severe side effect of antithyroid drugs. According to our results and a literature review, it occurs almost exclusively during the first ten weeks of treatment and is probably related to the drug dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Agranulocytosis; Antithyroid Agents; Cohort Studies; Dose-Response Relationship, Drug; Female; Germany; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hyperthyroidism; Leukocyte Count; Male; Methimazole; Middle Aged; Prevalence; Recombinant Proteins; Time Factors

Prognosis in aplastic anemia is usually linked to the degree of hypoplasia in the bone marrow and pancytopenia in the blood. The authors were, therefore, intrigued when a patient with methimazole-associated aplastic anemia who satisfied criteria for severe disease recovered rapidly and completely once her drug was withdrawn. Review of the English language literature revealed ten fully documented cases of aplastic anemia associated with use of the antithyroid drugs methimazole, carbimazole, and propylthiouracil. Analysis of the ten and of an eleventh case presented here indicated that the disorder is typically characterized by severe pancytopenia and profound marrow hypoplasia, yet surprisingly good prognosis, ie, minimum survival of more than 70% with partial or complete recovery from symptoms and cytopenias in survivors within 2-5 weeks. The only deaths, both in the 1950s, were from brain hemorrhage in patients who were not transfused with platelets. The discrepancy between the clinical and laboratory severity of antithyroid drug-associated aplasia, on the one hand, and its relatively good prognosis and short term course, on the other, should be kept in mind when considering these patients for bone marrow transplantation or for therapy with antithymocyte globulin.

Topics: Adult; Agranulocytosis; Anemia, Aplastic; Female; Humans; Methimazole; Propylthiouracil

Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful.

Topics: Adult; Agranulocytosis; Antibody Formation; Cross Reactions; Drug Hypersensitivity; Female; Graves Disease; Humans; Hyperthyroidism; Immunity, Cellular; Methimazole; Middle Aged; Propylthiouracil

Over the past four decades, a great deal has been learned about the pharmacology and mechanisms of action of antithyroid drugs. Their ability to inhibit hormone biosynthesis involves complex interactions with thyroid peroxidase and thyroglobulin, many of which are still poorly understood. Their spectrum of activity is much wider than previously thought, and a number of clinically important extrathyroidal actions have been identified. Despite a greater appreciation for the intricacies of antithyroid-drug pharmacology, controversies still surround the use of these agents in the treatment of thyrotoxicosis. These controversies are apt to continue until the pathophysiology of Graves' disease is fully elucidated.

Topics: Adult; Agranulocytosis; Autoimmune Diseases; Chemical and Drug Induced Liver Injury; Child; Female; Fetus; Graves Disease; Humans; Hyperthyroidism; Immunity; Immunoglobulins; Infant, Newborn; Insulin Antibodies; Leukopenia; Lupus Vulgaris; Methimazole; Milk, Human; Pregnancy; Pregnancy Complications; Propylthiouracil; Vascular Diseases

Topics: Agranulocytosis; Antithyroid Agents; Carbimazole; Eye Manifestations; Female; Follow-Up Studies; Goiter; Humans; Hyperthyroidism; Imidazoles; Methimazole; Pregnancy; Propylthiouracil; Thyroxine; Time Factors; Triiodothyronine

Despite the requirement of routine blood tests during thiamazole treatment in Japan, granulocytopenia among patients treated with thiamazole has been occasionally reported to the Pharmaceuticals and Medical Devices Agency (PMDA). To characterize granulocytopenia in patients with thiamazole in Japan, the effects of routine blood tests were examined in a cohort of new users of thiamazole or propylthiouracil utilizing the MID-NET. The occurrence of granulocytopenia (neutrophil count ≤ 1,500/μL) in a given period was compared between patients with and without blood test results prior to the period. The trend in neutrophil count during thiamazole treatment was also compared between patients with and without granulocytopenia. A nested case-control study based on the cohort was conducted to identify potential risk factors for granulocytopenia during thiamazole treatment. In the new user cohort including 4,371 patients treated with thiamazole, the occurrence of granulocytopenia in patients who had undergone blood tests at all previous periods was similar or higher than that among those who had not undergone blood test in all previous periods (e.g., adjusted odds ratio in period 2 was 1.63). The neutrophil count was relatively lower in the group of patients with granulocytopenia even before the occurrence of granulocytopenia. In a nested case-control study, an upward tendency of the risk was observed when a patient was co-prescribed anti-arrhythmic drugs or antiulcer drugs with thiamazole. The characteristics of granulocytopenia during thiamazole treatment elucidated in this study should be recognized in clinical practice for the proper use of thiamazole.

Topics: Agranulocytosis; Antithyroid Agents; Case-Control Studies; Humans; Hyperthyroidism; Japan; Methimazole

Topics: Agranulocytosis; Antithyroid Agents; COVID-19 Drug Treatment; Humans; Methimazole; Pandemics; SARS-CoV-2

A woman in her 30s presented to the emergency department with new-onset sore throat and fever. She had recently been diagnosed with Graves' disease 3 months prior. As a result, she was initiated on atenolol and methimazole for management. Her methimazole dosing had been stable at 15 mg daily for the month prior to presentation. Investigation revealed severe neutropenia and jaundice. She was found to have concomitant agranulocytosis and cholestatic jaundice secondary to methimazole.Methimazole was discontinued on admission and the patient received granulocyte colony-stimulating factor for an absolute neutrophil count (ANC) of zero. She was placed on broad-spectrum antibiotics and intravenous steroids for epiglottic and supraglottic oedema noted on bedside laryngoscopy. ANC and bilirubin improved over a 2-week hospital course. She was discharged on a temporary regimen of propranolol, dexamethasone and potassium iodide until she was able to undergo successful thyroidectomy for definitive management of Graves' disease outpatient.

Topics: Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Jaundice, Obstructive; Methimazole; Neutropenia

Adverse drug reactions have been linked with HLA alleles in different studies. These HLA proteins play an essential role in the adaptive immune response for the presentation of self and non-self peptides. Anti-thyroid drugs methimazole and propylthiouracil have been associated with drug induced agranulocytosis (severe lower white blood cell count) in patients with B*27:05, B*38:02 and DRB1*08:03 alleles in different populations: Taiwanese, Vietnamese, Han Chinese and Caucasian.. In this study, informatics methods were used to investigate if any sequence or structural similarities exist between the two associated HLA-B alleles, compared with a set of "control" alleles assumed not be associated, which could help explain the molecular basis of the adverse drug reaction. We demonstrated using MHC Motif Viewer and MHCcluster that the two alleles do not have a propensity to bind similar peptides, and thus at a gross level the structure of the antigen presentation region of the two alleles are not similar. We also performed multiple sequence alignment to identify polymorphisms shared by the risk but not by the control alleles and molecular docking to compare the predicted binding poses of the drug-allele combinations.. Two residues, Cys67 and Thr80, were identified from the multiple sequence alignments to be unique to these risk alleles alone. The molecular docking showed the poses of the risk alleles to favour the F-pocket of the peptide binding groove, close to the Thr80 residue, with the control alleles generally favouring a different pocket. The data are thus suggestive that Thr80 may be a critical residue in HLA-mediated anti-thyroid drug induced agranulocytosis, and thus can guide future research and risk assessment.

Topics: Adaptive Immunity; Agranulocytosis; Alleles; Amino Acid Sequence; Antithyroid Agents; Asian People; Binding Sites; Drug-Related Side Effects and Adverse Reactions; Genetic Predisposition to Disease; HLA-B Antigens; Humans; Medical Informatics; Methimazole; Propylthiouracil; Protein Binding; White People

Agranulocytosis is a rare but very serious complication of thyrostatic therapy. In severe hyperthyroidism, the removal of circulating thyroid hormones by plasmapheresis may be an effective therapeutic option. This report describes the therapeutic difficulties and successful preoperative treatment with plasmapheresis in a 63-year-old patient admitted to the Endocrinology Clinic with severe hyperthyroidism, during the course of giant toxic nodular goiter and agranulocytosis, which occurred after 2 weeks of taking methimazole. During hospitalization, methimazole treatment was discontinued and therapy with steroids, a beta blocker, propylthiouracil, Lugol's solution, lithium carbonate, and antibiotics were initiated. Granulocyte colony growth stimulating factor was also used to resolve agranulocytosis. Due to the failure to achieve euthyreosis using this approach, we decided to conduct thyroid surgery, as a life-saving action, after preparation of the patient by plasmapheresis. Two plasmapheresis procedures were performed, resulting in a decrease in the concentration of free thyroid hormones. Total thyroidectomy was performed and there were no complications during surgery. We conclude that plasmapheresis may be considered as an effective alternative treatment option for the preparation of patients with hyperthyroidism for surgery, when the clinical situations prevent the use of conventional treatments for hyperthyroidism and when immediate life-saving surgery is necessary.

Topics: Agranulocytosis; Antithyroid Agents; Electrocardiography; Female; Goiter, Nodular; Humans; Hyperthyroidism; Methimazole; Middle Aged; Plasmapheresis; Preoperative Care; Thyroidectomy; Treatment Outcome

Paediatric hyperthyroidism cases are mostly caused by Grave's disease. Thyroid storm is a life-threatening condition seen rarely, in severe thyrotoxicosis, occurring in about 1%-2% of patients with hyperthyroidism. Antithyroid medications and beta-blockers are typically the first-line management of thyroid storm. We report a challenging case of a 15-year-old girl who presented with thyroid storm in the setting of septic shock and methimazole-induced agranulocytosis. Since the first-line agents were contraindicated, plasmapheresis was used to control the thyroid storm and as a bridging therapy to the definitive therapy of early thyroidectomy. This is the first paediatric case report that outlines the use of plasmapheresis in the management of complicated thyrotoxicosis in a setting of septic shock.

Topics: Adolescent; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Methimazole; Sepsis; Thyroid Crisis

Agranulocytosis occurs in 0.2-0.5% of patients treated with the antithyroid drugs (ATDs) methimazole and propylthiouracil. The objectives of this study were to evaluate the risk of ATD-related agranulocytosis in patients with amiodarone-induced thyrotoxicosis (AIT), and to compare it with the agranulocytosis risk in patients with thyrotoxicosis due to other etiologies treated with ATDs.. This was a retrospective cohort study. Participants were 14,781 adult patients with thyrotoxicosis, newly treated with an ATD between January 1, 2002, and December 31, 2015. Among them were 593 patients treated by ATDs due to AIT. The main outcome measures were incidence rates and crude and adjusted hazard ratios using univariate and multivariable Cox regression models for ATD-related agranulocytosis within one year of treatment initiation, in association with AIT.. Agranulocytosis occurred in 28 (0.19%) of patients newly treated with methimazole or propylthiouracil during the first year of follow-up. Of these 28 patients, 8/593 (1.35%) were AIT patients and 20/14,188 (0.14%) were thyrotoxic patients that was not AIT related (p < 0.001). Incidence rates were 22 (9.47-43.36) cases/1000 person-years of follow-up in AIT, and 1.79 (1.09-2.76)/1000 person-years of follow-up in non-AIT thyrotoxicosis (p < 0.0001). In univariate Cox regression analysis, risk for ATD agranulocytosis associated with AIT was 9.71 (4.28-22.05) compared to the risk in non-AIT thyrotoxicosis. In a multivariable model, adjusting for age, sex, body mass index, smoking history, year of cohort entry, diabetes mellitus, hypertension, renal failure, beta blockers, calcium channel blockers, anti-aggregants, and dose of ATDs, the risk associated with AIT was 5.70 (2.14-15.21). In a model adjusted for a propensity score to receive amiodarone, risk for ATD agranulocytosis associated with AIT was 6.32 (1.22-32.70).. ATD use is associated with a higher risk for agranulocytosis in patients with AIT.

Topics: Adult; Aged; Agranulocytosis; Amiodarone; Antithyroid Agents; Female; Humans; Male; Methimazole; Middle Aged; Proportional Hazards Models; Propylthiouracil; Retrospective Studies; Risk; Thyrotoxicosis

Topics: Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Drug Substitution; Emergencies; Female; Humans; Hyperthyroidism; Lung Abscess; Methimazole; Middle Aged; Propylthiouracil; Tomography, X-Ray Computed

Agranulocytosis is a rare and serious adverse effect of antithyroid drugs, with unknown etiology. The present study aimed to uncover genetic susceptibility and underlying mechanisms of antithyroid drug-induced agranulocytosis (ATDAC). We studied two independent families with familial Graves' disease, of which several members developed ATDAC. In addition, six sporadic ATDAC patients with Graves' disease were investigated. Whole exome sequencing analysis of affected and unaffected family members was performed to identify genetic susceptibility variants for ATDAC, followed by functional characterization of primary granulocytes from patients and unrelated healthy controls. Whole exome sequencing, cosegregation analysis, and stringent selection criteria of candidate gene variants identified NOX3 as a genetic factor related to ATDAC. Functional studies revealed increased apoptosis of methimazole-treated granulocytes from patients carrying NOX3 variants. In conclusion, genetic variants in NOX3 may confer susceptibility to antithyroid drug-induced apoptosis of granulocytes. These findings contribute to the understanding of the mechanisms underlying ATDAC.

Topics: Agranulocytosis; Antithyroid Agents; Apoptosis; Case-Control Studies; Exome; Female; Genetic Predisposition to Disease; Granulocytes; Graves Disease; Humans; Male; Methimazole; NADPH Oxidases; Pedigree

Thioamides antithyroid-drugs (ATDs) are important in hyperthyroid disease management. Identification of the susceptibility locus of ATD-induced agranulocytosis is important for clinical management. We performed a genome-wide association study (GWAS) involving 20 patients with ATD-induced agranulocytosis and 775 healthy controls. The top finding was further replicated. A single-nucleotide polymorphism (SNP), rs185386680, showed the strongest association with ATD-induced agranulocytosis in GWAS (odds ratio (OR) = 36.4; 95% confidence interval (CI) = 12.8-103.7; P = 1.3 × 10(-24)) and replication (OR = 37; 95% CI = 3.7-367.4; P = 9.6 × 10(-7)). HLA-B*38:02:01 was in complete linkage disequilibrium with rs185386680. High-resolution HLA typing confirmed that HLA-B*38:02:01 was associated with carbimazole (CMZ)/methimazole (MMI)-induced agranulocytosis (OR = 265.5; 95% CI = 27.9-2528.0; P = 2.5 × 10(-14)), but not associated with propylthiouracil (PTU). The positive and negative predictive values of HLA-B*38:02:01 in predicting CMZ/MMI-induced agranulocytosis were 0.07 and 0.999. Approximately 211 cases need to be screened to prevent one case. Screening for the risk allele will be useful in preventing agranulocytosis in populations in which the frequency of the risk allele is high.

Topics: Agranulocytosis; Antithyroid Agents; Carbimazole; Case-Control Studies; Female; Genome-Wide Association Study; HLA-B Antigens; Humans; Linkage Disequilibrium; Methimazole; Polymorphism, Single Nucleotide; Predictive Value of Tests; Propylthiouracil

Antithyroid drug (ATD)-induced agranulocytosis is a rare but life-threatening disease. Clinical features of ATD-induced agranulocytosis and outcomes remain incompletely understood.. Patients with clinically diagnosed ATD-induced agranulocytosis were retrospectively studied, involving 9690 patients who were referred for radioiodine treatment during a 15-year period (2000-2015) in China. There were 114 cases of agranulocytosis attributable to ATD included, and their clinical characteristics and therapy outcomes were analyzed.. The female-to-male ratio of ATD-induced agranulocytosis was 10.4:1. The mean age (±standard deviation) of the patients with ATD-induced agranulocytosis was 41.7 ± 12.3 years. The methimazole and propylthiouracil doses given at the onset were 22.9 ± 8.0 mg/day and 253.6 ± 177.5 mg/day, respectively. ATD-induced agranulocytosis occurred in 45.1%, 74.3%, and 88.5% of patients within 4, 8, and 12 weeks of the onset of ATD therapy, respectively. Fever (78.9%) and sore throat (72.8%) were the most common symptoms when agranulocytosis was diagnosed. The mean recovery time of agranulocytosis was 13.41 ± 7.14 days. Recovery time in the granulocyte colony-stimulating factor (G-CSF)-treated group (12.7 ± 6.0 days) did not differ from that in the group not treated with G-CSF (16.4 ± 10.6 days; p = 0.144). Treatment with (131)I was successful in 87/98 patients (88.8%). The success rate of (131)I was equivalent (p = 1.000) between the groups receiving methimazole (88.2%, 75/85) and propylthiouracil (92.3%, 12/13).. This largest single-institution study in China shows that ATD-induced agranulocytosis tends to occur within the first 12 weeks after the onset of ATD therapy. For patients with ATD-induced agranulocytosis, G-CSF does not improve the recovery time of agranulocytosis, and (131)I is an optimal treatment approach.

Topics: Adult; Agranulocytosis; Antithyroid Agents; China; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies; Treatment Outcome

Antithyroid medications such as methimazole and propylthiouracil are commonly used to treat hyperthyroid disorders. Thionamide-induced agranulocytosis is a rare but life-threatening potential side effect of these medicines. In addition to routine monitoring of blood counts, healthcare workers caring for patients on such medication need to be mindful of atypical presentations of acute agranulocytosis throughout the treatment course. The manifestations of underlying infectious aetiologies can be mistaken for more common illness and result in delayed diagnosis. We present a case of a 41-year-old woman receiving methimazole for Grave's disease, who presented to outpatient care with high fever, pharyngitis, lymphadenopathy and jaundice. After failing to respond to empiric antibiotics, a diagnosis of neutropenia was made and the patient was admitted for inpatient care with eventual recovery following a course of granulocyte colony-stimulating factor. A diagnosis of atypical Bartonella henselae was eventually made and treated appropriately. The patient was later discharged and underwent radioactive iodine ablation.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Bartonella henselae; Doxycycline; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Immunologic Factors; Insect Bites and Stings; Methimazole; Treatment Outcome

Agranulocytosis is a serious adverse effect of antithyroid drugs (ATDs) and mainly develops within three months after the start of uninterrupted ATD treatment. Agranulocytosis can also develop for the first time after interruption and subsequent resumption of the same ATD treatment. However, little is known with regard to agranulocytosis that develops after resumption of the same ATD treatment.. We investigated the characteristics of patients who developed agranulocytosis during their second or later course of ATD treatment.. A total of 81 patients at our hospital were diagnosed with ATD-induced agranulocytosis. In 14 of the cases (methimazole (MMI), n=10; propylthiouracil (PTU), n=4), the agranulocytosis developed for the first time in the context of the second or later course of treatment with the same ATD; those patients were designated the "resumed group." The 35 patients (MMI, n=28; PTU, n=7) who developed agranulocytosis during their first uninterrupted course of ATD therapy were designated the "first group.". The median total duration of ATD treatment before the diagnosis of agranulocytosis was 559 days (range 86-1775 days), and the median interval between the final day of the previous course and the first day of the course in which agranulocytosis was diagnosed was 916.5 days (range 153-8110 days). There were no cases in which agranulocytosis developed when treatment with the same ATD was resumed after discontinuation for less than five months. The difference between the start of ATD treatment in the course in which agranulocytosis was diagnosed and the time interval at which agranulocytosis was diagnosed was similar when comparing the first group and the resumed group (39 (20-98) days in the first group vs. 32.5 (21-95) days in the resumed group; n.s.). There were no significant differences between the groups in terms of granulocyte count at the time agranulocytosis was diagnosed, mortality rate, or the interval between the diagnosis of agranulocytosis and recovery.. When ATD treatment is resumed, patient follow-up is essential in order to monitor for the development of agranulocytosis.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Antithyroid Agents; Drug Monitoring; Electronic Health Records; Female; Granulocytes; Graves Disease; Hospitals, Urban; Humans; Japan; Leukopoiesis; Male; Methimazole; Middle Aged; Propylthiouracil; Time Factors; Young Adult

Agranulocytosis is a serious complication of antithyroid drugs (ATD) treatment of thyrotoxicosis. The aim of our work was to assess the occurrence of agranulocytosis in Graves disease (GD) patients admitted for radioactive iodine 131I (RAI) treatment to our thyroid unit.. We analyzed retrospectively a cohort of 603 GD patients (500 women and 103 men; mean age 51.5 ± 12.7 years) who received RAI between 1999 and 2012. Of them, 327 (54 %) patients were originally treated with carbimazole (CBZ), 215 (36 %) with methimazole (MMI) and 61 (10 %) with propylthiouracil (PTU).. Agranulocytosis due to ATD was the cause of RAI treatment in 7 patients of 603. All of them were women (mean age 48.7 years; range 23-78). In 4 patients, agranulocytosis occurred on MMI treatment, and in 3 patients on CBZ. After recalculation of CBZ to the equipotent dose of MMI, the mean ATD dose was 22.4 mg MMI/day (range 9-40). No agranulocytosis due to PTU was found in our cohort. The time from beginning ATD treatment to agranulocytosis was 20-41 days. In 5 patients there was a development of fever, while in 2 patients the complication was diagnosed from routine blood count. The mean duration of agranulocytosis was 5.9 days (range 4-8).. Agranulocytosis incidence in our cohort of patients was 1.2 %, while in most reports the prevalence ranged from 0.2 to 0.5 %. In all patients, agranulocytosis occurred early, and in one third it was asymptomatic when found. The aim of our report is to bring attention to a relatively rare, but potentially serious, complication of ATD treatment.

Topics: Adult; Aged; Agranulocytosis; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

Agranulocytosis is a rare but dreaded side-effect of thiamazole. A 61-year-old woman presented at the emergency department with fever and dyspnoea. Because she had recently started therapy with thiamazole for hyperthyroidism, a case of agranulocytosis was feared. Laboratory findings did indeed reveal an absolute neutrophil count of zero. Broad-spectrum antibiotics were given immediately, granulocyte-colony stimulating factor was started and she was admitted to the ICU for supportive care. Unfortunately, she died a day after admission. In this case report, we wanted to place the focus on the importance of this severe side-effect. We emphasize the value of warning the patient, preferably in writing, about the risk of agranulocytosis. We also draw attention to the fact that every doctor must know about agranulocytosis. In this case, the patient consulted her family doctor because she had a sore throat and fever, but was admitted to the hospital only three days after the onset of the symptoms. We believe the risk of agranulocytosis should be understood by every doctor and that the publication of many cases such as this could help heighten general awareness of possibly fatal side-effects like agranulocytosis.

Topics: Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Fatal Outcome; Female; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Leukocyte Count; Methimazole; Middle Aged

Agranulocytosis is a rare yet life-threatening complication of methimazole therapy for hyperthyroidism. We present the case of a 37-year-old female recently started on methimazole for hyperthyroidism who presented to our facility for evaluation of suspected thyroid storm. In addition to having abnormal thyroid indices, she was noted to have an odontogenic abscess, and was septic with profound neutropenia. Her symptoms resolved quickly following incision and drainage of her abscess and treatment with broad-spectrum antibiotics. Her neutrophil count improved significantly following cessation of methimazole and administration of granulocyte colony-stimulating factor. Diagnosis was initially confounded by the similarity between symptoms of early sepsis and those of thyroid storm. This case report discusses the factors leading to diagnostic delay and highlights the dangerous manifestations of neutropenia in patients on methimazole therapy.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Diagnosis, Differential; Female; Humans; Hyperthyroidism; Methimazole; Sepsis; Thyroid Crisis

Agranulocytosis is a rare but serious complication of antithyroid drug (ATD) therapy. Characteristics of agranulocytosis have been reported in only a small number of patients.. We studied 754 cases of ATD-induced agranulocytosis reported over 30 years. The age distribution and sex ratio were compared with those in 12 503 untreated Graves' patients at Kuma Hospital. The annual number of new Graves' patients in Japan was estimated from the Japan Medical Data Center Data Mart-Pharmacovigilance health insurance receipt database.. Agranulocytosis developed within 90 days after starting ATD therapy in most patients (84.5%). The methimazole dose given at onset was 25.2 ± 12.8 mg/d (mean ± SD). The mean age was 43.4 ± 15.2 years, and the male to female ratio was 1:6.3. When compared with patients at Kuma Hospital, patients with agranulocytosis were older (P < .001) and more females (P < .0001). Of 211 patients with more than 1 granulocyte measurement before onset, 131 (62%) showed normal counts (>1000/μL) within 2 weeks before onset, demonstrating real sudden onset of agranulocytosis. In contrast, some of the 20 patients with more than 4 measurements showed gradual decreases in granulocyte counts. Analysis of physician reports for 30 fatal cases revealed that some deaths might have been prevented. The number of new Graves' patients treated with ATD was estimated at about 35 000 per year, and the incidence rate of agranulocytosis was 0.1% to 0.15% in Japan.. This is the largest study of agranulocytosis. Agranulocytosis tends to occur abruptly within 3 months after initiation of ATD therapy, although it develops gradually in some patients. Providing every patient with sufficient information on agranulocytosis is critical.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Agranulocytosis; Anemia, Aplastic; Antithyroid Agents; Drug Therapy, Combination; Female; Graves Disease; Hospitals, Urban; Humans; Incidence; Japan; Leukopoiesis; Male; Methimazole; Middle Aged; Pancytopenia; Pharmacovigilance; Propylthiouracil; Sex Distribution

Both Graves disease and Guillain-Barre syndrome (GBS) are autoimmune disorders caused by impaired self-tolerance mechanisms and triggered by interactions between genetic and environmental factors. GBS in patients who suffer from other autoimmune diseases is rarely reported, and the development of postinfectious GBS in a patient with Graves disease has not been previously reported in the literature. Herein, we report a patient with Graves disease who developed postinfectious GBS during a course of methimazole-induced agranulocytosis.

Topics: Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Guillain-Barre Syndrome; Humans; Immunoglobulins, Intravenous; Methimazole; Middle Aged; Opportunistic Infections; Thyroidectomy; Treatment Outcome

This study is aimed to explore the relationship between bone marrow characteristics and clinical prognosis of antithyroid drug (ATD) induced agranulocytosis. A retrospective study was conducted in the first affiliated hospital of the University of South China. A total of 33 hospitalized patients diagnosed with ATD-induced agranulocytosis were analyzed. The bone marrow characteristics were classified into two types. Type I was characterized by reduction or absence of granulocytic precursors and type II was recognized as hypercellular bone marrow with dysmaturity of granulocytic cells. Bone marrow of 20 cases (61%) were characterized with type I whereas 13 cases (39%) with type II. The median duration of neutrophil recovery and high-grade fever were 4.7 ± 1.0 days and 3.6 ± 2.5 days respectively for type II, compared to 8.0 ± 2.8 days and 8.6 ± 3.1 days for type I (p < 0.01 in both compared groups). However, there was no significant difference between the two types in terms of age, median duration of drug administration before the diagnosis of agranulocytosis, the amount of neutrophil count on admission and the total administration dose of granulocyte-colony stimulating factor (G-CSF) before bone marrow examination. Two cases of type I died of complications from infection. This study showed that the bone marrow characteristics of ATD-induced agranulocytosis could be classifed into two types. Also, the clinical prognosis was closely related to the bone marrow features. Type I is the dominant type which is usually associated with worse clinical prognosis compared to type II.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone Marrow; Cell Differentiation; China; Female; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte Precursor Cells; Hospitals, University; Humans; Hyperthyroidism; Male; Methimazole; Middle Aged; Prognosis; Propylthiouracil; Retrospective Studies; Young Adult

Although antithyroid drug (ATD)-induced hematopoietic damage is a significant concern, it has not been comprehensively investigated.. Our objective was to describe the clinical features of ATD-induced hematopoietic damage.. This was a retrospective cohort study in Tokyo, Japan.. Between January 1983 and December 2002, 50,385 patients at Ito Hospital were diagnosed with Graves' disease. We retrospectively reviewed their medical, pathological, and laboratory records between January 1983 and December 2010.. Incidence and clinical features of ATD-induced agranulocytosis and pancytopenia were evaluated.. Of 55 patients with documented hematopoietic damage, 50 had agranulocytosis and 5 had pancytopenia. All of them received ATD, either methimazole (n = 51) or propylthiouracil (n = 4). Median intervals between initiation of ATD therapy and the onset of agranulocytosis and pancytopenia were 69 d (range, 11-233 d) and 41 d (range, 32-97 d), respectively. Either anemia or thrombocytopenia was also documented in seven of the 50 patients with agranulocytosis. Agranulocytosis was the first manifestation of hematopoietic damage in four of the five patents with pancytopenia. Hematopoietic damage recovered with supportive measures including granulocyte colony-stimulating factor (n = 37), steroids (n = 10), and other supportive measures (n = 8) in 54 patients, whereas the remaining patient died of complications from infection. This study failed to identify the risk factors for ATD-induced hematopoietic damage.. This study showed that ATD cause hematopoietic changes, which are occasionally severe and potentially fatal. The pathogenesis of agranulocytosis and pancytopenia might overlap, and additional studies are warranted to clarify this and to establish an optimal treatment strategy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Agranulocytosis; Antithyroid Agents; Child; Cohort Studies; Female; Graves Disease; Hematopoiesis; Humans; Japan; Male; Methimazole; Middle Aged; Pancytopenia; Propylthiouracil; Retrospective Studies; Tokyo; Young Adult

Agranulocytosis is a life-threatening disorder characterised by a greatly decreased number of circulating neutrophils below 500/μL. This article presents two cases of agranulocytosis in patients treated with pegylated interferon and ribavirin due to chronic hepatitis C. Interferon induced hyperthyroidism, which required the use of a tyreostatic. Anti-thyroid drugs (ATD) used to treat hyperthyroidism can cause agranulocytosis. The synergistic reaction of ATD and interferon on bone marrow cannot be excluded.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Antiviral Agents; Drug Therapy, Combination; Female; Hepatitis C, Chronic; Humans; Hyperthyroidism; Interferon alpha-2; Interferon-alpha; Methimazole; Middle Aged; Polyethylene Glycols; Propylthiouracil; Recombinant Proteins; Ribavirin; Time Factors; Viral Load

Agranulocytosis is a rare adverse effect of methimazole. The usual duration of treatment prior to the onset of agranulocytosis is approximately 1 to 4 months, and can be as long as 1 year. Agranulocytosis together with hepatotoxicity is an extremely rare idiosyncratic side effect of methimazole treatment. We present an unprecedented case of a Grave's disease patient who showed a strong reaction to methimazole with obvious agranulocytosis and hepatotoxicity which developed only six days after administration. This case, along with a literature review, is offered with the aim to increase the awareness of physicians of sudden onset agranulocytosis and hepatotoxicity from methimazole.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone Marrow; Drug-Related Side Effects and Adverse Reactions; Female; Graves Disease; Humans; Liver; Methimazole; Time Factors

Agranulocytosis/granulocytopenia is a rare side effect of thyreostatics. Earlier publications state that for thiamazole this side effect occurs during the first few months of treatment. In two patients this thiamazole-induced agranulocytosis/granulocytopenia only occurred after years of treatment. A 53-year-old man presented with fever after a visit to Suriname. He had used thiamazole for 12 years for Graves' hyperthyroidism. The second patient, a 31-year-old woman, presented at the emergency department with fever and sore throat after 13 years of intermittent treatment with thiamazole. Both patients had an agranulocytosis/granulocytopenia and leukopenia. This was thought to be a side effect of thiamazole and blood values normalised after cessation of therapy. Both patients were treated empirically with broad-spectrum antibiotics during the agranylocytic period. They then received radioactive sodium iodide. To our knowledge this case report is the first to describe agranulocytosis/granulocytopenia following long-term treatment with thiamazole.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Time Factors; Treatment Outcome

Agranulocytosis is an uncommon but serious complication of Graves' disease under thionamide therapy. In some patients removal of circulating thyroid hormones and thyroid antibodies by plasmapheresis is an effective adjunctive therapeutic option. In perioperative settings, however, plasmapheresis may cause excess bleeding intraoperatively due to coagulation factor depletion unless fresh frozen plasma (FFP) products are used in the replacement fluid mix. Double filtration plasmapheresis (DFPP) in which only a small amount of albumin supplementation is used may be a potential alternative to conventional apheresis interventions where clotting factor depletion is problematic. We report a case of a patient with Graves' disease complicated with intravenous immunoglobulin responsive methimazole-induced agranulocytosis/hemophagocytosis who underwent successful preoperative DFPP treatment in preparation for thyriodectomy. In addition to conventional apheresis using FFP replacement, DFPP may offer an effective adjunct option in the management of hyperthyroid patients needing emergent surgical interventions.

Topics: Adult; Agranulocytosis; Female; Graves Disease; Humans; Lymphohistiocytosis, Hemophagocytic; Methimazole; Plasmapheresis; Preoperative Care; Treatment Outcome

Topics: Aged; Agranulocytosis; Anti-Bacterial Agents; Antithyroid Agents; Debridement; Diagnosis, Differential; Fasciitis, Necrotizing; Female; Follow-Up Studies; Humans; Hyperthyroidism; Methimazole; Pseudomonas aeruginosa; Pseudomonas Infections

Hyperthyroidism is mainly caused by Graves' disease and toxic adenoma or multinodular goiter. In Europe, treatment of both disorders is usually started with antithyroidal drugs such as methimazole. Complications include agranulocytosis and the risk is dose-dependent. The starting dose of methimazole should not exceed 15-20 mg/d. Propylthiouracil can cause severe liver failure, leading to liver transplantation or death. Propylthiouracil, therefore, should not be used as first line agent and is only recommended when an antithyroid drug is to be started during the first trimester of pregnancy or in individuals who have experienced adverse responses to methimazole. Toxic adenoma is finally treated with radioioidine. To reduce the risk of treatment failure, antithyroidal drugs should be stopped at least one week prior to radioiodine. For Graves' disease, remission is unlikely if antibodies against the TSH-receptor remain above 10 mU/l after 6 months of antithyroidal treatment and radioiodine or thyroidectomy can be recommended. Thyroidectomy should be performed as (near) total thyreoidectomy.

Topics: Adenoma; Agranulocytosis; Antithyroid Agents; Female; Goiter, Nodular; Graves Disease; Humans; Hyperthyroidism; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Thyroid Neoplasms; Thyroidectomy

Topics: Adult; Agranulocytosis; Colony-Stimulating Factors; Cyclosporine; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Humans; Methimazole; Prednisone; Treatment Failure

Antithyroid drugs (ATDs) are prescribed as the initial therapy for the majority of patients with Graves' disease in many areas of the world. Although, it is well known that agranulocytosis is one of the most serious side effects of ATDs, there has not yet been any conclusive evidence that the prevalence of agranulocytosis induced by ATDs is dose related. This study was performed to determine if the prevalence of agranulocytosis is different depending on the starting dosage of ATDs in patients with Graves' disease.. Until 1996, we had typically prescribed 30 mg/d of methimazole (MMI) as the initial dosage for the treatment of Graves' disease at our institution. We changed the initial MMI dosage to 15 mg/d as a general rule in 1997. As a consequence, we acquired two groups of patients with Graves' disease who received different dosages of MMI. We retrospectively compared the prevalence of MMI-induced agranulocytosis in patients who received 15 mg/d of MMI to those who received 30 mg/d of MMI.. There were 2087 subjects treated with 30 mg/d of MMI and 2739 treated with 15 mg/d of MMI. The prevalence of agranulocytosis in the 30 mg/d group was significantly higher than in the 15 mg/d group (0.814% vs. 0.219%, respectively, p < 0.01). The prevalence of agranulocytosis plus neutropenia in the 30 mg/d group was also significantly higher than in the 15 mg/d group (1.581% vs. 0.474%, respectively, p < 0.001).. It is very likely that MMI-induced agranulocytosis occurs with a larger dosage of MMI and is dose related. Considering both the effectiveness and the risk of serious side effects, we recommend 15 mg/d of MMI as the starting dosage for the treatment of Graves' disease.

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Middle Aged; Neutropenia; Neutrophils; Retrospective Studies; Young Adult

Topics: Agranulocytosis; Antithyroid Agents; Humans; Methimazole; Thyroid Gland

LATIN is a multinational case-control study designed to identify risk factors for agranulocytosis and to estimate the incidence rate of the disease in some Latin American countries.. Each study site in Brazil, Argentina and Mexico conducted an active search of agranulocytosis patients in hematology clinics and looked for possible associations with drug use.. The overall incidence rate was 0.38 cases per 1 million inhabitant-years. Agranulocytosis patients more often took medications already associated with agranulocytosis than controls (p = 0.01), mainly methimazole (OR 44.2, 95% CI 6.8 to infinity). The population attributable risk percentage (etiologic fraction) was 56%. The use of nutrient supplements was more frequent among patients than controls (p = 0.03).. Agranulocytosis seems to be very rare in Latin America. The lower than expected number of cases identified during the study period precluded estimation of the risk associated to individual drugs, with the exception of methimazol. However, this is the longest series of agranulocytosis cases ever gathered in Latin America, and information on drug exposures was collected prospectively. The conclusion is that drug-induced agranulocytosis does not seem to be a major public health problem in the study regions.

Topics: Aged; Agranulocytosis; Antithyroid Agents; Case-Control Studies; Child; Data Collection; Female; Humans; Incidence; Interviews as Topic; Latin America; Male; Methimazole; Middle Aged; Occupational Exposure; Risk Factors; Surveys and Questionnaires

Antithyroid drugs have been used for more than 50 years for the management of hyperthyroidism. Most patients tolerate treatment well but some may develop life threatening side effects such as agranulocytosis and aplastic anemia (AA). We review all cases of antithyroid drug induced AA and describe, as illustrative cases, two women with Graves' disease who developed AA after 8 and 24 weeks of carbimazole (CBM) and methimazole (MMI) treatment respectively.. To date, at least 34 cases of aplastic anemia (AA) due to antithyroid drugs [(1 with CMZ, 31 with MMI, and 2 with propylthiouracil (PTU)] have been published, not including the two patients described here. In addition, at least another 14 patients in whom AA developed after treatment with antithyroid drugs (11 with CMZ, and 3 with MMI) have been reported in Yellow Card Scheme data analysis. Patients with AA usually exhibit sudden onset of symptoms after a relative short time of exposure to the drugs, and all have concomitant agranulocytosis. Most have a rapid recovery following discontinuation of the drug and supportive treatment. Although only two antithyroid drug induced AA deaths have been published, the mortality rate was higher in the Yellow Card Scheme data analysis.. Aplastic anemia associated with antithyroid drug treatment is rarer than antithyroid drug associated agranulocytosis. The prognosis of patients with antithyroid drug induced AA is good overall, but may not be as favorable as that of antithyroid drug induced isolated agranulocytosis.

Topics: Adult; Agranulocytosis; Anemia, Aplastic; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Kaplan-Meier Estimate; Methimazole; Middle Aged

The relation between the incidence of methimazole (methylmercaptoimidazole; MMI)-induced agranulocytosis and initial MMI dose was evaluated in a group of 514 patients with Graves' disease who were treated between 1995 and 2005. One hundred and forty-six (28.40%) patients had received an initial dose of 30 mg MMI and 277 (53.89%) patients had been treated with 15 mg MMI. Nine patients (1.75%) developed agranulocytosis due to MMI treatment. Six (4.11%) of 146 patients who received an initial dose of 30 mg MMI, two (4.54%) of 44 patients given an initial dose of 20 mg MMI, and one (0.36%) of 277 patients given an initial dose of 15 mg MMI developed agranulocytosis. There was a statistically significant difference in agranulocytosis incidence between patients receiving an initial dose of 30 mg MMI and those who received an initial dose of 15 mg. Although 8 (4.10%) of 195 patients in the high-dose group (20 mg or higher) developed agranulocytosis, only 1 (0.31%) of 319 patients in the low-dose group (15 mg or lower) did. In conclusion, the incidence of agranulocytosis with low-dose MMI therapy was ten times lower than that of the high-dose regimen.

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Dose-Response Relationship, Drug; Female; Graves Disease; Humans; Incidence; Male; Methimazole; Middle Aged; Retrospective Studies

Topics: Adult; Agranulocytosis; Bone Marrow; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Male; Methimazole; Methylprednisolone; Plasma Cells; Thrombocytosis; Treatment Outcome

Topics: Adrenergic beta-Antagonists; Aged; Agranulocytosis; Amiodarone; Anti-Arrhythmia Agents; Antithyroid Agents; Atrial Fibrillation; Chest Pain; Cholangitis; Glucocorticoids; Humans; Hyperthyroidism; Hypothyroidism; Male; Methimazole; Plasmapheresis

Granulocyte colony-stimulating factor (G-CSF) levels in serum were determined by a highly-sensitive chemiluminescent enzyme immunoassay (limit of detection, 0.5 pg/ml) in 54 patients with Graves' disease including 6 patients complicated with methimazole-induced agranulocytosis. Serum G-CSF levels in patients with Graves' disease were not different from normal subjects and did not correlate with serum FT4 level or circulating neutrophil counts. Before the onset of agranulocytosis, there was no difference in serum G-CSF level between the patients complicated with agranulocytosis and the uncomplicated patients. When circulating neutrophil counts decreased to less than 0.5 x 10(9)/L, serum G-CSF level elevated with the mean of 106.8 +/- 82.2 (SD) pg/ml, but the level did not correlate with the duration of agranulocytosis. Interestingly, maximum serum G-CSF level during the treatment with recombinant human G-CSF (100 microg/day) was related to bone marrow finding at the onset of agranulocytosis and correlated with the duration of agranulocytosis (r = 0.824, p < 0.05). In conclusion, measuring serum G-CSF levels with a highly-sensitive chemiluminescent enzyme immunoassay revealed that 1) thyrotoxicosis does not affect serum G-CSF level, 2) serum G-CSF level during antithyroid drug treatment does not play an important role in development of agranulocytosis, 3) the maximum serum G-CSF level in the course of agranulocytosis is related to the responsiveness of bone marrow to G-CSF and the recovery time from agranulocytosis.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Bone Marrow; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Luminescent Measurements; Male; Methimazole; Middle Aged; Neutrophils; Recombinant Proteins

In this study, we retrospectively analyzed 18 patients in whom antithyroid drug (ATD)-induced agranulocytosis developed during treatment of Graves' disease. All patients were more than 20 years of age, and we saw no correlation between age and the development of agranulocytosis. In 17 of 18 patients, ATD-induced agranulocytosis developed within 2 to 12 weeks of starting ATD treatment. Development of agranulocytosis was related to the dose of ATD. In some patients, agranulocytosis developed abruptly, and even weekly routine WBC and granulocyte counts failed to predict all case occurrences. Fever and sore throat were the earliest symptoms of agranulocytosis; patients who developed either of these symptoms were closely monitored immediately with WBC and granulocyte count examinations. In this series of patients, treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) increased the granulocyte counts, whereas the effectiveness of glucocorticoid treatment was not confirmed.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

A 65-year-old woman with Graves' disease presented marked diurnal changes in white blood cell (WBC) and granulocyte counts. Granulocyte count was low and sometimes decreased to 0.2-0.3 x 10(9)/l in the early morning and increased in the afternoon irrespective of her thyroid status. She did not develop sore throat or fever during the investigation period. The present study indicates that these unusual diurnal changes in WBC and granulocyte counts should be considered in the differential diagnosis of agranulocytosis in Graves' disease patients treated with an antithyroid drug.

Topics: Aged; Agranulocytosis; Antithyroid Agents; Circadian Rhythm; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Leukocyte Count; Methimazole

Three patients, females aged 62, 67 and 32 years, were presented with fever and sore throat and had severe agranulocytosis (granulocyte count < 100/microliter). All had Graves' disease and were being treated with thiamazole 30 mg once a day. Thiamazole was discontinued and treatment with antibiotics initiated. None of the patients received granulocyte-colony stimulating factor (G-CSF). The mean recovery time of granulocytes was 9 days and there were no fatalities. Patients who receive antithyroid agents should be warned against the serious and potentially lethal side effect of agranulocytosis.

Topics: Adult; Aged; Agranulocytosis; Antithyroid Agents; Bone Marrow Examination; Female; Fever; Graves Disease; Humans; Methimazole; Middle Aged; Pharyngitis; Remission Induction; Sepsis

Topics: Aged; Agranulocytosis; Antithyroid Agents; Female; Focal Infection; Gallium Radioisotopes; Humans; Hyperthyroidism; Methimazole; Pneumonia, Bacterial; Pseudomonas Infections; Radionuclide Imaging

Topics: Agranulocytosis; Antithyroid Agents; Diagnosis, Differential; Escherichia coli Infections; Female; Follow-Up Studies; Furunculosis; Humans; Methimazole; Middle Aged; Skin Ulcer

To analyse the routine WBC count's effect on predicting antithyroid drugs-induced agranulocytosis developing and risk factors of antithyroid drugs-induced agranulocytosis.. Retrospective analysis of 18 Graves' cases with agranulocytosis induced by antithyroid drugs during 1984-1995.. Most of antithyroid drugs-induced agranulocytosis happens 2-12 weeks after the administration of antithyroid drug, and are related with the drug's doses. Some agranulocytosis happens abruptly, routine WBC and granulocyte count can not predict some agranulocytosis developing. Fever and throat sore are the intitial symptoms of agranulocytosis, if it happens, the WBC and granulocyte count must be checked immediately. The treatment of granulocyte-macrophage colony stimulating factor is effective, the corticosteroid therapy seems not to be useful for the recovery of granulocyte count.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Retrospective Studies

Topics: Aged; Agranulocytosis; Antithyroid Agents; Female; Fever; Graves Disease; Humans; Methimazole; Pharyngitis

This prospective study was designed to investigate the usefulness of granulocyte count measurements 4 hours after injection of granulocyte colony-stimulating factor (G-CSF) for detecting recovery from antithyroid drug (ATD)-induced granulocytopenia or agranulocytosis. Granulocyte and white blood cell counts were measured 4 hours and 24 hours after patients with ATD-induced granulocytopenia had been given an injection of 75 micrograms of G-CSF (1.1 to 1.9 micrograms/kg; 1.5 +/- 0.2 micrograms/kg [mean +/- standard deviation]). Thirty-seven patients were studied and divided into three groups based on their initial granulocytopenic granulocyte count: 28 with mild (granulocyte count 0.501 to 1.0 x 10(9)/L), 6 with moderate (granulocyte count 0.101 to 0.5 x 10(9)/L), and 3 with severe (granulocyte count less than 0.1 x 10(9)/L) ATD-induced granulocytopenia. Twenty-five of the 28 patients with mild granulocytopenia and 4 of the 6 patients with moderate granulocytopenia were found to have recovered from the granulocytopenia both 4 hours and 24 hours after injection, and their granulocyte counts remained normal thereafter. However, the other 3 patients with mild granulocytopenia, 2 patients with moderate granulocytopenia, and all 3 patients with severe granulocytopenia had not recovered by either 4 or 24 hours after the G-CSF injection. Despite daily G-CSF injections, the granulocyte continued to decrease in most cases. It took 2 to 11 days for these counts to recover from granulocytopenia. These results indicate that granulocyte count measurement 4 hours after injection of G-CSF is useful for detecting recovery from ATD-induced granulocytopenia or agranulocytosis and for predicting disease severity. Accordingly, its measurement enables physicians to make an appropriate decision about whether a patient with ATD-induced granulocytopenia should be treated in the hospital or in the outpatient clinic.

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Graves Disease; Humans; Kinetics; Leukocyte Count; Male; Methimazole; Middle Aged; Propylthiouracil; Prospective Studies

We report here a patient with recurrent Graves' disease on hemodialysis. She also suffered from angina pectoris, which was probably a manifestation of Graves' disease due to the increased oxygen demands in the presence of fixed coronary lesions. Although antithyroid drugs induced mild granulocytopenia, propylthiouracil (PTU) or methimazole (MMI) was not discontinued during the administration of granulocyte colony-stimulating factor (G-CSF). The patient received sodium iodine-131 therapy, and became euthyroid with no chest pain. To our knowledge, this is the first case that illustrated the usefulness of G-CSF for antithyroid drug-induced granulocytopenia prior to thyroid ablation for Graves' disease complicated with chronic renal failure and angina pectoris.

Topics: Agranulocytosis; Angina Pectoris; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Iodine Radioisotopes; Kidney Failure, Chronic; Methimazole; Middle Aged; Propylthiouracil; Renal Dialysis

Topics: Agranulocytosis; Antithyroid Agents; Blood Cell Count; Drug Monitoring; Humans; Methimazole

To determine the association between HLA class II genes and methimazole-induced agranulocytosis in patients with Graves disease.. Case-control study.. Kuma Hospital, which specializes in thyroid diseases, in Kobe, Japan.. 24 patients with Graves disease who had methimazole-induced agranulocytosis diagnosed by peripheral granulocyte counts of less than 0.5 x 10(9)/L, and 68 patients with Graves disease treated with methimazole, who were free from agranulocytosis. Controls were 525 healthy, unrelated Japanese student volunteers at Kyushu University in Japan.. All HLA class II genes were analyzed for polymorphisms at the DNA level by using the polymerase chain reaction sequence-specific oligonucleotide probes method. The allele frequencies in the agranulocytotic Graves disease group were compared with those in the nonagranulocytotic Graves disease and control groups.. A strong positive association was seen in DRB1*08032 between the agranulocytotic group and both the control and nonagranulocytotic Graves disease groups.. The HLA DRB1*08032 allele was strongly associated with susceptibility to methimazole-induced agranulocytosis, suggesting that cellular autoimmunity may be involved in its development.

Topics: Agranulocytosis; Antithyroid Agents; Autoimmunity; Graves Disease; HLA-DR Antigens; Humans; Methimazole; Polymorphism, Genetic; T-Lymphocytes

The haemopoietic growth factors are relatively new additions to the treatment of drug-induced bone marrow suppression. Treatment with growth factors may induce primitive cells to enter into cell cycle. In clinical practice they have beneficial effects on the neutropenia following cytotoxic chemotherapy, bone marrow transplantation, and it may be effective in severe chronic neutropenia by cause drugs. One of the classes of drugs which cause serious agranulocytosis are the antithyroid drugs. A thyrotoxic patient with methimazole-induced agranulocytosis was treated with recombinant human granulocyte-monocyte colony-stimulating factor (rHu GM-CSF). Seven days following treatment with daily subcutaneous injection of 270 micrograms rHu GM-CSF combined with antibiotics and glucocorticosteroids, granulocytes reappeared in the peripheral blood and the sepsis resolved. No side effects of the treatment were observed. The combination of rHu GM-CSF and glucocorticosteroids was successful in restoring normal granulocyte count.

Topics: Aged; Agranulocytosis; Antithyroid Agents; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Methimazole; Recombinant Proteins; Thyrotoxicosis

The application of granulocyte-macrophage and granulocyte colony stimulation factors (GM-CSF and G-CSF) has been progressively increased in the treatment of patients with agranulocytosis. The aim of our study was to compare the time of neutrophil recovery in patients with severe agranulocytosis treated with G-CSF or GM-CSF and the historical control group. We have studied 6 patients with agranulocytosis treated with stimulating factors and 7 patients in historical control group. Most of the patients have been exposed to thiamazole or non-steroid antiinflammatory drugs. Our results demonstrate that patients receiving colony stimulating factor have a significantly shorter period of recovery (the mean time 8.7 +/- 1.98 days) than the historical control group (the mean time 11.0 +/- 2.24 days). We observed also a shorter time of antibiotico-therapy and hospitalization in the group of patients treated with colony stimulating factor.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Antifungal Agents; Drug Evaluation; Female; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infection Control; Male; Methimazole; Middle Aged

Topics: Agranulocytosis; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Injections, Subcutaneous; Male; Methimazole; Middle Aged; Recombinant Proteins; Time Factors

Methimazole 5 mg three times daily was prescribed in 1994 spring to a woman, aged 53 years, with relapsed hyperthyroidism. The drug was discontinued six weeks after initiation because of leukopenia. Two weeks still later, the patient developed chills, high fever, and a sore throat. The leukocyte count was 1,100/mm3 with 23% granulocytes, 76% lymphocytes and 1% monocytes. The granulocyte count stopped decreasing only three weeks after the drug was discontinued when the recombinant human granulocyte colony-stimulating factor (rhG-CSF) was given; the patient recovered uneventfully. Thus we recommend that the peripheral leukocyte count of patients who receive methimazole therapy must be carefully monitored during the first three months. Furthermore, the use of rhG-CSF for methimazole-induced agranulocytosis abbreviates the period required for marrow recovery after cessation of this offensive drug.

Topics: Agranulocytosis; Antithyroid Agents; Female; Granulocyte Colony-Stimulating Factor; Humans; Methimazole; Middle Aged; Recombinant Proteins

After coronary angiography a 66-year-old man developed manifest hyperthyroidism (fT3 8.7 pg/ml, fT4 3.7 ng/dl) marked by tremor, restlessness and sweating. The hyperthyroidism was controlled by high dosages of thiamazole (240 mg daily) and lithium (24-36 mmol daily). But the white cell count dropped from 8,000/microliters to 4,900/microliters on the eighth day. Although the thiamazole dose was reduced to 40 mg daily, the granulocytopenia became more severe and, on the 24th day of treatment, agranulocytosis occurred (neutrophilic granulocyte count 200/microliters), although the thiamazole had been discontinued. The patient was then isolated and treated prophylactically with ofloxacin. Simultaneously he received 5 micrograms/kg granulocyte-colony stimulating factor (G-CSF) subcutaneously daily for 7 days. On the sixth day of this treatment the granulocyte count was 520/microliters, next day 3,800/microliters, and after a further 2 days it overshot to 31,000/microliters, then gradually returning to normal values. -It is recommended that the use of G-CSF should be considered also for thyrostatic-induced agranulocytosis, because it may shorten this dangerous phase.

Topics: Aged; Agranulocytosis; Granulocyte Colony-Stimulating Factor; Humans; Hyperthyroidism; Male; Methimazole; Patient Isolation; Thyroid Function Tests

G-CSF was applied in three patients with acute, iatrogenic, immunological agranulocytosis (after ticlopidine, thimazol and aminoglutethimide) complicated by severe infections. Before this treatment was started no improvement had been achieved despite the administration of antibiotics, and corticosteroids for 4 to 9 days. Two patients had anaemia and one--thrombocytopenia probably due to the damage to the earlier, common progenitor cells. In bone marrow smears a plasmocytic reaction reaching 11-13% of total cell counts was observed. After G-CSF all patients showed a prompt amelioration of clinical symptoms, and the leucocyte count raised in several days up to 11.0-73.0 x 10(3)/microliters. Simultaneously young cellular forms of granulocyte lineage appeared in peripheral blood.

Topics: Adult; Agranulocytosis; Aminoglutethimide; Female; Granulocyte Colony-Stimulating Factor; Humans; Leukocyte Count; Methimazole; Ticlopidine; Treatment Outcome

A 26-year-old woman was admitted to hospital with high fever, severe tonsillitis, and gastroenteritis. Because of Graves' disease she had been treated with methimazole for 18 months. Leukopenia and agranulocytosis in combination with a typical bone marrow, exhibiting a complete arrest of myelopoiesis at the stage of promyelocytes led to the diagnosis of an antithyroid therapy induced agranulocytosis. After 1 week of antibiotic treatment without changes in neutrophil counts, granulocyte colony stimulating factor treatment at a dose of 300 micrograms/day subcutaneously was started. Twenty-four hours after the first administration the neutrophil counts began to rise, to 4389/microliters, with a maximum after the third administration and stabilizing at normal levels within 10 days. Since agranulocytosis is considered to be a severe and fatal complication of methimazole therapy, treatment with granulocyte colony stimulating factor seems to be useful for this life-threatening condition.

Topics: Adult; Agranulocytosis; Bone Marrow; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Immunologic Factors; Infections; Leukocyte Count; Methimazole

A 35-year-old female hematology technician with Graves' disease developed agranulocytosis a few days after starting therapy with Tapazole (methimazole). Because of a recent report of use of recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with propylthiouracil-induced agranulocytosis, 5 micrograms/kg/day G-CSF was administered and her granulocyte count returned to normal after three doses, on the sixth day after the last dose of methimazole. We conclude that in patients with drug-induced agranulocytosis, the use of G-CSF, in addition to discontinuation of the offending drug, hastens recovery and reduces morbidity.

Topics: Adult; Agranulocytosis; Blood Cell Count; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Graves Disease; Humans; Methimazole; Recombinant Proteins

The authors treated a patient with methimazol (Metothyrin)-induced agranulocytosis with human recombinant granulocyte-macrophage colony stimulating factor (GM-CSF). On day seven, after combined antibiotics, corticosteroid and at a dose of 270 ug daily subcutaneous GM-CSF therapy the septic state of the patients rapidly cured and the leucocytes reached the peripheric blood. No side effects were found. The publication of this case history might help to determine the place of human GM-CSF-s therapy in the treatment of agranulocytosis of different origin.

Topics: Administration, Cutaneous; Adult; Aged; Agranulocytosis; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Hyperthyroidism; Leukocyte Count; Methimazole

Topics: Agranulocytosis; Clozapine; Drug Therapy, Combination; Female; Humans; Methimazole; Middle Aged; Thyrotoxicosis

Topics: Agranulocytosis; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Methimazole; Middle Aged; Remission, Spontaneous

Agranulocytosis, although extremely infrequent, is a serious complication of antithyroidal drug therapy in patients with hyperthyroidism. Presently, there is no specific therapy for this life-threatening complication, and recovery time is highly variable. Recently, recombinant human granulocyte colony-stimulating factor (rhG-CSF) was reported to be effective in shortening the recovery time of the neutropenia in patients undergoing chemotherapy. The present study was undertaken to determine the efficacy of rhG-CSF administration in patients with methimazole-induced (MMI) agranulocytosis. Thirty-four patients (7 males and 27 females, ages 16-68 yr) with MMI agranulocytosis were divided into 3 groups: group A (n = 11) was treated with antibiotics only; group B (n = 11) received antibiotics and dexamethasone, 8 mg/day; and group C (n = 12) was treated with antibiotics and im injections of rhG-CSF, 75 micrograms/day. Patients in groups A and B were studied retrospectively. When rhG-CSF became available, patients in group C were studied prospectively. Bone marrow sternal punctures were performed in all group C patients who were then divided into 2 subgroups according to the granulocyte to erythrocyte count ratio (G:E). Group C1 (n = 6) had a G:E ratio of less than 0.5, and group C2 (n = 6) had a ratio of more than or equal to 0.5. Recovery time in all groups was defined as the number of days required for the peripheral granulocyte count to be greater than 1.0 x 10(9)/L. There was no significant difference in recovery time between groups A and B: 10.1 +/- 2.2 and 12.3 +/- 1.9 days (mean +/- SE), respectively. P was not significant; the administration of dexamethasone proved to be ineffective in shortening the time for recovery from peripheral granulocytes. On the other hand, recovery time was significantly shorter in group C (6.8 +/- 1.2 days mean +/- SE) compared with groups A and B (P < 0.05). Group C2 recovered in 2.2 +/- 0.6 days whereas group C1 took much longer, 9.8 +/- 1.3 days (P < 0.001). There was a direct correlation between the G:E ratio and the peripheral leucocyte count, r = 0.806, P < 0.01. Furthermore, rhG-CSF significantly shortened recovery time when the peripheral granulocyte count was greater than 0.1 x 10(9)/L (group C2) compared with patients whose counts were less than 0.1 x 10(9)/L (group C1), 2.2 +/- 0.4 vs. 8.6 +/- 1.3 days, respectively (P < 0.001). These data indicate that administration of steroids is ineffective in shortening the du

Topics: Adult; Agranulocytosis; Female; Granulocyte Colony-Stimulating Factor; Granulocytes; Humans; Leukocyte Count; Male; Methimazole; Recombinant Proteins; Treatment Outcome

The primary objective of this study was to ascertain the effectiveness of granulocyte colony-stimulating factor in the treatment of antithyroid drug-induced granulocytopenia of varying degree. Sixteen patients with Graves' disease with antithyroid drug-induced granulocytopenia (granulocyte counts < 1.0 x 10(9)/L) each received a daily dose of 75 micrograms of granulocyte colony-stimulating factor administered subcutaneously. Within 24 hours of the first injection, the granulocyte count increased (0.6 to 12.3 x 10(9)/L) in all 10 patients with mild granulocytopenia (granulocyte counts between 0.5 and 1.0 x 10(9)/L) and all three with moderate granulocytopenia (granulocyte counts < 0.5 x 10(9)/L). The three remaining patients with severe granulocytopenia (agranulocytic), whose granulocyte counts were zero, did not recover from granulocytopenia until the 6th, 7th, and 14th days of treatment with granulocyte colony-stimulating factor. Examination of bone marrow taken at the onset of the disease in all three agranulocytic patients showed a prominent decrease in granulocytic series, while identical examination in six of eight patients with mild to moderate granulocytopenia showed close to normal granulocytic series. There was no elevation of serum granulocyte colony-stimulating factor concentration in four patients with mild granulocytopenia and one with moderate granulocytopenia at the onset of their disease, whereas those of the remaining three patients with severe granulocytopenia (agranulocytic) increased at onset of agranulocytosis. This information led us to conclude that: (1) granulocyte colony-stimulating factor is effective in the treatment of antithyroid drug-induced mild to moderate granulocytopenia and (2) in severe agranulocytic cases, granulocyte colony-stimulating factor is not effective. Accordingly, we were again reminded of the importance of early diagnosis and treatment of antithyroid drug-induced agranulocytosis.

Topics: Adult; Aged; Agranulocytosis; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Recombinant Proteins

Five patients with drug-induced agranulocytosis received 300 micrograms recombinant human granulocyte colony-stimulating factor (rh G-CSF) subcutaneously twice daily for 2-5 days. G-CSF therapy resulted in a steep increase of the neutrophil count, which was faster than that in patients with spontaneous recovery reported in the literature. In all four patients with infectious complications fever rapidly declined with the increase of granulocytes. G-CSF may be useful in the management of drug-induced agranulocytosis.

Topics: Adult; Agranulocytosis; Dipyrone; Female; Granulocyte Colony-Stimulating Factor; Humans; Male; Methimazole; Middle Aged; Recombinant Proteins

A 36-year-old patient, euthyroid under methimazole treatment, was admitted because of an active Graves' ophthalmopathy and found to have a transient granulocytopenia. Forty-five days after this episode she developed classical agranulocytosis because of which the methimazole was stopped. The agranulocytosis occurred more than 20 months after the initiation of antithyroid drug therapy. Other causes for the initial phase of granulocytopenia were not found.

Topics: Adult; Agranulocytosis; Drug Monitoring; Female; Granulocytes; Graves Disease; Humans; Leukocyte Count; Methimazole; Time Factors

We evaluated the determination of serum G-CSF in the diagnosis of granulocytopenia due to methimazole (MMI) in 54 patients with Graves' disease, while they were being treated with MMI, by way of measuring WBC counts and serum levels of G-CSF, thyroid hormones, IgE, and interleukin-2. Serum TSH was measured by immunoradiometric assay, serum G-CSF was done by enzyme immunoassay, thyroid hormones and IgE were done by radioimmunoassay, and serum Interleukin-2 was done by enzyme-linked immunosorbent assay. The population whose G-CSF levels were higher than the minimum detectable level (30pg/ml) was 6 (30%) in normal subjects, 4 (22%) in patients with untreated Graves' disease, 2 (12%) in patients with treated euthyroid Graves' disease, 3 (23%) in patients with Graves' disease who had gone through agranulocytosis, and 2 (33%) in patients with Graves' disease complicated with granulocytopenia. There was no significant change in WBC counts for 4 weeks, but there was a significant difference between WBC counts before treatment and those at 8 weeks after treatment. We observed no significant change of serum G-CSF levels in patients with Graves' disease under treatment. However, there were significantly high levels of serum G-CSF and significantly low counts of WBC in patients with Graves' disease complicated with granulocytopenia induced by MMI, compared with those in normal subjects, patients with untreated Graves' disease, patients with treated euthyroid Graves' disease, and patients with euthyroid Graves' disease who had gone through agranulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Agranulocytosis; Bone Marrow Cells; Feedback; Female; Granulocyte Colony-Stimulating Factor; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Middle Aged

Topics: Adult; Agranulocytosis; Female; Granulocyte Colony-Stimulating Factor; Humans; Methimazole

A 61-year-old female patient, treated for hyperthyroidism with thiamazole, developed a severe maturation arrest in the granulocytic lineage and a total agranulocytosis. Subcutaneous GM-CSF was started immediately and given for 6 days. Bone marrow samples were taken before GM-CSF therapy and on days 3 and 8. An increased number of colonies per 10(5) bone marrow cells documented before institution of GM-CSF treatment was followed by a gradual decline to normal values. An increase of granulocyte count to > 0.5 x 10(9) l-1 was recorded on the 4th day of treatment and was preceded by an increase in the number of immature granulocyte precursors in the bone marrow on day 3. The patient was discharged on day 8 and experienced no adverse effects of GM-CSF treatment. Haematopoietic growth factor therapy has a place in the management of patients with drug induced neutropenia/agranulocytosis, which should be further delineated by prospective studies.

Topics: Agranulocytosis; Bone Marrow Examination; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Granulocytes; Hemoglobins; Humans; Injections, Subcutaneous; Leukocyte Count; Methimazole; Middle Aged; Platelet Count

The in vivo response to recombinant human granulocyte-monocyte colony-stimulating factor (rHu GM-CSF) in facilitating the reconstitution of granulomonopoiesis was evaluated in a patient with Graves' disease who developed severe aplastic anemia during methimazole therapy. After 10 days of treatment with rHu GM-CSF, the neutrophil and monocyte counts rose to 1.65 x 10(9)/l and 0.41 x 10(9)/l, respectively. However, the patient was still dependent on erythrocyte and platelet transfusions. Two days after rHu GM-CSF withdrawal, the neutrophil count dropped off to 0.41 x 10(9)/l.rHu GM-CSF was reinitiated for 2 days along with glucocorticosteroids. With this combined therapeutic approach, the neutrophil count returned to normal and remained stable, and both Hb and platelet values began to improve. It is concluded that the combination of rHu GM-CSF and glucocorticosteroids can be used as a therapeutic option that may lead to beneficial results in drug-induced aplastic anemia.

Topics: Adolescent; Agranulocytosis; Anemia, Aplastic; Female; Glucocorticoids; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Leukocyte Count; Methimazole; Neutrophils; Recombinant Proteins

Retrospective analysis of 11 Chinese patients with Graves' thyrotoxicosis developing agranulocytosis during anti-thyroid treatment was done. Seven of them received methimazole and 4 received carbimazole. None of the 11 patients had taken propylthiouracil. The major chief complaints were high fever (100%), chillness (91%), and sore throat (73%). The duration of drug treatment prior to the detection of agranulocytosis ranged from 13 to 63 days (mean +/- 1SE: 33.1 +/- 16.1). At the time of agranulocytosis detected, the peripheral leukocyte counts were 0.5 to 2.1 X 1000/mm3 (mean +/- 1SE: 1.05 +/- 0.47 X 1000/mm3), absolute neutrophil counts 0 to 450/mm3 (mean +/- 1SE: 54.27 +/- 132.12/mm3), and hemoglobin 8.2 to 15.9 g/dl (mean +/- 1SE: 11.85 +/- 2.24 gm/dl). Three of the 11 patients had positive bacterial blood cultures. The recovery time of absolute neutrophil counts above 500/mm3 ranged from 3 to 25 days (mean +/- 1SE: 10.5 +/- 6.6) after discontinuation of antithyroid drugs. Mortality was found in 2 of them (18%).

Topics: Adolescent; Adult; Agranulocytosis; Antithyroid Agents; Carbimazole; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Thyrotoxicosis

Topics: Adult; Agranulocytosis; Graves Disease; Humans; Liver; Methimazole; Propylthiouracil

The paper deals with agranulocytosis as one of the side effects of methimazole. The analysis of 7 cases allows some conclusions in respect to prevention, early detection and treatment of this rare but serious complication.

Topics: Adult; Aged; Agranulocytosis; Humans; Methimazole; Middle Aged; Thyrotoxicosis

Topics: Agranulocytosis; Antithyroid Agents; Depression, Chemical; Female; Graves Disease; Humans; Methimazole; Pregnancy; Pregnancy Complications; Propylthiouracil; Tablets; Thyroid Hormones

This study was aimed at establishing the importance of routine monitoring of white blood cell counts in patients with Graves' disease receiving antithyroid drug treatment. In the 12-year period from 1975 to 1987, 15,398 patients with Graves' disease receiving treatment with antithyroid drugs were seen at our clinic. Of these, 55 (0.4%) were found to have agranulocytosis. Agranulocytosis was defined as a granulocyte count of 0.5 x 10(9)/L or less. In only 12 of the 55 patients was agranulocytosis detected after the occurrence of infection (symptomatic; classic agranulocytosis). The remaining 43 patients were asymptomatic when agranulocytosis was detected during routine white blood cell count monitoring. However, 14 of these 43 patients became symptomatic several days after withdrawal of antithyroid drug treatment despite antimicrobial treatment (asymptomatic to symptomatic). Twenty-nine patients who were treated appropriately had no symptom of infection throughout the course of the disease, despite the absence of or an extremely small number of granulocytes in circulation (asymptomatic). These results suggest that a "routine monitoring" of the white blood cell count could be the most effective way of predicting and detecting agranulocytosis due to antithyroid drug treatment.

Topics: Adult; Agranulocytosis; Female; Granulocytes; Graves Disease; Humans; Leukocyte Count; Male; Methimazole; Propylthiouracil

Bone marrow CFU-GM and cluster forming cells were studied in ten patients in different stages of drug-induced agranulocytosis using a methylcellulose cell culture technique in vitro. In the aplastic phase of the disease (A), the number of both CFU-GM and cluster forming cells was decreased in comparison to normal values. In the regenerative phase of the disease (R), the number of both granulocytic progenitors increased but did not reach normal values. In patients considered to be recovered from acute agranulocytosis (Rec), a decreased number of progenitors persisted indicating residual damage at this granulocytic cell level. It is suggested that agranulocytosis is due to isolated damage of granulocytic cells and predictable cascade of events within different cell compartments could be used as an in vivo model for investigation of the regulation of granulopoiesis.

Topics: Agranulocytosis; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow; Cells, Cultured; Colony-Forming Units Assay; Humans; Methimazole; Pyrazoles; Pyrazolones

The authors studied 389 Graves' hyperthyroid patients receiving either high propylthiouracil (PTU) or methimazole (MMI) daily doses or low doses to evaluate whether adverse effects were related to the thionamide drugs or its daily dose regimen. Group 1 patients (n = 286) received high PTU (728 +/- 216 mg/day, n = 92) or MMI (60 +/- 19 mg/day, n = 94) doses, and group 2 patients (n = 103) were treated with low PTU (255 +/- 85 mg/day, n = 39) or MMI (23 +/- 10 mg/day, n = 64) doses. Major adverse effects were observed in 11 (2.8%) patients. Of these, four (1.0%) had agranulocytosis, two (0.5%) were granulocytopenic and five (1.3%) had hepatotoxicity. Agranulocytosis occurred in two patients from each group, 0.7% and 1.9%, respectively from group 1 and group 2. There was no significant difference between the groups or the types of thionamide. There also was no correlation with the patients' age. All of the patients were hyperthyroid, and its onset occurred in the first to third month of treatment. Full recovery was achieved in all cases after drug withdrawal. Four of 5 patients with hepatotoxicity were treated with high PTU doses, and one patient received low MMI doses (p less than .05). All patients were euthyroid. Arthralgias, skin rash and gastric intolerance, the minor adverse effects of thionamides studied, were observed in 52 (13.4%) of the patients. Although no significant differences were found, most of the patients experiencing side effects were from group 1 an received MMI therapy. These adverse effects did not demand drug withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Agranulocytosis; Chemical and Drug Induced Liver Injury; Child; Dose-Response Relationship, Drug; Drug Eruptions; Graves Disease; Humans; Hyperthyroidism; Joints; Methimazole; Middle Aged; Pain; Propylthiouracil; Stomach Diseases

We reviewed the records of approximately 7000 Japanese patients whose hyperthyroidism was treated with methimazole (MMI) alone. Four patients (Group I) developed agranulocytosis during a second course of MMI therapy and eight patients (Group II) during an initial course. Six patients (three in each group) received less than 30 mg MMI daily. Agranulocytosis occurred after more than 2 months of therapy (12 weeks-1 year) in five patients. Seven patients were less than 40 years of age. One patient displayed a gradual protracted development of agranulocytosis. These results indicate that agranulocytosis after MMI may occur irrespective of dose, age, duration of treatment, and with a second exposure.

Topics: Adult; Agranulocytosis; Female; Graves Disease; Humans; Japan; Leukocyte Count; Male; Methimazole; Middle Aged; Thyroid Function Tests

The authors describe a case of successful treatment of medicamentous agranulocytosis (induced by mercasolyl) using hemoperfusion, an extracorporeal method for the treatment of intoxications. In the severe total intoxication syndrome, application of hemoperfusion in multimodality therapy of myelotoxic agranulocytosis improves the disease prognosis.

Topics: Acute Disease; Agranulocytosis; Combined Modality Therapy; Critical Care; Female; Graves Disease; Hemoperfusion; Humans; Methimazole; Middle Aged; Thyroidectomy

Topics: Adult; Agranulocytosis; Colony-Stimulating Factors; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Growth Substances; Humans; Methimazole

This paper reports a case of agranulocytosis that developed in a patient with hyperthyroidism two months after the administration of methimazole. The patient manifested symptoms of fever, sore throat, profound leukopenia, and oral complications such as generalized gingival necrosis and mucosa ulceration, which subsequently abated upon withdrawal of the drug. Dental practitioners should be aware of the potential of agranulocytosis associated with methimazole therapy. The oral manifestations should be kept in mind.

Topics: Adult; Agranulocytosis; Female; Gingivitis, Necrotizing Ulcerative; Humans; Hyperthyroidism; Methimazole

Topics: Agranulocytosis; Humans; Methimazole

The mechanism for agranulocytosis induced by antithyroid drugs is not established. The few available studies have proposed an immune-mediated process against mature granulocytes. We investigated the effect of methimazole and propylthiouracil and serum from a patient with methimazole-induced agranulocytosis on marrow myeloid colony growth. In the presence of normal serum or patient's recovery serum, antithyroid drugs had no effect on the growth of CFU-GM colonies from normal or patient's marrow. However, the patient's serum obtained during agranulocytosis inhibited the in vitro myeloid colony growth from both autologous and allogeneic bone marrow. These results are compatible with an immune-mediated mechanism for methimazole-induced agranulocytosis rather than a direct toxic effect of the drug on abnormally sensitive cells.

Topics: Adult; Agranulocytosis; Bone Marrow; Colony-Forming Units Assay; Female; Graves Disease; Humans; Methimazole; Propylthiouracil; Stem Cells

Topics: Adult; Agranulocytosis; Female; Graves Disease; Humans; Methimazole

We review the cases of hepatic injury from propylthiouracil, methimazole and carbimazole in the English language literature and compare them to cases of agranulocytosis in a recent review. The data on hepatotoxicity confirm the findings for agranulocytosis that low-dose methimazole is safer than propylthiouracil and that methimazole toxicity is more common over 40 years old. In contrast, propylthiouracil hepatotoxicity often occurs in younger patients. Most cases of hepatic injury occur in the first few months of drug therapy as with agranulocytosis. The reason that methimazole typically causes cholestatic hepatitis while propylthiouracil causes cytotoxic hepatitis remains unknown.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Carbimazole; Chemical and Drug Induced Liver Injury; Child; Female; Humans; Male; Methimazole; Middle Aged; Propylthiouracil

Topics: Agranulocytosis; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Thyroid Crisis

Studies of in vitro immunoreactivity to propylthiouracil (PTU), methimazole (MMI), and carbimazole (CARB), as assessed by peripheral blood lymphocyte transformation and 2 antibody tests, were carried out in 12 patients with Graves' hyperthyroidism who had developed agranulocytosis during treatment with PTU (11 patients) or CARB (1 patient) from 1 week to 10 yr earlier. Significant lymphocyte transformation responses to antithyroid drugs (stimulation indices greater than mean +/- 2 SD for normal subjects) were found in 5 of 6 patients tested, in 1 patient to PTU only, in 3 patients to MMI only, and in 1 patient to both PTU and MMI, but in none of 10 patients currently being treated with PTU who did not develop agranulocytosis. Circulating antibodies causing neutrophil agglutination in the presence of antithyroid drugs were demonstrated, using the indirect Coombs test, in 5 of 7 patients tested, in 2 patients to PTU only, in 3 patients to CARB only and in 1 patient (the only one tested with MMI) to PTU and MMI. Lymphocyte transformation and antibody tests to PTU were both carried out in 6 patients. Of these, both tests were positive in one patient, both negative in 3 patients, and 1 negative and 1 positive in 2 patients. In the 1 patient in whom both tests were carried out with CARB (patient 3), tests were negative, whereas in the 1 patient in whom both tests were carried out with MMI (patient 3), 1 test was positive, whereas the other was negative. Thus, in patients in whom both tests were carried out using the same drug, correlation between lymphocyte transformation responses and the detection of neutrophil antibodies was found in 5 of 6 cases. Antibodies reactive with neutrophils were also detected in 2 of the 5 patients tested using an enzyme-linked immunosorbent assay. In this test antibodies to PTU or MMI were not demonstrated. Possible mechanisms for the neutrophil depression in relation to these findings are discussed. It is concluded that patients with Graves' disease may be prone to develop this complication of antithyroid drug therapy because of underlying immunological abnormalities.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Antithyroid Agents; Autoantibodies; Carbimazole; Female; Graves Disease; Humans; In Vitro Techniques; Lymphocyte Activation; Male; Methimazole; Middle Aged; Neutrophils; Propylthiouracil

Topics: Agranulocytosis; Female; Humans; Methimazole; Middle Aged

Topics: Aged; Agranulocytosis; Dose-Response Relationship, Drug; Humans; Methimazole; Middle Aged

Topics: Adult; Agranulocytosis; Antithyroid Agents; Female; Graves Disease; Humans; Iodine; Methimazole; Propranolol; Thyroidectomy

Topics: Adolescent; Agranulocytosis; Cecal Diseases; Colonoscopy; Female; Humans; Inflammation; Methimazole

The records of all patients with antithyroid drug-related agranulocytosis at two Boston hospitals (Group 1, 14 patients), as well as the published case reports of 36 patients with this syndrome (Group 2) were reviewed. The clinical characteristics of these patients were then compared with those of 50 hyperthyroid patients who had taken antithyroid medication without untoward hematologic reactions (Group 3). The mean ages of patients in Group 1 and Group 2 were significantly greater than that of Group 3 (50.6 +/- 16 years versus 35.7 +/- 13.7 years, p less than 0.001; 46.3 +/- 18.7 years versus 35.7 +/-- 13.7 years, p less than 0.02). By chi-square analysis, the relative risk of developing agranulocytosis in patients over age 40 was 6.4 times that among younger patients (p less than 0.001). The mean doses of methimazole in Group 1 and Group 2 were significantly higher than that in Group 3 (43.8 +/- 9.9 mg/d versus 29.5 +/- 10.4 mg/d, p less than 0.001; 40.7 +/- 15.7 mg/d versus 29.5 +/- 10.4 mg/d, p less than 0.02), with and 8.6-fold increased risk of agranulocytosis with doses greater than 40 mg/d (p less than 0.01). In contrast, the mean doses of propylthiouracil did not differ among the three groups. These data suggest that antithyroid drugs should be administered cautiously to patients over age 40. Because no cases of agranulocytosis were seen with methimazole doses less than 30 mg/d, low-dose methimazole therapy may be safer than high-dose therapy or treatment with conventional doses of propylthiouracil.

Topics: Adolescent; Adult; Age Factors; Aged; Agranulocytosis; Female; Graves Disease; Humans; Male; Methimazole; Middle Aged; Propylthiouracil; Sex Factors

A population of patients with agranulocytosis admitted to a general hospital over a period of 12 yr was studied retrospectively in order to determine the causes of the disease. Of the 48 cases identified, 31 (65%) had drug-induced neutropenia, whereas 17 (35%) had chronic neutropenia unrelated to the use of drugs. Eight patients had an underlying hematological malignancy. Patients with agranulocytosis not induced by drugs more frequently had hepatomegaly, splenomegaly, enlarged lymph glands, or thrombocytopenia together with severe anemia. In contrast, drug-induced agranulocytosis was more severe, with a higher incidence of positive blood cultures, low cellularity of initial bone marrow aspirates, and a shorter duration of neutropenia. Dipyrone and methimazole were the drugs most commonly associated with agranulocytosis. Dipyrone was probably the causative agent in two of the seven drug-induced fatalities. In view of these findings, and those of several previous reports, it is proposed that the use of dipyrone in Israel be severely restricted or discontinued altogether.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Aminopyrine; Anti-Bacterial Agents; Antineoplastic Agents; Bacterial Infections; Blood Cell Count; Bone Marrow Examination; Child; Child, Preschool; Dipyrone; Female; Humans; Israel; Leukemia; Lymphoma; Male; Methimazole; Middle Aged; Retrospective Studies; Tranquilizing Agents; Virus Diseases

A 45-year-old woman with thyrotoxicosis developed agranulocytosis after treatment with propylthiouracil. When the thyrotoxicosis recurred, accompanied by a severe psychotic reaction, administration of antithyroid medication was recommenced. The patient was given methimazole instead of propylthiouracil but, 10 weeks later, agranulocytosis again occurred. This is, to the best of our knowledge, the first report of a case in which agranulocytosis followed treatment with both propylthiouracil and methimazole in the same patient.

Topics: Agranulocytosis; Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Propylthiouracil; Recurrence

Topics: Adult; Agranulocytosis; Colony-Forming Units Assay; Humans; Hyperthyroidism; Lymphocyte Activation; Male; Methimazole

Topics: Adult; Agranulocytosis; Female; Humans; Methimazole

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Agranulocytosis; Female; Humans; Male; Methimazole; Middle Aged

Antineutrophil antibody capable of opsonising normal neutrophils was detected in the sera of 16 neutropenic patients receiving various drugs. A single drug was involved in 10 cases, multiple medication in 6. 4 patients received semisynthetic penicillins, 8 some form of antimicrobial, and 2 antithyroid agents. Neutrophil counts rose, and antineutrophil antibody activity declined or disappeared, after drug therapy was stopped. Opsonisation related to the semisynthetic penicillins was independent of complement but dependent on drug concentration. Complement-dependent opsonic activity was demonstrated in 2 patients (1 receiving methimazole and 1 receiving multiple medication) and in the patient receiving methimazole this activity was shown to reside in the IgM serum-fraction. In another patient receiving multiple drugs, a complement-independent IgG antibody was demonstrated.

Topics: Adolescent; Adult; Aged; Agranulocytosis; Chlorothiazide; Chlorpromazine; Complement C3; Drug Hypersensitivity; Drug Therapy, Combination; Female; Humans; Immunoglobulin G; Immunoglobulin M; Male; Methimazole; Middle Aged; Neutropenia; Neutrophils; Opsonin Proteins; Penicillins; Quinidine

Topics: Adult; Agranulocytosis; Chemical and Drug Induced Liver Injury; Female; Humans; Methimazole; Middle Aged

Propylthiouracil and methimazole are used widely in the treatment of hyperthyroid disorders. The most important complication of the use of these drugs is depression of the neutrophilic granulocyte count. Granulocytopenia occurs in about 4 percent and agranulocytosis occurs in about 0.3 percent of treated patients. Although this depression of the granulocyte count is reversible after the drug is discontinued, serious infection frequently accompanies agranulocytosis and accounts for almost all deaths related to the drugs. It is important to be aware of the clinical features of granulocytopenic reactions due to antithyroid drugs.

Topics: Agranulocytosis; Humans; Hypothyroidism; Methimazole; Propylthiouracil

A method has previously been described which detected xenogeneic and allogeneic antibodies to human granulocytes by their inhibition of the normal phagocytosis-associated hexose monophosphate shunt (HMS) activity. This method was used to study three patients with acute agranulocytosis secondary to antithyroid drug administration. Two patients with methimazole and one patient with propylthiouracil induced agranulocytosis were studied. Serum samples from each of these three patients taken during the acute phase of agranulocytosis had inhibitory effects on phagocytosis-associated HMS activity in leukocytes from both normal donors and the patients after their full recovery from agranulocytosis. IgM but not IgG prepared from acute sera in two patients was also inhibitory. Disruption of IgM disulfide bonds by dithiothreitol destroyed its inhibitory activity. The possibility of drug-dependent immune destruction of leukocytes in these patients is discussed.

Topics: Adult; Agranulocytosis; Antithyroid Agents; Drug Hypersensitivity; Female; Granulocytes; Graves Disease; Humans; Immunoglobulin M; Leukopenia; Methimazole; Phagocytosis; Propylthiouracil; Remission, Spontaneous

Topics: Acute Disease; Aged; Agranulocytosis; Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole

Seventy-three cases of thyrotoxicosis were treated at Lloyd Noland Hospital with methimazole, propylthiouracil or both. Two cases of agranulocytosis occurred (2.7%) secondary to methimazole. Both responded to hospitalization, reverse isolation, and antibiotic coverage with complete recovery of the peripheral blood picture. The toxicity of methimazole is noted. The need for careful monitoring of blood counts during therapy and immediate discontinuance of the drug at the first clinical sign of granulocytopenia is stressed.

Topics: Adult; Agranulocytosis; Anti-Bacterial Agents; Blood Cell Count; Female; Humans; Hyperthyroidism; Methimazole; Pharyngitis

Topics: Adult; Agranulocytosis; Female; Humans; Male; Methimazole; Propylthiouracil

Topics: Agar; Agranulocytosis; Animals; Bone Marrow; Bone Marrow Cells; Cell Division; Cells, Cultured; Chloramphenicol; Clone Cells; Dose-Response Relationship, Drug; Gold; HeLa Cells; Humans; L Cells; Malates; Mercaptopurine; Methimazole; Mice; Neutrophils; Phenylbutazone; Sulfides; Thiouracil

Topics: Agranulocytosis; Bone Marrow; Bone Marrow Cells; Cells, Cultured; Humans; Methimazole; Neutrophils; Phenylbutazone; Thiomalates

Topics: Agranulocytosis; Antithyroid Agents; Drug Eruptions; Humans; Hyperthyroidism; Imidazoles; Male; Methimazole; Pruritus; Urticaria

Topics: Agranulocytosis; Chemical and Drug Induced Liver Injury; Cholestasis; Humans; Hyperthyroidism; Liver; Male; Methimazole; Middle Aged

Topics: Agranulocytosis; Aminopyrine; Bone Marrow; Erythrocyte Count; Erythropoiesis; Hematopoiesis; Humans; Leukocyte Count; Methimazole; Methylthiouracil; Pyrazoles; Time Factors

Topics: Adult; Aerospace Medicine; Agranulocytosis; Antithyroid Agents; Female; Humans; Hyperthyroidism; Imidazoles; Male; Methimazole; Middle Aged

Topics: Agranulocytosis; Animals; Antibodies; Antigen-Antibody Complex; Antithyroid Agents; Basophils; Cytoplasm; Cytoplasmic Granules; Drug Eruptions; Eosinophilia; Eosinophils; Female; Guinea Pigs; Heart Failure; Humans; Hyperthyroidism; Imidazoles; Immunoassay; Jaundice; Leukocyte Count; Methimazole; Middle Aged; Neutrophils

Topics: Agranulocytosis; Drug Therapy; Hyperthyroidism; Imidazoles; Methimazole; Toxicology

Topics: Agranulocytosis; Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Toxicology

Topics: Agranulocytosis; Antithyroid Agents; Humans; Hyperthyroidism; Methimazole; Toxicology

Topics: Agranulocytosis; Antithyroid Agents; Humans; Methimazole

Topics: Agranulocytosis; Antithyroid Agents; Humans; Methimazole

Topics: Agranulocytosis; Antithyroid Agents; Humans; Methimazole

Topics: Agranulocytosis; Antithyroid Agents; Chemical and Drug Induced Liver Injury; Hepatitis; Humans; Methimazole

Topics: Agranulocytosis; Antithyroid Agents; Humans; Methimazole

Topics: Agranulocytosis; Humans; Hyperthyroidism; Imidazoles; Methimazole