methimazole and Pancytopenia

Occurrence of pancytopenia in patients with untreated hyperthyroidism is extremely rare. To the best of our knowledge, only 30 cases have been reported in the English literature. Accurate diagnosis and appropriate tailored therapy are challenging due to the variegated causes of pancytopenia and the potential hematological toxicity of antithyroid drugs (ATDs).. We present a 51-year-old Caucasian man with newly diagnosed Graves' disease showing pancytopenia and liver dysfunction. Although in this context the use of ATDs is still under debate, low-dose methimazole therapy was able to induce resolution of both pancytopenia and liver dysfunction, along with euthyroidism restoration.. Searching in the English literature for previous studies, we identified only 30 cases worldwide to form our database. A demographic as well as clinical, laboratory, and histopathological analysis was performed. In most cases, the recovery of biochemical euthyroidism through the use of ATDs induced the resolution of pancytopenia (at laboratory and histological levels). Our review provides clinical, laboratory, and histopathological features of Graves's hyperthyroidism-related pancytopenia with a view to improving the knowledge of this rare hematological complication and assisting in the decision-making process regarding therapeutic options.

Topics: Antithyroid Agents; Graves Disease; Humans; Male; Methimazole; Middle Aged; Pancytopenia

A 27-year-old male patient who presented to the emergency room with complaints of sweating, palpitations, heat intolerance, insomnia and weight loss for the last 3 months. His medical history was significant for hypertension. On examination, he was tachycardic, hypertensive, had tremors of the upper extremities and a smooth goitre with a thyroid bruit. Laboratory assessment revealed a suppressed thyroid-stimulating hormone, high free thyroxine and positive thyroid receptor antibodies. Complete blood count showed pancytopenia. As part of the work-up for pancytopenia, haptoglobin, ferritin, Coombs test, reticulocyte count hepatitis B and C antibodies were done, all of which were normal. Patient was started on methimazole, propranolol and hydrocortisone. His symptoms improved through the hospital course and he was subsequently discharged. Thyroidectomy was done once the patient's hyperthyroidism was controlled. Levothyroxine was started for the control of postsurgical hypothyroidism. Six months after thyroidectomy, the patient was euthyroid and the pancytopenia resolved.

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Immunoglobulins, Thyroid-Stimulating; Male; Methimazole; Pancytopenia; Thyroidectomy; Thyrotropin; Thyroxine; Treatment Outcome

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

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

Typical presentations of hyperthyroidism are palpitation, nervousness, tremor, malaise, and weight loss. Hyperthyroidism affects nearly every system in the body, and some patients may manifest neurologic or hematologic symptoms. Atypical presentations of hyperthyroidism often pose a great challenge in diagnosis and treatment. We report a case of Basedow's paraplegia and pancytopenia that was precipitated by hyperthyroidism. The unusual manifestations led to unnecessary examinations and delayed the treatment of hyperthyroidism. The classical symptoms of Basedow's paraplegia are subacute symmetric weakness of the lower extremities with areflexia and sparing sensation or sphincter involvement. Control of the hyperthyroidism mitigated the neurologic and hematologic complications and prevented unnecessary studies.

Topics: Adrenergic beta-Antagonists; Adult; Antithyroid Agents; Female; Humans; Hyperthyroidism; Methimazole; Pancytopenia; Paraplegia; Propranolol

Aplastic anemia (AA) is mediated by T-cell autoimmunity in the majority of cases; it is rare and mostly idiopathic in children. We describe a child, who developed AA following Graves' disease which could not be attributed to antithyroid drugs. We hypothesized that both diseases were caused by similar autoimmune process. We monitored the blood counts and did not administer any conventional treatment for AA assuming that the existing anti- hematopoietic stem cell humoral and cellular immunity might subside with induction of remission of Grave's disease. The child went into complete remission with the treatment of the Graves' disease.

Topics: Anemia, Aplastic; Antithyroid Agents; Blood Cell Count; Bone Marrow; Child; Female; Graves Disease; Hormone Replacement Therapy; Humans; Iodine Radioisotopes; Methimazole; Pancytopenia; Recurrence; Remission Induction; Thyrotoxicosis; Thyroxine; Treatment Refusal

Severe pancytopenia is a rare but severe complication of thyrotoxicosis. In this report, we describe four patients with Graves' disease who presented with pancytopenia at diagnosis. Methimazole (30-40 mg/d) or propylthiouracil (400 mg/d) restored normal hematopoiesis in three of the patients. The remaining patient evolved to aplastic anemia under therapy with methimazole (60 mg/d), but had an increased peripheral blood count that almost reached normal values after radioiodinetherapy and standard immunosuppressive treatment with antithymocyte globulin (700 mg/d, intravenous infusion for 5 days), oral cyclosporin (400 mg/d), prednisone (30-60 mg/d), and granulocyte colony-stimulating factor (150 microg subcutaneous injection, 3 times per week). We conclude that: (1) a hematologic evaluation of all patients with Graves' disease should be performed before administering antithyroid drugs, (2) antithyroid drugs may be administered to patients with pancytopenia and bone marrow hypercellularity but a reevaluation of the bone marrow must be done if there is no recovery of the peripheral blood cell count when euthyroidism state is achieved, (3) standard immunosuppressive treatment of aplastic anemia caused by antithyroid drugs restores normal hematopoiesis, and (4) a thyroid evaluation of patients with pancytopenia should be done, even though no related symptoms are found.

Topics: Adolescent; Adult; Aged; Female; Graves Disease; Humans; Male; Methimazole; Pancytopenia

Topics: Adult; Anti-Bacterial Agents; Antithyroid Agents; Bone Marrow; Bone Marrow Diseases; Drug Therapy, Combination; Female; Gingival Hemorrhage; Graves Disease; Humans; Methimazole; Pancytopenia; Pharyngitis; Plasma Cells; Thyroidectomy; Tonsillitis

Pancytopenia is a rare complication of the thionamide therapy reported secondary to aplastic anemia, the bone marrow being invariably hypocellular. We present a case of a 16-year-old female with Graves' disease who presented with massive bone marrow plasmocytosis mimicking multiple myeloma. The patient had already been on methimazole for a month when she was admitted to the Pediatric Unit with the diagnosis of sepsis. CBC revealed pancytopenia. Bone marrow aspirations showed hypocellular-normocellular bone marrow, 98% of plasma cells. At that time, MMI was discontinued and the patient was started on broad-spectrum antibiotics, dexamethasone, and G-CSF. Bone marrow aspiration day +4 still showed hypo-normocellular marrow, with remaining 6% plasma cells. Myeloma screen was negative; ANC >1,000 at day +7, platelets >50,000 at day +24. Twenty-four months after patient's discharge, her clinical condition, CBC, and bone marrow remained normal. To our knowledge this is the first report of pancytopenia due to MMI, where the usual hypoplasia found is replaced by massive plasmocytosis.

Topics: Adolescent; Antithyroid Agents; Bone Marrow; Bone Marrow Diseases; Diagnosis, Differential; Female; Graves Disease; Humans; Leukocytosis; Methimazole; Multiple Myeloma; Pancytopenia; Plasma Cells

We report a 49-year-old man with primary hyperthyroidism who presented with pancytopenia. The patient presented with leg edema, sinus tachycardia, cardiomegaly, and pleural effusions, all from congestive heart failure. Laboratory data showed pancytopenia and primary hyperthyroidism; echocardiogram showed diffuse hyperkinesis of the left ventricular wall and right ventricular overloading. The bone marrow was moderately hypercellular and compatible with arrested hematopoiesis. Pancytopenia and heart failure improved after administration of methimazole and diuretics. However, high levels of thyroid hormone recurred with pancytopenia 4 months after admission. Therefore, subtotal thyroidectomy was performed, and the levels of thyroid hormones and peripheral blood cell counts have remained normal. Pancytopenia may be caused by hyperthyroidism.

Topics: Antithyroid Agents; Blood Cell Count; Bone Marrow; Cardiomegaly; Diuretics; Edema; Heart Failure; Humans; Leg; Male; Methimazole; Middle Aged; Pancytopenia; Pleural Effusion; Recurrence; Tachycardia, Sinus; Thyroidectomy; Thyrotoxicosis

A 45-year-old woman was referred to our hospital because of hyperthyroidism complicated by atrial fibrillation and heart failure. Laboratory data revealed pancytopenia, with a white blood cell count of 2,600/microliter, red blood cell count of 330 x 10(4)/microliter, and platelet count of 6.2 x 10(4)/microliter. The patient had normal transaminase levels, but tests for hepaplastin and cholinesterase showed values of 34% and 1.4 U/ml, respectively, indicating liver dysfunction. There was also decreased excretion of indocyanine green. After initiation of treatment with 30 mg thiamazole and 20 mg propranolol daily, the patient's thyroid function normalized and the other abnormal laboratory findings such as pancytopenia and liver dysfunction also disappeared. Pancytopenia is a rare complication of hyperthyroidism. In this case, various laboratory abnormalities were normalized by antithyroid therapy alone, indicating that the hyperthyroidism itself was closely related to the pathogenesis of pancytopenia and liver dysfunction.

Topics: Antithyroid Agents; Female; Humans; Hyperthyroidism; Liver Diseases; Methimazole; Middle Aged; Pancytopenia

Topics: Adult; Antithyroid Agents; Graves Disease; Humans; Kidney Failure, Chronic; Male; Methimazole; Pancytopenia; Propylthiouracil

A case of hyperthyroidism associated with pancytopenia has been reported. A 51-year-old woman was hospitalized for the investigation of struma, peripheral edema and fatigue. Hormonal studies revealed hyperfunction of the thyroid gland. Hematological examinations showed normocytic normochromic anemia, leukopenia and thrombocytopenia with hyperplastic bone marrow and increased serum iron levels. Elevations of the anti-thyroidal antibody and anti-microsomal antibody, and a decrease in CH50 titer were observed. A Coombs' test and anti-leukocytic antibody and anti-thrombocytic antibody tests were negative. The numbers of erythrocyte and thrombocyte were normalized after the administration of methimazole for three months as were the findings of the bone marrow and the serum iron level. However, leukopenia was maintained due to the effect of methimazole. It should be suggested that the etiology of pancytopenia might be due to hyperthyroidism. Although the mechanism of pancytopenia in a patient with hyperthyroidism is unclear, it might be related to the reduced life-span of whole blood components and/or partially to the autoimmune mechanism.

Topics: Female; Humans; Hyperthyroidism; Methimazole; Middle Aged; Pancytopenia