Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The current working hypothesis on the pathogenesis of autoimmune disease focuses on the interactions between susceptibility genes and environmental stimuli. In Graves' disease it is postulated that aberrant expression of HLA class II antigens on thyroid epithelial cells permits the presentation of specific thyroid antigen to activated lymphocytes. Evidence suggests that thyrocyte HLA-DR expression is secondary to the production of cytokines by presensitized T-lymphocytes. A 20-yr-old woman and her 18-yr-old brother presented with classical findings of Graves' disease with ophthalmopathy within a year of each other. Diagnosis was confirmed by demonstration of elevated serum levels of T4 and T3, strongly positive titers of TSH binding inhibitory immunoglobulins, and histological examination after subtotal thyroidectomy. Eight years previously, acute life-threatening aplastic anemia in the brother led to therapeutic transplantation of bone marrow from his sister. After the procedure, 100% of his peripheral leucocytes were genotype 46,XX. HLA typing performed before transplantation and 2 months after thyroidectomy in the female indicated complete identity with her brother's leukocytes for class I and class II antigens. Thyroid autoantibodies at this time were weakly positive. Although the concordance of thyroid disease in these patients could be due to chance, the patients were of different sexes, the family history was negative, and neither the probands nor the first degree relatives bore the HLA-DR3/B8 antigens. We propose that the male passively acquired a clone of programmed or activated lymphocytes from his sister and that his hyperthyroidism was not primarily dependent on exposure to specific thyroid-derived antigen.
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PMID:Concordant Graves' disease after bone marrow transplantation: implications for pathogenesis. 200 10

Thyroid function was evaluated in children surviving disease-free for 2 years or more following bone marrow transplantation (BMT) for severe aplastic anemia (27 patients), acute non-lymphoblastic leukemia (28 patients), and acute lymphoblastic leukemia (25 patients). Pre-BMT conditioning consisted of high dose chemotherapy and total lymphoid irradiation with 750 cGy for patients with severe aplastic anemia, and for patients with leukemia, high dose chemotherapy and single dose total body irradiation with 750-850 cGy (33 patients) or fractionated total body irradiation with 1320 cGy (20 patients). Compensated hypothyroidism (elevated thyroid stimulating hormone (TSH) with a normal thyroxine index) occurred in 20/80 patients with a median time of onset of 12.3 months post-BMT (range 4-30). No patients developed primary hypothyroidism (elevated thyroid stimulating hormone with low thyroxine index). In seven patients, compensated hypothyroidism was transient with TSH returning to normal at a median of 60 months post-BMT (range 11-75). Six patients with compensated hypothyroidism received thyroid hormone replacement therapy. Time to development of compensated hypothyroidism was associated (p = 0.03) with underlying disease and radiation (11 of 27 patients with severe aplastic anemia + total lymphoid irradiation versus nine of 53 patients with leukemia + total body irradiation). In aplastic anemia patients, but not patients with leukemia, the incidence of thyroid hypofunction 5 years post-transplant was significantly higher (p less than 0.001) in those receiving methotrexate alone (82%) as prophylaxis for graft-versus-host disease compared with those receiving a regimen of methotrexate, antithymocyte globulin and prednisone (16%).
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PMID:Thyroid dysfunction following bone marrow transplantation: long-term follow-up of 80 pediatric patients. 235 Jun 28

Thyroid function studies were followed serially in 27 long-term survivors (median 33 months) of bone marrow transplantation. There were 15 men and 12 women (median age 13 1/12 years, range 11/12 to 22 6/12 years). Aplastic anemia (14 patients) and acute nonlymphocytic leukemia (eight patients) were the major reasons for bone marrow transplantation. Pretransplant conditioning consisted of single-dose irradiation combined with high-dose, short-term chemotherapy in 23 patients, while four patients received a bone marrow transplantation without any radiation therapy. Thyroid dysfunction occurred in 10 of 23 (43 percent) irradiated patients; compensated hypothyroidism (elevated thyroid-stimulating hormone levels only) developed in eight subjects, and two patients had primary thyroid failure (elevated thyroid-stimulating hormone levels and low T4 index). The abnormal thyroid studies were detected a median of 13 months after bone marrow transplantation. The four subjects who underwent transplantation without radiation therapy have remained euthyroid (median follow-up two years). The only variable that appeared to correlate with the subsequent development of impaired thyroid function was the type of graft-versus-host disease prophylaxis employed; the irradiated subjects treated with methotrexate alone had a higher incidence of thyroid dysfunction compared to those treated with methotrexate combined with antithymocyte globulin and prednisone (eight of 12 versus two of 11, p less than 0.05). The high incidence and subtle nature of impaired thyroid function following single-dose irradiation for bone marrow transplantation are discussed.
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PMID:Thyroid dysfunction among long-term survivors of bone marrow transplantation. 675 76

Thyroid dysfunction has been reported following single dose and fractionated radiation in the context of bone marrow transplantation (BMT). Limited data are available regarding this complication following hyperfractionated radiation. We undertook a retrospective analysis of thyroid function in 150 patients who received BMT at our institution, and who were alive and disease-free for at least 1 year after transplant. There were 100 pediatric patients and 50 adult patients, with a median follow-up of 6.2 years for the whole group. These patients had acute (n = 91) or chronic leukemias (n = 36), severe aplastic anemia (n = 18) or immunodeficiency disorders (n = 5). The majority of the patients received radiation-based cytoreductive regimens including 129 patients who received hyperfractionated total body irradiation (TBI) to a total dose of 1375 cGy or 1500 cGy and 10 patients who received total lymphoid irradiation (TLI) to a total dose of 600 cGy. Twenty two patients of the cohort of 150 patients (14.7%) and 21 of the 139 patients (15.1%) who received hyperfractionated radiation were found to have developed hypothyroidism, 11-88 months after transplant (median 49 months). Eight patients had received 1375 cGy and 12 patients 1500 cGy TBI, while one patient was treated with 600 cGy TLI and one patient was treated with chemotherapy only (busulfan and cyclophosphamide). Three patients had primary thyroid failure with an elevated TSH and a low T4 index, while 19 patients had compensated hypothyroidism with an elevated TSH but a normal T4 index. Six of eight patients with untreated compensated hypothyroidism recovered spontaneously.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thyroid dysfunction following bone marrow transplantation using hyperfractionated radiation. 774 58

Thyroid function was investigated in 35 children after allogeneic BMT. The study was longitudinal and all patients were followed for at least 5 years. Once a year TSH, T4, T3 and the TRH test were performed. Patients with severe aplastic anemia (n = 6) were transplanted without total body irradiation (TBI) and they had no detectable alterations in thyroid function. Patients with leukemia (n = 27) were conditioned with 10 Gy TBI in one fraction. The accumulated frequencies of thyroid dysfunction were 3 of 27 (11%) with high TSH and low T3 or T4 levels, and 10 of 27 (37%) with high basal TSH and normal T3 and T4 levels. An additional 11 of 27 (41%) had an exaggerated TSH response in the TRH test and normal basal TSH and T3/T4 levels. Only 3 of 27 (11%) continued to have normal values. Treatment with levo-thyroxine (L-T4) was given to the patients with a high basal TSH level. As 24 of 27 (89%) children had signs of disturbance in the thyroid axis, prophylactic L-T4 treatment for a few years after BMT with TBI may be of value. The main cause of a change in thyroid function after BMT seems to be conditioning with TBI.
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PMID:Thyroid function in children after allogeneic bone marrow transplantation. 801 54

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.
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PMID:Adverse effects of thyroid hormone preparations and antithyroid drugs. 886 63

Aplastic anemia is a rare but severe complication of thionamide therapy. Although colony-stimulating factors have been used extensively in thionamide-induced agranulocytosis with good results, the same might not apply to aplastic anemia. We present a case of a patient with methimazole-induced aplastic anemia in which, as administration of recombinant human granulocyte-monocyte colony-stimulating factor for a week did not result in an increase in peripheral blood cell count, standard immunosuppressive treatment was needed to restore normal hematopoiesis. The clinical characteristics of this patient are compared with those of previous cases of thionamide-induced aplastic anemia, especially with the only other reported patient in which colony-stimulating factors were used.
Thyroid 1997 Feb
PMID:Methimazole-induced severe aplastic anemia: unsuccessful treatment with recombinant human granulocyte-monocyte colony-stimulating factor. 908 74

The major adverse reactions of antithyroid drugs are hematologic; aplastic anemia (AA) is one of the rarest and most severe complications. Use of recombinant human hemopoietic colony-stimulating factor was reported to be of benefit in patients who developed agranulocytosis, although there is still some doubt regarding the efficacy in AA. We present a case of a 58-year-old female patient with Graves' disease who developed AA in the third exposure to methimazole (MMI). The withdrawal of MMI and early treatment with 5 microg/kg per day recombinant human granulocyte colony-stimulating factor (G-CSF) for 9 days, allowed a favorable recovery of peripheral blood cell count. We conclude that the use of hemopoietic colony stimulating factors might be a suitable means to achieve the correction of severe thionamide-induced hematologic adverse reactions.
Thyroid 1998 Sep
PMID:Methimazole-induced aplastic anemia in third exposure: successful treatment with recombinant human granulocyte colony-stimulating factor. 977 51

We reviewed the medical history of 26 women with differentiated thyroid cancer who became pregnant after receiving therapeutic doses of radioactive iodine (131I) in order to document the possibility of a greater risk for disorders in these pregnancies. There were a total of 39 pregnancies, 6 of which occurred during the first year after therapy. In 3 cases the following anomalies were encountered: a male suffering Trisomy 18 (Edward's syndrome), a female with constitutional aplastic anemia, and a male with a congenital hip dysplasia. Of the 33 pregnancies that occurred after the first year post-therapy, there were 2 spontaneous abortions and a male effected by ureteral stenosis. Based on these data, although it cannot be confirmed that these congenital disorders are due to the 131I therapy, we recommend that pregnancy be avoided for the first year after therapy.
Thyroid 1998 Nov
PMID:Conception after iodine-131 therapy for differentiated thyroid cancer. 984 14

Aplastic anemia is a rare but severe complication of methimazole (MMI) treatment for Graves' disease. We present a case of a 53-year-old Japanese female who had been treated with 30 mg/d of MMI for 30 days for Graves' disease and was subsequently admitted to the Japan Self Defense Forces (JSDF) Central Hospital with a mild sore throat and high-grade fever that began the previous day. The patient had a reduced white blood cell count (WBC) count of 0.9 x 10(3) per microliter with severe granulocytopenia and increased lymphocytes, a platelet count of 49 x 10(3) per microliter, and hemoglobin of 10.6 g/dL. Bone marrow (BM) aspirates showed hypocellular bone marrow with plasmacytosis. Because of poor recovery of her peripheral blood values after withdrawal of MMI, she was given transfusions of platelets and erythrocytes thereafter. This is the second report of plasmacytosis in bone marrow of MMI-induced aplastic anemia, and suggests that immunogenic mechanisms may cause this rare complication.
Thyroid 2004 Mar
PMID:Methimazole-induced aplastic anemia caused by hypocellular bone marrow with plasmacytosis. 1507 6


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