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Biomedical subjects

Sumihisa Kubota

Publications and source records attributed to Sumihisa Kubota.

At least 19 recordsLinked to original sources
PubMed2006

Effect of levo-thyroxine replacement on non-high-density lipoprotein cholesterol in hypothyroid patients.

CONTEXT: Recently, non-high-density lipoprotein cholesterol (non-HDL-C), a measure of total cholesterol minus HDL-C, has emerged as a predictor of cardiovascular disease. OBJECTIVE: We evaluated the effect of L-T4 replacement on non-HDL-C levels in patients with primary hypothyroidism. METHODS: Thirteen patients with overt hypothyroidism and 26 patients with subclinical hypothyroidism participated in the study. The lipid profiles, including non-HDL-C, were measured in patients with hypothyroidism before and 3 months after L-T4 replacement was started. RESULTS: After L-T4 replacement, the serum concentrations of all lipoproteins, exclusive of lipoprotein (a) [Lp(a)], were significantly decreased in patients with overt hypothyroidism. In patients with subclinical hypothyroidism, the serum concentrations of total cholesterol, non-HDL-C, remnant-like particle cholesterol, and apolipoprotein B (Apo B) were significantly decreased, whereas no significant changes in the serum concentrations of low-density lipoprotein cholesterol, HDL-C, triglycerides, apolipoprotein A-I, and Lp(a) were observed. In all 39 patients, the reduction in the non-HDL-C levels correlated with the reduction in the low-density lipoprotein cholesterol, remnant-like particle cholesterol, and Apo B levels. However, the reduction in the non-HDL-C levels did not correlate with the reduction in the HDL-C, Lp(a), and apolipoprotein A-I levels. CONCLUSIONS: This study is the first to show that L-T4 replacement may reduce serum concentrations of non-HDL-C in patients with hypothyroidism. The study also suggests that such altered serum concentrations of non-HDL-C in hypothyroidism may be related to the disturbed metabolism of low-density lipoprotein, remnant lipoprotein, and Apo B.

Adult↗
PubMed2006

Sporadic congenital hyperthyroidism due to a germline mutation in the thyrotropin receptor gene (Leu 512 Gln) in a Japanese patient.

Constitutively activating thyrotropin receptor (TSHR) germline mutations have been identified as a molecular cause of congenital hyperthyroidism. We here describe a Japanese woman who had presented with severe hyperthyroidism and advanced bone age as a neonate. She underwent neurosurgical intervention for craniosynostosis, and presented with perodactylia and mild mental retardation with hydrocephalus. Hyperthyroidism has been refractory to antithyroid drug therapy in the absence of antithyrotropin receptor antibodies during follow-up of 20 years, resulting in an enlarged goiter. Analysis of the patient's genomic DNA showed a heterozygous thymine-to-adenine point mutation in exon 10 of TSHR at position 1535 which was not present in the parents' DNA. This mutation, changing leucine to glutamine in codon 512 in the third transmembrane region, was previously identified as a somatic mutation in toxic thyroid nodules and was shown to increase basal cAMP production in vitro. To our knowledge, this is the first report of a germline mutation of TSHR causing sporadic congenital nonautoimmune hyperthyroidism in a Japanese patient.

Adult↗
PubMed2006

Two-day thionamide withdrawal prior to radioiodine uptake sufficiently increases uptake and does not exacerbate hyperthyroidism compared to 7-day withdrawal in Graves' disease.

The appropriate period of antithyroid drug (ATD) discontinuation before radioiodine therapy is the most critical problem in Graves' disease patients under going treatment with ATD. To determine the optimal period that does not alter the outcome of radioiodine therapy or exacerbate hyperthyroidism, we compared serum FT4 levels at radioiodine uptake (RAIU) and therapy outcomes between a 2-day withdrawal group and 7-day withdrawal group. We prospectively recruited 43 patients for the 2-day withdrawal protocol and retrospectively reviewed 49 patients treated with radioiodine following the protocol of 7-day withdrawal. There was no significant difference in RAIU between the 2 groups. The mean serum FT4 level measured on the first day of 24-h RAIU of the 7-day group was significantly higher than that in the 2-day group. There were no significant differences in the outcomes at each point (6 months, 1 year, and 2 years after therapy) between the 2 groups. Our results indicated that withdrawal of ATD for 2 days is superior to 7 days in that 2 days discontinuation did not exacerbate hyperthyroidism. In order to prevent serum thyroid hormone increase after ATD withdrawal and radioiodine therapy, a 2-day ATD withdrawal period before radioiodine therapy may be useful for high-risk patients such as the elderly and patients with cardiac complications. We believe that the 2-day ATD withdrawal method may be useful for patients undergoing treatment with ATD who are to undergo radioiodine therapy.

Adult↗
PubMed2006

A case of hypothyroid Graves' disease following external radiation therapy to the cervical region.

A case of hypothyroid Graves' disease occurred following external radiation therapy to the cervical region is described. Severe hypothyroidism developed in a 56-year-old man 6 months after external radiation therapy for submandibular cancer. Serological evaluation of thyroid autoimmunity revealed the presence of antithyroid antibodies and thyrotropin-binding inhibitory immunogloblins (TBII). Diplopia, limitation of downward gaze, and palpebral edema developed 2 years after levothyroxine replacement therapy. Ocular magnetic resonance imaging revealed marked hypertrophy of the bilateral extraocular muscles with signal hyperintensity on T2-weighted images. This infiltrative ophthalmopathy showed marked improvement after additional treatment with high-dose methylprednisolone and orbital radiation, in parallel with a decrease in TBII. These results suggest that radiation-associated thyroidal injury might be associated with the etiology of hypothyroid Graves' disease.

Carcinoma, Squamous Cell↗
PubMed2006

Four cases of Graves' disease which developed after painful Hashimoto's thyroiditis.

We report four cases of Graves' disease that developed after painful Hashimoto's thyroiditis. All were middle-aged women, who had high titers of anti-thyroid antibodies and thyrotoxicosis at the onset of painful Hashimoto's thyroiditis. After 2 to 7 years, they developed Graves' disease with positive antibody against the thyrotropin receptor. Their clinical courses of Graves' disease went favorably due to the treatment with antithyroid drug or radioactive iodine therapy. Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis and is one form of destructive thyroiditis. Thyroid damage due to painful Hashimoto's thyroiditis may be associated with the development of Graves' disease.

Antithyroid Agents↗
PubMed2006

HLA-DPB1*0202 is associated with a predictor of good prognosis of Graves' disease in the Japanese.

Whereas most patients with Graves' disease (GD) have antibodies against the thyrotropin receptor, which are measured as thyrotropin-binding inhibitory immunoglobulin (TBII), the TBII of 10% or less of Japanese patients with GD is undetectable at the first visit and throughout the entire clinical course, and these patients tend to respond well to medications and follow the better clinical course. Therefore, the absence of TBII at the first visit may be a predictor of good prognosis. Ninety-seven patients with GD who had remained TBII negative for at least 2 years from the onset, as well as 142 typical TBII-positive GD patients, were examined to reveal the HLA-linked immunogenetic background for this predictor. Compared with a healthy control population, the frequencies of HLA-A*0206 (OR=2.17, p=9.73x10(-4)) and DPB1*0501 (OR=3.26, p=3.31x10(-7)) carriers were increased in the typical patients, whereas those of HLA-A*0201 (OR=2.16, p=1.92x10(-3)), A*0207 (OR=3.19, p=7.17x10(-4)), and DPB1*0202 (OR=3.13, p=3.97x10(-4)) were increased in the TBII-negative group. These two patient groups were associated with similar HLA-A alleles and different HLA-DPB1 alleles, suggesting the presence of two genetic factors for GD within the HLA region; one is HLA-A linked and may be related to thyroid organ specificity, the other is HLA-DP linked and may control the severity of autoimmunity.

Alleles↗
PubMed2005

Thyrotoxicosis caused by weight-reducing herbal medicines.

The weight-reducing herbal medicines "Dream Shape" and "Ever Youth" became available in Japan in 2000. Herein, we describe 12 patients who developed thyrotoxicosis after taking them. The thyroid hormone content of 1 capsule or tablet of herbal medicine, measured following Pronase digestion and ethanol extraction, was approximately 1 mug of triiodothyronine and 3 to 4 mug of thyroxine. Two of us took 10 capsules or tablets of Dream Shape or Ever Youth, and changes in thyroid hormone levels were observed during the first 24 hours. Serum free triiodothyronine levels began to rise 2 hours after ingestion and reached peak levels at 4 to 8 hours; changes in free thyroxine and thyrotropin levels were small during the first 24 hours. Similar herbal medicines may have been distributed to other countries via the Internet. Resultant factitious thyrotoxicosis can create diagnostic and therapeutic confusion, particularly in patients with thyroid disease.

Administration, Oral↗
PubMed2005

Acute suppurative thyroiditis after fine-needle aspiration causing thyrotoxicosis.

A case of thyrotoxicosis caused by acute suppurative thyroiditis after repeated fine-needle aspiration (FNA) is described. A 39-year-old woman with atopic dermatitis showed rapid enlargement of a left thyroid cyst after a third FNA. She had a high fever, painful swelling of the left thyroid, and elevated thyroid hormone levels. Ultrasonography revealed abscess formation in the left thyroid cyst. The cytologic examination of an FNA specimen showed abundant neutrophils, and culture of the aspirate yielded Staphylococcus aureus. Because antibiotic treatment for 1 month failed to improve the inflammatory findings, the patient subsequently underwent left thyroid lobectomy, which resulted in the normalization of thyroid function and the resolution of inflammation. Thyroid infection had possibly been induced by needle-track seeding, because atopic skin favors colonization by S. aureus because of local immunologic deficiency. FNA is a useful and safe technique for aspirating fluid from thyroid cysts, but special care is required in patients with atopic dermatatis to avoid bacterial infection.

Adult↗
PubMed2005

Successful use of iodine and levothyroxine to treat Graves' disease in a pregnant patient with allergy to antithyroid drugs and high thyrotropin-binding inhibitor immunoglobulin after radioiodine therapy.

High titer of thyrotropin-binding inhibitor immunoglobulin (TBII) in patients with Graves' disease can cause fetal hyperthyroidism during pregnancy. Prevention of fetal hyperthyroidism by administration of antithyroid drug (ATD) and levothyroxine (LT(4)) to pregnant patients who previously received ablative therapy has been reported. We administered iodine and LT(4) to a patient during gestation, because she had a severe adverse reaction to ATD. Although gestation proceeded normally, the infant showed transient neonatal hyperthyroidism right after birth. We believe that the fetus would have developed hyperthyroidism if we had not administered iodine to the mother. Administration of iodine and LT(4) to a pregnant patient with Graves' disease showing a high TBII after ablative therapy should be considered in rare patients with allergy to ATD.

Adult↗
PubMed2005

Successful treatment for recurrent painful Hashimoto's thyroiditis by total thyroidectomy.

Painful Hashimoto's thyroiditis is an atypical variant of Hashimoto's thyroiditis characterized by thyroid pain and fever. In patients with this condition, anti-inflammatory agents are not always effective as in those with subacute thyroiditis. Therefore, long-term pain management is an important issue. We report herein four cases of painful Hashimoto's thyroiditis requiring total thyroidectomy to relieve thyroid pain and histologic findings of the thyroid gland. All patients had high titers of anti-thyroperoxidase (TPO) and thyroglobulin antibodies. Three were hypothyroid, and the other was euthyroid. During the first visit, four patients had fever and/or thyroid pain with elevated C-reactive protein or erythrocyte sedimentation rate, and they were treated with oral corticosteroids given continuously or intermittently for 9 to 48 months. Because a reduction or discontinuation of corticosteroids caused recurrent painful attacks, the decision was made to perform surgery. After total thyroidectomy, their symptoms disappeared. The histopathologic characteristics of these hypothyroid cases were advanced fibrosis and destructive thyroid architecture. One euthyroid case showed a mild fibrous change and the presence of foreign body type giant cells. In conclusion, total thyroidectomy is the effective and reliable treatment for patients with recurrent painful Hashimoto's thyroiditis. Pathologic characteristics include advanced fibrosis and destructive thyroid architecture.

Adult↗
PubMed2005

Effect of high dose methylprednisolone pulse therapy followed by oral prednisolone administration on the production of anti-TSH receptor antibodies and clinical outcome in Graves' disease.

Little is known about the immunosuppressive effect of glucocorticoids on TSH receptor antibodies. We observed the long-term prognosis and serum TSH binding inhibitor immunoglobulin (TBII) levels in patients with Graves' ophthalmopathy who had received intravenous methylprednisolone pulse therapy (pulse therapy) followed by oral prednisolone administration in order to ascertain how long the immunosuppressive effect of glucocorticoids continued. This is the first report on the effect of pulse therapy on Graves' disease outcome. We observed 67 patients who were treated by antithyroid drugs (ATD) alone for 2 years after pulse therapy. TBII was evaluated before and 3, 6, 12, 18, and 24 months after pulse therapy. The mean TBII decreased significantly 3 months after pulse therapy (p<0.001), and was maintained until 24 months. There were 24 patients whose TBII was positive (>15%) at 24 months, in whom the mean TBII decreased significantly 3 to 6 months after pulse therapy (p<0.001), but increased again at 12 to 24 months (p<0.05). Thus, the immunosuppressive effect of glucocorticoids may be lost at 12 months after pulse therapy in these patients. The remission rate in the pulse therapy group was 40.98%, and that of the control patient group was 48.57%. There was no significant difference between the two. These results suggest that the immunosuppressive effect of pulse therapy was temporary, and that pulse therapy did not increase remission rate of Graves' disease.

Administration, Oral↗
PubMed2004

SNPs in the promoter of a B cell-specific antisense transcript, SAS-ZFAT, determine susceptibility to autoimmune thyroid disease.

Autoimmune thyroid disease (AITD) is caused by an immune response to self-thyroid antigens and has a significant genetic component. Antisense RNA transcripts have been implicated in gene regulation. Here we have identified a novel zinc-finger gene, designated ZFAT (zinc-finger gene in AITD susceptibility region), as one of the susceptibility genes in 8q23-q24 through an initial association analysis using the probands in the previous linkage analysis and a subsequent association analysis of the samples from a total of 515 affected individuals and 526 controls. The T allele of the single-nucleotide polymorphism (SNP), Ex9b-SNP10 located in the intron 9 of ZFAT, is associated with increased risk for AITD (dominant model: odds ratio = 1.7, P = 0.000091). The Ex9b-SNP10 falls into the 3'-UTR of truncated-ZFAT (TR-ZFAT) and the promoter region of the small antisense transcript of ZFAT (SAS-ZFAT). In peripheral blood lymphocytes, SAS-ZFAT is exclusively expressed in CD19+ B cells and expression levels of SAS-ZFAT and TR-ZFAT seemed to correlate with the Ex9b-SNP10-T-associated ZFAT-allele, inversely and positively, respectively. The Ex9b-SNP10 is critically involved in the regulation of SAS-ZFAT expression in vitro and this expression results in a decreased expression of TR-ZFAT. These results suggested that the SNP-associated ZFAT-allele plays a critical role in B cell function by affecting the expression level of TR-ZFAT through regulating SAS-ZFAT expression and that this novel regulatory mechanism of SNPs might be involved in controlling susceptibility or resistance to human disease.

B-Lymphocytes↗