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Biomedical subjects

Nobuyuki Amino

Publications and source records attributed to Nobuyuki Amino.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

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↗

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↗

A prophylactic infusion of calcium solution reduces the risk of symptomatic hypocalcemia in patients after total thyroidectomy.

BACKGROUND: Several risk factors have been associated with post-operative transient hypocalcemia after thyroid surgery. However, there are no studies evaluating preventive measures to avoid symptomatic postoperative hypocalcemia. Although intravenous infusion of calcium improves hypocalcemic symptoms, it is unknown whether prophylactic infusion prevents symptoms of postoperative hypocalcemia. PATIENTS AND METHODS: Five hundred and forty-seven patients underwent total thyroidectomy. Two groups were identified: group A (n = 243) received prophylactic intravenous drip infusion of 78-156 mg of calcium solution at 3-8 hours after operation, and group B (n = 304) received no prophylactic treatment. Prophylactic infusion was used only once if the patients did not have symptoms of hypocalcemia. Serum calcium (Ca) levels, intact parathyroid hormone (i-PTH) levels on the first postoperative day (1st POD), and the prevalence of symptoms of hypocalcemia were prospectively analyzed. RESULTS: The serum Ca levels at the 1st POD in group A patients (7.91 +/- 0.49 mg/dl, mean +/- SD) was significantly higher than group B patients (7.65 +/- 0.54, P < 0.0001), while the serum i-PTH levels were not significantly different between the two groups. The prevalence of numbness and/or tetany before noon on the 1st POD was significantly lower in group A patients. Prophylactic infusion of calcium solution reduced the prevalence of tetany from 8.6% to 2.1%. CONCLUSION: A prophylactic infusion of calcium solution after total thyroidectomy may be useful in reducing the development of symptomatic hypocalcemia and reduces the patients' risk of having discomfort and anxiety due to hypocalcemia.

Calcium↗

Needle tract implantation of follicular neoplasm after fine-needle aspiration biopsy: report of a case.

We herein report a 28-year-old woman with a follicular neoplasm showing subcutaneous needle tract implantation. One month after fine-needle aspiration biopsy (FNAB) for a tumor measuring 2.5 cm, the patient became aware of a subcutaneous nodule measuring about 1 cm at the needle insertion site. FNAB smear of this nodule showed poorly cohesive clusters of follicular cells with nuclear crowding, overlapping and resetting with some microfollicular architecture. Total thyroidectomy and resection of the subcutaneous nodule were performed. Although there was no capsular or vascular invasion of the nodule, the lesion was diagnosed as follicular carcinoma because of the subcutaneous seeding. Ki-67 labeling indices of the thyroid nodule and implanted tumor were higher than 5%. Furthermore, although galectin-3 was completely negative in the thyroid nodule, it was heterogeneously positive in the implanted tumor. It is therefore suggested that high cell proliferating activity as a characteristic of the original nodule and the subsequently obtained invasive characteristic of the implanted tumor contributed to this event. To date, there has not been any recurrence of the implanted lesion. Because implanted follicular carcinoma can be surgically removed, this complication should not impair the usefulness of FNAB.

Adult↗

Thyroxine to triiodothyronine hyperconversion thyrotoxicosis in patients with large metastases of follicular thyroid carcinoma.

OBJECTIVE: We experienced two cases of follicular thyroid carcinoma with distant metastases, which showed high levels of free triiodothyronine (T(3)) while free thyroxine (T(4)) levels remained in the low or normal range. In this report, we described the detail of these cases and examined the cause of T(3) thyrotoxicosis. DESIGN: In one of the cases, quantitative measurement of types I and II iodothyronine deiodinase mRNAs was performed using a surgically dissected tissue from the primary tumor and a distant metastasis. MAIN OUTCOME: In the both tissues, types I and II iodothyronine deiodinase mRNAs were expressed in the same level as in the normal thyroid tissues. CONCLUSION: These results suggest that T(3) thyrotoxicosis in our patients was caused by hyperconversion of administered levothyroxine to T(3). In the follow-up of patients with distant metastases of follicular carcinoma, not only free T(4), but also free T(3) should be tested to avoid the excessive administration of levothyroxine.

Adenocarcinoma, Follicular↗

Usefulness of ultrasonography for diagnosis of malignant lymphoma of the thyroid.

BACKGROUND: Recent developments in ultrasonography (US) and the prevalence of ultrasound-guided fine needle aspiration biopsy (US-FNAB) has enabled physicians to detect and diagnosis thyroid diseases, including thyroid malignant lymphoma, much more easily. METHODS: We describe our diagnostic strategy for malignant lymphoma on US screening. We screened possible malignant lymphoma patients by US characteristics such as enhanced posterior echoes. RESULTS: Among 170 patients suspected of malignant lymphoma between 2000 and 2004, 74 (43.5%) were also diagnosed as having or suspected of lymphoma by US-FNAB. Five patients dropped out, and 67 of 69 patients who underwent surgical examination were pathologically diagnosed as having lymphoma. Finally, 79 (47.9%) of 165 US-suspected patients were confirmed as having lymphoma. Only 21.5% of lymphoma patients complained of rapidly growing goiter. CONCLUSION: US screening for goiters contributes markedly to diagnosis of lymphoma at an early phase, facilitating early initiation of therapy.

Adult↗

Thrombospondin 1 mRNA as a candidate for a marker to detect thyroid-derived fibroblasts in fine needle aspiration biopsy of the thyroid.

Possible interference of fibroblasts is suggested in aspiration biopsy nucleic acid diagnosis (ABND). However, detection of fibroblasts in the aspirates is difficult, because the gene expression profiles of thyroid malignancies and fibroblasts are much alike in many aspects. To identify a specific marker for thyroid-derived fibroblasts, the data of the serial analysis of gene expression (SAGE) were compared to screen differentially expressed genes between fibroblasts and thyroid normal and tumor tissues. In the SAGE data, 5 genes were identified to be differentially expressed. Among these, thrombospondin 1 (TSP-1, THBS1) mRNA was the most differentially expressed. Further, the overexpression of TSP-1 mRNA in fibroblasts was confirmed by real-time RT-PCR analysis using 73 thyroid normal and tumor tissues and 7 cultures of thyroid-derived fibroblasts. These results suggest that TSP-1 mRNA is a possible marker for contamination of thyroid-derived fibroblasts.

Biomarkers↗

Tensin3 is a novel thyroid-specific gene.

Thyroid-specific genes, such as thyroid peroxidase, thyroglobulin, Na+/I- symporter and thyroid-stimulating hormone receptor, play fundamental roles in thyroid function and relate to many pathological conditions. Using sequence specific-differential display, we detected three genes that showed higher expression levels in normal thyroid tissues than in thyroid tumor tissues. After subcloning and sequencing analysis, one of the genes was revealed to be tensin3. The expression level of tensin3 was examined with real-time quantitative PCR analysis. Its expression levels were more depressed in thyroid tumor tissues than in normal thyroid tissues. The decrease was even more evident in two anaplastic carcinomas. High and moderate levels of tensin3 mRNA expression were observed in the thyroid and placenta respectively. Tensin3 mRNA was expressed only in low levels in other tissues, such as the brain, heart, lung, liver, pancreas, kidney, skeletal muscle, white blood cells and prostate. These results show that tensin3 is a novel thyroid-specific gene and further investigations may reveal its relation to thyroid function or thyroid disease.

Humans↗

Congenital combined pituitary hormone deficiency attributable to a novel PROP1 mutation (467insT).

BACKGROUND: Combined pituitary hormone deficiency (CPHD) is an anterior pituitary disorder, commonly resulting in growth retardation. PROP1 gene mutations appear to be frequently responsible for CPHD, particularly in Middle and Eastern Europe and the Americas, but few cases have been reported in Japan. PATIENTS AND DESIGN: Two sisters (aged 8.4 and 4.3 years at presentation) exhibited proportional short stature from about 2 years of age. Genetic analysis determined the nature and location of mutations. RESULTS: Pituitary size by magnetic resonance imaging (MRI) indicated only slight hypoplasia, while hormone analysis revealed deficiencies in secretion of growth hormone (GH), thyroid stimulating hormone, prolactin and gonadotropins; adrenocortinotropin secretion appeared adequate. Genetic analysis revealed a novel familial inherited PROP1 mutation. A unique insertion mutation was found in codon 156 (467insT) located in the transcription-activating region of the PROP1 gene. The resulting PROP1 protein (191 amino acids) would lack the transcription activation domain and consequently be non-functional. CONCLUSION: Gene analysis suggested that the siblings had inherited a unique autosomal recessive PROP1 gene mutation resulting in severe GH deficiency and subsequent growth retardation.

Base Sequence↗

Decreased relative expression level of trefoil factor 3 mRNA to galectin-3 mRNA distinguishes thyroid follicular carcinoma from adenoma.

The expression level of trefoil factor 3 (TFF3) mRNA is a marker for distinguishing thyroid follicular adenomas from carcinomas. However, when measuring the expression level of TFF3 mRNA in fine needle aspiration biopsies, an appropriate internal control mRNA, of which expression is restricted in thyroid epithelial--derived cells, is necessary, since they are often contaminated with a considerable number of blood cells, which do not express TFF3 mRNA. In this study, we evaluated the efficiency of molecular-based diagnosis of thyroid follicular carcinoma by measuring the relative expression of TFF3 mRNA by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) using galectin-3 mRNA as an internal control. The TFF3/galectin-3 mRNA ratio (T/G ratio) was measured in 54 follicular adenomas and 29 follicular carcinomas. It was markedly decreased in 7 follicular carcinomas of widely invasive type and with evident distant metastases. When the cutoff point was set at 16.0 by a receiver operator characteristic curve, the TG ratio showed good agreement with the pathological diagnosis [kappa=0.55; 95% confidence interval (CI), 0.34-0.77]. This agreement was better when the pathologically questionable cases were excluded (kappa=0.72; 95% CI, 0.49-0.95). Quantification of the T/G ratio may be a useful tool for the distinction between follicular adenomas and carcinomas, which is the most difficult in thyroid pathology.

Adenocarcinoma, Follicular↗