Yuji Hiromatsu

Localization of ectopic parathyroid glands using technetium-99m sestamibi imaging: Comparison with magnetic resonance and computed tomographic imaging

The aim of the study was to compare the accuracy of technetium-99m sestamibi imaging for localization of ectopic parathyroid glands in patients with hyperparathyroidism with that of magnetic resonance (MR) and computed tomographic (CT) imaging. Eleven patients with primary (n=3) or secondary (n=8) hyperparathyroidism were studied with99mTc sestamibi parathyroid imaging CT and MR imaging. Images of the neck were acquired at 10 min and 2–3 after tracer injection. The three patients with primary hyperparathyroidism and five patients with secondary hyperparathyroidism underwent parathyroidectomy. The ectopic glands were confirmed by histopathological examination of the resected specimens. In respect of 20 parathyroid glands in the eight patients explored surgically, the sensitivity and specificity of sestamibi imaging were 70% (14/20) and 88%, respectively, those of CT, 40% (8/20) and 88%, and those of MR imaging, 60% (12/20) and 88%. Of these patients, three had parathyroid adenomas while five had hyperplasia (17 glands). Sestamibi imaging localized eight ectopic parathyroid glands, which were surgically confirmed (six were located in the thymus and two in the mediastinum). In one patient explored surgically, the ectopic gland was located outside the field of the MR coil. Although the remaining three cases of secondary hyperparathyroidism were not confirmed surgically, these patients demonstrated sestamibi uptake in five parathyroid glands, including three ectopic glands. MR images demonstrated abnormal parathyroid glands in the same regions as sestamibi imaging. Our data indicate that99mTc-sestamibi imaging should be used initially to localize the ectopic parathyroid glands in patients with hyperparathyroidism for anatomical guidance prior to MR or CT imaging.

Inhibitory effects of nicotinamide on recombinant human interferon-gamma-induced intercellular adhesion molecule-1 (ICAM-1) and HLA-DR antigen expression on cultured human endothelial cells.

Intercellular adhesion molecule-1 (ICAM-1), HLA-A, B, C and HLA-DR antigen on endothelial cells (EC) play important roles in the development of inflammatory processes in autoimmune disorders. In the present study, we investigated the effect of nicotinamide, an inhibitor of poly(ADP ribose) synthetase, on interferon-gamma (IFN gamma)-induced ICAM-1 and HLA-DR antigen expression on the surface of cultured human umbilical vein endothelial cells, assessed by flow cytometry, and EC proliferation by counting cell numbers and [3H]thymidine incorporation assays. Nicotinamide dose-dependently inhibited the IFN-gamma-induced ICAM-1 and HLA-DR antigen expression, but not HLA-A, B, C antigen expression on cultured EC. Furthermore, nicotinamide significantly inhibited endothelial cell proliferation, as assessed by [3H]thymidine incorporation assay. Our findings suggest that nicotinamide may suppress mononuclear cell infiltration, antigen presentation and angiogenesis in the lesions of autoimmune disorders by reducing both IFN gamma-induced ICAM-1 and HLA-DR antigen expression on EC, and EC proliferation. Therefore, nicotinamide can be used for the treatment and prevention of the development of autoimmune disorders.

Hashimoto's thyroiditis: history and future outlook.

Dr. Hakaru Hashimoto (Figure 1), born 5 May 1881, was the third son of a prominent family who had practiced medicine for generations in Iga Ueno, Mie Prefecture, Japan. He was one of the first graduates to receive a bachelor’s degree from the Fukuoka Medical College of Kyoto Imperial University in 1907. Hakaru Hashimoto received tutelage and training from Professor Miyake of the Department of Surgery of Fukuoka Medical College. Professor Miyake also instructed Dr. Hashimoto on the technique of assessing excised thyroid glands microscopically. In 1912, at the age of 30, Hakaru Hashimoto reported a distinct new disease in ‘Archiv fur Klinische Chirurgie”, a German journal of clinical surgery. His paper, which consisted of 30 pages and 5 illustrations and centered on histological changes in thyroid tissue, discussed the results of his examination of thyroid tissue samples taken from four women. Hakaru Hashimoto further explained in his report that the new pathological characteristics he had identified, namely infiltration of lymphoid and plasma cells, formation of lymphoid follicles with germinal centers, fibrosis, degenerated thyroid epithelial cells and leukocytes in the lumen, were histologically similar to those of Mikulicz’s disease. He expressed confidence that he had discovered a new disease, which he named “struma lymphomatosa”, emphasizing the lymphoid cell infiltration and formation of lymphoid follicles with germinal centers, neither of which had previously been reported.

T-Cell–Mediated Immunity in Thyroid-Associated Ophthalmopathy

Thyroid-associated ophthalmopathy (TAO) is considered to be an autoimmune inflammatory disorder of the extraocular muscles and the orbital fat/connective tissue. Recent studies analyzing T cells infiltrating retrobulbar tissues generated important insights into the immunopathogenesis of TAO. The present review focuses on advances in our understanding of mechanisms responsible for the autoimmune inflammation in TAO, especially T cell migration to the inflammatory site, T cell activation by autoantigens and costimulatory signals and their cytokine profile. The elucidation of these processes might lead to the development of novel therapeutic strategies directed against autoreactive T cells.

Relationship between clinicopathological factors and fluorine-18-fluorodeoxyglucose uptake in patients with papillary thyroid cancer

ObjectiveTo examine the relationship between clinicopathological factors and fluorine-18-fluorodeoxyglucose (18F-FDG) uptake in patients with papillary thyroid cancer (PTC). Materials and methodsFifty-four patients were included in this study.18F-FDG positron emission tomography was performed before surgery. Immunohistochemistry of glucose transporter (GLUT) was performed using postoperative histopathological specimens. We investigated the relationship between maximum standardized uptake value (SUVmax) and GLUT-1, GLUT-3, and GLUT-4 expression/SUVmax and prognostic risk factors {tumor size, age, sex, extrathyroidal extension, and lymph node metastasis [ly (+)]}. ResultsGLUT-3 and GLUT-4 expressions significantly correlated with SUVmax (GLUT-3: r=0.38, P=0.008; GLUT-4: r=0.46, P=0.001), but GLUT-1 did not (r=0.21, P=0.147). The tumor size correlated with SUVmax (r=0.5, P<0.001), but GLUT-1, GLUT-3, and GLUT-4 did not (GLUT-1: r=0.006, P=0.681; GLUT-3: r=0.05, P=0.705; GLUT-4: r=−0.17, P=0.217). Both SUVmax and GLUT-4 expressions were statistically significant with ly (+) (SUVmax: P=0.012; GLUT-4: P=0.018), but GLUT-1 and GLUT-3 expressions were not (GLUT-1: P=0.165; GLUT-3: P=0.499). There was no significant difference between other clinicopathological factors and SUVmax or any GLUT expressions. Conclusion 18F-FDG uptake in PTC may be determined by GLUT-3 and GLUT-4 expressions and may be related to tumor size and lymph node metastasis of PTC. 18F-FDG uptake may reflect tumor progression of PTC.

Interleukin‐13 gene polymorphisms in patients with Graves’ disease

objective  In patients with Graves’ disease (GD), an elevation of serum immunoglobulin E (IgE) has been recently reported to be associated with the severity of hyperthyroidism and ophthalmopathy. Interleukin 13 (IL‐13) is a major cytokine involved in IgE synthesis and therefore may be a potential candidate gene contributing to the development of GD or influencing the clinical course of the disease.

Progress in Thyroid-Associated Ophthalmopathy

185 AN INTERNATIONAL SYMPOSIUM on progress in thyroid-associated ophthalmopathy (TAO) was held as a satellite to the 12th International Thyroid Congress, in Kyoto. The program addressed basic research and clinical management aspects of TAO. The symposium comprised 19 invited lectures and a poster session. The first part focused on research aspects of pathogenesis of TAO and autoimmunity in TAO. The second part focused on the clinical investigation of TAO. In the last part of the symposium, recent advances in the clinical management of TAO were discussed. Speakers included endocrinologists, basic scientists, surgeons, and ophthalmologists. Although TAO is considered to be an autoimmune disorder, the primary autoantigen and mechanism for its association with thyroid autoimmunity have not been fully elucidated. The major research topics addressed at the symposium included the role of autoimmunity against the thyrotropin (TSH) receptor as the putative primary autoantigen in the pathogenesis of TAO, animal models of TAO using TSH receptor cDNA immunization, the nature of eye muscle antigens and their relationship to the eye muscle component of TAO, and the role of cytokines and T-cell immunity in the development of ophthalmopathy. The natural history of TAO has been addressed by several investigators. Recent advances in methods for the assessment of the severity and activity of TAO, including the importance of quantifying quality of life. The conventional treatments of TAO, including steroids, orbital irradiation, and surgery, have been reviewed and reevaluated. A new approach for the management of TAO has been proposed. It is our great honor and pleasure to publish a special issue, Progess in Thyroid-Associated Ophthalmopathy , in Thyroid. This volume of the Journal comprises 15 papers, which are representative of current trends in basic and clinical research into TAO and its management. We do hope that all the readers will share the important information on progress in TAO and promote future strategies for the research and management of TAO.

Usefulness of whole PTH assay in patients with renal osteodystrophy-Correlation with bone scintigraphy

ObjectiveIntact parathyroid hormone (PTH) assay has recently been reported to be effective in evaluating both 1-84 PTH (whole PTH) and inactive 7-84 PTH. Inactive 7-84 PTH is considered to be increased in hemodialysis patients and to prevent the effects of 1-84 PTH, and intact PTH is considered to overestimate the PTH activity in these patients. As such, a whole PTH assay has recently been developed. The purpose of this study was to examine the usefulness of a whole PTH assay using the bone to soft tissue (B/ST) ratio on bone scintigraphy.MethodTwenty-five hemodialysis patients were included in our study. In all patients, bone scintigraphy and a blood test [whole PTH, intact PTH, alkaline Phosphatase (ALP), calcium (Ca), and phosphorus (P)] were performed. Regions of interest (ROIs) were drawn around the cranium, lumbar vertebrae, left femoral neck, and soft tissue of the medial left thigh to obtain the B/ST ratio.ResultsThe B/ST ratio of the cranium and left femoral neck correlated with whole PTH and intact PTH. In particular, the B/ST ratio of the cranium correlated most significantly with the value of whole PTH. Whole PTH levels correlated with intact PTH levels (r = 0.891, p < 0.0001).ConclusionOur data indicate that a whole PTH assay may be useful in evaluating PTH activity using the B/ST ratio. The B/ST ratio of the cranium may reflect the bone metabolism of hemodialysis patients.

In situ studies of orbital tissue from patients with thyroid-associated ophthalmopathy

Extensive studies have attempted to establish the nature of the orbital autoantigen(s) and the mechanism for the development of thyroid-associated ophthalmopathy (TAO). Histologic examination of the orbital tissues of patients with TAO has revealed lymphocytic infiltration in the extraocular eye muscles (EM) with an accumulation of glycosaminoglycans and some damage of EM fibers. CD4+, CD8+, CD45RO+ T cells and macrophages are predominant in EM during the active stage of TAO. Both Th1 and Th2 cytokines are present in EM tissues. The expression of HLA-DR on EM is seen in association with lymphocytic infiltration. The lack of the expression of B7 or B70 suggests that the aberrant expression of HLA-DR on EM may play a role in peripheral tolerance to EM antigens. Heat shock protein-70 is expressed in EM fibers from most of patients with TAO, suggesting that EM is the target of the autoimmune reaction. 1D, a candidate 64 kDa EM antigen, is present in both thyroid and EM. However, its clinical relevance has not...

A clinical assessment of the relationship between bone scintigraphy and serum biochemical markers in hemodialysis patients

BackgroundRenal osteodystrophy is a metabolic bone disease and a common complication of end-stage chronic renal failure and maintenance dialysis treatment. In this study, we examined the correlation between quantifying bone scintigraphy and serum biochemical markers in hemodialysis patients.MethodsBone scintigraphy with technetium-99m-hydroxy-methylene-diphosphonate (99mTc-HMDP) was performed on 28 patients on maintenance hemodialysis. Bone scintigraphy was performed using a standard protocol and was quantified by setting regions of interest (ROIs) over selected regions. The bone-to-soft-tissue ratio (B/ST ratio) at each region was calculated in all patients. The B/ST ratios were then compared with serum biochemical markers.ResultsThe B/ST ratio for the skull correlated well with serum bone-specific alkaline Phosphatase (BAP) (r = 0.735, ? > 0.001), serum deoxypyridinoline (DPD) (r = 0.806, ? > 0.001) and intact parathyroid hormone (intact PTH) (r = 0.701, ? > 0.001). The B/ST ratio for the lumbar spine correlated with intact PTH (r = 0.387, ? > 0.05) but not with serum BAP or serum DPD. The B/ST ratio for the femoral neck correlated with serum DPD (r = 0.431, ? > 0.05) and intact PTH (r - 0.449, ? > 0.05) but not with serum BAP.ConclusionsOur data suggest that quantitative bone scintigraphy is a sensitive and useful method for evaluating bone metabolism in hemodialysis patients. The B/ST ratio for the skull may reflect changes of bone metabolism in hemodialysis patients.