鈴木 敦詞

Post-transplantation bone diseases negatively affect the quality of life of solid organ recipients. Secondary or tertiary hyperparathyroidism is a frequent complication in kidney transplantation (KTx) recipients. Treatment with immunosuppressive agents including glucocorticoids can lead to deterioration in bone metabolism in these patients. In the present study, we explored the effects of a three-year treatment period with oral alendronate (ALN) in long-term KTx recipients. Post-KTx recipients were recruited (n = 24, M/F = 12/12, mean age 52.0 +/- A 7.8 years) into this study. All patients were prescribed methylprednisolone (4.07 +/- A 0.86 mg/day) with various immunosuppressive agents. Before treatment with oral ALN (35 mg/week), the mean concentrations of intact parathyroid hormone (iPTH) and 25-hydroxyvitamin D were 139.2 +/- A 71.4 pg/mL and 20.8 +/- A 4.1 ng/mL, respectively. After 36 months of ALN treatment, mean iPTH levels increased slightly (+20.9 %). Treatment with ALN reduced bone-specific alkaline phosphatase (-35.4 %), serum type I collagen N-terminal telopeptide (-31.2 %) and osteocalcin (-55.6 %) levels. ALN did not increase bone mass after 24 months. Four patients with the highest baseline iPTH levels suffered a clinical osteoporotic fracture during the 36-month ALN treatment period. Higher iPTH levels with chronic kidney disease (CKD) at baseline were associated with the incidence of new clinical fractures during ALN treatment. In conclusion, anti-resorptive therapy with ALN can suppress bone turnover even when iPTH concentration is elevated in long-term KTx recipients. However, hyperparathyroidism with CKD seems to be associated with new clinical fractures during ALN treatment.

生命を脅かすような甲状腺中毒状態は甲状腺クリーゼと呼ばれ,内分泌疾患の代表的な救急疾患の1つである.甲状腺機能検査では通常の甲状腺中毒症と区別できず,臨床的症状・徴候に基づいて診断される.まれな病態であるが,見過ごされる場合も多々あり,放置すれば死に至る.緊急治療開始を要し,現在でも致死率は10%以上に達する.早期の診断と治療が重要であるが,エビデンスに基づいた診断基準が我が国で初めて作成された.(著者抄録)

Background: Thyroid storm (TS) is life threatening. Its incidence is poorly defined, few series are available, and population-based diagnostic criteria have not been established. We surveyed TS in Japan, defined its characteristics, and formulated diagnostic criteria, FINAL-CRITERIA1 and FINAL-CRITERIA2, for two grades of TS, TS1, and TS2 respectively. Methods: We first developed diagnostic criteria based on 99 patients in the literature and 7 of our patients (LIT-CRITERIA1 for TS1 and LIT-CRITERIA2 for TS2). Thyrotoxicosis was a prerequisite for TS1 and TS2 as well as for combinations of the central nervous system manifestations, fever, tachycardia, congestive heart failure (CHF), and gastrointestinal (GI)/hepatic disturbances. We then conducted initial and follow-up surveys from 2004 through 2008, targeting all hospitals in Japan, with an eight-layered random extraction selection process to obtain and verify information on patients who met LIT-CRITERIA1 and LIT-CRITERIA2. Results: We identified 282 patients with TS1 and 74 patients with TS2. Based on these data and information from the Ministry of Health, Labor, and Welfare of Japan, we estimated the incidence of TS in hospitalized patients in Japan to be 0.20 per 100,000 per year. Serum-free thyroxine and free triiodothyroine concentrations were similar among patients with TS in the literature, Japanese patients with TS1 or TS2, and a group of patients with thyrotoxicosis without TS (Tox-NoTS). The mortality rate was 11.0% in TS1, 9.5% in TS2, and 0% in Tox-NoTS patients. Multiple organ failure was the most common cause of death in TS1 and TS2, followed by CHF, respiratory failure, arrhythmia, disseminated intravascular coagulation, GI perforation, hypoxic brain syndrome, and sepsis. Glasgow Coma Scale results and blood urea nitrogen (BUN) were associated with irreversible damages in 22 survivors. The only change in our final diagnostic criteria for TS as compared with our initial criteria related to serum bilirubin concentration >3mg/dL. Conclusions: TS is still a life-threatening disorder with more than 10% mortality in Japan. We present newly formulated diagnostic criteria for TS and clarify its clinical features, prognosis, and incidence based on nationwide surveys in Japan. This information will help diagnose TS and in understanding the factors contributing to mortality and irreversible complications.

Background: Interactions between CD40 and its ligand (CD40L) have important roles in T-cell-dependent activation of B cells, which may be related to the thyrotoxic activity of Graves' disease (GD). Soluble forms of CD40 ligand (sCD40L) are released from activated T cells and platelets, and several types of inflammatory cytokines are increased in patients with hyperthyroid GD. The aim of this study was to assess sCD40L and other cytokines as clinical indicators of disease activity or as possible markers of remission in GD. Methods: Serum levels of sCD40L, interleukin 18 (IL-18), tumor necrosis factor-alpha (TNF alpha), and TNF alpha receptors 1 and 2 (TNFR1 and TNFR2) were investigated in patients with active GD (GD-A), intractable GD (GD-IT), inactive GD (GD-IA), GD in remission (GD-R), and Hashimoto's thyroiditis (HT), and in control subjects (CON). Results: Serum concentrations of sCD40L were higher in the GD-A and GD-IT groups than in the HT and CON groups. Similarly, serum concentrations of IL-18, which induces Th1 cytokines, such as interferon-gamma, were higher in the GD-A and GD-IT groups than in all other groups. Serum levels of TNFR1 and TNFR2 were also significantly higher in the GD-A than in all other groups. The mean serum concentration of TNF alpha was higher in the GD-R compared with the GD-A and GD-IT groups, although the difference was not significant. Serum sCD40L concentrations in the GD-R group were lower than in the GD-A and GD-IT groups. Finally, the ratio of serum TNF alpha to sCD40L was higher in the GD-R group than in the GD-A and GD-IT groups. This is the first report that serum sCD40L is increased in active GD, and that the serum TNF alpha:sCD40L ratio is a marker for remission in GD. Conclusions: Our results suggest that not only thyrotoxicosis, but also the activity of the immunoreaction presenting as anti-thyrotropin receptor antibodies (TRAb) titer in GD, affects inflammatory cytokine serum profiles. Serum profiles of cytokines vary in patients with GD depending on disease activity. An elevated serum TNF alpha:sCD40L ratio indicates declining disease activity and reflects a shift from Th2 to Th1 dominance, suggesting that suppression of sCD40L or increased production of TNF alpha is required to initiate or maintain remission of GD.

Background: Chronic elevation of cardiac troponin T (TnT) levels as measured by conventional assays is strongly associated with structural heart disease and cardiovascular events. A new high-sensitivity assay for TnT makes it possible to measure concentrations more than a factor of 5 lower than the limits of detection of conventional assays. We evaluated the utility of serum TnT as a risk marker of cardiovascular disease in 409 outpatients with type-2 diabetes mellitus (T2DM). Results: TnT was detectable (&gt 0. 002 ng/mL) in 80% of patients, and elevation in TnT levels (&gt 0. 014 ng/mL) was found in 19. 3%, suggesting a higher prevalence of structural heart diseases in T2DM patients. A history of cardiovascular disease was noted in 89 (22%) patients. Patients with diabetic microvascular complications and those with abnormal electrocardiogram including left ventricular hypertrophy had higher TnT levels. Patients with increased levels of TnT (&gt 0. 014 ng/mL) were older, had higher values of N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein, cystatin C, and urinary albumin/creatinine ratio, had lower values of hemoglobin and estimated glomerular filtration rate, and had a higher prevalence of cardiovascular disease compared with those without increased TnT levels. In stepwise logistic analysis, NT-proBNP (odds ratio 7. 40 per 10-fold increase, P &lt 0. 0001) and cystatin C (18. 0 per 1. 0 mg/L, P &lt 0. 0001) were independently associated with elevation of TnT levels. HsTnT level, cystatin C, and HDL-cholesterol were also independent risk factors for history of major cardiovascular diseases in T2DM patients. Conclusion: This new high-sensitivity TnT assay may be useful for stratifying cardiovascular risk in outpatients with T2DM. © 2011 The Japan Diabetes Society.