An asymptomatic, 68-year-old Japanese man visited our hospital for further examination of subclinical hypothyroidism. At the first visit, the serum TSH level was markedly elevated (36.6 μIU/mL), but ...the serum level of free T4 was within the reference interval. Thyroid dysfunction due to dietary iodine excess was initially suspected. However, even after iodine restriction, his thyroid function tests were the same as at the first visit, which suggested false elevation of the TSH level. The TSH levels were compared among three different measurement systems, which showed a similar tendency of TSH elevation above the reference interval, but the different TSH elevation levels among the measurement methods suggested the existence of some interfering substance. Neither serial dilution of the patient’s serum nor polyethylene glycol and protein G precipitation tests showed any significant changes in the recovery rate. IgG-bound macro-TSH was ruled out. The TSH peak on gel filtration chromatography was located at a molecular size greater than IgA, which suggested the presence of IgA-bound TSH. After precipitation with Jacalin, which binds specifically to IgA, the TSH level decreased from 30.7 μIU/mL to 2.01 μIU/mL, within the reference interval. Thus, IgA-bound macro-TSH was identified. Macro-TSH is a rare condition in which an immunoglobulin-bound, high-molecular-weight form of TSH results in a false elevation of the serum TSH level. When there is a discrepancy between the results of thyroid function tests and clinical symptoms, and macro-TSH is suspected, it is necessary to know that not only IgG-bound TSH but also IgA-bound TSH could be the cause.
The present study aimed to establish new reference intervals (RIs) for serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in Japanese children and ...adolescents aged 4 to 19 years. A total of 2,036 (1,611 girls, 425 boys) participants were included over a 17-year period; they all tested negative for antithyroid antibodies (TgAb, TPOAb) and were found to have no abnormalities on ultrasonography. RIs were determined by nonparametric methods. The results showed that serum fT3 was significantly higher in the 4–15-year-olds than in the 19-year-olds. The serum fT4 was significantly higher in the 4–10-year-olds than in the 19-year-olds. The serum TSH was significantly higher in the 4–12-year-olds than in the 19-year-olds. All of them gradually decreased with age to approximate the adult levels. The upper limit of TSH was lower in those aged 13 to 19 years than in adults. The differences were examined by sex. The serum fT3 was significantly higher in boys than in girls between the ages of 11 and 19 years. The serum fT4 was significantly higher in boys than in girls between the ages of 16 and 19 years. There did not seem to be any sex difference in those under 10 years of age. In conclusion, serum fT3, fT4, and TSH levels in children and adolescents differ from those in adults. It is important to evaluate thyroid function using the new RIs that are appropriate for chronological age.
Graves’ disease has been reported to affect the clinical features of moyamoya disease (MMD), an occlusion of the circle of Willis. This study aimed to clarify the characteristics of MMD in patients ...with Graves’ disease. This was a single-center, retrospective study. The prevalence and clinical features of MMD patients among all patients with thyroid disease who visited Ito Hospital from January 2005 to December 2019 were evaluated. The relationship between MMD and hyperthyroidism was analyzed in new-onset Graves’ disease patients during the same period. Of all 394,422 patients with thyroid disease, 88,180 had Graves’ disease, and 40 had MMD with Graves’ disease, i.e., the prevalence was 45.36 per 100,000 patients with Graves’ disease (0.0454%). The median age at onset of MMD was 39 years (interquartile range, 31–54 years), with a male to female ratio of 1:12. The most common time that MMD was diagnosed was within 1 year after the onset of Graves’ disease, in 9 of 40 patients (22.5%), and 19 of 40 patients (47.5%) underwent bypass surgery for MMD. In MMD with Graves’ disease, headache was the most frequent symptom, and ischemic types of stroke and bilateral lesions were common. Of 23,347 patients with new-onset Graves’ disease, 7 were diagnosed with MMD and the incidence of MMD was 5.94 patients per 100,000 person-years. Most patients developed MMD symptoms during hyperthyroidism. Although MMD is a rare condition, it should be noted that it can occur with Graves’ disease.
Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the ...evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves’ disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.
Phylogeographic history of Japanese macaques Ito, Tsuyoshi; Hayakawa, Takashi; Suzuki–Hashido, Nami ...
Journal of biogeography,
June 2021, 2021-06-00, 20210601, Volume:
48, Issue:
6
Journal Article
Peer reviewed
Open access
Aim
Understanding patterns and processes of geographic genetic variation within and among closely related species is the essence of phylogeography. Japanese macaques, also called snow monkeys, have ...been extensively studied, particularly in the fields of sociobiology, ecology and experimental biology; however, our knowledge of their evolutionary history is relatively limited. In this study we aimed to elucidate the geographic patterns of genetic variation in Japanese macaques and the processes that underlie them.
Location
Japan.
Taxa
Japanese macaque, Macaca fuscata; rhesus macaque, M. mulatta; Taiwanese macaque, M. cyclopis.
Methods
Double‐digest restriction site‐associated DNA (RAD) sequencing was used to identify genome‐wide single nucleotide variants. We used fineRADstructure, ADMIXTURE and principal component analyses to estimate the genetic population structure. Phylogenetic relationships were then inferred based on neighbour‐net, neighbour‐joining, maximum likelihood and SVDquartets algorithms. We assessed gene flow using demographic inference and ABBA‐BABA tests, and estimated past distributions during the Last Glacial Maximum (LGM) using ecological niche modelling.
Results
Japanese macaques show a sister group relationship with a clade comprising Chinese rhesus, Indian rhesus and Taiwanese macaques. Japanese macaques comprise major north‐eastern and south‐western clades, with a boundary located near central Japan, and gene flow between the north‐eastern and south‐western lineages was detected. Refugia during the LGM were estimated to be distributed in limited areas along the south coasts of the Japanese archipelago.
Main conclusions
Phylogeographic variation of Japanese macaques is likely due mainly to northeast–southwest divergence, which resulted from withdrawal into refugia during the glacial period, and subsequent gene flow.
Abstract
Context
Thyroid mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal lymphoma with a favorable prognosis.
Objective
To provide information on long-term outcomes that ...would facilitate establishment of the optimal management strategy for thyroid lymphoma.
Design, Setting, and Participants
Medical records of 107 patients (median age 67 years, 20 males, 87 females) who were diagnosed with localized thyroid MALT lymphoma stage IE or IIE at Ito Hospital were retrospectively reviewed.
Main Outcome Measure
Overall and event-free survival (EFS).
Results
Initial treatments included radiation therapy (RT) alone (n = 58), combined modality therapy (CMT) (n = 48), or chemotherapy alone (n = 1). All 107 patients responded to the treatment, six of whom experienced relapse. Only one patient died of lymphoma. The 5-year overall survival (OS) and EFS rates were 94% 95% confidence interval (CI), 87% to 97% and 92% (95% CI, 85% to 95%), respectively, and the 10-year OS and EFS rates were 91% (95% CI, 83% to 95%) and 84% (95% CI, 74% to 90%), respectively. Of the 106 patients with information available on adverse events, 71 patients (67%) developed hypothyroidism after primary thyroid lymphoma treatment. The CMT group showed additional chemotherapy-induced adverse reactions in the form of neutropenia, neuropathy, constipation, and pneumonia. The 5-year OS rates of patients treated with CMT and RT were 93% (95% CI, 81% to 98%) and 94% (95% CI, 84% to 98%), respectively.
Conclusions
Long-term outcomes of localized thyroid MALT lymphoma are favorable with all initial treatment modalities.
We studied outcomes of 107 cases of localized thyroid MALT lymphoma. This study, the largest-scale long-term study ever, showed that outcomes are favorable with all initial treatment modalities.
Long-lasting fear-related disorders depend on the excessive retention of traumatic fear memory. We previously showed that the palmitoylation-dependent removal of synaptic ...α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors prevents hyperexcitation-based epileptic seizures and that AMPA receptor palmitoylation maintains neural network stability. In this study, AMPA receptor subunit GluA1 C-terminal palmitoylation-deficient (GluA1C811S) mice were subjected to comprehensive behavioral battery tests to further examine whether the mutation causes other neuropsychiatric disease-like symptoms. The behavioral analyses revealed that palmitoylation-deficiency in GluA1 is responsible for characteristic prolonged contextual fear memory formation, whereas GluA1C811S mice showed no impairment of anxiety-like behaviors at the basal state. In addition, fear generalization gradually increased in these mutant mice without affecting their cued fear. Furthermore, fear extinction training by repeated exposure of mice to conditioned stimuli had little effect on GluA1C811S mice, which is in line with augmentation of synaptic transmission in pyramidal neurons in the basolateral amygdala. In contrast, locomotion, sociability, depression-related behaviors, and spatial learning and memory were unaffected by the GluA1 non-palmitoylation mutation. These results indicate that impairment of AMPA receptor palmitoylation specifically causes posttraumatic stress disorder (PTSD)-like symptoms.
Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves’ orbitopathy (GO). This study aimed to clarify the incidence and risk ...factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves’ disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16–1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15–1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96–4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.
Although untreated Graves’ disease (GD) is associated with a higher risk of cardiac complications and mortality, there is no well-established way to predict the onset of thyrotoxicosis in clinical ...practice. The aim of this study was to identify important variables that will make it possible to predict GD and thyrotoxicosis (GD + painless thyroiditis (PT)) by using a machine-learning-based model based on complete blood count and standard biochemistry profile data. We identified 19,335 newly diagnosed GD patients, 3,267 PT patients, and 4,159 subjects without any thyroid disease. We built a GD prediction model based on information obtained from subjects regarding sex, age, a complete blood count, and a standard biochemistry profile. We built the model in the training set and evaluated the performance of the model in the test set by using the artificial intelligence software Prediction One. Our machine learning-based model showed high discriminative ability to predict GD in the test set (area under the curve AUC 0.99). The main contributing factors to predict GD included age and serum creatinine, total cholesterol, alkaline phosphatase, and total protein levels. We still found high discriminative ability even when we restricted the variables to these five most contributory factors in our prediction model (AUC 0.97) built by using artificial intelligence software showed high GD prediction ability based on information regarding only five factors.
The efficacy of potassium iodide (KI) for Graves’ disease (GD) has been reported, although few clinical reports have examined the long-term efficacy of treatment. The objective of this study was to ...investigate the efficacy and limitations of KI treatment for GD. This study enrolled patients newly diagnosed with mild GD, defined as free thyroxine (FT4) <5.0 ng/dL, between July 2014 and June 2016. KI was started at a dose of 50 mg/day, and if FT4 values did not decrease after initiation of treatment, doses were increased to 100 mg/day. Patients for whom thyroid hormone levels could not be controlled with KI at 100 mg/day were regarded as non-responders. Of the 122 patients (13 males, 109 females) included in this study, 71 (58.2%) responded to KI therapy. The remaining 51 patients (41.8%) were non-responders. The median duration required to judge non-responsiveness was 5.9 months. Multiple logistic regression analysis performed on parameters measured at the initial visit indicated FT4 (odds ratio (OR) 2.19, 95% confidence interval (CI) 1.28–3.75; p = 0.0007) and male sex (OR 3.58, 95%CI 1.04–12.3; p = 0.04) were significantly associated with KI responsiveness. Receiver operating characteristic (ROC) curve analysis of the relationship between FT4 and KI responsiveness indicated an FT4 cut-off of 2.76 ng/dL was optimal for differentiating between responders and non-responders. KI therapy was effective and safe for about 60% of patients with mild GD.
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