The burden of disease of X-linked hypophosphatemia (XLH) in East Asia is poorly understood. This was a cross-sectional study using an online questionnaire to evaluate health-related quality of life (HRQOL) and disease complications in Japanese and Korean patients with XLH. Adults with XLH and the caregivers of children <18 years of age with XLH in Japan and Korea were surveyed. Respondents disclosed demographic data, family history, diagnostic history, medical history, surgical history, disease-specific clinical symptoms, treatment, medications, and use of ancillary equipment. Patient-reported outcomes (PROs; the Western Ontario and McMaster Universities Osteoarthritis Index, the brief pain inventory, and the 36-item short form health survey version 2) were used to assess pain, disability, and HRQOL in adults. Of those surveyed, all 14 children (100%) and 30/32 adults (93.8%) were receiving treatment for XLH. However, despite oral phosphate and active vitamin D use, short stature, gait abnormalities, dental conditions, and decreased physical function were reported. Stapling of the growth plates was reported in 14.3% of children but no adults. Adult patients reported high rates of bone pain (59.4%) and joint pain (65.6%). Caregivers of children with XLH also reported the occurrence of bone pain (35.7%) and joint pain (35.7%). Many adult patients had a history of impaired renal function (9.5%), nephrocalcinosis (15.6%), hyperparathyroidism (15.6%), and parathyroidectomy (6.3%), all of which are associated with conventional XLH treatments. These data show that patients (both pediatric and adult) continue to have symptoms such as pain, disability, and various complications despite receiving conventional therapies.

Metabolic syndrome (MetS) is cluster of metabolic diseases, including abdominal obesity, hyperglycemia, high blood pressure, and dyslipidemia, that directly escalate the risk of type 2 diabetes, heart disease, and stroke. Thioredoxin-interacting protein (TXNIP) is a binding protein for thioredoxin, a molecule that is a key inhibitor of cellular oxidation, and thus regulates the cellular redox state. Epigenetic alteration of the TXNIP-encoding locus has been associated with components of MetS. In the present study, we sought to determine whether the level of TXNIP methylation in blood is associated with MetS in the general Japanese population. DNA was extracted from the peripheral blood cells of 37 subjects with and 392 subjects without MetS. The level of TXNIP methylation at cg19693031 was assessed by the bisulfite-pyrosequencing method. We observed that TXNIP methylation levels were lower in MetS subjects (median 74.9%, range 71.7–78.4%) than in non-MetS subjects (median 77.7%, range 74.4–80.5%; p = 0.0024). Calculation of the confounding factor-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for hypomethylation revealed that subjects with MetS exhibited significantly higher ORs for hypomethylation than did those without MetS (OR, 2.92; 95% CI, 1.33–6.62; p = 0.009). Our findings indicated that lower levels of TXNIP methylation are associated with MetS in the general Japanese population. Altered levels of DNA methylation in TXNIP at cg19693031 might play an important role in the pathogenesis of MetS.

The Japanese Society of Thyroid Pathology and the Japan Association of Endocrine Surgeons developed the eighth edition of the General Rules for the Description of Thyroid Cancer (GRDTC) in December 2019. This article describes the pathological diagnosis of the GRDTC, which has been improved through repeated revisions based on the experience of Japanese pathologists and translated into English to introduce the Japanese diagnostic standard to foreign countries. In this edition of the GRDTC, the histopathological classification and descriptions differ in some respects from those of the fourth edition of the World Health Organization (WHO) classification as revised in 2017. For example, the GRDTC does not adopt the concept of borderline lesions (FT-UMP, WDT-UMP, and NIFTP) of the WHO, taking into consideration the popular histological criteria accepted by Japanese pathologists. The cytological reporting system of the GRDTC was partly modified from the Bethesda system in 2015. It has an additional cyst fluid category separated from the unsatisfactory category that has been demonstrated to be useful in Japan. This translated edition makes it easy to submit Japanese clinicopathological studies of thyroid tumors in an international journal. We also wish to contribute to the improvement, standardization, and globalization of the pathological diagnosis of thyroid tumors.

The etiology of central diabetes insipidus (DI) is classified into (1) idiopathic, (2) familial, and (3) secondary. Of these, familial central diabetes insipidus shows an autosomal dominant inheritance. We herein report a case in which this disease was diagnosed based on a family history of nocturnal enuresis. A 40-year-old man had had symptoms of polydipsia, polyuria and nocturia since childhood and found that his daughter had the same symptoms. Despite reaching nine years old, his daughter’s nocturnal enuresis still had not improved, resulting in her consulting a pediatrician. She was suspected of having familial neurohypophyseal diabetes insipidus (FNDI) based on her family history and was referred along with her father for a detailed examination and treatment. A hypertonic saline load test (HSLT) to evaluate the arginine vasopressin (AVP) reaction was performed in both the proband and his daughter. The results showed no increase in AVP levels in response to high plasma osmolality. The water deprivation test (WDT) revealed he was suffering from partial DI. Based on the above findings and considering the possibility of familial central diabetes insipidus, we performed a gene mutation analysis of AVP-neurophysin II (NPII). Both the father and daughter had an exon 2 abnormality in this gene (c232_234delGAG; pGlu78del), and this gene mutation is known to cause NPII protein abnormality, abolishing the function of AVP as a carrier protein. This case was considered to have provided an opportunity to understand the role of an NPII gene abnormality in familial central diabetes insipidus.