STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179.

Thyrotropin (TSH) is the master regulator of thyroid gland growth and function. Resistance to TSH (RTSH) describes conditions with reduced sensitivity to TSH. Dominantly inherited RTSH has been linked to a locus on chromosome 15q, but its genetic basis has remained elusive.

Survey of potentially inappropriate prescriptions for common cold symptoms in Japan: A cross-sectional study.

Background: Common cold is among the main reasons patients visit a medical facility. However, few studies have investigated whether prescriptions for common cold in Japan comply with domestic and international evidence.

Objective: To determine whether prescriptions for common cold complied with domestic and international evidence.

Background factors associated with academic motivation for attending medical school immediately after admission in Japan: A single-center study.

Background: To become a doctor with a high level of professionalism and ethical standards, it is important to have and maintain a high level of motivation right from medical school. However, studies in Japan have not quantitatively investigated the factors related to motivation immediately after enrollment. This study aimed to identify the demographic factors that influence the motivation of medical students immediately after admission.

Cognitive Bias and Diagnostic Errors among Physicians in Japan: A Self-Reflection Survey.

This cross-sectional study aimed to clarify how cognitive biases and situational factors related to diagnostic errors among physicians. A self-reflection questionnaire survey on physicians' most memorable diagnostic error cases was conducted at seven conferences: one each in Okayama, Hiroshima, Matsue, Izumo City, and Osaka, and two in Tokyo. Among the 147 recruited participants, 130 completed and returned the questionnaires.

Japan's Academic Barriers to Gender Equality as Seen in a Comparison of Public and Private Medical Schools: A Cross-Sectional Study.

Gender inequalities persist in Japanese academic medicine. Some public medical schools have introduced various types of career support for women physicians, whereas few private schools have. Few studies describe the representation of women at different academic ranks and adequacy of career support in public and private medical schools in Japan.

Factors and impact of physicians' diagnostic errors in malpractice claims in Japan.

Background: Diagnostic errors are prevalent and associated with increased economic burden; however, little is known about their characteristics at the national level in Japan. This study aimed to investigate clinical outcomes and indemnity payment in cases of diagnostic errors using Japan's largest database of national claims.

Methods: We analyzed characteristics of diagnostic error cases closed between 1961 and 2017, accessed through the national Japanese malpractice claims database.

The Utility of Virtual Patient Simulations for Clinical Reasoning Education.

Virtual Patient Simulations (VPSs) have been cited as a novel learning strategy, but there is little evidence that VPSs yield improvements in clinical reasoning skills and medical knowledge. This study aimed to clarify the effectiveness of VPSs for improving clinical reasoning skills among medical students, and to compare improvements in knowledge or clinical reasoning skills relevant to specific clinical scenarios. We enrolled 210 fourth-year medical students in March 2017 and March 2018 to participate in a real-time pre-post experimental design conducted in a large lecture hall by using a clicker.

Primary care doctor fostering and clinical research training in Sweden: Implications for Japan.

In 2018, a new training program for primary care physicians was launched in Japan. As physicians responsible for the training of new primary care physicians, we have faced many problems, particularly in rural areas. The influence of this new program on primary care physicians in rural areas of Japan has not been sufficiently investigated.

A case of an infant with congenital combined pituitary hormone deficiency and normalized liver histology of infantile cholestasis after hormone replacement therapy.

Congenital combined pituitary hormone deficiency (CPHD) may present with cholestasis in the neonate or during early infancy. However, its precise mechanism is unknown. A 3-mo-old boy presented with cryptorchidism and hypoplastic scrotum after birth.

Guidelines for Mass Screening of Congenital Hypothyroidism (2014 revision).

Purpose of developing the guidelines: Mass screening for congenital hypothyroidism started in 1979 in Japan, and the prognosis for intelligence has been improved by early diagnosis and treatment. The incidence was about 1/4000 of the birth population, but it has increased due to diagnosis of subclinical congenital hypothyroidism. The disease requires continuous treatment, and specialized medical facilities should make a differential diagnosis and treat subjects who are positive in mass screening to avoid unnecessary treatment.

Guidelines for diagnosis and treatment of 21-hydroxylase deficiency (2014 revision).

Purpose of developing the guidelines: The first guidelines for diagnosis and treatment of 21-hydroxylase deficiency (21-OHD) were published as a diagnostic handbook in Japan in 1989, with a focus on patients with severe disease. The "Guidelines for Treatment of Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency) Found in Neonatal Mass Screening (1999 revision)" published in 1999 were revised to include 21-OHD patients with very mild or no clinical symptoms. Accumulation of cases and experience has subsequently improved diagnosis and treatment of the disease.

Frequencies of spontaneous breast development and spontaneous menarche in Turner syndrome in Japan.

The Growject® database on human GH treatment in Turner syndrome was analyzed in the Turner Syndrome Research Collaboration, and the relationships of the frequencies of spontaneous breast development and spontaneous menarche with karyotype and GH treatment were investigated. One hundred and three cases started GH treatment with 0.5 IU/kg/ week (0.

Clinical case seminar in pediatric thyroid disease.

Pediatric thyroid diseases cover a large spectrum of congenital and acquired forms, ranging from congenital primary or central hypothyroidism, autoimmune thyroid disease, iodine deficiency, rare genetic defects of thyroid hormone action, metabolism and cell membrane transport to benign nodules and malignant tumors. The previous 15 papers of the textbook Paediatric Thyroidology gave a systematic overview of the current knowledge and guidelines on all these diseases. In this final paper, the authors collected a series of patient histories from their clinics illustrating frequently encountered clinical problems and providing key learning points and references to each case.

Resistance to thyroid hormone.

Resistance to thyroid hormone (RTH) or thyroid hormone action defect (THAD) is the most frequent form of syndromes of reduced sensitivity to thyroid hormone. It is characterized by variable tissue hyposensitivity to thyroid hormone. RTHβ (formerly only RTH) is caused by mutations in the thyroid hormone receptor β gene (THRB).

[Thyroid hormone and skeletal metabolism].

The role of the hypothalamic-pituitary-thyroid axis is important in normal skeletal development, gain of bone mass, and regulation of adult bone metabolism. Hypothyroidism in childhood causes delayed bone maturation and growth disturbance and thyroid dysfunction in adult induces altered bone remodeling and an increased risk of bone fracture. Thyroid hormone actions in skeletal cells are mainly mediated by thyroid hormone receptor α (TRα) .

Clinical and genetic aspects of hypophosphatasia in Japanese patients.

Objective: We examined the clinical and genetic features of hypophosphatasia (HPP) in Japanese patients. HPP is a rare metabolic bone disorder of bone mineralisation caused by mutations in the liver/bone/kidney alkaline phosphatase (ALPL) gene, which encodes tissue-non-specific alkaline phosphatase isoenzyme. 

Methods: We retrospectively investigate the incidence and clinical features of 52 patients with paediatric HPP who were born between 1999 and 2010.

[Monogenic obesity in human].

Obesity is a heterogeneous pathologic condition that is driven by interactions between multiple genetic and environmental factors. The discovery of leptin has provided the useful clue to the molecular dissection of central pathways involved in the regulation of food intake and body weight. Monogenic obesity in human has been documented.

Long-term 3,5,3'-triiodothyroacetic acid therapy in a child with hyperthyroidism caused by thyroid hormone resistance: pharmacological study and therapeutic recommendations.

Background: The effectiveness of short-term 3,5,3'-triiodothyroacetic acid (TRIAC) therapy for the treatment of hyperthyroidism caused by thyroid hormone resistance (RTH) has been documented. Here, we report a 3-year course of TRIAC therapy in an RTH boy, with a quantitative evaluation of the therapeutic effects and pharmacological study of TRIAC.

Patient Findings: The gene encoding the thyroid hormone receptor beta (THRB) of the patient carries a P453T mutation.

Favorable impact of growth hormone treatment on cholesterol levels in turner syndrome.

Background: Patients with Turner syndrome (TS) are prone to having metabolic abnormalities, such as obesity, dyslipidemia, hypertension, hyperinsulinemia and type 2 diabetes mellitus, resulting in increased risks of developing atherosclerotic diseases.

Objective: To determine the effect of growth hormone (GH) therapy on serum cholesterol levels in prepubertal girls with TS enrolled in the Turner syndrome Research Collaboration (TRC) in Japan.

Patients And Methods: Eighty-one girls with TS were enrolled in the TRC, and their total cholesterol (TC) levels before GH therapy were compared with reported levels of healthy school-aged Japanese girls.

Homozygous thyroid hormone receptor β-gene mutations in resistance to thyroid hormone: three new cases and review of the literature.

Context: The most common cause of resistance to thyroid hormone (RTH) is heterozygous thyroid hormone receptor β (THRB) gene mutations. Homozygous mutations in the THRB gene are a rare event.

Objective: In this study, the clinical findings of three new patients (belonging to two families) homozygous for mutations in the THRB gene are compared to three other families in which affected individuals lack a normal TRβ.

Novel compound heterozygous mutations in the SBP2 gene: characteristic clinical manifestations and the implications of GH and triiodothyronine in longitudinal bone growth and maturation.

Objective: Mutations in the selenocysteine insertion sequence binding protein 2 gene (SECISBP2 also known as SBP2) lead to a multisystemic disorder. Our objectives are to examine the clinical manifestations of the present patient and evaluate the effects of GH and triiodothyronine (T(3)) for longitudinal bone growth and maturation.

Methods: A Japanese boy presented with unusual thyroid function tests (normal or slightly elevated TSH, low-normal or slightly decreased free T(3) (FT(3)), and elevated free thyroxine (FT(4))), short stature without GH deficiency, and delayed bone maturation.

Resistance to thyroid hormone due to a novel thyroid hormone receptor mutant in a patient with hypothyroidism secondary to lingual thyroid and functional characterization of the mutant receptor.

Background: We describe a rare case of congenital hypothyroidism and an extremely high serum thyrotropin (TSH) level caused by a combination of resistance to thyroid hormone (RTH) and a lingual thyroid. As the RTH mutant, R316C, was new, the optimum dose of levothyroxine was unclear. To aid in assessment of the therapy, we characterized the mutant R316C thyroid hormone receptor (TR) and compared it with a common mutant, R316H, using in vitro studies.

Longitudinal evaluation of patients with a homozygous R450H mutation of the TSH receptor gene.

Background/aim: The R450H mutation of the TSH receptor (TSHR) gene has been frequently observed in Japanese patients with resistance to TSH. The purpose of this study was to clarify the phenotype of patients with a homozygous R450H mutation of the TSHR gene; the mutant receptor has previously demonstrated moderately impaired function in vitro.

Methods: We performed a clinical investigation of 5 Japanese patients who had hyperthyrotropinemia as neonates, in whom a homozygous R450H mutation of the TSHR gene had been demonstrated by genetic sequencing analysis.

Molecular and clinical findings and their correlations in Silver-Russell syndrome: implications for a positive role of IGF2 in growth determination and differential imprinting regulation of the IGF2-H19 domain in bodies and placentas.

Silver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic features and is frequently caused by hypomethylation (epimutation) of the H19-DMR. Although molecular and clinical studies have extensively been performed for SRS patients themselves, such studies have not been carried out for placentas. We identified 20 epimutation-positive and 40 epimutation-negative Japanese SRS patients and obtained placental weight data from 12 epimutation-positive and ten epimutation-negative patients and paraffin-embedded placental tissues for molecular and histological examinations from three epimutation-positive and two epimutation-negative patients.