Satoshi Narumi

Ectopic thyroid is a rare developmental anomaly. In ectopic thyroid, thyroid tissue develops outside its normal position (anterior to the trachea), and it can occur within or outside the migratory pathway of the thyroid gland primordium. Ectopic thyroid tissue located in two sites is referred to as dual ectopic thyroid. This report describes a case of transient congenital hypothyroidism (CH) who had dual ectopic thyroid glands: one located at the base of the tongue (within the migratory pathway) and the other in the left parapharyngeal space (outside the migratory pathway). A 24-year-old woman, diagnosed with CH in the neonatal period, had been treated with levothyroxine. Since levothyroxine was discontinued at the age of 7 years, her thyroid function has remained normal. At 24 years of age, she was reevaluated because of throat discomfort. Although her thyroid function remained normal, ultrasonography revealed two ectopic thyroid masses. 99mTc thyroid scintigraphy confirmed thyroid tissue in both locations. Genetic analysis did not reveal any suspicious genetic changes related to CH. Currently, she is under observation without treatment. This rare case of dual ectopic thyroid with transient CH underscores the importance of anatomical evaluation and long-term follow-up in patients with neonatal thyroid disorders.

Following the LEAP and PETIT studies demonstrating that early allergen introduction can prevent food allergies, Japan’s Ministry of Health, Labor and Welfare revised its weaning guideline in 2019. The updated guideline recommended earlier egg introduction and noted that delaying specific foods may increase allergy risk. This study examined trends in the timing of solid food introduction among Japanese infants before and after this revision. We conducted a retrospective analysis using data from the parenting application Papatto Ikuji collected between 2014 and 2023. After excluding outliers and errors, 59,433 infants were analyzed. The age at solid food introduction was examined by birth year. From 2014 to 2018, the age distribution showed two peaks at 5 and 6 months. After 2019, the 6-month peak declined, leaving a single 5-month peak by 2021. These findings suggest that national guideline revisions substantially influenced caregivers’ feeding behaviors, leading to earlier solid food introduction in Japan.

MIRAGE syndrome is a multisystemic disorder with a poor prognosis, caused by gain-of-function mutations in the SAMD9 gene. To date, no comprehensive reports on the systemic manifestations and management of MIRAGE syndrome in adult survivors. Here, we present the case of a 22-year-old man long-term survivor of MIRAGE syndrome with a wide range of clinical presentations and complications. From the neonatal period, he exhibited the core features of MIRAGE syndrome: myelodysplasia, recurrent infection, growth retardation, adrenal hypoplasia, atypical external genitalia, and enteropathy. Additionally, brain imaging at 5 years of age revealed new findings, including basal ganglia and white matter lesions, calcification, infarction, and ventricular enlargement. Subsequently, proteinuria was detected at 6 years of age, which gradually progressed to end-stage renal disease. At 21 years of age, he received a living-donor kidney transplant from his father, the first transplant reported for this syndrome. Genetic analysis identified a congenital SAMD9 mutation (p.Gln1286Lys) and three acquired reversion mutations. These revision mutations mitigated his hematologic complications but did not fully restore immune function. In addition to persistent immunological and endocrine dysfunction, the patient has developed progressive neurological and metabolic abnormalities over time. Multidisciplinary management, including prophylactic intravenous immunoglobulin therapy, renal replacement therapy and transplantation, and endocrine support, was provided and may have contributed to his long-term survival. This case highlights the evolving clinical spectrum of MIRAGE syndrome and underscores the importance of careful longitudinal monitoring for patients who survive beyond early childhood.

Head shape undergoes rapid changes during infancy, but the age-dependent changes in cranial asymmetry remain inadequately characterized. This study aims to analyze factors associated with these parameters, and to establish reference curves in Japanese infants. Two indices of head shape, the cranial vault asymmetry index (CVAI) and cranial index (CI) were collected from 127,605 Japanese infants via a smartphone app. We performed univariate and multivariate analyses to identify factors associated with CVAI and CI. Using 72,726 data derived from infants born via spontaneous vaginal delivery with normal birth weight, reference curves for CVAI and CI were constructed. CVAI exhibited a peak at 3–4 mo of age, followed by a gradual decline, whereas CI increased until approximately 6 mo of age. Boys had significantly higher CVAI than girls. Low birth weight was associated with low CI. Reference curves revealed distinct age-specific patterns, with CVAI peaking at 3–4 mo and declining thereafter, and CI increasing until around 6 mo. In conclusion, this study provides the first reference curves for CVAI and CI that can be applied for Japanese infants. The findings highlight the natural course of cranial asymmetry and proportionality, emphasizing the importance of age-specific assessment.

Children with Down syndrome (DS) have a high prevalence of thyroid dysfunction; however, age-related changes in thyroid hormone profiles remain unclear. We investigated the age-related changes in thyroid function in children with DS. We retrospectively analyzed the thyroid function test results of 762 patients with DS aged 3–14 years without known thyroid disease, and compared them with those of 764 age-matched controls with idiopathic short stature. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels and the FT3/FT4 ratio were compared between patients with DS with/without congenital heart disease (CHD) and gastrointestinal malformations. In each age group, the log-transformed TSH distribution exhibited similar standard deviation and kurtosis, but showed consistently higher mean values in patients with DS than in controls. Mean FT3 levels were slightly lower in the DS group, except at ages 11–12 years. Mean FT4 levels were slightly lower in the DS group after 9 years of age. The mean FT3/FT4 ratio was lower in the DS group at ages 3–8 years but normalized after 9 years of age. Patients with DS and CHD had higher TSH levels than those without CHD after 11 years of age, whereas FT3, FT4, and the FT3/FT4 ratio showed no significant differences. A rightward shift in serum TSH distribution was observed in patients with DS without thyroid disease, suggesting that TSH levels are generally high in patients with DS. These variations highlight the need for personalized management of thyroid function in patients with DS.

Objective: To assess the background, psychosocial, and menstrual factors associated with premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) in a community‐based cohort. Methods: A prospective cohort study was conducted using data from users of a menstrual tracking application. Participants were classified into control, PMS, or PMDD groups based on responses to the Japanese version of the premenstrual symptoms screening tool (PSST). Primary outcomes included background factors (e.g., healthcare literacy, stress coping), psychosocial measures (psychological distress, sleep quality, and work–home balance), and menstrual characteristics (average cycle length [CL], CL variability, abnormal cycle length, and menstrual symptoms). Age‐adjusted multinomial logistic regression models were used to examine associations. Results: A total of 7227 individuals were included; 23% met criteria for PMS and 10% for PMDD. Both PMS and PMDD were associated with younger age, smoking history (current and past), more adverse childhood experiences, lower healthcare literacy, and higher maladaptive coping scores. PMDD was additionally linked to being married and co‐residing with children, while PMS was associated with alcohol consumption. Both groups reported higher levels of psychological distress, poor sleep quality, and negative work–home balance. Although the prevalence of abnormal cycle length did not differ between groups, menstrual symptom burden was greater in both PMS and PMDD. Conclusion: Premenstrual disorders are associated with a wide range of sociodemographic and psychosocial difficulties. Although menstrual irregularities were similar across groups, menstrual symptom burden was markedly higher. These findings underscore the need for targeted, multidisciplinary support.

Selecting optimal therapeutic interventions for febrile urinary tract infection (f-UTI) is crucial to prevent complications such as kidney scarring. While current clinical guidelines provide risk-stratified imaging recommendations, they are largely based on Western populations and lack specific predictors for which children will ultimately require therapeutic interventions. This study aimed to establish risk stratification criteria for East Asian children with first-episode f-UTI. This retrospective single-center study analyzed patients aged 2–24 months with first-episode f-UTI. All patients underwent a standardized diagnostic and management protocol, including kidney–bladder ultrasound (KBUS) and voiding cystourethrography (VCUG), to ensure uniform evaluation. The primary outcome was “requirement for therapeutic intervention,” defined as one or more of the following: (1) urological surgery (2) antimicrobial prophylaxis (for vesicoureteral reflux grade ≥III) and (3) antimicrobial treatment for recurrent f-UTI. Multivariate logistic regression was performed to identify independent predictors associated with the interventions. A total of 216 patients were included (median age: 4 months). Overall, 59 patients required therapeutic interventions. Non- Escherichia coli infection (OR 3.3, 95% CI 1.3–8.7) and abnormal KBUS findings (OR 5.3, 95% CI 2.7–10.6) were identified as independent predictors. The sensitivity and specificity of the factors for predicting therapeutic intervention were 64.4% and 73.2%, respectively. This study identified non- E. coli infection and abnormal KBUS findings as key predictors for therapeutic interventions in East Asian children with first-episode f-UTI. These findings suggest that a more targeted approach based on these factors may optimize risk stratification and patient selection for VCUG, improving clinical decision-making.

Purpose: Nonautoimmune hypothyroidism is characterized by hypothyroidism and negative thyroid autoantibodies with limited knowledge of its clinical and genetic characteristics. The aim was to characterize the clinical and genetic features of nonautoimmune hypothyroidism. Methods: This retrospective study included 1470 treatment-naive adult hypothyroid patients (serum TSH >10 mU/L) born before 1979 and were followed up at Ito Hospital, Tokyo, Japan. Of these, 220 patients were diagnosed with idiopathic nonautoimmune hypothyroidism by thyroid autoantibody measurements. Sequencing of 13 genes associated with nonautoimmune hypothyroidism was performed of 101 of the 220 patients. Clinical characteristics, including thyroid function and morphology, were systematically evaluated. Results: The proportion of idiopathic nonautoimmune hypothyroidism among the 1470 patients with treatment-naive nontransient hypothyroidism was 15.0%. Idiopathic nonautoimmune hypothyroidism patients had lower serum TSH (17.0 vs 28.3 mU/L; P < .001), higher serum fT4 (11.5 vs 8.9 pmol/L; P < .001), and a smaller thyroid volume (13.4 vs 24.9 g; P < .001) than autoimmune hypothyroidism patients. Genetic analysis showed that 5.0% of the analyzed idiopathic nonautoimmune hypothyroidism patients had a Mendelian disorder, with PAX8 being the most commonly affected gene. An additional 19% of the analyzed patients carried monoallelic variants in hypothyroidism-associated genes, such as DUOX2, DUOXA2, SLC26A4, TG, TPO, and TSHR, that cause autosomal recessive genetic defects. Conclusion: In patients with treatment-naive adult nonautoimmune hypothyroidism, thyroid dysfunction was milder and thyroid volume was smaller than in patients with autoimmune hypothyroidism. Mendelian forms were rare, but the unexpectedly high frequency of monoallelic variant carriers suggests that these variants may confer genetic risk for nonautoimmune hypothyroidism.