Several studies have reported an association between age at menarche and the onset of type-1 diabetes mellitus (T1DM). This review compared the age at menarche in patients who had menarche after T1DM diagnosis with that of patients who were healthy and/or had menarche before T1DM diagnosis. Searches were conducted using four databases. The outcome was the age at menarche of patients who had menarche after T1DM diagnosis and patients who were healthy and/or had menarche before T1DM diagnosis. A qualitative analysis was performed using the JBI (Joanna Briggs Institute) Critical Appraisal. Quantitative analysis of the mean differences was performed using Revman 5.4 tool. A total of 1952 studies were obtained from the initial search. The final results were 13 articles that met the inclusion criteria for the qualitative assessment and eight for the quantitative assessment. Eight studies included 1030 patients who had menarche after being diagnosed with T1DM and 1282 patients who were healthy and/or had menarche before T1DM diagnosis. The meta-analysis showed a cumulative effect on a mean difference of 0.87 (95% CI: 0.75; 0.99, p-value < 0.00001), indicating a later age at menarche in patients who had menarche after T1DM diagnosis. The age at menarche was later in patients who had menarche after T1DM diagnosis compared to healthy subjects and those who had menarche beforehand.

This study aimed to examine the clinical characteristics of young children diagnosed with maturity-onset diabetes (MODY) using urine glucose screening at schools. The study participants were 70 non-obese children who were clinically diagnosed with type 2 diabetes through urine glucose screening at schools in Tokyo between 1974 and 2020. Of these children, 55 underwent genetic testing, and 21 were finally diagnosed with MODY: MODY2 in eight, MODY3 in eight, MODY1 in four and MODY5 in one. A family history of diabetes was found in 76.2% of the patients. Fasting plasma glucose levels did not differ between the different MODY subtypes, while patients with MODY 3, 1, and 5 had significantly higher levels of glycosylated hemoglobin and 2-hour glucose in an oral glucose tolerance test than those with MODY2. In contrast, most patients exhibit mild insulin resistance and sustained β-cell function. In the initial treatment, all patients with MODY2 were well controlled with diet and exercise, whereas the majority of those with MODY3, 1, and 5 required pharmacological treatment within one month of diagnosis. In conclusion, urine glucose screening in schools appears to be one of the best opportunities for early detection of the disease and providing appropriate treatment to patients.

The objectives of this study were to (1) compare peak expiratory flow (PEF), physical activity (PA), and core performance among normal-weight, overweight, and obese adolescents and (2) explore the relationships between PEF, physical activity, core performance, and anthropometric measurements across these groups. Ninety adolescents aged 10–13 yr were categorized based on BMI: normal weight (n = 30, 5th to < 85th percentile, BMI-Z score –2 to < 1), overweight (n = 30, 85th to < 95th percentile, BMI-Z score 1 to < 2), and obese (n = 30, > 95th percentile, BMI-Z score > 2). PEF and percent-predicted values of PEF (PEF% pred) values were calculated. Waist and neck circumferences were measured. Physical activity levels were assessed using the Physical Activity Questionnaire for Older Children (PAQ-C), from which total and subscores were derived. Core performance was evaluated through modified push-up (MPU) and sit-up tests. The PEF% pred and PAQ-C scores showed no significant differences between groups (p > 0.05). However, MPU repetition rates were significantly lower in obese adolescents compared to overweight (p = 0.019) and normal-weight peers (p < 0.001). There was a significant correlation between PEF% pred and PAQ-C total scores (p = 0.014), as well as out-of-school subscores (p = 0.039) in overweight adolescents. Similarly, PEF% pred was linked to MPU repetitions in obese adolescents (p = 0.029). Obese adolescents exhibited decreased core performance relative to their overweight and normal-weight counterparts, which correlated with the PEF% pred. Physical activity was associated with PEF% pred exclusively in overweight adolescents.

Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes that presents with uncontrolled hyperglycemia during the first 6 months of life. NDM is a rare disease in which gene variants mainly cause β-cell loss or dysfunction (6q24 duplication, KCNJ11, and ABCC8). Although NDM is primarily treated through insulin therapy, it is highly challenging to manage blood glucose levels using insulin therapy during infancy. In contrast, KCNJ11 and ABCC8 mutant patients received oral sulfonylureas (SU) instead of insulin injections; however, the dose and frequency differ among individuals. Continuous glucose monitoring (CGM) is useful in patients with type 1 diabetes; but reports on patients with NDM are lacking. Herein, we report two cases of NDM with the KCNJ11 variant. We used CGM not only during insulin injection therapy but also after switching to oral SU therapy. The CGM data can also be used to determine the dose and frequency of SU. Furthermore, long-term CGM may be useful for adjusting SU dose and frequency, and maintaining good glycemic control not only during insulin injection but also during oral SU therapy.

Heavy traumatic brain injury (TBI) may lead to the manifestation of either syndrome of inappropriate secretion of antidiuretic hormones (SIADH) or central diabetes insipidus (CDI). We present a case of TBI where SIADH transformed into CDI within a remarkably short timeframe. A previously healthy 4-yr-old boy was admitted to our hospital with hyponatremia and elevated urinary sodium level on the day following a traumatic head injury. Within 150 min after initiating SIADH treatment, a significant increase in urine volume and a decrease in urinary sodium levels were observed. Therefore, the treatment plan was modified to include desmopressin. By the 5th day of admission, the urine volume gradually stabilized and normalized without the need for further desmopressin treatment. Mild TBI can give rise to various conditions that may undergo rapid changes. Closely monitoring serum and urine electrolytes, along with urine volume, is imperative for the administration of appropriate and timely treatment.

Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) is a bone dysplasia caused by a pathogenic variant of fibroblast growth factor receptor 3 (FGFR3). Pathogenic variants in FGFR3 also cause thanatophoric dysplasia (TD) and achondroplasia. Although the findings of SADDAN and TD during the fetal and neonatal periods are similar, they differ in their long-term prognoses. We conducted FGFR3 analysis in one male patient because of the difficulty in differentiating SADDAN from TD during the neonatal period. We found that the patient had a pathogenic variant, p. Lys650Met, which was similar to that previously reported in patients with SADDAN. Reports on long-term survival in patient with SADDAN are scarce, and there have been no reports of treatment with GH. We administered GH therapy for a markedly short stature. After treatment, his height increased by 4 cm each year for 4 years, the frequency of hospitalizations due to respiratory failure decreased, and the health improved. FGFR3 analysis is useful for diagnosing SADDAN during the early neonatal period. GH therapy may have contributed to the patient’s long-term survival.

Pseudohypoparathyroidism (PHP) is a rare disorder characterized by convulsions, tetany, and sensory abnormalities caused by hypocalcemia due to parathyroid hormone (PTH) resistance. Only few patients present with involuntary movements. We report the case of a 7-yr-old girl with PHP and involuntary movements triggered by running. Initially, she was suspected of having paroxysmal kinesigenic dyskinesia and was treated with carbamazepine (CBZ). Involuntary movements were reduced. However, 2 months post-treatment, she experienced convulsions during a fever. Blood tests and brain computed tomography revealed hypocalcemia, hyperphosphatemia, elevated intact PTH, and calcifications in the frontal cortex and basal ganglia. The patient showed no features of Albright’s hereditary osteodystrophy. The involuntary movements disappeared after the discontinuation of CBZ and initiation of calcium and active vitamin D preparations. Methylation-specific multiplex ligation-dependent probe amplification for the GNAS region and microsatellite analysis of chromosome 20 led to the diagnosis of PHP1B caused by epimutation. In 15 reported cases, with or without intracranial calcification, PHP-associated involuntary movements disappeared or became less severe with treatment for hypocalcemia; in eight of 11 cases, they were triggered by exercise or movement. PHP-associated hypocalcemia can trigger exercise-induced involuntary movements owing to lowered serum ionized calcium levels. In such patients, early blood tests are vital for the differential diagnosis of PHP.

Hypothalamic-pituitary Langerhans cell histiocytosis (HP-LCH) is often associated with arginine vasopressin deficiency (AVD). Patients with AVD caused by HP-LCH rarely develop an impaired osmotic threshold for thirst (OTT). Improvement in OTT among such patients has not been reported in the literature. To our knowledge, here we report the first case of AVD due to HP-LCH in which hypodipsia resolved during chemotherapy. A nine-year-old Japanese girl presented with polydipsia, polyuria, anorexia, and hypernatremia (149.8 mEq/L) and was diagnosed with AVD secondary to HP-LCH. Visual analog scale examination showed a reduced OTT following the water deprivation test. During chemotherapy for Langerhans cell histiocytosis (LCH), serum sodium concentrations became stable between 138.9 and 142.9 mEq/L under the replacement of desmopressin. Repeated visual analog scale examinations showed that she experienced a sense of thirst at a serum sodium concentration of 142.3–144.6 mEq/L, at which she did not experience any thirst prior to the initiation of chemotherapy. These data suggest that chemotherapy directly improved the OTT in our patient. Improved mechanical compression or infiltration of the hypothalamus related to OTT may lead to the recovery of the sense of thirst. This report highlights the potential role of chemotherapy for solitary HP-LCH in patients with hypodipsia and AVD.

Adipsic hypernatremia is typically caused by congenital dysplasia of the hypothalamus and pituitary or brain tumors. However, cases of adipsic hypernatremia without underlying organic abnormalities are rare, and some cases have been reported to be complicated by hypothalamic-pituitary dysfunction. The patient in this case was a 9-yr-old boy who was referred to our hospital because of hypernatremia. His growth chart revealed that he had rapidly become obese since infancy, with growth retardation since the age of seven. His hands and feet were very cold, and he had erythema on his abdomen, indicating possible autonomic dysregulation due to hypothalamic dysfunction. Several hormone load tests showed severe GH deficiency (GHD) and marked hyperprolactinemia (peak: 302.8 ng/mL). Magnetic resonance imaging revealed no organic abnormalities in the hypothalamus and pituitary gland. GH replacement therapy was initiated. Although his growth rate improved, obesity persisted. To the best of our knowledge, this is the first report of adipsic hypernatremia without organic intracranial abnormalities that was treated with GH. Moreover, the patient’s prolactin levels were higher than those reported in previous studies. In conclusion, adipsic hypernatremia requires the evaluation of pituitary function and appropriate therapeutic interventions.

Noonan syndrome is a congenital disorder characterized by distinctive facial appearance, congenital heart defects, short stature, and skeletal dysplasia. Although boys with Noonan syndrome frequently exhibit cryptorchidism, a mild form of 46,XY disorders of sex development (DSD), they barely manifest more severe genital abnormalities. Here, we report a boy with ambiguous genitalia, short stature, and non-specific dysmorphic features. He had no cardiac abnormalities or skeletal dysplasia. His score in the Noonan syndrome diagnostic criteria (36 of 157 points, 23%) was lower than the cutoff for diagnosis (50%). Whole-exome sequencing identified a de novo heterozygous variant (c.922A>G: p.Asn308Asp) in PTPN11 and a maternally inherited hemizygous variant (c.1439C>T: p.Pro480Leu) in FLNA. The PTPN11 variant was a known causative mutation for Noonan syndrome. FLNA is a causative gene for neurodevelopmental and skeletal abnormalities and has also been implicated in 46,XY DSD. The p.Pro480Leu variant of FLNA was assessed as deleterious by in silico analyses. These results provide evidence that whole-exome sequencing is a powerful tool for diagnosing patients with atypical disease manifestations. Furthermore, our data suggest a possible role of digenic mutations as phenotypic modifiers of Noonan syndrome.

Patients with diffuse congenital hyperinsulinism (CHI) refractory to drug therapy require subtotal or near-total pancreatectomy. Although almost all patients develop diabetes postoperatively, the clinical course and timing of insulin therapy remain unclear. A 7-yr-old girl presented with recurrent hypoglycemia shortly after birth and a relatively elevated insulin level, which confirmed the diagnosis of CHI. Genetic analysis revealed compound heterozygous ATP-binding cassette, Subfamily C, Member 8 pathogenic variants and diffuse CHI was suspected. Because her condition was refractory to diazoxide and octreotide, she underwent a subtotal pancreatectomy at the age of 4 mo. The drug therapy was discontinued. Although an oral glucose tolerance test at the age of 2 yr showed hyperglycemia after loading, continuous glucose monitoring (CGM) revealed that her daily glucose trends were almost within the 70–180 mg/dL range, and mild hypoglycemia appeared during the daytime. After the age of 6 yr, CGM showed an elevation in glucose trends from midnight to early morning, suggesting that insulin secretion was attenuated and hepatic glucose production was insufficiently suppressed. Insulin therapy was initiated at the age of 7 yr. These results indicate that CGM can be useful for making treatment decisions.

Carbohydrate restriction is not typically recommended for children with type 1 diabetes mellitus (T1DM) because of concerns regarding growth retardation, ketoacidosis, severe hypoglycemia, and dyslipidemia. There is no consensus regarding the effects of carbohydrate restriction on the growth of children with T1DM. However, some previously reported cases of T1DM exhibited growth retardation during carbohydrate restriction, whereas others showed no obvious impairment. A female child with T1DM exhibited severe height growth velocity impairment during carbohydrate restriction in early childhood. Her height standard deviation score (SDS) was 1.12 at the initial T1DM diagnosis (2 yr and 11 mo of age) and –1.33 at 4 yr and 8 mo of age. Her height velocity was only 1.7 cm/yr (SDS –7.02). Discontinuing carbohydrate restriction substantially improved her height growth velocity. Implementing a carbohydrate-restricted diet in children with T1DM can negatively affect height growth velocity.

The most common cause of persistent hypoglycemia in newborns and children is congenital hyperinsulinism (CHI). Remarkable advancements in diagnostic tools and treatments, including novel imaging and genetic techniques, and continuous subcutaneous octreotide administration, have improved the prognosis of diazoxide-unresponsive CHI; however, in clinical practice, some issues remain. Here, we report a case series consisting of four adenosine triphosphate-sensitive potassium-associated CHI cases, discuss the practical use of new international guidelines published in 2023, and suggest clinical issues associated with CHI management. Based on the clinical experience of two diffuse and two focal CHI cases, we employed an updated treatment strategy, including genetic diagnosis to determine treatment plans, careful catheter management, switching from octreotide to long-acting somatostatin, effective utilization of a continuous glucose monitoring (CGM) device, measures for feeding problems, and individualized and systematic developmental follow-up. Particularly, our cases suggest a safe method of switching from octreotide to lanreotide, elucidate the efficacy of home-based CGM monitoring, and indicate need for personalized support for feeding problems. Severe CHI is a rare and challenging disorder; thus, further accumulation of experience according to new treatment strategies is essential in generating high-quality evidence for the development and approval of new treatment options.