Clinical Pediatric Endocrinology最新文献

Differences of sex development (DSD) are congenital conditions in which chromosomal, gonadal, and anatomical sex characteristics are discordant with typical male or female development. These clinical practice guidelines provide evidence-based recommendations for the diagnosis and management of individuals with DSD across the lifespan. The guidelines were developed by a multidisciplinary committee of specialists representing pediatric endocrinology, adult endocrinology, urology, gynecology, psychiatry, and psychology. The committee employed a systematic review of the literature and used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to assess the strength of recommendations and the quality of evidence. Key areas addressed include the initial management of infants with atypical genitalia, diagnostic approaches, hormonal treatment, surgical interventions, gonadal tumor risk assessment, fertility preservation, and the transition from pediatric to adult care. The guidelines integrate international best practices with Japan's unique sociocultural, healthcare, and legal contexts for optimal DSD management and aim to improve clinical care for individuals with DSD while acknowledging the limited high-quality evidence in many aspects of DSD management.

Adipocytokines are proteins with systemic metabolic effects, and additional adipocytokines have been identified. Adipocytokines are present in the serum, and obesity-mediated inflammation can alter their expression. Breast milk also contains adipocytokines that may influence infant metabolism and growth. Nonetheless, the relationship between circulating and milk adipocytokines during maternal inflammation and their effects on infant development remain unclear. We conducted a comprehensive literature review of studies published between 2000 and 2024 in PubMed to analyze the associations between obesity-mediated inflammation and adipocytokines in maternal serum and breast milk and to explore their potential effects on infant growth and metabolic health. We focused on updated evidence for the legacy adipocytokines leptin, adiponectin, TNF-α, and IL-6 and the emerging adipocytokines chemerin, neuregulin-4, and betatrophin. The results indicated that although obesity-mediated inflammation affected circulating adipocytokines, their levels were not consistently reflected in breast milk. Leptin, chemerin, and betatrophin were more influenced by lipoinflammation than adiponectin, IL-6, and TNF-α. Neuregulin-4 was present in milk, and its serum levels decreased during gestational diabetes. Some adipocytokines were correlated with infant growth; however, the evidence remains inconclusive. Importantly, no adverse metabolic or growth outcomes were linked to changes in milk adipocytokine profiles. These findings support the promotion of breastfeeding as part of infant health strategies, even in the context of maternal lipoinflammation.

Fulminant type 1 diabetes mellitus (FT1DM) is a subtype of type 1 diabetes (T1DM) with an acute onset. There are limited reports on FT1DM in pediatric patients. Here, we report the case of a Japanese female infant with FT1DM, representing the youngest female with FT1DM documented to date. The patient was referred to our hospital at 10 mo of age. Although her laboratory findings met the diagnostic criteria for severe diabetic ketoacidosis, her HbA1c level was not excessively high. Anti-glutamic acid decarboxylase and anti-insulinoma-associated protein-2 antibodies were not detected. Test results for insulin autoantibodies were positive. The glucagon stimulation-loading test revealed a C-peptide level of < 0.6 ng/mL. At 8 yr of age, the patient was diagnosed with Graves' disease. Human leukocyte antigen typing and analysis of a single-nucleotide polymorphism (rs3782151) in CSAD/lnc-ITGB7-1 revealed that the patient was predisposed to FT1DM owing to these two factors. Her findings at the disease onset fulfilled the diagnostic criteria for FT1DM. Although rare in FT1DM, the patient developed Graves' disease, a complication commonly associated with autoimmune T1DM. Moreover, although her condition at onset and genetic predisposition were consistent with those of FT1DM, her clinical course resembled that of autoimmune T1DM.

Neonatal hyperthyroidism (NH) mostly commonly occurs in infants born to mothers with Graves' disease. NH in extremely low birth weight (ELBW) infants has been rarely described. Here, we report a case of NH in an infant born at 29 wk 6 d of gestation with a birth weight of 825 g. The mother had untreated Graves' disease during pregnancy. During the 2^nd wk of life, the infant developed persistent tachycardia (heart rate > 160 beats per min). Diagnosis of NH was made according to the results of her thyroid function: thyroid-stimulating hormone,< 0.005 mU/L (Reference range: 0.8-12.0 mU/L); free triiodothyronine, 5.1 pg/mL (Reference range: 2.3-4.2 pg/mL); free thyroxine, 38.5 pmol/L (Reference range: 10-33 pmol/L); and thyroid-stimulating hormone receptor antibody, 7.6 IU/L (Reference range: ≤ 1.22 IU/L). Carbimazole was administered. After 1 wk of treatment, levothyroxine was added due to a rapid decline in thyroid function. The treatment regimen was adjusted to achieve normal thyroid function. Her heart rate normalized with no significant hemodynamic instability or long-term complications during her hospitalization or follow-up visits. NH should be considered in ELBW infants with a maternal history of Graves' disease who present with persistent tachycardia. Monitoring thyroid function may be required more closely in ELBW infants when NH management is administered.

Growth charts are essential tools for monitoring the physical development of children. We analyzed data from a nationwide Japanese birth cohort of 98,987 participants to create eight growth charts stratified by birth weight in 500-gram increments. Infants with birth weight < 2,500 g showed significant improvements in height and weight standard deviation (SD) scores by 4 yr of age. Boys and girls weighing 500-999 g at birth had average length/height SD scores of -6.40 and -8.20, which improved to -1.26 and -1.17 by 4 yr of age, respectively. Conversely, infants with birth weight ≥ 3,500 g showed decreased height and weight SD scores by 4 yr of age. Boys and girls weighing ≥ 4,000 g had average length/height SD scores of 1.87 and 2.10 at birth, which decreased to 0.34 and 0.51 by 4 yr of age, respectively. These findings reveal distinct growth patterns for different birth weight categories, highlighting the impact of birth weight on early childhood growth trajectories. The growth charts developed here serve as a valuable tool for evaluating children born small or large. These charts enable a more accurate monitoring of children's growth and can be useful in both clinical and public health settings.

KCNJ11 is one of the major causative genes for congenital hyperinsulinism (CHI) characterized by neonatal and infantile hypoglycemia. Although one readthrough KCNJ11 variant has been identified in a patient with CHI, the pathogenicity of the substitution has yet to be confirmed. Here, we identified two heterozygous nucleotide substitutions separated by one nucleotide (c.[1170C>T;1172G>T], alternative description, c.1170_1172delinsTTT) in one allele of KCNJ11 in a neonate with CHI and his father with mild CHI-compatible features. The c.1170C>T and c.1172G>T variants were assumed to be silent p.(Ser390Ser) and readthrough p.(Ter391LeuextTer93) substitutions, respectively. These results suggest that a mutant KCNJ11 protein containing 93 additional amino acids at the C-terminus is likely to exert dominant-negative effects on the wildtype protein and that monoallelic KCNJ11 readthrough variants constitute a rare etiology of CHI.

This study compared the age at onset of puberty among boys with short stature (prepubertal height SD score (SDS) ≤ -2.0 SD) who were small-for-gestational age (SGA) and those who were appropriate-for-gestational age (AGA), as well as healthy boys from the Ogi Growth Study. The study population consisted of boys who presented with short stature between 2008 and 2023. The study included 238 boys, including 229 whose age at puberty onset was auxologically determined and nine whose physical evaluations were performed at the onset of puberty. Of them, 40 were included in the SGA group and 198 in the AGA group. The control group consisted of 227 healthy boys from the Ogi Growth Study whose puberty was auxologically determined. Prepubertal height SDS was not significantly different between the SGA and AGA groups. Age at puberty onset was significantly earlier in the SGA group (10.87 ± 0.98 yr) than in the AGA group (11.90 ± 1.06 yr). Moreover, age at puberty onset was significantly earlier in the SGA group and significantly later in the AGA group than in the control group (11.28 ± 0.95 yr). Therefore, when following children with short stature, clinicians should consider the likelihood of early puberty if they are SGA.

Allgrove syndrome (AS), an uncommon multisystem disorder, is characterized by the classic clinical triad of alacrimia, achalasia, and adrenal insufficiency, and is typically limited to glucocorticoid deficiency with preserved mineralocorticoid (MC) function. Here, we present the case of a 5-yr-old girl with alacrimia since birth, failure to thrive, and generalized hyperpigmentation for the past two years, who presented to the emergency department with an altered sensorium. Upon admission, the patient was found to have hypoglycemia and hyponatremia. After subsequent evaluation, the patient was diagnosed with phenotypically incomplete AS with mineralocorticoid insufficiency and harbored a novel homozygous mutation in exon 7 of the AAAS gene (c.618del; p.Ser207LeufsTer84). Treatment with hydrocortisone and fludrocortisone yielded remarkable outcomes. Given the variable presentations of this condition, a high index of clinical suspicion and awareness of atypical features are essential for early diagnosis and initiation of coordinated care to prevent unnecessary morbidity and mortality. When AS is suspected, molecular genetic testing should be performed to confirm the diagnosis, plan management, and provide genetic counseling.

Graves' disease (GD) is the most common cause of pediatric thyrotoxicosis; however, differentiating it from other conditions is challenging. A high free triiodothyronine-to-free thyroxine ratio (FT3/FT4) ratio has been established as an indicator of GD in adults. In this retrospective observational study, we aimed to investigate the utility of the FT3/FT4 ratio as a screening marker for pediatric GD by analyzing the medical records of 105 patients aged 1-18 years who presented with thyrotoxicosis at three hospitals in Japan. The participants were divided into a GD group (TSH receptor antibody > 2.0 IU/L and requiring antithyroid drug for at least six months; n = 70) and a non-GD group (n = 35). The median (range) of the FT3/FT4 ratio was significantly higher in the GD group than in the non-GD group (3.41 [1.90-5.22] vs. 2.92 [1.50-4.40]; p < 0.05). Receiver operating characteristic curve analysis of the FT3/FT4 ratio revealed an area under the curve of 0.693 (95% confidence interval [CI], 0.577-0.808). At the optimal cutoff value of 2.88, the FT3/FT4 ratio demonstrated a sensitivity of 0.86 (95% CI: 0.80-0.91) and a specificity of 0.51 (95% CI: 0.39-0.62) for GD screening. These findings suggest the usefulness of the FT3/FT4 ratio as a screening marker for pediatric GD.