This single-center, observational, retrospective study aimed to evaluate the diagnostic accuracy of pelvic ultrasonographic parameters for detecting central precocious puberty (CPP) in a cohort of female pediatric patients undergoing gonadotropin stimulation tests. The study population consisted of 47 female patients with a suspicion of CPP. Thirty four out of 47 patients (72.34%) were subsequently diagnosed with CPP based on the current laboratory diagnostic criteria (LH peak > 5 IU/L). The ultrasonography results of 39 out of 47 patients (82.97%) were categorized as pubertal, while 31 out of 34 participants (91.17%) in the CPP group exhibited pubertal ultrasonography features. In 13 out of 47 girls (27.65%), a CPP diagnosis was ruled out; however, among these 13 patients, eight exhibited pubertal ultrasonography features suspicious of CPP. We observed a robust concordance between the GnRH test results indicative of pubertal activation and the presence of pubertal pelvic ultrasonographic features in 31 out of 34 children (91.17%). A significant correlation was found between ovarian volume and basal LH and LH/ FSH ratio, and also for basal LH, LH peak, LH/FSH ratio and peak LH/FSH ratio (p = 0.026, p = 0.011, p = 0.031, p = 0.004, respectively). Pelvic ultrasonography had a sensitivity of 91.17% and a specificity of 38.46% in differentiating CPP from premature thelarche.

Obesity is associated with mild chronic inflammation, frequently observed along with increased platelet and white blood cell (WBC) levels in adults. We aimed to clarify the relationship between peripheral blood cell count, body mass index standard deviation score (BMI-SDS), and adipocytokine levels in obese adolescents. Participants included 31 patients with obesity (age: 13.1 ± 3.1 yr) and 28 normal-weight controls (age: 13.3 ± 1.9 yr). Obesity was defined as a percentage of overweight ≥ 20%; patients with type 2 diabetes were excluded. As sex differences were observed in blood cell counts, the analysis was performed after adjusting for sex differences. The obese group has significantly higher WBC, red blood cell, and platelet counts, as well as high serum leptin levels and Homeostasis Model Assessment of insulin resistance (HOMA-IR) scores compared with those of the control group. In all participants, BMI-SDS significantly correlated with WBC and platelet counts. Platelet count correlated with serum leptin and glucose levels, whereas WBC count correlated with serum leptin, insulin, HOMA-IR, and glucose levels. Statistical analysis showed that serum leptin level significantly influenced the platelet count and HOMA-IR score affected WBC count. Increased platelet and WBC counts in adolescents with obesity may increase the risk of thrombosis.

CHARGE syndrome is a clinically heterogeneous condition that typically presents with a loss-of-function mutation in CHD7. SOX2 anophthalmia syndrome is a rare condition associated with hypogonadism and hearing loss. Herein, we describe the case of a Japanese boy presenting with a micropenis, bilateral cryptorchidism, cupped ear, right facial nerve palsy, and bilateral hearing loss, clinically meeting the diagnostic criteria for CHARGE syndrome, but with optic nerve hypoplasia, which is atypical for the syndrome. Therefore, a genetic analysis (next-generation sequencing) was performed. In addition to the missense variant p.[Arg1940Cys] in CHD7, a novel nonsense variant, p. [Tyr110*] in SOX2 was identified. Although most features, including genital abnormalities and hearing loss, were clinically compatible with CHARGE syndrome caused by a CHD7 variant, optic nerve hypoplasia may have been caused by a pathogenic SOX2 variant. Prior research has shown that SOX2 is related to the development of male genitalia and the inner ear. Therefore, the genital abnormalities and hearing loss in this patient may be attributed to both the CHD7 and SOX2 variants. Furthermore, the interactions between SOX2 and CHD7 may have affected symptoms independently or reciprocally.

SLC26A4 causes Pendred syndrome (PS) and nonsyndromic hearing loss. PS is distinguished based on perchlorate discharge test abnormality, goiter, and hypothyroidism in some patients. The pathophysiology of thyroid dysfunction in PS differs from that of autoimmune thyroid disease, in that it is considered to be caused by an iodide organification defect. It is believed that both diseases may incidentally coexist, and that SLC26A4 may play an important role in the etiology of autoimmune thyroid disease. Herein, we describe a case of a girl with hearing loss who had two pathogenic SLC26A4 variants and tested positive for thyroid peroxidase (TPO) antibody. She was diagnosed with hearing loss and vestibular aqueduct enlargement at the age of 4 yr. Deafness gene screening revealed two pathogenic SLC26A4 variants. As SLC26A4 variants can cause PS, the patient underwent thorough thyroid examination. Her thyroid gland was within the physiological range of mild enlargement. Although thyroid function test results were normal, the patient tested positive for TPO antibody. The patient was diagnosed with “suspected PS” and “suspected Hashimoto’s thyroiditis,” both of which increase the risk of developing hypothyroidism. Evaluating the comorbidity of Hashimoto’s thyroiditis with the SLC26A4 variant in terms of complications is critical.

To date, heterozygous loss-of-function variants of RFX6 have been identified in 13 families with diabetes. Here, we present initial clinical information regarding a young male with diabetes who carried a heterozygous nonsense variant of RFX6 (p.Arg377Ter) previously reported in his family with diabetes. At 11 yr and 7 mo of age, the patient experienced severe thirst and hyperglycemia (331–398 mg/dL). Laboratory tests revealed elevated levels of glycated hemoglobin (HbA1c) (47 mmol/mL, 6.5%) and the Homeostatic Model for Insulin Resistance (HOMA-IR) (3.4). Blood glucose self-monitoring demonstrated grossly normal blood glucose levels, together with occasional postprandial hyperglycemia, and a few episodes of hypoglycemia. An oral glucose tolerance test revealed mild hyperglycemia and a delayed peak insulin level. His laboratory indices improved over two years with self-control of diet and exercise. These results indicate that the initial presentation of RFX6-variant-associated diabetes includes occasional hyperglycemia and hypoglycemia in response to changes in lifestyle. The possible association between RFX6 variants and mild insulin resistance requires further validation in future studies.

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors often linked to underlying genetic variants. Genetic analysis can promote gene-adjusted, specific follow-up, and surveillance protocols for both patients and their families at risk. We report the case of a 7-yr-old boy with bilateral pheochromocytoma, which recurred a year after partial adrenalectomy. The patient’s father developed bilateral pheochromocytomas at 25 yr of age. Both individuals possessed a novel heterogeneous in-frame duplication germline variant of VHL, yet neither exhibited other clinical manifestations of von Hippel–Lindau disease (VHL). Traditionally, VHL missense mutations have been associated with a higher risk of PPGL development, whereas truncating mutations typically confer a lower risk. In-frame duplication variants are rarely observed in patients with VHL but may lead to changes in the three-dimensional structure of the translated protein, similar to truncating variants. Our analysis suggests that these in-frame duplications of amino acids in specific regions may cause pheochromocytomas in a manner similar to missense variants. Further accumulation of VHL cases with various genotypes and standardized open-access worldwide databases, including longitudinal and specific clinical data linked to genotypes, is required. It is crucial to consider genetic analyses for pediatricians who may diagnose childhood-onset PPGL.

Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) is a subtype of type 1 diabetes. Although SPIDDM is not rare among Japanese children, there are few reports on endogenous insulin secretory capacity and anti-pancreatic islet autoantibodies in pediatric SPIDDM. We followed the trends in endogenous insulin secretory capacity and anti-pancreatic islet autoantibody titers in two pediatric SPIDDM cases over several years. Case 1 developed insulin deficiency eight months after diabetes diagnosis; as her insulinoma-associated antibody test result was positive, insulin therapy was initiated. Fourteen months after the diagnosis, she tested positive for glutamic acid decarboxylase autoantibodies (GADA) and was diagnosed with SPIDDM. Case 2 was mildly positive for GADA at the onset of diabetes, but became a high titer during the course of the disease. Fourteen months after the diagnosis of diabetes, he became mildly insulin deficient, and insulin therapy was initiated. However, his insulin secretory capacity was preserved for 60 mo after the onset. SPIDDM is generally indistinguishable from type 2 diabetes at diagnosis; therefore, repeated evaluation of the insulin secretory capacity and anti-islet autoantibodies facilitates early diagnosis and appropriate treatment, especially in nonobese children with type 2 diabetes.