Serum kisspeptin levels mainly depend on ovarian expression of Kiss1 mRNA in female rats.

The hypothalamic kisspeptin/KISS1 receptor system is essential for puberty onset and reproductive development. Although serum kisspeptin might be associated with puberty, its levels, according to developmental stage, and its origin still remain unclear. This study evaluated the changes in serum kisspeptin levels during puberty and the corresponding Kiss1 mRNA and protein expression in various organs of female rats to identify the source of serum kisspeptin. Tissues from several organs, including the ovaries and anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC) in the hypothalamus, were obtained for assessing Kiss1 mRNA and protein expressions. Serum kisspeptin levels progressively increased with developmental stages until the peripubertal stage. The ovaries showed the highest Kiss1 expression among the organs examined. Next, we explored the changes in serum kisspeptin levels and hypothalamic Kiss1 expression in ovariectomized and estradiol-treated ovariectomized rats. Serum kisspeptin levels decreased regardless of estradiol treatment; Kiss1 expression was enhanced by ovariectomy and estradiol treatment in the ARC, while it was decreased by ovariectomy and enhanced by estradiol in the AVPV, suggesting that serum kisspeptin may be associated with pubertal development and mainly depended on ovarian Kiss1 expression. Thus, serum kisspeptin levels are associated with puberty and may serve as a downstream marker of ovarian reproductive function.

Management of Central Precocious Puberty in Children with Hypothalamic Hamartoma.

Hypothalamic hamartoma (HH) is a rare, congenital, and benign lesion of the tuber cinereum, typically presenting with central precocious puberty (CPP), gelastic seizure, and developmental delay. This study aimed to investigate CPP in HH patients and compare clinical features between before and after gonadotropin-releasing hormone (GnRH) agonist treatment. A total of 30 HH patients under 18 years of age who visited Severance Children's Hospital between January 2005 and May 2020 were retrospectively reviewed. Fourteen patients were male (46.7%) and sixteen (53.3%) were female, with a mean age at diagnosis was4.2 ± 2.9 years. During follow-up, 24 patients (80.0%) were diagnosed with CPP, 15 patients (50.0%) had gelastic seizure, and 13 patients (43.3%) had developmental delay. The gelastic seizure was significantly associated with sessile type HH rather than pedunculated type HH (85.7% vs. 18.8%, p = 0.001). After GnRH agonist treatment, discrepancies between bone age and chronological age decreased (3.3 ± 1.3 years to 2.0 ± 1.7 years, p = 0.002). Additionally, height standard deviation score for bone age was increased, and predicted adult height increased significantly in females, while males showed an increasing trend. Clinical symptoms of HH were closely associated with the location of HH, and GnRH agonist treatment was safe and effective in the management of CPP caused by HH.

Association of Vitamin D Status and Physical Activity with Lipid Profile in Korean Children and Adolescents: A Population-Based Study.

Dyslipidemia is one of the important influencing factors of cardiovascular health in the youth, and thus, assessment of its etiology is important. We aimed to investigate the association of dyslipidemia with vitamin D and physical activity in Korean children and adolescents. Data of 3183 subjects aged 12-18 years in the Korea National Health and Nutrition Examination Survey were analyzed. Participants were divided into subgroups according to sex, body mass index, 25-hydroxyvitamin D levels, and lipid profile. The mean 25-hydroxyvitamin D level was 16.15 ng/mL, which was below normal. In total, 79.3% of the subjects had vitamin D deficiency. Females had lower vitamin D levels and a higher incidence of dyslipidemia compared to males. Vitamin D deficiency was significantly associated with high density lipoprotein cholesterol (HDL-C) levels. The low HDL-C group consisted of a higher proportion of subjects with vitamin D deficiency and low physical activity. This study suggests that vitamin D deficiency is prevalent in Korean children and adolescents. Vitamin D deficiency and low physical activity are related with low HDL-C levels. Maintaining sufficient vitamin D levels and physical activity may help prevent dyslipidemia.

Cushing syndrome with acute kidney injury due to ureteral stones in a 6-year-old boy.

Cushing syndrome (CS) is rare in children. The clinical presentation of CS varies according to extent and duration of glucocorticoid excess, and urolithiasis is a common complication. We report the first case of a patient with CS associated with acute kidney injury (AKI) due to urolithiasis. A 6-year-old boy presented to the Emergency Department with seizure. On physical examination, he had clinical features of CS and high blood pressure. Brain computed tomography (CT) suggested posterior reversible encephalopathy syndrome due to hypertension. On evaluation of hypertension, laboratory tests suggested adrenocortical tumor, but abdominal CT suggested pheochromocytoma. During further evaluation, his condition deteriorated with AKI due to bilateral ureteral stones, for which the patient underwent continuous renal replacement therapy in the intensive care unit. After controlling hypercortisolism with etomidate and performing ureteral stent indwelling, an adrenal mass was resected and histologically confirmed as an adrenocortical adenoma. We review the clinical manifestations, diagnosis, and management of CS associated with urolithiasis and AKI. Early recognition and careful monitoring of urolithiasis in CS patients are important to avoid severe complications of urolithiasis.

A case of primary hyperparathyroidism due to an intrathymic ectopic parathyroid adenoma in a 15-year-old boy.

Hypercalcemia due to primary hyperparathyroidism (PHPT) is uncommon in children. PHPT is typically caused by a single parathyroid adenoma. Ectopic parathyroid adenomas account for 6%-16% of all parathyroid adenomas and are rare in children but should be considered in cases that present with hypercalcemia. We report the case of a 15-year-old boy with PHPT due to an intrathymic ectopic parathyroid adenoma. Neck ultrasonography and Tc-99m-sestamibi (MIBI) scanning with single-photon emission computed tomography/computed tomography (SPECT/CT) revealed ectopic parathyroid adenoma in the thymus. Video-assisted thoracoscopic surgery was performed to remove the ectopic parathyroid adenoma. Pathology showed intrathymic ectopic parathyroid adenoma. After surgery, the patient's serum calcium level immediately normalized. Intact parathyroid hormone (iPTH) and alkaline phosphatase levels returned to normal ranges within 3 months. Delayed diagnosis of PHPT can cause end-organ damage; a timely diagnosis is especially critical to preserve bone and renal function. If ectopic parathyroid adenomas are well localized in preoperative imaging evaluation and intraoperative iPTH level decreases after resection, ectopic parathyroidectomy without bilateral neck exploration may be performed to avoid unnecessary morbidity.

Adolescents with thyroid nodules: retrospective analysis of factors predicting malignancy.

Thyroid nodules are less common in children than in adults. However, pediatric thyroid nodules have a higher rate of malignancy compared to those in adults, and increased risk of metastasis and recurrence. In the present study, we analyzed the clinical features as well as laboratory and thyroid ultrasound (US) findings of children and adolescents with thyroid nodules to identify predictive factors of thyroid cancer. We retrospectively analyzed 275 patients with thyroid nodules under 18 years of age who visited Severance Children's Hospital between January 2005 and May 2017. Among them, 141 patients who underwent ultrasonography-guided fine needle aspiration biopsy (FNAB), and four patients without FNAB who underwent surgical resection, were included in this study. The remaining 125 patients without FNAB and five patients with follow-up loss after FNAB were excluded. Clinical, laboratory, and US data were evaluated in 145 patients to establish the potential predictive factors of thyroid cancer. Thyroid malignancies were observed in 101 patients. Grade 2 goiters were seen more often in benign nodule group. Hypoechoic nodules, nodules with microcalcifications, abnormal lymph nodes, and irregular margins were findings significantly associated with thyroid cancer. The findings of hypoechoic nodule, nodule with microcalcifications, and abnormal lymph nodes showed statistical significance in predicting thyroid cancer.Conclusion: Hypoechoic nodules, nodules with microcalcifications, and abnormal lymph nodes are predictive factors for thyroid cancer in children. Therefore, further diagnostic evaluations, including FNAB, should be considered in patients with such findings.What is Known:• Thyroid nodules are less common in children than in adults, but pediatric thyroid nodules have a higher rate of malignancy, and also have increased risk of metastasis and recurrence.• Research on ways to predict thyroid cancer have mostly been accomplished in adult patients, and the application of risk stratification system has not been fully satisfactory in children, which requires further studies in pediatric thyroid nodules.What is New:• Hypoechoic nodules, nodules with microcalcifications, and abnormal lymph nodes are predictive factors for thyroid cancer in Korean children.

Regulation of synaptic Rac1 activity, long-term potentiation maintenance, and learning and memory by BCR and ABR Rac GTPase-activating proteins.

Rho family small GTPases are important regulators of neuronal development. Defective Rho regulation causes nervous system dysfunctions including mental retardation and Alzheimer's disease. Rac1, a member of the Rho family, regulates dendritic spines and excitatory synapses, but relatively little is known about how synaptic Rac1 is negatively regulated. Breakpoint cluster region (BCR) is a Rac GTPase-activating protein known to form a fusion protein with the c-Abl tyrosine kinase in Philadelphia chromosome-positive chronic myelogenous leukemia. Despite the fact that BCR mRNAs are abundantly expressed in the brain, the neural functions of BCR protein have remained obscure. We report here that BCR and its close relative active BCR-related (ABR) localize at excitatory synapses and directly interact with PSD-95, an abundant postsynaptic scaffolding protein. Mice deficient for BCR or ABR show enhanced basal Rac1 activity but only a small increase in spine density. Importantly, mice lacking BCR or ABR exhibit a marked decrease in the maintenance, but not induction, of long-term potentiation, and show impaired spatial and object recognition memory. These results suggest that BCR and ABR have novel roles in the regulation of synaptic Rac1 signaling, synaptic plasticity, and learning and memory, and that excessive Rac1 activity negatively affects synaptic and cognitive functions.