Carney Complex (CNC) is a rare genetic disorder characterized by multiple endocrine and nonendocrine neoplasms, primarily driven by mutations in the PRKAR1A gene. This study explores the clinical heterogeneity in CNC patients, with a focus on adrenal and extra adrenal involvement and its impact on patient outcomes. We present three pediatric cases with unique clinical manifestations. Case 1: A 12-year-old female with ACTH-independent cyclic Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). The patient's condition progressed, leading to complications such as obesity, depression, and short stature, ultimately requiring bilateral adrenalectomy. Case 2: A 9-year-old male presented with an intranasal osteochondromyxoma and a large cell calcifying sertoli cell tumor. In the followup he developed hypocortisolism secondary to ACTH deficiency, with further complications including central precocious puberty and a growth hormone-secreting pituitary adenoma. Case 3: A 12-year-old female with adrenal insufficiency due to ACTH deficiency, complicated by a pituitary adenoma and a recurrent cardiac myxoma. Over time, the patient developed ACTH-independent Cushing syndrome secondary to PPNAD, necessitating bilateral adrenalectomy. Multiple fusiform aneurysms were also discovered after the recurrence of atrial myxoma. All cases highlight the absence of a consistent genotype-phenotype correlation in CNC, emphasizing the need for individualized management strategies. The findings underscore the complexity of diagnosing and treating CNC, particularly in pediatric populations, and call for further research into the underlying molecular mechanisms to develop more targeted therapies.

Central precocious puberty (CPP) can reduce adult height. Studies comparing the efficacy of gonadotropin-releasing hormone analogue (GnRHa) monotherapy with combination therapies show inconsistency. This work aims to synthesize evidence comparing the effects of GnRHa monotherapy and combination therapies on height-related outcomes in children with CPP. Data sources included PubMed, EMBASE, Cochrane Library, Wanfang Data, and CNKI through December 31, 2024. Study selection included randomized controlled trials (RCTs) and cohort studies involving children aged 12 years or younger with CPP or early puberty, reporting height-related outcomes and a follow-up of 6 months or more. Data were pooled using common- or random-effects models and reported as mean differences (MDs) with 95% CIs for primary outcomes, including height gain (adult height minus pretreatment predicted adult height [PAH]), PAH change (posttreatment PAH minus pretreatment PAH), and growth velocity (GV) in children with CPP. A total of 70 studies (30 RCTs and 40 cohort studies; 5266 children) were included. Growth hormone (GH) combination therapy significantly improved PAH change (MD, 3.48 cm; 95% CI, 2.98-3.98) and GV (MD, 1.82 cm/y; 95% CI, 1.32-2.31) in RCTs, and height gain (MD, 3.81 cm; 95% CI, 2.77-4.84) and PAH change (MD, 3.06 cm; 95% CI, 2.26-3.86) in cohort studies, compared with GnRHa monotherapy. However, high heterogeneity remains across outcomes, even after subgroup analysis of treatment duration and GH dose, which limits the certainty of these findings. Stanozolol, oxandrolone, and estrogen showed improved growth outcomes, although evidence was limited. Longer treatment durations and higher GH doses were associated with greater benefits. GH combination therapy enhances growth outcomes in children with CPP compared to GnRHa alone. Stanozolol, oxandrolone, and estrogen show promise but require further research. Personalized combination regimens and additional long-term RCTs are needed, particularly involving male patients and non-GH adjunctive therapies.

To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and central precocious puberty (CPP) in children, with emphasis on sex-specific threshold effects and mediation pathways. This cross-sectional study enrolled 494 CPP patients (female: 413; male: 81) and 2,259 age-matched healthy controls who underwent ​liquid chromatography-tandem mass spectrometry (LC-MS/MS) based 25(OH)D quantification, Tanner-Whitehouse 3 bone age assessment, and hormonal profiling. Dose-response relationships were analyzed via restricted cubic splines (RCS), and causal mediation analysis with 1,000 bootstrap resamples were quantified using structural equation models. CPP patients exhibited significantly lower 25(OH)D levels than controls (median (IQR): females, 20.00 (14.00-24.20) vs. 23.40 (18.10-29.22) ng/mL, P < 0.001; males, 21.60 (16.00-27.10) vs. 23.30 (18.30-28.83) ng/mL, P = 0.033), with higher deficiency rates (females: 49.6% vs. 33.0%; males: 43.2% vs. 32.8%). RCS analysis revealed inverse 25(OH)D-CPP associations, with threshold concentrations at 35.4 ng/mL (females) and 19.5 ng/mL (males).​ Each 1 ng/mL increment in serum 25(OH)D was associated with 3.6% reduced risk of advanced pubic hair maturation (adjusted OR = 0.964, P = 0.009). Sex-stratified logistic regression showed elevated CPP risks in vitamin D-insufficient/deficient groups versus sufficient counterparts: females (OR = 2.13, P = 0.037; OR = 2.26, P = 0.030) and males (OR = 3.89, P = 0.059; OR = 4.71, P = 0.034). Mediation analysis identified bone age acceleration (64.6% mediation) and gonadotropin activation (14.6%) dominated pathways in females. Vitamin D demonstrated sex-dimorphic associations with CPP risk, requiring higher protective thresholds in females. Bone age acceleration and gonadotropin activation emerged as primary mediators in females. These findings advocated sex-specific vitamin D supplementation strategies for CPP prevention.

To explore the clinical characteristics of primary intracranial germ cell tumors (iGCT) and analyze the risk factors for the occurrence of neuroendocrine dysfunction. Methods: A case series study was conducted. The data of 130 children diagnosed with iGCT who were admitted to the Department of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, from February 2021 to December 2023 was collected. The clinical characteristics of iGCT were summarized, including general information, clinical manifestations, imaging findings, laboratory tests and outcomes. Children were divided into groups aged 0-9 and 10-18 years, and divided into group non-neuroendocrine dysfunction, group partial neuroendocrine dysfunction and group combined hypothalamic and pituitary-target gland axis dysfunction. Multivariate Logistic regression was employed for statistical analysis to identify risk factors for neuroendocrine dysfunction in iGCT children. Results: A total of 130 iGCT children were included, with an age of (10±3) years, 87 males and 43 females. Among them, 82 children (63.1%) had germinoma and 48 children (36.9%) had non-germinomatous germ cell tumors (NGGCT). One hundred and ten children (84.6%) had single lesions, including 47 cases in the sellar region, 29 cases in the pineal region and 34 cases in the basal ganglia region. Multi-leisions presented in the 20 children (15.4%), with 10 cases in the sellar+pineal region, 6 cases in the sellar+basal ganglia region, 3 cases in the pineal+ganglia region and 1 case in the sellar+pineal+basal ganglia region. Dissemination was presented to 26 children (20.0%). Initial clinical manifestations presented with symptoms of cranial hypertension like headache and vomiting in 75 cases, vision changes in 28 cases, limb movement disorders in 42 cases, diabetes insipidus in 67 cases, precocious puberty in 23 cases, growth retardation in 22 cases and delayed puberty in 2 cases. Among the 72 children aged 0-9 years, 37 cases (51.4%) had germinoma and 35 cases (48.6%) had NGGCT, while among the 58 children aged 10-18 years, 45 cases (77.6%) had germinoma and 13 cases (22.4%) had NGGCT. Non neuroendocrine dysfunction group included 39 children, partial neuroendocrine dysfunction group 54 children, and combined hypothalamic and pituitary-target gland axis dysfunction group 37 children. Univariate analysis showed statistical difference in gender, disease duration, tumor location, and serum human chorionic gonadotropin level among the 3 groups (all P<0.05). Multivariate Logistic regression analysis revealed that girl (OR=5.29, 95%CI 1.54-18.16) and long disease duration (OR=1.07, 95%CI 1.01-1.14) were risk factors for neuroendocrine dysfunction in iGCT patients (both P<0.05). Conclusions: iGCT occurs in children of all ages, with a higher incidence in males. The proportions of germinoma and NGGCT are similar in children aged 0-9 years, while germinoma is more common in patients aged 10-18 years. The clinical symptoms are atypical and diverse. Female gender and longer disease duration demonstrate the presence of neuroendocrine dysfunction in iGCT. 目的： 探讨儿童原发性中枢神经系统生殖细胞肿瘤（iGCT）的临床特征，并分析其发生神经内分泌学功能障碍的危险因素。 方法： 病例系列研究。收集2021年2月至2023年12月于首都医科大学附属北京天坛医院儿科住院的130例iGCT患儿的病例资料，包括一般资料、临床表现、头颅影像资料、内分泌学相关检查及预后情况等。根据年龄分为0~9岁和10~18岁组。根据患儿神经内分泌功能水平分为未合并神经内分泌功能障碍组、仅下丘脑或垂体功能减低组和下丘脑及垂体功能均减低组3组。总结iGCT患儿临床特征，并通过Logistic回归模型分析其发生神经内分泌功能障碍的危险因素。 结果： 130例iGCT患儿中男87例、女43例，发病年龄（10±3）岁。82例（63.1%）为生殖细胞瘤，48例（36.9%）为非生殖细胞瘤性生殖细胞肿瘤（NGGCT）。110例（84.6%）为单一病灶，其中鞍区47例、松果体区29例、基底节区34例；20例（15.4%）为多病灶，其中鞍区+松果体10例、鞍区+基底节6例、松果体+基底节3例、鞍区+松果体+基底节1例。26例（20.0%）存在脑室或脊髓播散。首诊头痛、呕吐等颅高压症状75例，视力下降、视野缺损28例，肢体运动功能障碍42例，有多饮多尿表现67例，性早熟23例，生长发育迟缓22例，性发育延迟表现2例。72例0~9岁患儿中生殖细胞瘤37例（51.4%）、NGGCT 35例（48.6%）。58例10~18岁患儿中生殖细胞瘤45例（77.6%）、NGGCT 13例（22.4%）。未合并神经内分泌功能障碍组39例，仅下丘脑或垂体功能减低组54例，下丘脑及垂体功能均减低组37例，3组患儿的性别、病程、原发肿瘤部位及血清人绒毛膜促性腺激素水平差异均有统计学意义（均P<0.05）。多因素Logistic回归分析结果表明女性（OR=5.29，95%CI 1.54~18.16）及长病程（OR=1.07，95%CI 1.01~1.14）是iGCT患儿合并神经内分泌功能障碍的危险因素（均P<0.05）。 结论： iGCT男性好发，可发生于儿童各年龄阶段，0~9岁儿童生殖细胞瘤与NGGCT比例相近，10~18岁生殖细胞瘤比例高。iGCT临床症状不典型且多样，女性、长病程是影响iGCT是否合并神经内分泌功能障碍的重要因素。.

This study utilized the FDA Adverse Event Reporting System (FAERS) to assess signals of adverse events (AEs) associated with cinacalcet, aiming to enhance its safe and rational clinical application. Adverse event reports related to cinacalcet were extracted from the FAERS database from the first quarter of 2004 to the first quarter of 2025. The AE reports were categorized by Preferred Terms (PTs) and System Organ Classes (SOCs), and risk signals were analyzed using disproportionality analysis. Among 30,540 AE reports where cinacalcet was the primary suspect drug, females exhibited a higher reporting frequency than males (47.30% vs. 39.80%). The highest proportion of reports was observed in the 60-74 age group (23.85%). Most AEs predominantly occurred within <7 days (11.14%) or ≥60 days (26.35%) of drug administration. A total of 78 significant PT signals were detected, including known AEs such as nausea, vomiting, loss of appetite, abdominal discomfort, hypocalcemia and epigastric pain, aligning with the drug's prescribing information. Additionally, several AEs previously undocumented in the drug's specifications were observed, including precocious puberty, parathyroid hemorrhage, hypoproteinemia, pancreatic atrophy, monocytopenia, cardiac death and arrhythmia. Patient evaluation should be conducted prior to the clinical use of cinacalcet, particularly for individuals with heart failure, hepatic or renal insufficiency, and hypocalcemia. Close monitoring of electrolytes and vigilance for gastrointestinal, cardiovascular, and endocrine-related AEs are recommended. Prompt interventions should be implemented in cases of adverse reactions or disease progression to prevent serious complications or deterioration.