Journal of Clinical Research in Pediatric Endocrinology最新文献

Graves' disease (GD) is the leading cause of childhood hyperthyroidism, resulting from excessive thyroid hormone production. In some cases, it can cause alterations in mineral homeostasis, including calcium, phosphorus, and magnesium, which are often overlooked. Hyperthyroidism increases osteoclastic bone resorption, and mild to moderate hypercalcemia occurs in approximately 20-50% of affected patients, typically resolving with appropriate therapy. Although uncommon, symptomatic hypercalcemia in the setting of GD requires immediate evaluation and management. An 8-year-11-month-old girl was brought to the clinic, presenting with recurrent nausea, vomiting, and fatigue. She had multiple hospital admissions over the previous seven months due to drug reaction with eosinophilia and systemic symptoms (DRESS) and acute inflammatory demyelinating polyneuropathy (AIDP). Blood tests showed hyperthyroidism, marked hypercalcemia and hypomagnesemia. She showed tachycardia and weight loss. Based on the Burch-Wartofsky Point Scale, she was diagnosed with impending thyroid storm. Treatment was initiated with intravenous hydration, furosemide, dexamethasone, along with oral methimazole and propranolol. Within a few days, her general condition improved, her heart rate decreased, and gastrointestinal symptoms resolved and serum calcium levels normalized. Follow-up tests showed stable thyroid function and normal calcium levels. This case highlights that symptomatic hypercalcemia associated with GD and suggests that hyperthyroidism should be considered in the differential diagnosis of unexplained persistent nausea and vomiting.

Background: Data on the impact of aromatase inhibitor (AI) therapy on final or near-final adult height (FNFH) in males with short stature is limited. This study investigates whether AI therapy improves FNFH in males with advanced or rapidly advancing bone age (ABA) and compromised predicted adult height.

Methods: Data were collected through retrospective chart review. Descriptive statistics were used to characterize the study cohort. Fisher's exact test and the Wilcoxon rank-sum test were used to compare outcomes.

Results: Of 72 patients reviewed, 59 (82%) received anastrozole, 11 (15%) received letrozole, and 2 (2.8%) switched from anastrozole to letrozole. Median treatment duration was 25 months (IQR: 18-32). Most common diagnoses included growth hormone deficiency (31%), early puberty and premature adrenarche (18%), idiopathic short stature (15%), overweight/obesity (14%). Growth hormone (GH) was used in 66%. The overall median gain in height (FNFH minus initial predicted height) was 1.2 cm (IQR: -1.9-4.2). Letrozole-treated patients showed a greater median height gain (4.2 cm, IQR: 0.6-13) compared to the anastrozole group (0.8 cm, IQR: -2.6-3.5; p=0.013) and reached a FNFH closer to mid-parental height (MPH) (p=0.031). Longer duration of treatment, therapy at earlier puberty stages, and GH therapy were all significantly associated with greater gain in height (p-values: 0.005, 0.012, and 0.022).

Conclusion: Our findings suggest that letrozole is associated with greater gain in height compared to anastrozole in males with ABA. Other factors associated with greater gains are treatment at earlier stages of puberty, longer duration of treatment and concurrent GH therapy.

Patients diagnosed with craniopharyngioma often experience rapid and pronounced weight gain that can progress to severe hypothalamic obesity. This phenomenon is predominantly attributed to disruption of critical hypothalamic regulatory circuits, caused either by direct tumor infiltration or by treatment-related injury. Hypothalamic obesity is best conceptualized within the broader framework of hypothalamic syndrome, a complex clinical disorder encompassing multiple neuroendocrine deficits, impairments in circadian homeostasis, dysregulation of hunger, satiety, and thirst mechanisms, disturbances in thermoregulatory control, and a wide range of cognitive, sleep-related, and psychosocial abnormalities. Hypothalamic syndrome may also develop secondary to nonmalignant parasellar pathologies, including germ cell tumors, gliomas, Rathke's cleft cyst, and Langerhans cell histiocytosis, as well as traumatic hypothalamic injury following traumatic brain insult. Long-term prognosis is frequently poor, driven by elevated risks of metabolic syndrome, cardiovascular disease, diminished health-related quality of life, and increased rates of premature mortality. Management remains particularly challenging. Recently, a personalized and risk-stratified therapeutic framework has been proposed to guide clinical decision-making and optimize outcomes. Several pharmacologic interventions, such as centrally acting stimulants, glucagon-like peptide-1 receptor agonists, and the melanocortin-4 receptor agonist setmelanotide, have demonstrated potential in promoting weight reduction. Bariatric surgery may also yield clinical benefit; however, the use of irreversible procedures in pediatric populations presents substantial ethical and legal challenges. There remains an urgent need for therapeutic strategies that emphasize preservation of hypothalamic structure and function, alongside continued research into targeted and emerging interventions for more effective management of hypothalamic syndrome.

Introduction: HbA1c remains the standard biomarker for long-term glycemic control, but it lacks precision in capturing short-term glucose variability and acute excursions. This limitation is especially relevant in children with type 1 diabetes (T1D) who use continuous glucose monitoring systems (CGMS) and automated insulin delivery (AID) systems.

Aim: To evaluate the temporal relationship between HbA1c and the glucose management indicator (GMI), and their associations with CGMS-derived glycemic parameters over 12-weekperiod in children and adolescents with T1D using AIDsystems.

Material-methods: In this retrospective cross-sectional observational study,81 children and adolescents with T1D on the Medtronic MiniMed 780G™ system were included.CGMS data covering 12weeks prior to HbA1c measurement were analyzed in two-week intervals.Correlations between HbA1c,GMI, andCGMS metrics were assessed.

Results: HbA1c was positively correlated with all GMI values,with the strongest correlation observed for the last six-weekGMI (r=0.728,p<0.001). The mean difference between HbA1c and last12-weekGMI was0.57% (95%CI:-1.13to 2.27).GMI demonstrated stronger correlations than HbA1c with time in range (TIR),time above range(TAR),and time below range(TBR).Notably, in individuals with similar TIR (~70%), HbA1c values varied widely (6.6-9.6% /48-81mmol/mol),while GMI remained stable (6.8-7.1%).

Discussion: HbA1c exhibited the strongest correlation with GMI calculated over the last six weeks,suggesting that it primarily reflects recent glycemic trends rather than cumulative exposure.GMI also showed closer alignment with CGMS-derived indices such as TIR,TAR,and TBR,indicating its enhanced sensitivity in capturing day-to-day glycemic variability,especially in suboptimally controlled individuals.

Conclusion: Given its temporal limitations,HbA1c may not reliably capture 12-weekglycemic patterns in pediatric AIDusers.GMI, as CGMS-derived metric,offers a more consistent and clinically actionable estimate of glycemic control,supporting its integration into routine care for children with T1D.

Objective: This study aimed to investigate the relationship between leucine-rich alpha-2-glycoprotein 1 (LRG1), hepatosteatosis, and insulin resistance (IR) in obese children, and to evaluate the potential role of LRG1 as a biomarker in these metabolic conditions.

Methods: A total of 172 children (100 obese, 72 non-obese) were enrolled. Obese subjects were further grouped by hepatosteatosis and IR status. Anthropometric measurements, biochemical parameters, and inflammatory markers including LRG1, adiponectin, and tumor necrosis factor-α (TNF-α) were evaluated. Associations between these markers and metabolic parameters were analyzed.

Results: Obese children had significantly higher body mass index (BMI), BMI Standard Deviation Scores (SDS), waist and upper arm circumferences, triceps skinfold (TSF) thickness, total and percentage of body fat (PBF), and elevated systolic (SBP) and diastolic blood pressure (DBP) (p<0.001). Laboratory findings revealed glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), alanine aminotransferase (ALT), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and lower high-density lipoprotein cholesterol (HDL-C) in the obese group (p<0.05). LRG1 levels did not differ by obesity or hepatosteatosis status but were significantly lower in those with IR (p=0.03). LRG1 was negatively correlated with waist circumference, DBP, insulin, HOMA-IR, TG, TC, and LDL-C, and positively with HDL-C (p<0.05). Adiponectin showed inverse correlations with waist circumference, SBP, insulin, HOMA-IR, TC, LDL-C, TG, and a positive correlation with HDL-C (p<0.05).

Conclusion: Findings suggest LRG1 may not serve as a direct biomarker for hepatosteatosis in obese children but is negatively associated with IR and dyslipidemia. These results highlight a complex role for LRG1 in obesity-related metabolic dysfunction and support further longitudinal and pathophysiological studies.

Objective: The aim of this study was to evaluate muscle mass and strength in children and adolescents with disorders of sex development (DSD) whose sex assignment was determined by a multidisciplinary team, comparing these parameters both among the DSD cases and with healthy controls, and to assess the impact of hormone replacement therapy (HRT) on these outcomes.

Methods: 78 DSD cases and 118 healthy controls were included. Gender assignment followed multidisciplinary council decisions; some DSD cases underwent gender-appropriate surgical interventions, and HRT was initiated as puberty approached. Participants were divided into four age groups (<5, 5-10, 10-15, and ≥15 years), and anthropometric measures, pubertal status, muscle mass and strength, skinfold thickness, and sex hormone profiles were assessed.

Results: Among DSD cases, 30.8% had 46,XX DSD, 53.8% had 46,XY DSD, and 15.4% had mixed gonadal dysgenesis (MGD); ambiguous genitalia was the most common referral reason, and CYP21A2 was the most frequently identified mutation. In individuals aged ≥15 years, 46,XX DSD cases, regardless of gender of rearing, had lower height standard deviation scores (SDS) than healthy peers, whereas 46,XY DSD cases raised as females had higher height SDS than other DSD subgroups (p<0.01). In Individuals aged ≥15 years, muscle strength was highest in 46,XY DSD males and healthy males (p<0.01). Participation in sports was associated with higher muscle mass in both groups (p=0.03). Muscle strength correlated positively with serum testosterone (p< 0.001, R = 0.563).

Conclusion: Chromosomal sex predominantly influenced final height, whereas muscle strength aligned with gender of rearing and testosterone levels.

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.

Introduction: Growth hormone deficiency (GHD) is a rare but important cause of short stature in children. Although GH stimulation tests remain the gold standard for diagnosis, establishing a definitive diagnosis continues to be challenging. In this study, we aimed to evaluate the diagnostic performance of the peak-to-basal ratio and difference for identifying GHD in children.

Materials-methods: We retrospectively analyzed 265 patients with short stature who were evaluated for GHD with growth hormone stimulation tests. ΔGH was defined as the difference between peak and basal GH levels. The GH ratio was calculated as the ratio of peak to basal GH levels.

Results: Data were collected from 265 patients (182 prepubertal) with a median age at presentation of 10.6 years (IQR: 6.13-12.42), of whom 46.7% were female. In total, 146 patients met the diagnostic criteria for GHD. ΔGH and GH ratio during the L-Dopa and Clonidine stimulation tests were significantly lower in the GHD group (p<0.001). A ΔGH cutoff of ≤7.08 in the clonidine test demonstrated excellent discriminative ability, with both sensitivity and specificity above 80%, and an AUC close to 0.9, suggesting that this parameter may may provide supportive diagnostic information for GHD.

Conclusion: To the best of our knowledge, ΔGH has been explored only in a limited number of studies. This study investigated diagnostic accuracy of difference (ΔGH) or ratio of peak-to-basal GH on a large cohort of children with short stature. The supportive diagnostic performance observed in our cohort suggests that ΔGH is clinically useful in routine practice.

Variants in the Col1a1 gene typically lead to a connective tissue disorder called osteogenesis imperfecta (OI), which is characterized by increased bone fragility that may be associated with blue sclera, dentinogenesis imperfecta and hearing loss. However, the coexistence of pes equinovarus and OI is rare, and to date, no genetic basis has been described. We report a female patient who was admitted with short stature, and growth hormone replacement treatment was initiated following a diagnosis of growth hormone deficiency. She also had blue sclera, a bulbous nose, flexion contractures in both knee joints, tightness of Achilles tendons and hamstrings and bilateral pes planovarus. In infancy casting had also been applied due to bilateral pes equinovarus and she had experienced one bone fracture. Whole exome sequencing revealed a heterozygous pathogenic variant (c.2956G>A) in the Col1a1 gene. Pathogenic variants in the Col1a1 gene have been associated with OI. This rare variant of the Col1a1 gene should be considered in cases presenting with both pes equinovarus and joint contractures, particularly when accompanied by signs of increased bone fragility.

Objective: To assess gender-typed preferences and gender identity in children with and without variations in sex developments (VSDs).

Methods: In this cross-sectional study, 78 children with VSDs (ages 3-12; mean age = 7 years; 55% White, non-Hispanic) recruited through specialty clinics in the United States and 78 children without VSDs (ages 3-13; mean age = 7 years; 55% White, Non-Hispanic) recruited through university-based community databases completed assessments of gender-typed toy, clothing and peer preferences, continuous and categorical measures of gender identity, and perceived similarity to boys and to girls.

Results: Generally, children with and without VSDs did not differ in their gender development on 5 of 7 measures for each gender group. Children raised as girls who had VSDs had more masculine toy preferences, t(84.89) = 3.421; p = 0.001; d = 0.698, and viewed themselves as more similar to boys, t(67.43) = 2.994; p = 0.004; d = 0.648, than comparison children raised as girls. Boys with VSDs selected more masculine toys (t(55.17) = 2.413; p = 0.019; d = 0.623), and responded in a more-masculine way on the continuous gender identity measure (t(38.40) = 2.364; p = 0.023; d = 0.621), than did boys in the community comparison sample, though these effects, unlike the effects amongst girls, were not robust against corrections for multiple comparisons.

Conclusion: During early and mid-childhood, VSDs were not strongly associated with differences in gender development. Future longitudinal research on the gender development of youth with VSDs is necessary, particularly as they mature into adolescence.