Rare endocrine diseases are complex conditions that require lifelong specialized care due to their chronic nature and associated long-term complications. In Korea, a lack of nationwide data on clinical practice and outcomes has limited progress in patient care. Therefore, the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Disease (OUTSPREAD) study was initiated. This study involves 30 centers across Korea. The study aims to improve the long-term prognosis of Korean patients with rare endocrine diseases by collecting comprehensive clinical data, biospecimens, and patient-reported outcomes to identify complications and unmet needs in patient care. Patients with childhood-onset pituitary, adrenal, or gonadal disorders, such as craniopharyngioma, congenital adrenal hyperplasia (CAH), and Turner syndrome were prioritized. The planned enrollment is 1,300 patients during the first study phase (2022–2024). Clinical, biochemical, and imaging data from diagnosis, treatment, and follow-up during 1980–2023 were retrospectively reviewed. For patients who agreed to participate in the prospective cohort, clinical data and biospecimens will be prospectively collected to discover ideal biomarkers that predict the effectiveness of disease control measures and prognosis. Patient-reported outcomes, including quality of life and depression scales, will be evaluated to assess psychosocial outcomes. Additionally, a substudy on CAH patients will develop a steroid hormone profiling method using liquid chromatography-tandem mass spectrometry to improve diagnosis and monitoring of treatment outcomes. This study will address unmet clinical needs by discovering ideal biomarkers, introducing evidence-based treatment guidelines, and ultimately improving long-term outcomes in the areas of rare endocrine and metabolic diseases.

Background/Aims: Endoscopic papillectomy (EP) is increasingly used as an alternative to surgery for managing benign ampullary neoplasms. However, post-EP resection margins are often positive or indeterminate, and there is no consensus on the management of ampullary adenomas with positive or indeterminate margins after EP. This study was designed to compare the longterm outcomes between resected margin-negative (RMN) and resected margin-positive/indeterminate (RMPI) groups and to identify factors associated with clinical outcomes. Methods: This retrospective analysis included patients with ampullary adenoma without evidence of adenocarcinoma who underwent EP between 2004 and 2016. The RMN and RMPI groups were compared for recurrence rates and recurrence-free duration during a mean followup duration of 71.7±39.8 months. Factors related to clinical outcomes were identified using multivariate analysis. Results: Of the 129 patients who underwent EP, 82 were in the RMN group and 47 were in the RMPI group. The RMPI group exhibited a higher recurrence rate compared to the RMN group (14.6% vs 34.0%, p=0.019). However, the recurrence-free duration was not significantly different between the groups (34.7±32.6 months vs 36.2±27.4 months, p=0.900). Endoscopic treatment successfully managed recurrence in both groups (75% vs 75%). Submucosal injection was a significant risk factor for residual lesions (hazard ratio, 4.11; p=0.009) and recurrence (hazard ratio, 2.57; p=0.021). Conclusions Although ampullary adenomas with positive or indeterminate margins after EP showed a higher rate of recurrence at long-term follow-up, endoscopic treatment was effective with favorable long-term outcomes. Submucosal injection prior to resection was associated with increased risk of recurrence and residual lesions.

Purpose: This study aimed to identify the association between coronavirus disease 2019 (COVID-19) transmission levels and undergoing glycated hemoglobin (HbA1c) test and complication screenings among patients with diabetes mellitus. Materials and Methods: We included a total of 3601 diabetes patients’ data from the 2020 Korean Community Health Survey to analyze the extent of the HbA1c testing and fundus examination, and 3592 diabetes patients’ data to analyze kidney disease screening. COVID-19 transmission levels were classified into low transmission (Busan, Gwangju, Daejeon, Ulsan, and Sejong) and high transmission (Daegu, where the first large outbreak of COVID-19 occurred in Korea). Multiple logistic regression was used to obtain adjusted odds ratio (ORs) and 95% confidence interval (CI) to determine the association of COVID-19 transmission levels with undergoing HbA1c testing and diabetes complication screening. Results: The proportion of subjects who underwent complication screening of diabetes was lower in the high transmission region (low transmission vs. high transmission: 42.3% vs. 38.0% for fundus examination; 48.9% vs. 45.7% for kidney disease screening). A high COVID-19 transmission level was associated with decreased odds of undergoing fundus examination (OR, 0.82; 95% CI, 0.69–0.98) and kidney disease screening (OR, 0.76; 95% CI, 0.63–0.91). However, COVID-19 transmission levels were not significantly associated with undergoing HbA1c testing. Conclusion A high level of COVID-19 transmission was associated with a decrease in undergoing fundus examination and kidney disease screening. To fully realize the potential benefit of diabetes complication screenings, further effort is required to identify and address challenges to obtaining these screenings, especially in outbreak regions.

Purpose: This study aimed to identify the association between coronavirus disease 2019 (COVID-19) transmission levels and undergoing glycated hemoglobin (HbA1c) test and complication screenings among patients with diabetes mellitus. Materials and Methods: We included a total of 3601 diabetes patients’ data from the 2020 Korean Community Health Survey to analyze the extent of the HbA1c testing and fundus examination, and 3592 diabetes patients’ data to analyze kidney disease screening. COVID-19 transmission levels were classified into low transmission (Busan, Gwangju, Daejeon, Ulsan, and Sejong) and high transmission (Daegu, where the first large outbreak of COVID-19 occurred in Korea). Multiple logistic regression was used to obtain adjusted odds ratio (ORs) and 95% confidence interval (CI) to determine the association of COVID-19 transmission levels with undergoing HbA1c testing and diabetes complication screening. Results: The proportion of subjects who underwent complication screening of diabetes was lower in the high transmission region (low transmission vs. high transmission: 42.3% vs. 38.0% for fundus examination; 48.9% vs. 45.7% for kidney disease screening). A high COVID-19 transmission level was associated with decreased odds of undergoing fundus examination (OR, 0.82; 95% CI, 0.69–0.98) and kidney disease screening (OR, 0.76; 95% CI, 0.63–0.91). However, COVID-19 transmission levels were not significantly associated with undergoing HbA1c testing. Conclusion A high level of COVID-19 transmission was associated with a decrease in undergoing fundus examination and kidney disease screening. To fully realize the potential benefit of diabetes complication screenings, further effort is required to identify and address challenges to obtaining these screenings, especially in outbreak regions.

Purpose: This study aimed to identify the association between coronavirus disease 2019 (COVID-19) transmission levels and undergoing glycated hemoglobin (HbA1c) test and complication screenings among patients with diabetes mellitus. Materials and Methods: We included a total of 3601 diabetes patients’ data from the 2020 Korean Community Health Survey to analyze the extent of the HbA1c testing and fundus examination, and 3592 diabetes patients’ data to analyze kidney disease screening. COVID-19 transmission levels were classified into low transmission (Busan, Gwangju, Daejeon, Ulsan, and Sejong) and high transmission (Daegu, where the first large outbreak of COVID-19 occurred in Korea). Multiple logistic regression was used to obtain adjusted odds ratio (ORs) and 95% confidence interval (CI) to determine the association of COVID-19 transmission levels with undergoing HbA1c testing and diabetes complication screening. Results: The proportion of subjects who underwent complication screening of diabetes was lower in the high transmission region (low transmission vs. high transmission: 42.3% vs. 38.0% for fundus examination; 48.9% vs. 45.7% for kidney disease screening). A high COVID-19 transmission level was associated with decreased odds of undergoing fundus examination (OR, 0.82; 95% CI, 0.69–0.98) and kidney disease screening (OR, 0.76; 95% CI, 0.63–0.91). However, COVID-19 transmission levels were not significantly associated with undergoing HbA1c testing. Conclusion A high level of COVID-19 transmission was associated with a decrease in undergoing fundus examination and kidney disease screening. To fully realize the potential benefit of diabetes complication screenings, further effort is required to identify and address challenges to obtaining these screenings, especially in outbreak regions.

Purpose: Magnetic resonance imaging (MRI) can be used for assessing the morphology of the pituitary gland in children with short stature. The purposes of this study were: (1) to determine if pituitary volume (PV) can distinguish patients with growth hormone (GH) deficiency from those with idiopathic short stature (ISS), (2) to validate an association between PV and severity of GH deficiency, and (3) to compare PV between good and poor response groups in children with GH deficiency or ISS after 1 year of treatment. Methods: Data were collected from the medical records of 152 children with GH deficiency or ISS who underwent GH stimulation test, sella MRI, and GH treatment for at least 1 year. Estimated PVs were calculated using the formula of an ellipsoid. We compared the PVs in patients with GH deficiency with those of patients with ISS. In addition, we assessed the association between PV and severity of GH deficiency, and we assessed growth response after treatment. Results: No difference was observed in PV between patients with GH deficiency and those with ISS. The severity of the GH deficiency seemed to be associated with PV (P=0.082), and the height of the pituitary gland was associated with severity of GH deficiency (P<0.005). The PV in the good response group was less than that of the poor response group in patients with GH deficiency (P<0.005), and PV showed no association with responsiveness to GH treatment in patients with ISS (P=0.073). Conclusion The measurement of PV cannot be used for differential diagnosis between GH deficiency and ISS. In patients with GH deficiency, PV tended to be smaller as the severity of GH deficiency increased, but the difference was not significant. PV may be a good response predictor for GH treatment. Further studies, including a radiomics-based approach, will be helpful in elucidating the clinical implications of pituitary morphology in patients with short stature.

Purpose: Glycosylated hemoglobin (HbA1c) is commonly used as a monitoring tool in diabetes. Due to the potential influence of insulin resistance (IR), HbA1c level may fluctuate over a person's lifetime. This study explores the long-term tracking of HbA1c level in individuals diagnosed with type 1 diabetes mellitus (T1DM) from infancy to early adulthood. Methods: The HbA1c levels in 275 individuals (121 males, 43.8%) diagnosed with T1DM were tracked for an average of 9.4 years. The distribution of HbA1c levels was evaluated according to age with subgroups divided by gender, use of continuous glucose monitoring (CGM), and the presence of complications. Results: HbA1c levels were highest at the age of 1 year and then declined until age 4, followed by a significant increase, reaching a maximum at ages 15–16 years. The levels subsequently gradually decreased until early adulthood. This pattern was observed in both sexes, but it was more pronounced in females. Additionally, HbA1c levels were higher in CGM nonusers compared with CGM users; however, regardless of CGM usage, an age-dependent pattern was observed. Furthermore, diabetic complications occurred in 26.8% of individuals, and the age-dependent pattern was observed irrespective of diabetic complications, although HbA1c levels were higher in individuals with diabetic complications. Conclusion HbA1c levels vary throughout the lifespan, with higher levels during adolescence. This trend is observed regardless of sex and CGM usage, potentially due to physiological IR observed during adolescence. Hence, physiological IR should be considered when interpretating HbA1c levels during adolescence.

Purpose: Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream medical intervention in these children, clinical data regarding this treatment are limited. Therefore, this study aimed to evaluate the effectiveness and safety of bisphosphonate therapy in such children. Methods: We conducted a retrospective study of 21 nonambulatory children (Gross Motor Function Classification System level V) with BMD z-score ≤ -2.0 who were treated with intravenous pamidronate for at least 1 year. These patients received pamidronate every 4 months at a dose of 1.0 to 3.0 mg/kg for each cycle and had regular follow-ups for at least 1 year. The main outcome measures were changes in BMD, risk rate of fracture, biochemical data, and adverse events. Results: The average duration of pamidronate treatment was 2.0±0.9 years, and the mean cumulative dose of pamidronate according to body weight was 7.7±2.5 mg/kg/yr. After treatment, the mean lumbar spine bone mineral content, BMD, and height-for-age-z-score-adjusted BMD z-score (BMDhazZ) significantly improved. The relative risk of fracture after treatment was 0.21 (p=0.0032), suggesting that pamidronate treatment reduced fracture incidence significantly. The increase in the average dose per body weight in each cycle significantly increased the changes in BMDhazZ. Conclusion Pamidronate treatment improved the bone health of nonambulatory children with low bone density without any significant adverse events. Independent of cumulative dosage and duration of treatment, the effectiveness of pamidronate increased significantly with an increase in the average dose per body weight in subsequent cycles.

Purpose: This study aimed to identify the association between coronavirus disease 2019 (COVID-19) transmission levels and undergoing glycated hemoglobin (HbA1c) test and complication screenings among patients with diabetes mellitus. Materials and Methods: We included a total of 3601 diabetes patients’ data from the 2020 Korean Community Health Survey to analyze the extent of the HbA1c testing and fundus examination, and 3592 diabetes patients’ data to analyze kidney disease screening. COVID-19 transmission levels were classified into low transmission (Busan, Gwangju, Daejeon, Ulsan, and Sejong) and high transmission (Daegu, where the first large outbreak of COVID-19 occurred in Korea). Multiple logistic regression was used to obtain adjusted odds ratio (ORs) and 95% confidence interval (CI) to determine the association of COVID-19 transmission levels with undergoing HbA1c testing and diabetes complication screening. Results: The proportion of subjects who underwent complication screening of diabetes was lower in the high transmission region (low transmission vs. high transmission: 42.3% vs. 38.0% for fundus examination; 48.9% vs. 45.7% for kidney disease screening). A high COVID-19 transmission level was associated with decreased odds of undergoing fundus examination (OR, 0.82; 95% CI, 0.69–0.98) and kidney disease screening (OR, 0.76; 95% CI, 0.63–0.91). However, COVID-19 transmission levels were not significantly associated with undergoing HbA1c testing. Conclusion A high level of COVID-19 transmission was associated with a decrease in undergoing fundus examination and kidney disease screening. To fully realize the potential benefit of diabetes complication screenings, further effort is required to identify and address challenges to obtaining these screenings, especially in outbreak regions.

This study aimed to enhance the physicochemical properties of sodium iodide-based root filling materials, particularly solubility. In earlier developmental stages, the iodoformcontaining paste exhibited high antibacterial efficacy but failed to meet only the solubility requirement among the ISO 6876 criteria. Therefore, this study focused on enhancing the physicochemical properties of the paste under development, particularly centering on reducing its solubility. Four experimental groups were established, including three control group. The previously developed D30 paste was named the Oil 33 group, and the control group was named the Vitapex® group. The Oil 50 group, in which the oil content was increased, and the Oil 45L group, in which lanolin was incorporated. The physical properties (solubility, pH, flowability, and film thickness) of the four pastes were evaluated according to the ISO 6876 standards. No significant differences were observed between the Oil 45L and Vitapex® groups in any of the physical property evaluations. While the Oil 33 and Oil 50 groups met the ISO 6876 standards for flowability and film thickness, the Oil 45L group met all the physical properties. However, reducing the overall oil content may be necessary to enhance the antimicrobial properties. The result of the physicochemical experiments showed that the Oil 45L group with the newly formulated composition and incorporated lanolin exhibited low solubility meeting the ISO 6876 standard of ≤ 3%. We were able to develop a paste with more stable solubility than previous iodide-based root-filling materials. Therefore, the oil content must be further adjusted to improve its antimicrobial properties. If other physical properties also meet the ISO 6876 standards and demonstrate excellent results in cytotoxicity tests, this root filling material could potentially replace existing options.