Purpose: This study aimed to examine the effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on final height outcomes in girls with idiopathic central precocious puberty (CPP) from the start of treatment to their postmenarche visit. Methods: We conducted a retrospective analysis of 200 girls with idiopathic CPP who received GnRHa therapy, focusing on auxological and clinical outcomes at treatment initiation, treatment completion, and the last, postmenarche visit. Results: The mean chronological age (CA) at GnRHa treatment initiation was 8.24±0.73 years. The mean duration of GnRHa treatment was 3.12±0.81 years. The average age at menarche was 12.73±0.56 years, occurring a mean of 17.15±5.52 months after completing GnRHa therapy. The predicted adult height (PAH) standard deviation score (SDS) after menarche (0.48±0.99) was significantly greater than before treatment (-1.33±1.46) (P<0.001). Factors including greater bone age advancement (P<0.001), lower height SDS for CA at treatment initiation (P<0.001), and higher midparental height SDS (P=0.001) were positively associated with an increase in PAH SDS at the last visit. However, near-final height and the increase in PAH SDS at the last visit were not significantly different between patients who received early treatment (<8 years) and those who received later treatment (8–9 years). Conclusion GnRHa treatment improved the final height outcomes in all girls with CPP, including those treated between 8 and 9 years of age.

Purpose: This study aimed to examine the effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on final height outcomes in girls with idiopathic central precocious puberty (CPP) from the start of treatment to their postmenarche visit. Methods: We conducted a retrospective analysis of 200 girls with idiopathic CPP who received GnRHa therapy, focusing on auxological and clinical outcomes at treatment initiation, treatment completion, and the last, postmenarche visit. Results: The mean chronological age (CA) at GnRHa treatment initiation was 8.24±0.73 years. The mean duration of GnRHa treatment was 3.12±0.81 years. The average age at menarche was 12.73±0.56 years, occurring a mean of 17.15±5.52 months after completing GnRHa therapy. The predicted adult height (PAH) standard deviation score (SDS) after menarche (0.48±0.99) was significantly greater than before treatment (-1.33±1.46) (P<0.001). Factors including greater bone age advancement (P<0.001), lower height SDS for CA at treatment initiation (P<0.001), and higher midparental height SDS (P=0.001) were positively associated with an increase in PAH SDS at the last visit. However, near-final height and the increase in PAH SDS at the last visit were not significantly different between patients who received early treatment (<8 years) and those who received later treatment (8–9 years). Conclusion GnRHa treatment improved the final height outcomes in all girls with CPP, including those treated between 8 and 9 years of age.

Constitutional mismatch repair deficiency (CMMRD) is a rare and highly aggressive cancer predisposition syndrome caused by biallelic germline mutations in mismatch repair genes. This condition is characterized by early-onset malignancies across multiple organ systems, including central nervous system tumors, hematological cancers, and gastrointestinal malignancies. CMMRD-associated tumors exhibit hypermutation and microsatellite instability, resulting in a high tumor mutation burden and rendering these malignancies responsive to immune checkpoint inhibitors (ICIs). ICIs targeting programmed cell death protein-1 and programmed cell death ligand 1 have demonstrated remarkable efficacy, particularly in hypermutated tumors, providing durable responses and improving survival outcomes. Advances in genetic and molecular diagnostics have enhanced the ability to identify CMMRD early, allowing for the implementation of comprehensive surveillance programs and improved management strategies. A multidisciplinary and individualized approach is essential for managing CMMRD patients. This review underscores the importance of early diagnosis, surveillance, and emerging therapeutic approaches to improve outcomes and quality of life for individuals and families affected by this devastating syndrome.

Constitutional mismatch repair deficiency (CMMRD) is a rare and highly aggressive cancer predisposition syndrome caused by biallelic germline mutations in mismatch repair genes. This condition is characterized by early-onset malignancies across multiple organ systems, including central nervous system tumors, hematological cancers, and gastrointestinal malignancies. CMMRD-associated tumors exhibit hypermutation and microsatellite instability, resulting in a high tumor mutation burden and rendering these malignancies responsive to immune checkpoint inhibitors (ICIs). ICIs targeting programmed cell death protein-1 and programmed cell death ligand 1 have demonstrated remarkable efficacy, particularly in hypermutated tumors, providing durable responses and improving survival outcomes. Advances in genetic and molecular diagnostics have enhanced the ability to identify CMMRD early, allowing for the implementation of comprehensive surveillance programs and improved management strategies. A multidisciplinary and individualized approach is essential for managing CMMRD patients. This review underscores the importance of early diagnosis, surveillance, and emerging therapeutic approaches to improve outcomes and quality of life for individuals and families affected by this devastating syndrome.

Constitutional mismatch repair deficiency (CMMRD) is a rare and highly aggressive cancer predisposition syndrome caused by biallelic germline mutations in mismatch repair genes. This condition is characterized by early-onset malignancies across multiple organ systems, including central nervous system tumors, hematological cancers, and gastrointestinal malignancies. CMMRD-associated tumors exhibit hypermutation and microsatellite instability, resulting in a high tumor mutation burden and rendering these malignancies responsive to immune checkpoint inhibitors (ICIs). ICIs targeting programmed cell death protein-1 and programmed cell death ligand 1 have demonstrated remarkable efficacy, particularly in hypermutated tumors, providing durable responses and improving survival outcomes. Advances in genetic and molecular diagnostics have enhanced the ability to identify CMMRD early, allowing for the implementation of comprehensive surveillance programs and improved management strategies. A multidisciplinary and individualized approach is essential for managing CMMRD patients. This review underscores the importance of early diagnosis, surveillance, and emerging therapeutic approaches to improve outcomes and quality of life for individuals and families affected by this devastating syndrome.

Constitutional mismatch repair deficiency (CMMRD) is a rare and highly aggressive cancer predisposition syndrome caused by biallelic germline mutations in mismatch repair genes. This condition is characterized by early-onset malignancies across multiple organ systems, including central nervous system tumors, hematological cancers, and gastrointestinal malignancies. CMMRD-associated tumors exhibit hypermutation and microsatellite instability, resulting in a high tumor mutation burden and rendering these malignancies responsive to immune checkpoint inhibitors (ICIs). ICIs targeting programmed cell death protein-1 and programmed cell death ligand 1 have demonstrated remarkable efficacy, particularly in hypermutated tumors, providing durable responses and improving survival outcomes. Advances in genetic and molecular diagnostics have enhanced the ability to identify CMMRD early, allowing for the implementation of comprehensive surveillance programs and improved management strategies. A multidisciplinary and individualized approach is essential for managing CMMRD patients. This review underscores the importance of early diagnosis, surveillance, and emerging therapeutic approaches to improve outcomes and quality of life for individuals and families affected by this devastating syndrome.

Purpose: This study aimed to examine the effects of gonadotropin-releasing hormone agonist (GnRHa) treatment on final height outcomes in girls with idiopathic central precocious puberty (CPP) from the start of treatment to their postmenarche visit. Methods: We conducted a retrospective analysis of 200 girls with idiopathic CPP who received GnRHa therapy, focusing on auxological and clinical outcomes at treatment initiation, treatment completion, and the last, postmenarche visit. Results: The mean chronological age (CA) at GnRHa treatment initiation was 8.24±0.73 years. The mean duration of GnRHa treatment was 3.12±0.81 years. The average age at menarche was 12.73±0.56 years, occurring a mean of 17.15±5.52 months after completing GnRHa therapy. The predicted adult height (PAH) standard deviation score (SDS) after menarche (0.48±0.99) was significantly greater than before treatment (-1.33±1.46) (P<0.001). Factors including greater bone age advancement (P<0.001), lower height SDS for CA at treatment initiation (P<0.001), and higher midparental height SDS (P=0.001) were positively associated with an increase in PAH SDS at the last visit. However, near-final height and the increase in PAH SDS at the last visit were not significantly different between patients who received early treatment (<8 years) and those who received later treatment (8–9 years). Conclusion GnRHa treatment improved the final height outcomes in all girls with CPP, including those treated between 8 and 9 years of age.

Purpose: The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). Gonadorelin (Relefact) is used for the test but is not always readily available; triptorelin is used as an alternative. The purpose of this study was to evaluate the diagnostic validity of the triptorelin test compared with the GnRH test in the diagnosis of CPP in girls. Methods: This retrospective study included 100 girls with premature thelarche (PT) who underwent a hypothalamic-pituitary-gonadal axis evaluation. In the overall group, 50 girls were tested with intravenous gonadorelin (Relefact) and 50 girls were tested with subcutaneous triptorelin acetate (Decapeptyl). Luteinizing hormone (LH) and follicle-stimulating hormone levels were measured at baseline and 30, 45, 60, and 90 minutes after gonadorelin injection or 30, 60, 90, and 120 minutes after triptorelin injection. Results: Clinical characteristics of age, height, weight, body mass index, and bone age were similar between the 2 groups. The highest LH level was reached 60 minutes after stimulation in both groups. Approximately 20% of the gonadorelin group and 24% of the triptorelin group were diagnosed with CPP (P=0.52). Among those diagnosed with CPP, the mean peak LH concentrations were 8.15 mIU/mL and 9.73 mIU/mL in the gonadorelin and triptorelin groups, respectively. Conclusion The triptorelin test showed similar trends of LH elevation and diagnostic rate compared with the traditional GnRH test for diagnosing CPP. This suggests that the triptorelin test may be a valid alternative to the GnRH test for differentiating CPP from self-limiting PT. Our study also demonstrated that a triptorelin stimulation test for up to 120 minutes was sufficient to diagnose CPP.

Purpose: Three-month gonadotropin-releasing hormone agonists (GnRHas) are expected to achieve better compliance in patients with central precocious puberty (CPP) compared to the monthly formulation. However, 1-month depot remains the dominant choice for conventional treatment worldwide. Our study aimed to investigate the long-term efficacy of a 3-month GnRHa for CPP treatment. Methods: In this retrospective study, 69 Korean girls with CPP were prescribed either triptorelin pamoate (TP) 3-month depot (n=29) or triptorelin acetate (TA) 1-month depot (n=40) and were followed for 1 year after the end of treatment. Auxological, radiological, and biochemical data were collected every 6 months. Results: Baseline characteristics were similar between the 2 groups. In the TP 3-month depot group, 27 of 29 patients (93.1%) exhibited suppressed luteinizing hormone level (below 2.5 IU/L) after 6 months of treatment, and this suppression level was reserved until the final injection. The degree of bone age advancement in the TP 3-month depot group decreased from 1.8±0.4 years at the start of treatment to 0.6±0.5 years at 1-year posttreatment. The gain in predicted adult height (PAH) 1 year after the end of treatment was similar between the TP 3-month and TA 1-month depot groups (5.2±3.1 and 5.3±2.4 cm, respectively; p=0.875). Conclusion A 3-month depot of triptorelin effectively inhibited gonadal and sex hormones, suppressed bone maturation, and increased PAH. For patient convenience, we suggest a 3-month GnRHa regimen as a promising CPP treatment option.

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.