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.

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.

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.

Familial male-limited precocious puberty (FMPP) is a rare form of gonadotropin-independent precocious puberty that is caused by an activating mutation of the LHCGR gene. Herein, we report a case of FMPP with a mutation of the LHCGR gene in a Korean boy with familial history of precocious puberty through 3 generations. A 16-month-old boy presented with signs of precocious puberty, including pubic hair, acne, and increased growth velocity. The patient's grandfather and father had a history of precocious puberty and profound short stature. On physical examination, the patient had prepubertal testes with pubic hair development appropriate for Tanner stage II. The stretched penile length was 7 cm (>2 standard deviation score), and observed bone age was that of a 4-year-old boy. Laboratory findings showed high serum testosterone (5.74 ng/mL [appropriate for Tanner IV–V]; normal range, <0.05 ng/mL) with suppressed luteinizing hormone (<0.07 mIU/mL) and normal serum level of follicular stimulating hormone (0.56 mIU/mL; normal range, 0.38–1.11 mIU/mL). Genetic testing revealed a pathogenic variant of LHCGR (c.1730 C>T (p.Thr577Ileu)), confirming FMPP. Bicalutamide and anastrozole were administered, and pubertal progression was sufficiently suppressed without any specific side effects. To our knowledge, this is the first case of genetically confirmed FMPP in Korea.

The Committee of Central Precocious Puberty of Korean Pediatrics and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based 2022 clinical practice guidelines for central precocious puberty in Korean children and adolescents. These guidelines provide the grade of recommendations, which includes both the strength of recommendations and the level of evidence. In the absence of sufficient evidence, recommendations are based on expert opinion. These guidelines have been revised and supplement the previous guidelines "Clinical Guidelines for Precocious Puberty 2011," and are drawn from a comprehensive review of the latest domestic and international research and the grade of recommendation appropriate to the domestic situation. This review summarizes the newly revised guidelines into 8 key questions and 27 recommendations and consists of 4 sections: screening, diagnosis, treatment, and long-term outcome of central precocious puberty.

Purpose: Overweight (OW)/obese girls tend to have an earlier pubertal onset than girls with normal weight. However, only a few studies have reported the progression of puberty in these girls. This study aimed to identify risk factors for rapid pubertal progression in OW/obese girls presenting with precocious breast development. Methods: This retrospective cohort study reviewed the medical records of 110 OW (body mass index [BMI] ≥85th percentile for age and sex) and 213 nonoverweight (NW, BMI <85th percentile for age and sex) girls who presented with breast budding before 8 years of age. OW girls were divided into 2 subgroups: girls with central puberty progression before 9 years of age (OW-RP) and those without (OW-SP). Results: Progression to central puberty before the age of 9 was more common in NW girls than in OW girls (83.8 % vs. 65.2 % in NW vs. OW group, p<0.001), and progression-free survival for 1, 2, and 3 years was higher in the OW group (p<0.001). In a subgroup analysis of OW girls, the OW-RP subgroup had more advanced bone age (BA) at the first visit (p=0.047) and higher initial luteinizing hormone (LH, p=0.010) levels than the OW-SP subgroup. Being NW (p=0.001) and having more advanced BA (p=0.023) at the initial workup were the risk factors for pubertal progression before age 9. Conclusion Pubertal progression seems to be slower in OW girls than in NW girls presenting with precocious breast development. However, it can progress rapidly in OW girls with particularly pronounced BA advancement and high LH levels at the initial workup.

Rhabdomyolysis associated with psychogenic polydipsia and hyponatremia is a rare condition that can cause substantial morbidity and mortality. We report a 14-year-old boy with psychogenic polydipsia who experienced recurrent hyponatremia and subsequent rhabdomyolysis. Treatment involved intravenous fluids and restriction of oral water intake. This case emphasizes the importance of early recognition and management of this condition. The possibility of rhabdomyolysis should be considered in patients with hyponatremia who have myalgia.

Diabetic ketoacidosis (DKA) is a medically fatal condition in poorly controlled hyperglycemia or newly diagnosed diabetes mellitus. Severe hypertriglyceridemia (HTG) is an uncommon complication of DKA and can be associated with acute pancreatitis (AP). We present the clinical manifestations, laboratory findings, and management of AP associated with HTG in a 14-year-old girl with DKA. The patient, with a 7-year history of type 2 diabetes presented with epigastric pain, 1 month after stopping insulin injection. DKA, severe HTG, and AP were diagnosed based on the laboratory and imaging tests. She recovered from DKA after conventional treatment for DKA, and her triglyceride (TG) level was reduced from 10,867 mg/dL to the normal range after 7 days of admission without antilipid medication. Given that her C-peptide level was not too low and considering her negative diabetes-related antibodies and high TG level, targeted gene panel sequencing was performed on the genes associated with diabetes and HTG. We identified a heterozygous mutation, c.4607C>T (p. Ala1537Val), in ABCC8 related to maturityonset diabetes of the young (MODY) 12. To our knowledge, this is the first reported case of HTG-induced AP with DKA in a patient with MODY. In addition, we reviewed the literature for pediatric cases of HTG with DKA. In patients with DKA, timely awareness of severe HTG related to insulin deficiency is crucial for improving the consequences of AP. We recommend considering AP in all DKA patients presenting with severe HTG to ensure early and proper management.

PURPOSE: It is well known that obesity is related to vitamin D deficiency (VDD). We investigated the response to vitamin D replacement in normal-weight and overweight children. METHODS: This was a prospective study including 62 Korean children with VDD. VDD was defined as a serum 25-hydroxycholecalciferol (25(OH)D) concentration <20 ng/mL. Overweight was defined as a body mass index (BMI)≥the 85th percentile (n=21), and normal weight as a BMI between the 5th and 84th percentiles (n=41). All participants received vitamin D3 supplementation (2,000 IU/day) for 8 weeks. The serum levels of 25(OH)D, PTH and biochemical parameters were measured before and after treatment. RESULTS: The mean age was 10.0±1.4 years in normal-weight children and 10.0±2.1 years in overweight children (P=0.93). After 8 weeks of treatment, 61.9% of normal-weight children and 47.6% of overweight children achieved vitamin D sufficiency (P =0.30). The mean serum 25(OH)D levels after vitamin D replacement were 33.8±7.6 ng/mL and 30.3±6.6 ng/mL in normal-weight and overweight children, respectively (P =0.10). The mean calcium/creatinine ratios after treatment were 0.09±0.07 and 0.08±0.06 in the normal-weight and overweight groups, respectively, and no hypercalciuria was found. In multiple regression analysis, the response to vitamin D replacement was influenced by the BMI (β=-1.0, P=0.03) and sex (β=-4.0, P=0.04). CONCLUSIONS: Eight weeks of vitamin D replacement (2,000 IU/day) is sufficient to overcome vitamin D deficiency in normal-weight and overweight children without any complications.
Body Mass Index ; Calcifediol ; Child ; Cholecalciferol ; Humans ; Hypercalciuria ; Obesity ; Overweight ; Prospective Studies ; Vitamin D Deficiency ; Vitamin D ; Vitamins

Neonatal hypocalcemia and congenital heart defects has been known as the first clinical manifestation of the chromosome 22q11.2 deletion syndrome (22q11DS). However, because of its wide clinical spectrum, diagnosis of 22q11DS can be delayed in children without classic symptoms. We report the case of a girl with the history of imperforate anus but without neonatal hypocalcemia or major cardiac anomaly, who was diagnosed for 22q11DS at the age of 11 after the onset of overt hypocalcemia. She was born uneventfully from phenotypically normal Korean parents. Imperforate anus and partial cleft palate were found at birth, which were surgically repaired thereafter. There was no history of neonatal hypocalcemia, and karyotyping by GTG banding was normal. At the age of 11, hypocalcemia (serum calcium, 5.0 mg/dL) and decreased parathyroid hormone level (10.8 pg/mL) was noted when she visited our Emergency Department for fever and vomiting. The 22q11DS was suspected because of her mild mental retardation and velopharyngeal insufficiency, and a microdeletion on chromosome 22q11.2 was confirmed by fluorescence in situ hybridization. The 22q11DS should be considered in the differential diagnosis of hypocalcemia at any age because of its wide clinical spectrum.
22q11 Deletion Syndrome* ; Anal Canal* ; Anus, Imperforate ; Calcium ; Child* ; Cleft Palate ; Delayed Diagnosis* ; Diagnosis ; Diagnosis, Differential ; DiGeorge Syndrome ; Emergency Service, Hospital ; Female* ; Fever ; Fluorescence ; Heart Defects, Congenital ; Humans ; Hypocalcemia* ; Hypoparathyroidism ; In Situ Hybridization ; Intellectual Disability ; Karyotyping ; Parathyroid Hormone ; Parents ; Parturition ; Velopharyngeal Insufficiency ; Vomiting