Annals of Pediatric Endocrinology & Metabolism最新文献

Long-acting growth hormones (LAGHs) represent a significant advancement in the treatment of pediatric growth hormone deficiency (GHD), offering an alternative to daily recombinant human growth hormone (rhGH) therapy. Traditional rhGH treatments, while effective, require daily injections, often leading to poor adherence due to the frequency of dosing, injection pain, and difficulties with storage and travel. In contrast, LAGHs, such as somatrogon, somapacitan, and lonapegsomatropin, are designed for once-weekly administration, improving patient compliance and quality of life. LAGHs have demonstrated non-inferiority to daily rhGH in phase 3 clinical trials, showing similar efficacy in terms of growth velocity and safety profiles. Despite these advantages, there remain concerns regarding the altered pharmacodynamics of LAGHs, such as the lack of pulsatile secretion and the potential for antibody formation. While the overall safety of LAGHs has been confirmed, some side effects, like lipoatrophy at the injection site, may occur, especially with PEGylated formulations. Guidelines for prescribing LAGHs are still evolving.. They are not yet approved for other conditions traditionally treated with rhGH, such as Turner or Noonan syndrome. Pediatric endocrinologists must carefully consider which patient groups would benefit most from this therapy, particularly those at risk for poor adherence to daily injections, such as patients undergoing multi-drug therapy, patients with needle phobia or behavioral disorders, very young children, adolescents, patients with separated parents, families that travel frequently, or children involved in activities like scouting. LAGHs present an opportunity to enhance therapeutic outcomes and adherence, but careful patient selection remains critical to maximizing their potential benefits.

Purpose: We evaluated the effectiveness of starting long-acting insulin early during managing diabetic ketoacidosis (DKA) in pediatric patients.

Methods: Patients with DKA were randomly assigned to receive either traditional DKA management protocol or concurrent administration of subcutaneous (SC) long-acting insulin alongside intravenous insulin during DKA treatment. The primary outcomes were the duration of insulin infusion and the adverse effects of the intervention, mainly hypoglycemia and hypokalemia.

Results: 100 pediatric patients with DKA were enrolled, 50 in each Group (Group I: received the conventional DKA management and Group II: received conventional DKA management plus subcutaneous long-acting insulin once daily). Patients in Group II showed a significant reduction in both the duration and dose of insulin infusion compared to Group I, with a median (IQR) of 72 hours (70.25-95.5) versus 68.5 hours (45.00-88.25) (p=0.0001), and an insulin dose of 4.04±1.17 units/kg versus 3.48±1.00 units/kg (p=0.016), respectively. Concurrent administration of subcutaneous long-acting insulin with intravenous insulin during DKA treatment was associated with a decreased risk of hypoglycemia (number of hypoglycemia events: Group I, 22 events; Group II, 12 events, p = 0.029), with no increased risk of hypokalemia compared to control Group (number of hypokalemia events: Group I, 12 events; Group II, 19 events, p = 0.147).

Conclusion: The current study showed that the co-administration of subcutaneous long-acting insulin in addition to the usual insulin infusion during DKA management in the pediatric population can lead to a shorter time of insulin infusion. In addition, this approach is not associated with increased risks of hypoglycemia or hypokalemia. Moreover, the co-administration of long-acting insulin may be associated with a decreased incidence of hypoglycemia.

Fatty acids play critical roles in maintaining the cellular functions of T cells and regulating T-cell immunity. This review synthesizes current research on the influence of fatty acids on T-cell subsets, including CD8+ T cells, TH1, TH17, Treg (regulatory T cells), and TFH (T follicular helper) cells. Fatty acids impact T cells by modulating signaling pathways, inducing metabolic changes, altering cellular structures, and regulating gene expression epigenetically. These processes affect T-cell activation, differentiation, and function, with implications for diseases such as autoimmune disease and cancer. Based on these insights, fatty acid pathways can potentially be modulated by novel therapeutics, paving the way for novel treatment approaches for immune-mediated disorders and cancer immunotherapy.

Purpose: There is controversy as to whether brain magnetic resonance imaging (MRI) should be performed on all children with growth hormone deficiency (GHD) including those judged to have mild GHD. This study was aimed to determine the frequency of pituitary or intracranial abnormalities in pediatric GHD and to identify risk factors that may predict pituitary or intracranial abnormalities.

Methods: A total of 95 pediatric GHD patients were included. Their medical records and brain magnetic resonance (MR) images were reviewed retrospectively.

Results: Abnormal pathogenic MR images were found in 14 patients (14.7%), including 10 (10.5%) with pituitary hypoplasia and 4 (4.2%) with pituitary stalk interruption syndrome. Serum levels of insulin-like growth factor-I (IGF-I), IGF-I standard deviation score (SDS), insulin-like growth factor binding protein 3 (IGFBP3), and growth hormone (GH) peak level of GH stimulation test were statistically significantly lower in the group with abnormal brain MRI. The frequency of abnormal MRI was statistically significantly higher in the complete GHD group. IGF-1 SDS showed the highest area under the curve which can predict the presence of brain abnormality with a sensitivity of 85% and a specificity of 71.4%, if IGF-1 SDS was less than -1.365. IGF-1, IGFBP3, and GH peak levels also showed good sensitivity of over 80% for predicting brain abnormalities with cutoff values of 70.285 ng/mL, 1,604 ng/mL, and 4.205 ng/mL, respectively.

Conclusion: The sensitivity and specificity of each cutoff value of IGF-1, IGF-1 SDS, IGFBP3, and GH peak levels were good and statistically significant in predicting brain MRI abnormalities. However, it was insufficient to predict all brain abnormalities with these variables. Therefore, we would like to recommend performing a brain MRI if a child is diagnosed with GHD.

Purpose: We compared the age at menarche and standard deviation score (SDS) of final height (FH) in permanent congenital hypothyroidism (CH) patients with those of healthy female adolescents and assessed their associations with CH screening-related variables or demographic factors.

Methods: In this cross-sectional study, we included 207 female CH patients and 598 healthy age-matched female adolescents. Ages at puberty onset and menarche, height at puberty and menarche, and the FH and its SDS were evaluated in the 2 groups and compared. Associations between screening variables and anthropometric data with age at menarche and SDS of FH were also assessed in CH patients.

Results: In the included population, 113 patients with CH and 453 healthy girls attained their FH. The mean ages at puberty onset and menarche in CH patients were higher than those in the healthy population (P<0.05). The mean height at menarche and the FH and its SDS were not different between the 2 groups (P>0.05). There was no significant association between FH SDS in CH patients and age of treatment (P=0.30). Age at menarche was significantly higher in CH patients with delayed age at treatment initiation (P=0.04). The difference between FH and target height was not significantly different among CH patients (P=0.83).

Conclusion: While CH patients had a significantly higher age at menarche compared to the healthy population, appropriate treatment changed this age to be similar to that in the healthy group. However, CH patients who experienced delayed treatment had a higher age at menarche. Age at treatment initiation was the only screening-related variable related to age at onset of menarche and puberty.

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.