Hormone Research in Paediatrics最新文献

Introduction: Management of diabetes mellitus in very young children presents challenges due to variable insulin sensitivity, unpredictable carbohydrate intake, and low insulin requirements. An automated insulin delivery (AID) system addresses some of these challenges and can be used with diluted insulin where indicated.

Methods: Retrospective case series of children aged <6 years with diabetes starting CamAPS FX AID with standard (U100) or diluted (U5 or U10) insulin at a single UK clinical centre between October 2020 and April 2022.

Results: AID was started for seven children with diluted insulin (median interquartile range [IQR] age 1.5 [0.6, 2.8] years, mean ± standard deviation HbA1c 83 ± 18 mmol/mol) and four with standard insulin (age 4.6 [3.9, 5.4] years, HbA1c 62 ± 13 mmol/mol). AID was started at a median (IQR) of 0.2 (0.1, 0.2) months post-diagnosis in the diluted group and 17.8 (7.7, 23.6) months in the standard group. At the most recent clinic visit (9.3 ± 4.8 months after starting AID in the diluted group and 12.0 ± 2.1 months in the standard group), time in target range (3.9-10.0 mmol/L) was 66.5 ± 6.8% and 54.0 ± 5.0%, respectively. Median time in hypoglycaemia (<3.9 mmol/L) was <4% in both groups. Glucose variability was 37.5 ± 4.2% in the diluted and 43.5 ± 4.7% in the standard group. There were no episodes of diabetic ketoacidosis or severe hypoglycaemia.

Conclusion: AID with both standard and diluted insulin can be used to safely manage diabetes in very young children with low total insulin requirements.

Introduction: Some children with classic congenital adrenal hyperplasia (CAH) achieve excellent control on very low glucocorticoid doses. We aimed to characterize these patients and assess the timing of their low-dose requirements.

Methods: We reviewed charts of patients with salt-wasting CAH due to 21-hydroxylase deficiency, defining low-dose glucocorticoid as <10 mg/m2/day. Demographic and growth data were compared with a matched group on standard doses.

Results: Among 154 patients with CAH, 14 (9%) required low-dose glucocorticoid therapy (<10 mg/m2/day), including 8 boys (57%) and 6 girls (43%). The average age at treatment initiation was 2.1 years, comparable to a matched group of 23 patients (48% boys). The low-dose group received 8.8 ± 1.2 mg/m2/day versus 14.9 ± 3.9 mg/m2/day in the matched group (p < 0.001), with similar fludrocortisone doses (0.1 ± 0.05 mg). No differences were observed in weight, height, or height velocity. Of the 14 patients on low-dose treatment, 3 experienced an increase in their glucocorticoid dose requirement above 10 mg/m2/day at ages 10.3, 10.8, and 8.5 years after being on 6.3-9.8 mg/m2/day for 6.4-8.5 years. The remaining 11 patients are currently on 5.89-10 mg/m2/day with a duration on low-dose therapy ranging from 0.48 to 8.65 years.

Conclusion: Our findings highlight a subgroup of patients with 21-hydroxylase deficiency who achieve good control on low glucocorticoid doses from early childhood. The factors underlying this and the transient need for low doses in some remain unclear.

Introduction: Hyponatremia is common in hospitalized pediatric patients, and in many cases, the diagnosis of the syndrome of inappropriate antidiuretic secretion (SIADH) remains challenging, with no gold standard for diagnosis. We assessed factors associated with hyponatremia in pediatric patients clinically diagnosed with SIADH and examined the validity of copeptin level as a useful tool to distinguish SIADH from non-SIADH causes of hyponatremia.

Methods: This observational study retrospectively analyzed 19 patients admitted to Children's Hospital of Orange County in 2021-2024 for hyponatremia. ROC analyses assessed the ability of copeptin level to distinguish diagnostic groups, determining the optimal threshold for classification.

Results: Pediatric patients with a diagnosis of SIADH had a significantly higher average urine sodium level (135.4 vs. 68.3, p = 0.036) and higher average copeptin level (median = 14.3 vs. 5.7, p = 0.036). ROC analyses determined copeptin had good ability to differentiate a clinical diagnosis of SIADH from non-SIADH causes of hyponatremia with sensitivity 83%, specificity 71%, PVP 83%, NPV 71%. A significantly higher percentage of patients with copeptin level greater than 8.0 pmol/L were diagnosed with SIADH (83.3% vs. 28.6%, p = 0.017).

Conclusion: Copeptin levels correlated with a clinical diagnosis of SIADH in hospitalized pediatric patients, particularly if elevated above 8.0 pmol/L at the time of hyponatremia, and the patient met the Schwartz and Bartter clinical criteria for SIADH. However, in some cases of SIADH, copeptin levels may be in normal range and could be considered inappropriately high for the degree of hyponatremia.

Introduction: Care of children with diabetes is best delivered by a specialist multidisciplinary team of paediatric endocrinologists, diabetes nurse educators, dietitians, and psychologists. The Allied Healthcare Paediatric Diabetes Educator Course for Africa (ADECA) is the first specialised paediatric diabetes educator training programme for nurses working in sub-Saharan Africa. The aim of the paper was to describe the course structure and evaluation findings of the first ADECA programme.

Methods: The ADECA course is a hybrid 1-year course, organised in six phases, including online modules, in-person modules, and work-based assessments. Fifteen nurses from seven sub-Saharan African countries were selected to undertake the first course. The course was evaluated using the Kirkpatrick model, which rates the results of training courses against four levels of criteria: reaction, learning, behaviour, and results.

Results: All nurses successfully completed the course. Overall, 100% strongly agreed that the "in-person" modules were beneficial and enjoyable, compared to 87.5% of nurses for the online modules. Eighteen months following completion, the nurses are contributing to care of children and young people with diabetes and taking a lead in training other healthcare professionals. Seventy-three percent have joined national committees, with 27% actively involved in developing national guidelines and influencing policy. Forty percent have presented at either national or international scientific conferences.

Conclusion: The ADECA course has successfully created a pool of competent paediatric diabetes nurse educators who can support children and their families as well as train other healthcare personnel in diabetes care and become future faculty members. This bespoke course can be adapted for use in other low-income countries.

Introduction: Uromodulin reflects nephron mass, while urinary neutrophil gelatinase-associated lipocalin (NGAL) indicates kidney injury. We hypothesized that low urinary uromodulin at type 1 diabetes mellitus (T1DM) onset may be linked to acute kidney injury (AKI) and that a higher urinary uromodulin-to-NGAL ratio, reflecting the balance between nephron mass and kidney stress, may reduce the risk of AKI. Our aim was to test these hypotheses.

Method: In this prospective study, 75 children (mean age: 8.6 ± 4.3 years) hospitalized for new-onset T1DM were enrolled. AKI was defined as a highest-to-basal serum creatinine ratio ≥1.5. Urinary NGAL and uromodulin levels were measured at admission and upon kidney injury resolution.

Results: Of 75 patients, 33 (44%) had diabetic ketoacidosis (11 severe, 10 moderate, 12 mild) and 33 (44%) developed AKI. At T1DM onset, patients with AKI had similar urinary uromodulin levels but higher urinary NGAL levels, higher uromodulin-to-creatinine ratio, and lower urinary uromodulin-to-NGAL ratio than those without AKI. The uromodulin-to-NGAL ratio correlated inversely with the highest-to-basal creatinine ratio (r = -0.42; p < 0.001), while NGAL correlated positively (r = 0.36; p = 0.001). Both urinary NGAL and the uromodulin-to-NGAL ratio at T1DM onset predicted the absence of AKI, with an areas under the receiver-operating characteristic curve of 0.66 (95% confidence interval [CI]: 0.54-0.79; p = 0.01) and 0.75 (95% CI: 0.63-0.86; p < 0.001), respectively.

Conclusion: Our findings suggest a potential interplay between nephron mass and kidney stress in AKI development at T1DM onset. While uromodulin levels alone were not associated with AKI, a higher urinary uromodulin-to-NGAL ratio - possibly reflecting better-preserved nephron mass under stress - may be linked to a reduced risk of AKI. Further confirmation is needed.

Background: Childhood obesity is a global health challenge driven by a complex interplay of genetic predispositions and environmental exposures. Genome-wide association studies have identified many obesity-associated loci, and polygenic risk scores (PRS) enable quantification of genetic susceptibility. Concurrently, lifestyle factors - including diet, physical activity, sleep, stress, and socioeconomic status - modify these genetic risks.

Summary: Healthy lifestyle practices can mitigate genetic risk, while unhealthy diets and sedentary habits amplify it. The review details how PRS, by capturing the cumulative effect of numerous small-effect variants, facilitate risk stratification in children. Furthermore, gene-environment interactions - from diet and exercise to sleep, stress, and socioeconomic conditions - might inform personalized intervention strategies, including tailored nutritional guidance, behavior modification, and targeted physical activity interventions initiated early.

Key message: Understanding gene-environment interactions is essential for refining risk assessments and developing personalized, equitable public health strategies. Future research should focus on enhancing multi-ancestry PRS accuracy, elucidating underlying biological pathways, and translating genetic insights into actionable, context-specific interventions to combat childhood obesity.

Introduction: Endocrine disorders present a major comorbidity in pediatric brain tumors and/or treatment-related damage, which results in impaired function of the hypothalamic-pituitary axes. The aim of the study was to assess the prevalence of endocrine disorders among a complete childhood brain tumor survivor cohort treated between 2008 and 2018 at our national center.

Methods: Children with primary brain tumors treated at the University Children's Hospital, University Medical Center Ljubljana, between 2008 and 2018 were included and evaluated by the endocrinologist in the years 2023/2024. Data on demographics, anthropometrics, tumor type, and therapy were gathered. The presence of endocrinopathies was determined by clinical examination and laboratory data.

Results: A total of 94 patients (mean age at the most recent follow-up 14.9 +/- 5.5 years, mean follow-up duration 8 +/- 3 years) were included in the study. At the time of final follow-up, 23% were diagnosed with an endocrine disorder. The most prevalent were hyposomatotropism, followed by central hypothyroidism, with panhypopituitarism affecting 10% of the cohort. Endocrine dysfunction was more frequently observed in survivors with tumors located in the suprasellar region, those who underwent radiotherapy, and those who presented with hydrocephalus. A significant decrease in height SDS was noted compared to baseline height at the time of treatment initiation (p < 0.02), with a more pronounced reduction among those who received craniospinal radiotherapy as part of the oncological treatment.

Conclusion: The findings highlight a high prevalence of endocrine disorders in childhood brain tumor survivors, particularly those with suprasellar or posterior fossa tumors, or those treated with radiotherapy. These results emphasize the need for regular and ongoing endocrine monitoring in this patient population following the completion of oncological treatment.

Introduction: Variants affecting a microsatellite on the noncoding region of chromosome 15q26.1 are associated with familial non-autoimmune thyroid abnormalities characterized by mild congenital hypothyroidism (CH) with elevated thyroglobulin (Tg) levels. Some individuals who carry these variants may develop multinodular goiter if left untreated. Although these variants have been recognized as genetic etiologies of CH, nongoitrous, 3 (CHNG3), the associated severity of CH remains unclear.

Method: A cohort of 63 participants diagnosed with CH at Tohoku University underwent screening for genetic variants on 15q26.1. We then analyzed the clinical phenotypes of the variant-carrying participants.

Results: We identified five 15q26.1 variant carriers from four families among the cohort. Family histories of thyroid abnormalities were documented in three of these 5 cases. The variant carriers had mild CH phenotypes, with two discontinuing levothyroxine treatment and the others requiring relatively low doses (1.33-1.89 µg/kg/day) at their final visit. During levothyroxine treatment, serum Tg and thyroid-stimulating hormone (TSH) levels were within the reference ranges at the majority of the evaluation points. Three of the five participants continued treatment into adulthood, whereas the other two discontinued it and maintained serum TSH levels within the reference range. All five participants exhibited normal intellectual development and stature.

Conclusion: These findings provide further evidence supporting the role of 15q26.1 variants as a common genetic etiology of CH, with clinical phenotypes including transient CH. Early genetic evaluation may facilitate the identification of 15q26.1 variant carriers among patients who are diagnosed with CH.

Introduction: The risk of celiac disease (CD) is high in children with type 1 diabetes (T1D). While some studies have linked CD in children with T1D to impaired growth and poorer glycaemic control, results have been inconsistent. Further, no study has examined the relevance of whether the diagnosis of CD is established before, in conjunction with, or after T1D. We aimed to examine whether CD influences body mass index (BMI) and glycaemic control in children with T1D, and whether the timing of the onset of CD is of relevance.

Methods: Swedish children diagnosed with T1D between 2005 and 2010 who were enrolled in the Better Diabetes Diagnosis study (N = 3,612; >90% national coverage) were included. The participants were screened for CD at T1D diagnosis and annually for 5 years. BMI-standard deviation score (BMI-SDS), glycaemic control (HbA1c), and diabetes ketoacidosis (DKA) were assessed at T1D diagnosis, BMI-SDS, and HbA1c at five annual follow-ups.

Results: Children diagnosed with CD at the same time as the T1D diagnosis had statistically significantly lower BMI-SDS compared to children without a CD diagnosis at all follow-up assessments. Children diagnosed with CD before T1D had a significantly lower BMI-SDS during the first 2 years of follow-up. CD status was not associated with HbA1c or DKA at T1D diagnosis or during follow-up.

Conclusion: Children diagnosed with T1D with known or identified CD at the time of diagnosis had a lower BMI-SDS up to 5 years after T1D diagnosis and may require additional nutritional support. The presence or timing of a CD diagnosis does not appear to be associated with glycaemic control in children with T1D.

Introduction: Diagnosing growth hormone (GH) deficiency (GHD) is challenging due to the low specificity of diagnostic tests, particularly in children during the prepubertal and early pubertal stages. Although sex steroid priming increases stimulated GH peak levels, its impact on spontaneous nocturnal GH values has not yet been reported. Priming may reduce discrepancies between spontaneous and stimulated GH testing, potentially improving diagnostic accuracy. We aimed to assess the impact of priming on combined spontaneous and stimulated GH testing and the occurence of divergent test results, as well as to evaluate short-term adverse events associated with priming.

Methods: This was a retrospective chart review of all 132 short children who underwent a nocturnal spontaneous GH secretion test followed by an arginine-insulin stimulation test over 30 years at the Department of Pediatrics, Örebro University Hospital, Sweden.

Results: Among the 132 children tested, 25 (19%) received priming prior to GH testing. Compared with nonprimed children, primed children presented higher peak and mean spontaneous GH values (14.2 μg/L [0.6-22.5] vs. 10.8 μg/L [0.2-27.0], p = 0.042 and 3.0 μg/L [0.3-6.9] vs. 2.3 μg/L [0.1-6.9], p = 0.007, respectively). Divergent results between the two GH tests were less common in primed children (4%) than in nonprimed children (23%, p = 0.027). Mild adverse events occured in three (12%) of the primed children.

Conclusion: Sex steroid priming prior to GH testing is well tolerated, enhances spontaneous nocturnal GH secretion, and reduces the frequency of divergent results between spontaneous and stimulated values. We recommend incorporating priming when evaluating children in prepuberty or early puberty for suspected GHD.