Hormone Research in Paediatrics最新文献

Introduction: Recombinant human growth hormone (rhGH) treatment of children with idiopathic isolated growth hormone deficiency (IIGHD) typically results in catch-up growth for several years followed by a period of normal growth. The effect of rhGH treatment on late pubertal height gain in adolescents with IIGHD has remained unclear. This study aimed to develop and validate a prediction model for height gain from mid-puberty to near adult height (NAH) in patients with IIGHD, treated with rhGH.

Methods: Data from the Dutch National Registry of Growth Hormone Treatment in Children were used, focusing on 151 patients who received rhGH treatment until NAH. Predictors included age, bone age, Tanner stage, and target height SDS minus height SDS at mid-puberty. Validation was performed in 33 males and 7 females who had a normal GH response in a GH stimulation test at mid-puberty and continued rhGH until NAH.

Results: The model explained 48% of the variance for males (residual SD 4.16 cm) and 18% for females (residual SD 3.64 cm). Validation showed a mean (SD) difference of 1.48 (2.36) cm for males and 3.57 (2.66) cm for females between predicted and attained NAH.

Conclusion: For females, explained variance was insufficient to reliably predict height gain. For GH sufficient males, the model can be used to assess efficacy of continuing or discontinuing rhGH treatment at mid-puberty in future studies.

Introduction: Hepatocyte nuclear factor-1α (HNF-1α) and hepatocyte nuclear factor-4α (HNF-4α) are transcription factors highly expressed in β-cells, hepatocytes, intestinal epithelial cells, and renal tubular cells. Variants in both HNF1A and HNF4A gene have been linked to maturity-onset diabetes of youth (MODY) and congenital hyperinsulinism (HI). To date, the association between HI, renal tubulopathy, and hepatopathy has been described only in patients with HNF-4α deficiency. HI due to HNF-1α deficiency has not been linked to extra-pancreatic features.

Case presentation: Our patient presented neonatal onset of HI and hepatomegaly, cholestasis, echographic features of liver steatosis, and renal tubulopathy (glycosuria, phosphaturia, aminoaciduria, uricosuria, proteinuria) from the first month of life. The molecular analysis revealed a heterozygous maternal variant c.4432G>A (p.Gly1478Ar) in the ABCC8 gene and a heterozygous maternal variant c.1859C>T (Thr620Ile) in HNF1A gene. We describe an 8-month follow-up and discuss possible pathogenetic mechanisms linking HNF1A-HI and features of extra-pancreatic involvement.

Conclusion: Our case describes a likely association between HI due to HNF-1α deficiency with liver and kidney involvement. Further cases are needed to validate our hypothesis and to establish if a genotype-phenotype correlation exists in case of extra-pancreatic involvement, as for the known HNF4A mutation-specific phenotype.

Introduction: Vitamin D-dependent rickets type IA (VDDR1A) is an autosomal recessive disorder characterized by defects in the biosynthesis of its active form 1,25-dihydroxyvitamin D due to mutations in the CYP27B1 gene, which encodes for 1α-hydroxylase. The present study aimed to evaluate the clinical characteristics, molecular genetic aetiology, and long-term outcomes of a large nationwide cohort of children with VDDR1A from Turkey.

Methods: In this multi-centre retrospective cross-sectional study, we collected clinical characteristics, laboratory features, molecular genetic analysis results, and long-term follow-up of a nationwide cohort of patients with VDDR1A using a web-based research network, CEDD-NET, for paediatric endocrinology research.

Results: In total, 118 patients (57 F, 61 M) with VDDR1A were recruited. The median age of the diagnosis was 1.7 years (0.2-18.3 years). The most common presenting complaints were skeletal deformity (n = 61), short stature (n = 45), and delay in walking (n = 42). The most common mutation was a splice-donor-site mutation (c.195+2T>G) (n = 42), followed by a 7-bp duplication 1319-1325dupCCCACCC (Phe443Profs*24) (n = 25), and two missense mutations p.K192E (c.574A>G) (n = 17) and c.1474C>T (p.R492W) (n = 12). The novel c.195+2T>C and c.1215_1215+2delTGTinsCGA splice-site and c.1144C>A missense variants were firstly described in our cohort.

Conclusion: The most common four mutations accounted for the underlying aetiology of VDDR1A in approximately 81% of the cohort, indicating Turkey may serve as a mutational hotspot or exhibit a founder effect for these variants. Our large cohort's results suggested no clear and clinically meaningful phenotype-genotype relationship in VDDR1A.

Background: Arginine vasopressin deficiency (AVP-D), previously called central diabetes insipidus (central DI), is the inability to concentrate urine despite elevated serum osmolality (i.e., volume depletion) related to inadequate production of the posterior pituitary hormone vasopressin. Without treatment, which typically consists of fluids and pharmacologic vasopressin analogs, AVP-D can quickly lead to hypernatremia and dehydration. Management of AVP-D in neonates and infants is particularly challenging for many reasons: their inability to communicate thirst, their limited renal concentrating capacity, the obligate fluids required for nutrition that may cause hyponatremia with anti-diuretic therapy, the lack of FDA-approved formulation of vasopressin analog in this age, the potential need for growth-related adjustments in nutrition, fluids, and vasopressin analogs, and a limited evidence base. Despite these challenges, multiple groups have reported experiences with the available pharmacologic options, including alternative formulations of desmopressin (buccal, standard oral tablet, orally disintegrating tablet [melt], subcutaneous) and thiazide diuretics.

Summary: The objective of this mini-review was to provide pragmatic guidance on the options for long-term outpatient management of AVP-D in neonates and infants.

Key messages: Management of AVP-D in neonates and infants necessitates special considerations. For each affected patient and family, weighing the relative merits and drawbacks of each approach is critical to identify the most appropriate option, which may also change over time.

Introduction: Pediatric diabetes educators (PDEs) are scarce in low-resource settings (LRSs), compromising diabetes care and increasing morbidity and mortality.

Methods: The Indian Society for Pediatric & Adolescent Endocrinology (ISPAE) developed ISPAE Diabetes Education And Learning (IDEAL), a 12-week virtual program with 24 interactive sessions of 2 h each, 58 faculty members, practical assignments, a rigorous exit exam, and ongoing post-certification engagement via WhatsApp.

Results: Since October 2021, 177 PDEs (128 nonphysicians, 49 physicians) have been trained in 8 batches, 9th batch completing. Teaching is in English, but assignments are accepted in 8 Indian languages. A total of 91% of trainees were women, 24% were persons with type 1 diabetes or their parents, and 50% were from smaller cities. Engagement was high, with a 91% attendance rate. Post-session test scores improved significantly (p < 0.05). IDEAL received the ISPAD Innovation Award (2023) and ISPAD endorsement. Eighty-five of the 177 IDEAL alumni ("IDEALites") completed a post-course survey. Of these, 88% are actively contributing to pediatric diabetes care and earning recognition and awards for their efforts.

Challenges: This study has the following limitations: limited hands-on experience, a demanding program, and language barriers.

Conclusion: IDEAL is a pioneering, structured, intensive, virtual, award-winning PDE training program. Being accessible and sustainable, it can serve as a practical model for other programs in LRS.

β thalassemia (βT) and α thalassemia (αT) are chronic hemolytic anemias caused by hereditary defects in the β or α chains of hemoglobin, respectively. According to the clinical picture, both forms of thalassemia are subdivided into minor, intermedia, or major. Previous guidelines focused on growth and endocrine dysfunctions in βT major, where the complications reported are consequences of iron toxicity. However emerging evidence shows that patients with other forms of thalassemia are also at risk of some endocrinopathies. This guideline provides consensus on the screening and management of endocrine complications of children and adolescents with different forms of thalassemia. The panel has 14 experts from 13 countries representing 8 societies. They reviewed literature up to 2024 for the highest available evidence on the subject and 42 recommendations were modified until at least 70% vote for agreement was achieved. Hypogonadism, delayed growth, and puberty are common in βT major and transfusion-dependent (TD) αT HbH disease and they are also reported in βT intermedia and non-TD αT HbH disease. Osteopenia, adrenal insufficiency, and reproductive dysfunction are reported only in βT major and TD αT HbH disease. In addition, hypothyroidism, diabetes, and hypoparathyroidism are also reported in TD and non-TD thalassemia. Adherence to modern transfusion and iron chelation can prevent or reverse endocrine complications. Regular screening should be conducted before the age of 10 years in patients with TD thalassemia and from 11 years onward in non-TD thalassemia. Those who received hematopoietic stem cell transplantation for βT major are at risk of endocrinopathies and should be managed similarly to individuals with TD thalassemia.

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.