Hormone Research in Paediatrics最新文献

Background: The use of automated insulin delivery (AID) devices is now widespread in the management of type 1 diabetes (T1D), being used for younger and older children, adolescents and adults. The integration of insulin pumps with continuous glucose monitors (CGM) and smart management software in AID systems has significantly improved glycemic management compared to the separate application of each diabetes technology. The efficacy of AID systems has been demonstrated in randomized controlled trials (RCTs) but it is their application in real-world studies that fully demonstrates their impact for people with T1D.

Summary: Available AID systems differ in how they are initiated and how they calculate and deliver insulin, which dictates the parameters that can be adjusted for each system. Here we discuss how each system can be best optimized for each individual user, taking into account their activities of daily life, including mealtimes and physical activity, with a focus on commercially available systems for pediatrics (Medtronic MiniMed 780G, Tandem Control IQ, Omnipod 5, CamDiab CamAPS and BetaBionics iLet. Another FDA-cleared AID is the Tidepool Loop, which, although not yet in real-world on-label use, is currently utilized in its open-source format). We also look at the essential process of initiating AID therapy with these devices and how to navigate the important first steps, once the decision to start using an AID system has been made.

Key messages: AID systems should be considered for all individuals with T1D who wish to use them, with a strong emphasis on ensuring equitable access to this technology. Achieving success with AID requires comprehensive guidance, education, and support with a focus on core diabetes management principles. These systems are relatively easy to initiate, from any prior therapy and at any time, including shortly after diagnosis, using personalized and appropriately proactive settings. Effective meal management remains crucial for achieving optimal glycemic control, while regular follow-up and timely adjustments to AID settings are essential for maintaining their effectiveness over time.

Introduction: Atrophic autoimmune thyroiditis (AAT) is a form of autoimmune hypothyroidism characterized by the absence of a goiter. Thyroid stimulation-blocking antibody (TSBAb) has been detected in a subset of pediatric AAT cases. Although the disappearance of TSBAb has been related with the recovery of thyroid function in adult AAT cases, similar outcomes have not been documented in pediatric cases.

Case presentation: A 2-year-old Japanese boy presented for evaluation of stunted growth from 1 year 10 months of age. Tests for congenital hypothyroidism were negative on newborn screening, and he had no significant medical history. However, he showed symptoms of hypothyroidism (inactiveness, hair loss, dry skin), and primary hypothyroidism was confirmed by blood test (serum TSH level, 818 mU/L; serum free T4 level, <0.40 ng/dL). The patient exhibited a unique antibody profile: positive for TSH receptor antibody (TRAb) and TSBAb and negative for anti-thyroglobulin antibody (TgAb) and anti-peroxidase antibody (TPOAb). He was treated with levothyroxine, after which his growth was normalized. During the 8-year follow-up, the patient's TSBAb levels decreased, allowing for the discontinuation of levothyroxine therapy.

Conclusion: We reported the case of a 2-year-old boy diagnosed with AAT who presented with a characteristic antibody profile, negative for TgAb and TPOAb, but positive for TRAb and TSBAb. During 8 years of follow-up, TSBAb seroconversion to negative was observed, leading to treatment discontinuation at age 10 years. This case suggests that monitoring of TSBAb after a diagnosis of AAT may be used to determine treatment discontinuation even in children.

Introduction: Differences of sex development (DSD) is a group of rare congenital conditions defined by chromosomal, gonadal and/or phenotypic discordance or atypical sex. The mini-puberty, corresponding to the transient postnatal activation of the hypothalamic-pituitary-gonadal axis, is an important diagnosis window in the clinical workup of infants with DSD. First objective was to compare clinical data as well as hormone levels during minipuberty between patients with and without a genetic diagnosis. Secondary objective was to assess the positive predictive value of specific hormone levels at M2, which represents the mid-point of mini-puberty, to differentiate between patients with and without a genetic diagnosis by NGS.

Methods: Our study included 57 children with 46,XY DSD born between September 2010 and August 2022 who had results from hormone level measurements during mini-puberty and a next-generation sequencing DSD gene panel.

Results: From genetic testing, the diagnostic yield was 49%. Hormone analysis during mini-puberty demonstrated variations in anti-Müllerian hormone, inhibin B, follicle-stimulating hormone and luteinizing hormone levels, with specific patterns observed in certain DSD conditions. Notably, levels of follicle-stimulating hormone >4 IU/L, anti-Müllerian hormone <235 pmol/L, and inhibin B <189 pg/mL at 2 months of life were associated with a higher probability of a genetic diagnosis.

Conclusion: This study proposes a less invasive diagnostic approach for 46,XY DSD children with palpable gonads at birth; it seems a single blood test around the second month of life for comprehensive analysis.

Background: The hypothalamus, a neuroendocrine gland centrally in the brain, weighs only on average 4 grams but is the captain on the ship of our energy balance. In the hypothalamus, signals of the satiety and hunger hormones are integrated and individuals with a dysfunctional hypothalamus develop obesity. The hypothalamus, however, integrates much more than the satiety and hunger hormones, and hypothalamic obesity may be the result of a combination of factors.

Summary: The consequences of hypothalamic dysfunction can be categorized in six different domains. By systematically evaluating each domain, the underlying cause for obesity may be better understood, and doors for successful management can be opened. The different domains are; pituitary gland dysfunction, behavioral problems, disturbance of the circadian rhythm, hyperphagia, low resting energy expenditure, and temperature dysregulation. All of these domains may contribute to the development of obesity and may be more or less present in the individual patient.

Key messages: Hypothalamic obesity is not one disease, but different underlying contributing factors may be present. Consequently, hypothalamic obesity management is not one-size-fits-all but needs to be personalized. In this paper, the current state of the art for both the diagnostics and approach of acquired hypothalamic obesity is reviewed.

Introduction: Growth retardation is common in children with chronic kidney disease (CKD) and reflects CKD severity. Recombinant human growth hormone (rhGH) treatment was approved for CKD in 1995. We describe treatment patterns and growth outcomes in children with congenital CKD in three pediatric nephrology departments.

Methods: We included patients with kidney transplantation performed between 2015 and 2020 at an age of 3-18 years. Data were collected at four timepoints: CKD diagnosis, initiation of rhGH, initiation of dialysis, and transplantation.

Results: Among 87 patients, 42 (48%) received rhGH. The median height at treatment initiation was -2.0 SDS, with a median height gain of +0.7 SD (p < 0.0001) in 1.7 years. Growth outcomes were negatively associated with older age and CKD stage 5. The 45 rhGH-untreated patients lost 0.6 SD (p = 0.02) from diagnosis to transplantation but maintained their height in the normal range. At transplantation, 26% of rhGH-treated and 9% of rhGH-untreated patients had a height SDS below -2 SDS. rhGH was initiated by nephrologists in 52% of cases and endocrinologists in 48%. Deviations from marketing authorization criteria were observed in 68% of cases: endocrinologists typically prescribed rhGH for children under 2 years, while nephrologists prescribed it for patients with a height above -2 SDS.

Conclusion: About half of CKD patients received rhGH treatment, resulting in significant height gain. Untreated patients were not adversely affected in terms of height. These data highlight the importance of careful monitoring of growth and rhGH treatment if needed in patients with CKD.

is not a required field for Obituaries.

Background: Childhood obesity has become a global pandemic and is one of the strongest risk factors for cardiovascular disease later in life. The correlation of epigenetic marks with obesity and related traits is being elucidated. This review summarizes the latest research and its challenges in the study of epigenetics of (childhood) obesity.

Summary: Epigenome-wide association studies helped identify novel targets and methylation sites that are important in the pathophysiology of obesity. In the future, such sites will become essential for developing methylation risk scores (MRS) for metabolic and cardiovascular diseases. Although MRS are very promising for predicting the individual risk of obesity, the implementation of MRS is challenging and has not been introduced into clinical practice so far.

Key messages: Future research will undoubtedly discover numerous methylation sites that may be involved in the development of obesity and its comorbidities, especially at a young age. This will contribute to a better understanding of the complex etiology of human obesity. From a clinical perspective, the overarching aim was to generate MRS that is robust for reliable and accurate prediction of obesity and its comorbidities.

Introduction: Pseudohypoparathyroidism 1A (PHP1A) is the best-known representative of inactivating parathyroid hormone (PTH)/PTHrP-signaling disorders (iPPSD). The associated phenotype develops over time and often includes hormonal resistances, short stature, and osteoma cutis. More complex and very early manifestations have also been reported. Neonatal complications may indicate a more severe course of the disease. Here, we report 3 patients with heterozygous GNAS variants and infancy onset of iPPSD2/PHP1A.

Case presentations: Patient 1 is a 15-month-old boy who presented with severe chronic noninfectious diarrhea and elevated thyroid-stimulating hormone (TSH) beginning at 1 month of age, leading to life-threatening failure to thrive. Patient 2 is a 4-year-old boy with a history of bronchopulmonary dysplasia as well as neonatal-onset severe pulmonary complications, including critical pulmonary bleeding and recurring pulmonary infections and TSH elevation. Patient 3 is a 4-year-old girl who exhibited signs of PTH resistance and progressive osteoma cutis at the age of 1-2 weeks and obesity at the age of 3 months.

Conclusion: The phenotypic spectrum of iPPSD2/PHP1A in neonates and infants may include severe gastrointestinal, pulmonary, and endocrine manifestations, which may delay diagnosis if not recognized as a spectrum disorder of Gsα deficiency. The cases support the hypothesis that early-life manifestations may indicate a more complicated course of the disease. Elevated PTH or TSH in infants with unclear symptoms or conditions should prompt evaluation for disorders of the iPPSD spectrum. In the absence of reliable predictors for the individual courses of PHP1A, in-depth clinical screening for possible manifestations beyond the classical spectrum is warranted even in infancy.

Introduction: This is a report of a child with congenital hyperinsulinism associated with a loss-of-function variant in KCNE1. KCNE1 encodes a human potassium channel accessory (beta) subunit that modulates potassium channel Kv7.1 (encoded by KCNQ1). Loss-of-function pathogenic variants in either the KCNQ1 or KCNE1 genes result in long QT syndrome by causing prolongation in the action potential duration at the cellular level. In addition to long QT syndrome, the phenotype associated with loss-of-function pathogenic variants in KCNQ1 is characterized by postprandial hyperinsulinemic hypoglycemia.

Case presentation: Clinical data for the proband were extracted from the medical records. The proband presented with fasting hypoglycemia due to hyperinsulinism in early childhood as well as postprandial hypoglycemia triggered by carbohydrates and by protein. Whole-exome sequencing was undertaken in genomic DNA isolated from proband and both parents. Whole-exome sequencing revealed a variant in KCNE1 inherited from the father, who also has a history of hyperinsulinism. Both the patient and father were subsequently diagnosed with long QT syndrome. The proband and father underwent phenotype testing including fasting test, oral glucose tolerance test, oral protein tolerance test, and exercise tolerance test.

Conclusions: This case illustrates that loss-of-function variants in KCNE1, similar to KCNQ1, are associated with a cardiac and a beta cell phenotype, and thus, this patient population should be screened for hypoglycemia, particularly in the postprandial state.