Hormone Research in Paediatrics最新文献

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and updates recommendations on the principles of intensive insulin regimens, including more intensive forms of multiple daily injections with new-generation faster-acting and ultra-long-acting insulins; a summary of adjunctive medications used alongside insulin treatment that includes details on pramlintide, metformin, glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RA) and sodium-glucose cotransporter inhibitors; and key considerations with regard to access to insulin and affordability to ensure that all persons with diabetes who need insulin can obtain it without financial hardship.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines represent a rich repository that serves as the only comprehensive set of clinical recommendations for children, adolescents, and young adults living with diabetes worldwide. This chapter builds on the 2022 ISPAD guidelines, and summarizes recent advances in the technology behind glucose monitoring, and its role in glucose-responsive integrated technology that is feasible with the use of automated insulin delivery (AID) systems in children and adolescents.

Introduction: CarboxypeptidaseE (CPE) is an enzyme involved in the neuropepetides/hormones processing. Its deficiency is associated with endocrinopathies comparable to those caused by proprotein convertase1/3(PC1/3) deficiency. In this case report we expand the clinical features of CPE deficiency by examining the index case's clinical/laboratory results, which are also indicative of PC1/3 deficiency.

Case presentation: The index case, 13.5 years old, had obesity, central hypothyroidism, developmental delay, hypogonadotropic hypogonadism, enuresis. A four-hour oral-glucose-tolerance-test revealed glucose intolerance with a partial insulin deficiency and postprandial hypoglycemia. Proinsulin level was high. Partial central diabetes insipidus was verified with a water-deprivation-test. Administration of desmopressin successfully alleviated the symptoms of polyuria-polydipsia and enuresis. Brain-derived-neurotrophic-factor level, which might be linked to ID, was low. The eight-month-old sibling had central hypothyroidism and hypotonicity,but has not yet developed obesity.

Conclusion: Patients with CPE deficiency should undergo evaluation not only for hypothyroidism and hypogonadism but also for glucose and water metabolism disorders. The presentation of new cases may lead to the discovery of novel findings, and the identification of other pituitary hormone deficiencies.

Introduction: Vosoritide is the first approved treatment for achondroplasia, a rare genetic disorder that results in disproportionate short stature. In clinical trials, vosoritide has shown a positive safety profile and increased height in children with achondroplasia. This paper shares the organizational structure, initiation, follow-up protocol, and findings of a vosoritide early access program (EAP) conducted in France.

Methods: Participants aged ≥5 years with achondroplasia and open epiphyses were eligible for enrollment in the EAP, conducted by six centers within the French national rare disease reference center for constitutional bone diseases network, from 24 June 2021 to 13 December 2022. Treatment consisted of once daily subcutaneous vosoritide 15 μg/kg. Safety and effectiveness (height, height Z-score, annualized growth velocity [AGV]) data over a 12-month follow-up period were collected.

Results: Among 62 enrolled participants, 57 started treatment with vosoritide within the EAP period with 38 completing at least 6 months and 22 at least 12 months of treatment. After 12 months of treatment, participants achieved a mean AGV of 6.0 cm/year, absolute gain in height of 6.2 cm, and increase in height Z-score referenced to the average stature population of 0.38. All adverse events were mild (mainly injection site reactions) and there were no discontinuations related to vosoritide treatment.

Conclusions: In this first use of vosoritide in a real-world setting, vosoritide had a positive benefit-risk ratio similar to that observed in vosoritide clinical trials. The French EAP provides a model that may be adapted and adopted for use in other countries.

Introduction: The objective of our study was to determine the prevalence of a delayed thyroid-stimulating hormone (TSH) rise in infants with congenital hypothyroidism (CH) born in Indiana. Additionally, we sought to determine whether there are differences in clinical or demographic factors associated with this delayed cohort compared to those seen in infants detected early.

Methods: Newborn screen (NBS) results were collected for all cases of CH diagnosed between 2012-2022. Infants with a delayed TSH rise had an initial normal NBS followed by an abnormal NBS, and a confirmatory serum TSH value >20 mU/mL. Binary logistic regression was performed to identify if demographic and clinical factors (gestational age, birth weight, race, sex, ethnicity, and maternal age) were associated with a delayed rise in TSH. Linear regression was used to assess the relationship between TSH concentration versus selected factors and timing of diagnosis.

Results: 73 infants met our inclusion criteria for a delayed diagnosis (16% prevalence). Lower gestational age and birth weight Z scores were associated with higher odds of a delayed TSH rise (each p ≤ 0.001). Lower TSH values were also found to be associated with a delayed diagnosis (p=0.010).

Conclusion: Our study confirms that prematurity is a significant contributing factor for having a delayed diagnosis of CH. In contrast, other demographic factors such as race, sex, ethnicity, and maternal age do not appear to be associated with a delayed diagnosis. Other post-natal factors that may be associated with an increased risk of a delayed rise in TSH in infants with CH require further exploration.

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 to compare clinical data as well as hormone levels during minipuberty between patients with and without a genetic diagnose. Secondary objectives were to assess the positive predictive value of specific hormone levels at M2 , the mid-point of mini-puberty, of age to differentiate between patients with and without a genetic diagnose 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 diagnose.

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 neuro-endocrine gland located 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 here treatment patterns and growth outcomes in children with congenital CKD in three pediatric nephrology departments.

Methods: We included patients with kidney transplantation (KT) performed between 2015 and 2020 at an age of 3 to 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.