Xanthippi Tseretopoulou

Introduction: The routine assessment of Quality of Life (QoL) is rarely performed in the clinical paediatric endocrine and needs further exploration. Methods: Between October 2022 and December 2023, 216 patients (M:F, 134:82) with a median age of 11.8 yrs (10th,90th: 5.6, 16) completed a total of 227 EQ5D questionnaires which included an assessment of five dimensions (mobility, self-care, participation in usual activities, pain or discomfort and anxiety/depression) as well as a visual analogue scale (VAS) assessment of overall health. Additional data were collected to assess presenting complaint, clinic outcome and number of encounters and specialties involved in the patient’s care within the preceding 12 months. Results: The median VAS was 90/100 (65,100) whilst the median Dimensions score was 6/15 (5,10) for 16yrs. The VAS score was negatively associated with the Dimensions score with the strongest correlation in >16yrs group, (r=-0.64, p=0.002). The best VAS and Dimensions scores were reported in the Early Puberty group at 99/100 and 5/15 respectively while the worst scores were reported in the Excess Weight group at 77.5/100 and 8/15, respectively. In a multivariate analysis, the number of specialties involved over the previous year was associated with a worse VAS score (p=0.001) and Dimensions score (p<0.001). Conclusions: The EQ5D can be used in paediatric endocrinology with a clear association with burden of illness as reflected by the complexity of the condition. EQ5D may represent a useful generic tool for the routine assessment of QoL in paediatric endocrinology.

Objective: Management of 21-hydroxylase deficiency (21-OHD) congenital adrenal hyperplasia (CAH) in early infancy is challenging, with extent of variation in management unclear. Design and Methods: Using the I-CAH Registry, we retrospectively reviewed management over the first 90 days of life of 154 infants with 21-OHD born in 2018-2023, across 33 centers in 18 countries. Results: Of 154 infants (92 female, 62 male), 136 were diagnosed postnatally, with median (10th centile, 90th centile) presentation age of Day 4 (0, 20.8). At initial hospital discharge, median doses of hydrocortisone (HC), fludrocortisone (FC), and salt were 17 (11.4, 39.6) mg/m2/day, 100 (50, 200) mcg/day and 3.5 (1.6, 8.7) mmol/kg/day, and at Day 90 (D90) 14.5 (8.7, 24.1) mg/m2/day, 100 (50, 200) mcg/day, and 2.1 (1.0, 5.2) mmol/kg/day, respectively. Hyponatremia, hyperkalemia, and hypoglycemia were reported in 70.0%, 71.9%, and 13.0% of infants, respectively. At D90, hyponatremia and hyperkalemia were reported in 7.4% and 28.6%, respectively. At D90, BP measurements were recorded in 30.5%, amongst whom 31.9% had hypertension reported. Median total hospitalization duration over 90 days was 9 days (2, 24). Adrenal crises were associated with 40. 6% of hospitalization episodes. Percentages (males:females) of cases seen by a pediatric endocrinologist, psychologist, pediatric endocrine nurse specialist, and surgeon by D90 were 95.9% (58:84), 33.3% (9:35), 42.1% (20:36), and 23.8% (0:35), respectively. Conclusions: Contemporary management of CAH in early infancy varies considerably. Hypertension and hyperkalemia are frequently reported. Our data may help inform development of quality indicators for benchmarking CAH care in infancy.

Context: Although the safety and effectiveness of recombinant human growth hormone therapy (rhGH) has been reported for several years, the level of consensus on the outcomes that should be reported is unclear. Objective: This work aims to understand the frequency and trends in reported outcomes of safety and effectiveness for rhGH therapy for growth hormone deficiency (GHD) in childhood. Methods: A systematic review was performed in 7 English- and Chinese-language databases. Eligibility criteria included all studies published between 2003 and 2022, with participants who started rhGH before age 16 years for GHD. Results: The 219 eligible studies that were identified included 171 cohort studies, 39 controlled trials, and 9 case-control studies. The median age of the participants at start of rhGH was 9.5 years (10th-90th: 7.1-11.9). The most commonly reported outcomes included change in height SDS in 117 (53%), height velocity in 105 (48%), insulin-like growth factor-1 (IGF-1) in 66 (30%), height in 63 (29%), bone age in 58 (26%), IGF-1 SDS in 45 (21%), injection site adverse events in 44 (20%), glucose concentration in 42 (19%), insulin-like growth factor-binding protein 3 in 34 (16%), and thyroid function in 30 (14%). Of the 342 different outcomes, 178 (52%) were considered as outcomes that were mainly focused on safety, 94 (28%) on efficacy, and 70 (20%) on both. Over the two decades, height SDS and height velocity remained the most frequently reported outcomes. Of the 342 outcomes, 9 (3%) were on quality of life and these were reported in 29 of 219 (13%) studies. Conclusion: The results of this systematic review allow the development of a core outcome set that is recommended for routine use in all children receiving rhGH for childhood GHD.

Objective To validate a short parent-reported outcome (PRO) questionnaire in young boys with conditions affecting sex development (PRO-CSD). Design Consecutive sample cross-sectional study. Setting A single tertiary children’s hospital in Glasgow, UK. Patients A total number of 98 parents of 98 affected boys with a median age of 3.1 years (10th, 90th: 0.7, 5.4). Interventions Completion of recently developed brief PRO-CSD consisting of a parent proxy-report (PPR) and a parent self-report (PSR). Main outcomes The study assessed test–retest reliability in 41 cases as intraclass correlation coefficients (ICCs) and group construct validity in 98 by exploring associations with seven demographic and clinical features. Results The median ICC for all items was 0.8 (0.6, 0.9). On the PSR, parents of boys with an external masculinisation score (EMS) of less than 7 out of 12 were more concerned about their child’s genitalia compared with those with an EMS of greater than 10.5 (p=0.01). An association with EMS was also observed for questions on future social concerns (pConclusions The psychometric properties of the PRO-CSD tool demonstrate its utility for the screening of parent-reported, condition-specific health-related quality of life outcomes in young boys with a CSD.

Background: It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events. Aim: Study temporal trends of AI related AE in the I-CAH Registry. Methods: In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019. Results: In 2022, a total of 513 children from 38 centers in 21 countries with a median of 8 children (range 1-58) per center had 2470 visits evaluated over a 3-year period (2019-2022). The median SDE per patient year in 2022 was 0 (0-2.5) compared to 0.3 (0-6) in 2019 (P = .01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the 2 cohorts. Of the 38 centers in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%), and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalization compared to 299 of 1099 SDEs (27%) in the 2019 cohort (P = .02). Conclusion: The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring.

Background: The reported occurrence and management of acute adrenal insufficiency–related adverse events in children vary widely between centres and may depend on available resources. Methods: Real world data from the I-CAH Registry from 44 centres [32 from high income (HIC) and 12 from low/middle income (LMIC) countries] and a total number of 607 children were linked to the results of a health care survey of local resources and clinical management of CAH completed by healthcare professionals. Resources included written and steroid emergency plans with one point assigned for each resource. Results: The median reported rate of sick day episodes per patient year per centre at HIC and LMIC centres was 0.69 (range 0, 6) and 0.49 (0,3) respectively (P=0.603). Although the availability of resources for management of adverse events was numerically greater at HIC centres vs LMIC with a median score of 4 (1,7) and 3 (2,6) respectively, this did not reach statistical significance (P=0.109). There was no significant association between the availability of resources and the (sick day episode) SDE rate in LMIC or HIC centres (P=0.195). The use of double dose hydrocortisone was reported more frequently in LMIC vs HIC centres (67% vs 22%, P=0.005). For management of adrenal crises, the most frequently reported medications included parenteral bolus hydrocortisone (100% in HIC vs 75% in LMIC, P=0.003) and saline solution (97% in HIC vs 83% in LMIC, P=0.112). Prednisolone was reported to be used more in LMIC (13% in HIC vs 42% in LMIC, P=0.033). Conclusions: There is no clear association at centres between the level of resources available and the rate of SDE. However, there are differences in the management of adrenal crises and may reflect local availability of drugs.

To provide an overview of the I‐CAH Registry. Following the successful roll‐out of the I‐DSD Registry in the 2000s, it was felt that there was a need for a registry for congenital adrenal hyperplasia (CAH) and this was launched in 2014 as a dedicated module within the original registry. In addition to supporting and promoting research, the I‐CAH Registry acts as an international tool for benchmarking of clinical care and it does this through the collection of standardised data for specific projects. Surveillance of novel therapies in the field of CAH can also be achieved via global collaborations. Its robust governance ensures adherence to the international standards for rare disease registries. Rare disease registries such as the I‐CAH Registry are important tools for all stakeholders involved in the care of people with CAH.

Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), event-free survival (EFS), relapse, and treatment-related toxicity (TRT) in children with cancer. Published studies on children with leukemia, lymphoma, and other solid tumors have shown that both under-nourished and over-nourished children at cancer diagnosis had worse OS and EFS. Particularly, the risk of death and relapse increased by 30–50% among children with leukemia with increased body mass index at diagnosis. Likewise, the risk of TRT was higher among malnourished children with osteosarcoma and Ewing sarcoma. Nutritional status seems to play a crucial role in clinical outcomes of children with cancer, thus providing a significant modifiable prognostic tool in childhood cancer management. Future studies with adequate power and longitudinal design are needed to further evaluate the association of nutritional status with childhood cancer outcomes using a more standardized definition to measure nutritional status in this population. The use of new technologies is expected to shed further light on this understudied area and give room to person-targeted intervention strategies.

The management of type 1 diabetes in infancy presents significant challenges. Hybrid closed loop systems have been shown to be effective in a research setting and are now available for clinical use. There are relatively little reported data regarding their safety and efficacy in a real world clinical setting. We report two cases of very young children diagnosed with type 1 diabetes at ages 18 (Case 1) and 7 months (Case 2), who were commenced on hybrid closed-loop insulin delivery using the CamAPS FX™ system from diagnosis. At diagnosis, total daily dose (TDD) was 6 and 3.3 units for Case 1 and 2 respectively. Closed loop was started during the inpatient stay and weekly follow up was provided via video call on discharge. Seven months from diagnosis, Case 1 has an HbA1C of 49 mmol/mol, 61% time in range (TIR, 3.9-10 mmol/L) with 2% time in hypoglycaemia (<3.9 mmol/L) with no incidents of very low blood glucose (BG) (<3 mmol/L, 54 mg/dL) over 6 months. Given the extremely small total daily dose of insulin in Case 2,we elected to use diluted insulin (insulin aspart injection, NovoLog, Novo Nordisk Inc., Plainsboro, NJ, USA, Diluting Medium for NovoLog®). Six months from diagnosis, the estimated HbA1c is 50 mmol/mol, TIR 76% with 1% hypoglycaemia and no incidents of very low blood glucose (BG) (<3 mmol/L, 54 mg/dL) over 6 months. We conclude that the use hybrid closed-loop can be safe and effective from diagnosis in children under 2 years of age with type 1 diabetes.