Reduction in pediatric growth hormone deficiency and increase in central precocious puberty diagnoses during COVID 19 pandemics.

BACKGROUND: While several studies have been published so far on the effect of COVID-19 pandemic on health care for non-COVID-19 diseases, to date no study evaluated the impact of the COVID-19 pandemic on the entire field of pediatric endocrinology. This study aimed to evaluate differences in pediatric endocrine stimulation tests after the advent of COVID-19 pandemics. METHODS: Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 and 2020 in a tertiary center. RESULTS: Overall, 251 tests were performed on 190 patients in 2020, compared to 278 tests on 206 patients in 2019 (- 10% tests; - 8% children evaluated). A significant reduction was found in tests to diagnose growth hormone deficiency (GHD) (- 35%), while LHRH tests increased (+ 22%). A reduction of 30% in GHD diagnosis was observed. Central precocious puberty (CPP) diagnosis increased by 38% compared to 2019, mainly in females. CONCLUSION: This study found a significant reduction of tests investigating GHD during COVID-19 pandemics. It also showed a clinically meaningful increase in cases of CPP in girls. These results suggest the need for families and pediatricians to monitor children's growth during isolation and enlighten new perspectives towards conditions associated with lockdown restrictions as increased screen time, social isolation, and children's anxiety as possible triggers of CPP.

Pediatric Adrenal Insufficiency: Challenges and Solutions.

Adrenal insufficiency is an insidious diagnosis that can be initially misdiagnosed as other life-threatening endocrine conditions, as well as sepsis, metabolic disorders, or cardiovascular disease. In newborns, cortisol deficiency causes delayed bile acid synthesis and transport maturation, determining prolonged cholestatic jaundice. Subclinical adrenal insufficiency is a particular challenge for a pediatric endocrinologist, representing the preclinical stage of acute adrenal insufficiency. Although often included in the extensive work-up of an unwell child, a single cortisol value is usually difficult to interpret; therefore, in most cases, a dynamic test is required for diagnosis to assess the hypothalamic-pituitary-adrenal axis. Stimulation tests using corticotropin analogs are recommended as first-line for diagnosis. All patients with adrenal insufficiency need long-term glucocorticoid replacement therapy, and oral hydrocortisone is the first-choice replacement treatment in pediatric. However, children that experience low cortisol concentrations and symptoms of cortisol insufficiency can take advantage using a modified release hydrocortisone formulation. The acute adrenal crisis is a life-threatening condition in all ages, treatment is effective if administered promptly, and it must not be delayed for any reason.

Omalizumab effectiveness in patients with a previously failed oral immunotherapy for severe milk allergy.

BACKGROUND: Some studies addressed the issue of omalizumab (OML) effectiveness in children starting their first oral immunotherapy (OIT) attempt but no study investigated the possible role of OML in the setting of patients with persisting milk allergy after a failed OIT attempt. METHODS: Single-center, prospective, observational study in a selected group of patients with a persisting and severe cow milk (CM) allergy associated with moderate allergic asthma, in which a previous OIT attempt had already failed. We performed an open oral food challenge (OFC) to identify patients who tolerated less than 173 mg of cow's milk protein. At the end of the recruitment, we have found four patients with a mean age of 16.25 years (8-24) who had suspended a previous OIT attempt and still reacted to an amount of CM equal or below 173 mg. Enrolled patients, after an 8-week course of OML along with a CM avoiding diet, underwent again an open OFC with CM to re-evaluate their threshold. Eventually, a new OIT course was started using the same OIT protocol of the previous attempt, maintaining cotreatment with OML for the first 12 months. For each patient, we documented: the threshold of CM at OFC, level of specific immunoglobulin E (IgE) and IgG4 for milk, and quality of life (QoL). RESULTS: During OIT the four patients experienced no reactions or extremely mild ones (oral itching, transient mild abdominal pain). All increased their threshold of CM in OML if compared with the baseline and maintained it long after that biologic therapy had discontinued. Specific milk proteins IgG4 levels significantly increased in all. CONCLUSION: In this series, OML was effective in patients with severe CM allergy who had previously failed OIT, allowing milk intake without adverse reactions and improving the QoL.

Lipoblastoma as a cause of secondary omental torsion in children: report of the first case.

Acute abdominal pain remains a major diagnostic challenge to date. Omental torsion is an infrequent cause of abdominal pain in children, which usually presents with non-specific symptoms. Herein, we report a case of persistent abdominal pain after a minor abdominal trauma. A solid mass was found in the lower abdomen at ultrasound imaging evaluation. Surgical exploration demonstrated an omental torsion secondary to a rare neoplasm of childhood.

Effects of Intraoperative Auditory Stimulation on Pain and Agitation on Awakening After Pediatric Adenotonsillectomy: A Randomized Clinical Trial.

Importance: Severe pain on awakening (POA) and emergence delirium (ED) are common following pediatric adenotonsillectomy. Effective preventive interventions are lacking. Objective: To determine the effects of intraoperative auditory stimulation on reduction of POA and ED after pediatric adenotonsillectomy. Design, Setting, and Participants: Single-center, double-blinded, 4-armed, randomized clinical trial of children undergoing adenotonsillectomy from March 2018 to May 2019 at a tertiary care pediatric referral center. Interventions: Children were randomized to 1 of the following groups: auditory stimulation with music, auditory stimulation with noise, ambient noise insulation with masking earplugs, and a control group receiving no intervention. Ear inserts were placed in the operating room once general anesthesia was administered. Stimulation parameters were based on the preoperative audiological evaluation and the appropriate fitting of the transduction system, including ambient noise level monitoring. Main Outcomes and Measures: The primary outcome was POA levels measured on 10-point scales according to age-appropriate validated tools. The secondary outcome was ED levels assessed according to the Pediatric Anesthesia Emergence Delirium 20-point scale. Results: A total of 104 consecutive healthy children (median [interquartile range] age at surgery, 5.0 [3.8-6.4] years) were included in the analysis. Music had a large effect size on POA (0.63; 98% CI, 0.43-0.84) and a medium effect size on ED (0.47; 98% CI, 0.21-0.75), while noise had a medium effect size on POA (0.47; 98% CI, 0.22-0.73) and a large effect size on ED (0.63; 98% CI, 0.44-0.85) compared with controls. The earplugs group showed a small effect size on POA and ED. Considering a clinically meaningful threshold of greater than 4 for POA and 10 or greater for ED at dichotomized analysis, a large effect size was achieved by music (1.39; odds ratio [OR], 0.08; 98% CI, 0.02-0.29; and 0.84; OR, 0.22; 98% CI, 0.06-0.75, respectively) and noise (0.97; OR, 0.17; 98% CI, 0.05-0.6; and 1.48; OR, 0.07; 98% CI, 0.02-0.26, respectively), while earplugs resulted in a small effect size. Conclusions and Relevance: In this randomized clinical trial, children undergoing adenotonsillectomy who received intraoperative auditory stimulation demonstrated a clinically meaningful decrease in POA and ED in the immediate postoperative period. Further research is needed to assess whether intraoperative auditory stimulation may decrease POA and ED in children undergoing other types of surgical procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT04112979.

Should Pediatric Endocrinologists Consider More Carefully When to Perform a Stimulation Test?

Introduction: Pediatric endocrinology rely greatly on hormone stimulation tests which demand time, money and effort. The knowledge of the pattern of pediatric endocrinology stimulation tests is therefore crucial to optimize resources and guide public health interventions. Aim of the study was to investigate the distribution of endocrine stimulation tests and the prevalence of pathological findings over a year and to explore whether single basal hormone concentrations could have saved unnecessary stimulation tests. Methods: Retrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 in a tertiary center. Results: Overall, 278 tests were performed on 206 patients. The most performed test was arginine tolerance test (34%), followed by LHRH test (24%) and standard dose Synachthen test (19%), while the higher rate of pathological response was found in insulin tolerance test to detect growth hormone deficiency (81%), LHRH test to detect central precocious puberty (50%) and arginine tolerance test (41%). No cases of non-classical-congenital adrenal hyperplasia were diagnosed. While 29% of growth hormone deficient children who performed an insulin tolerance test had a pathological peak cortisol, none of them had central adrenal insufficiency confirmed at low dose Synacthen test. The use of basal hormone determinations could save up to 88% of standard dose Synachthen tests, 82% of arginine tolerance + GHRH test, 61% of LHRH test, 12% of tests for adrenal secretion. Conclusion: The use of single basal hormone concentrations could spare up to half of the tests, saving from 32,000 to 79,000 euros in 1 year. Apart from basal cortisol level <108 nmol/L to detect adrenal insufficiency and IGF-1 <-1.5 SDS to detect growth hormone deficiency, all the other cut-off for basal hormone determinations were found valid in order to spare unnecessary stimulation tests.

Pattern and Features of Pediatric Endocrinology Referrals: A Retrospective Study in a Single Tertiary Center in Italy.

Introduction: The knowledge of the pattern and the features of pediatric endocrinology referrals is crucial to optimize resources and guide public health interventions. We explored the numbers and the reasons for referral to a pediatric endocrinology outpatient clinic and investigated their features in terms of assignment of priority ranks, sex, age differences, the prevalence of pathological findings among referred cases, and the agreement among referrals, final diagnosis, treatment, and follow-up. Methods: Retrospective study with data collection for pediatric endocrinology first visits between November 2012 and February 2019 in a tertiary center. Results: A total of 1930 first visits were performed with an overall number of referrals of 2,165, and an increasing trend over the years. The most frequent referral reasons were slow growth, precocious puberty, and obesity; 14% of visits were classified as "urgent" (<7 days), 35% as "deferrable" (<30 days), and 51% as "planned" (<180 days). Sex and age differences among referrals were detected, with criticality in the appropriate timing for referral. Thirty-eight percent of patients had pathological findings. In 4% of the cases the final diagnosis was not concordant with the reason for referral. Treatment was prescribed in 35% of cases, and 67% returned at least for one follow-up visit. Conclusion: The study highlighted the need to target medical education of primary care on the definition of priority ranks, the need for more extended observation periods for subclinical or para-physiological conditions, the appropriate timing for referral, based on the definition of conditions or the best window of intervention.

Use of ketamine by paediatricians in Italian paediatric emergency departments: a missed opportunity?

Procedural sedation and analgesia with ketamine are part of daily practice for children undergoing painful procedures in the paediatric emergency department (ED) of North America. A massive number of studies demonstrate ketamine's safety and efficacy in the hands of trained ED paediatricians, with few severe adverse events (SAEs) recorded. Since there are no data on ketamine's usage in Italian paediatric EDs, we created a survey to examine procedural sedation with ketamine in the EDs of the Italian PIPER (Pain in Paediatric Emergency Room) group, which includes 36 paediatric EDs providing 1.4 million paediatric visits each year. Results were reviewed using frequencies to describe responses. Thirty-two out of 36 centres replied to the questionnaire. In 6 (19%) out of 32 centres, ketamine is not used at all in the paediatric ED. In 6 centres (23%) of 26 which use ketamine, this drug is autonomously administered by the emergency paediatrician, whereas in 20 (77%) of them it is exclusively managed by the anaesthesiologist on call.Conclusion: ketamine is autonomously administered only by a small percentage of Italian emergency paediatricians. There is an increasing need for implementation of procedural sedation training and use of ketamine in the everyday practice outside the operating room in paediatric EDs. What is Known: • Ketamine is safely and efficaciously administered for children's procedural sedation and analgesia by trained emergency paediatricians in the everyday practice outside the operating room in North America. • In the Italian setting, there are no data at all concerning ketamine's usage by the emergency paediatricians for procedural sedation and pain control. What is New: • In this study emerged that ketamine is poorly administered by Italian emergency paediatricians for procedural sedation and analgesia outside the operating room. • A great deal of educational effort should be made to widen ketamine based procedural sedation availability in Italian emergency departments by spreading specific training tracks and guidelines.