Objective: The diagnosis of GH deficiency (GHD) in children and adolescents is established when GH concentrations fail to reach an arbitrary cut-off level after at least two provocative tests. The objective of the study was to define the optimal GH cut-offs to provocative tests in children and adolescents.Design: Retrospective study in 372 subjects who underwent evaluation of GH secretion. GH and IGF-I were measured by chemiluminescence assay in all samples. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal GH cut-offs and the diagnostic accuracy of provocative tests.Methods: Seventy four patients with organic GHD (GH peak 10μg/L to at least one test) were included in the study. The provocative tests used were arginine, insulin tolerance test (ITT) and clonidine. Diagnostic criteria based on cut-offs identified by ROC analysis (best pair of values for sensitivity and specificity) were evaluated for each test individually and for each test combined with IGF-I SDS.Results: The optimal GH cut-off for arginine resulted 6.5μg/L, 5.1μg/L for ITT and 6.8μg/L for clonidine. IGF-I SDS has low accuracy in diagnosing GHD (AUC=0.85). The combination of the results of provocative tests with IGF-I concentrations increased the specificity.Conclusions: The results of the ROC analysis showed that the cut-off limits which discriminate between normal and GHD are lower than those commonly employed. IGF-I is characterized by low diagnostic accuracy.

A number of studies have evaluated the role of IGF1 measurement in the diagnosis of growth hormone deficiency (GHD). This study aimed to evaluate the accuracy and the best cut-off of IGF1 SDS in the diagnosis of GHD in a large cohort of short children and adolescents. One-hundred and forty-two children and adolescents with GHD ((63 organic/genetic (OGHD), 79 idiopathic (IGHD)) and 658 short non-GHD children (median age 10.4 years) were included in the analysis. The two groups were subdivided according to age (G1 <6, G2 6 <9, G3 9 <12, G4 ≥12) and to pubertal status. Serum IGFI was measured by the same chemiluminescence assay in all samples and expressed as age- and sex-based SDS. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal IGF1 SDS cut-off and the diagnostic accuracy. Median IGF1 SDS was significantly lower in the GHD than in non-GHD patients. The area under the curve (AUC) was 0.69, with the best IGF1 cut-off of −1.5 SDS (sensitivity 67.61%, specificity 62.62%). The AUC was 0.75 for OGHD and 0.63 for IGHD. The accuracy was better in the pubertal (AUC = 0.81) than the prepubertal group (AUC = 0.64). In our cohort, IGF1 measurement has poor accuracy in discriminating GHD from non-GHD. Our findings confirm and reinforce the belief that IGF1 values should not be used alone in the diagnosis of GHD but should be interpreted in combination with other clinical and biochemical parameters.

Purpose Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod^™, an electronic, fully automated injection device designed to track the time, date and dose administered. Methods Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint—adherence to treatment—was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod^™, was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. Results The easypod^™ data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0–V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels. Conclusions The injection-recording system and other characteristics of easypod^™ could enhance the ability of physicians to monitor adherence to r-hGH treatment.

Objectives: To evaluate the effect of gender and puberty on cardiovascular risk factors (CVRF) in obese children and adolescents. Methods: One thousand four hundred and nine obese patients [age 9.7 (2.2–17.9) y; 646 Male] were studied. Subjects were stratified according to Tanner pubertal staging and age into prepubertal ≤ and >6 ys (G1 and G2), pubertal stage 2–3 (G3), and pubertal stage 4–5 (G4). Waist circumference (WC), systolic and diastolic blood pressure (SP, DP), fasting plasma glucose, insulin, post Oral Glucose Tolerance Test glucose and insulin, and lipids were evaluated. Insulin resistance was evaluated by HOMA index. Patients with no CVRF were considered metabolically healthy (MHO). Results: The percentage of MHO patients was 59.8% in G1 while was consistently around 30% in the other groups. WC was more frequently abnormal in G2 males. Pubertal progression was associated with a decrease in WC abnormalities. SP was more frequently abnormal in G4 males and pubertal progression was associated with higher prevalence of abnormal SP in males. Pubertal progression was associated with an increase in hypertension rate in both sexes. HOMA was more frequently abnormal in G2 and G3 females. HDL, LDL, and TG were more frequently abnormal in G2 females. Dyslipidemia rate was higher in G2 females. Pubertal progression was associated with higher prevalence of abnormal HDL in males. Conclusions: Sex and pubertal status influence the frequency of abnormalities of CVRF in obese children and adolescents. CVRF are already present in prepubertal age. Identifying patients with higher risk of metabolic complications is important to design targeted and effective prevention strategies.

Paediatric disorders of impaired linear growth are challenging to manage, in part because of delays in the identification of pathological short stature and subsequent referral and diagnosis, the requirement for long-term therapy, and frequent poor adherence to treatment, notably with human growth hormone (hGH). Digital health technologies hold promise for improving outcomes in paediatric growth disorders by supporting personalisation of care, from diagnosis to treatment and follow up. The value of automated systems in monitoring linear growth in children has been demonstrated in Finland, with findings that such a system is more effective than a traditional manual system for early diagnosis of abnormal growth. Artificial intelligence has potential to resolve problems of variability that may occur during analysis of growth information, and augmented reality systems have been developed that aim to educate patients and caregivers about growth disorders and their treatment (such as injection techniques for hGH administration). Adherence to hGH treatment is often suboptimal, which negatively impacts the achievement of physical and psychological benefits of the treatment. Personalisation of adherence support necessitates capturing individual patient adherence data; the use of technology to assist with this is exemplified by the use of an electronic injection device, which shares real-time recordings of the timing, date and dose of hGH delivered to the patient with the clinician, via web-based software. The use of an electronic device is associated with high levels of adherence to hGH treatment and improved growth outcomes. It can be anticipated that future technological advances, coupled with continued 'human interventions' from healthcare providers, will further improve management of paediatric growth disorders.

Growth hormone deficiency (GHD) is the most commonly affected pituitary hormone in childhood with a prevalence of 1 in 4000–10000 live births. GH stimulation testing (GHST) is commonly used in the diagnostic workup of GHD. However, GHD can be diagnosed in some clinical conditions without the need of GHST. The diagnosis of GHD in newborns does not require stimulation testing. Likewise infants/children with delayed growth and/or short stature associated with neuroradiological abnormalities and one or more additional pituitary hormone deficiencies may not need GHST. This review summarizes the current evidence on the diagnosis of GHD without stimulation tests.