Heterozygous GHR gene mutation in a child with idiopathic short stature

Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt-GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt-GHR compared to cells expressing only wt-GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subject

Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study

Purpose: We examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment. Methods: We studied 711 children (median baseline age 9.6 years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n = 78). Adverse events were assessed in all GH-treated patients. Results: The diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5 % of patients, followed by Turner syndrome (TS 6.6 %). Median starting GH dose was higher in patients with TS (0.30 mg/kg/week) than patients with GHD (0.23 mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6\u20133.7) years. Mean (95 % confidence interval) final height SDS gain was 2.00 (1.27\u20132.73) for patients with organic GHD (n = 18) and 1.19 (0.97\u20131.40) for patients with idiopathic GHD (n = 41), but lower for patients with TS, 0.37 ( 120.03 to 0.77, n = 13). Final height SDS was > 122 for 94 % of organic GHD, 88 % of idiopathic GHD and 62 % of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD. Conclusions: Data from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases

Heterozygous GHR gene mutation in a child with idiopathic short stature.

Abstract Several monogenic defects have been reported to be associated with idiopathic short stature. Focusing on growth hormone receptor (GHR)-gene alterations, the heterozygosity of the same gene defect may be associated with a range of growth deficits. We found a heterozygous mutation (V144I) within exon 6 of the GHR gene in a patient with a low level of insulin-like growth factor I (IGF-I), normal level of GH, and severe short stature. Despite the lack of statistical difference, an overall tendency for reduced wt-GH-induction of GHR activation and Jak/Stat signalling in cells transiently expressing GHR-V144I alone or co-expressing wt-GHR compared to cells expressing only wt-GHR was found when GH doses were increased. Our results suggest that, although GHR sequence variants are responsible for some functional alterations commonly observed in children with idiopathic short stature, these changes may not explain all the height deficits observed in these subjects

Prediction of histological grade of endometrial cancer by means of MRI

To evaluate the ability of MRI in predicting histological grade of endometrial cancer (EC)

Effectiveness of basal LH in monitoring central precocious puberty treatment in girls

Objectives Treatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis. Patients and methods Serum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy. Results At diagnosis, peaks of >5 IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1 IU/L in 70% and basal FSH levels of <1 IU/L in 10%. E2 were <20 pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3 IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1 IU/L was detected in 85% (p<0.01) and basal FSH ≤1 IU/L in 40% (p<0.01). Serum E2 ≤20 pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1 IU/L (p<0.01) and 38.3% FSH basal values <1 UI/mL (p<0.01). E2 ≤20 pg/mL was observed in 32.72% (p=NS). Conclusions Basal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy

SARS-CoV-2 Pandemic Impact on Pediatric Emergency Rooms: A Multicenter Study

From 9 March to 3 May 2020, lockdown was declared in Italy due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Our aim was to evaluate how the SARS-CoV-2 pandemic and related preventive strategies affected pediatric emergency rooms (ERs) during this period. We performed a retrospective cohort multicenter study, comparing the lockdown period to the corresponding period in 2019. We examined 15 Italian pediatric ERs in terms of visit rates, specific diagnoses (grouped as air communicable diseases and non-air communicable diseases), and triage categories. During the lockdown period, ER admissions decreased by 81% compared to 2019 (52,364 vs. 10,112). All ER specific diagnoses decreased in 2020 and this reduction was significantly higher for air communicable diseases (25,462 vs. 2934, p &lt; 0.001). Considering the triage category, red codes remained similar (1% vs. 1%), yellow codes increased (11.2% vs. 22.3%), and green codes decreased (80.3% vs. 69.5%). We can speculate that social distancing and simple hygiene measures drastically reduced the spread of air communicable diseases. The increase in yellow codes may have been related to a delay in primary care and, consequently, in ER admissions

Effects of Relaxed Lockdown on Pediatric ER Visits during SARS-CoV-2 Pandemic in Italy

Previously, we demonstrated an 81% reduction in pediatric Emergency Room (ER) visits in Italy during the strict lockdown due to the SARS-CoV-2 pandemic. Since May 2020, lockdown measures were relaxed until 6 November 2020, when a strict lockdown was patchily reintroduced. Our aim was to evaluate the impact of the relaxed lockdown on pediatric ER visits in Italy. We performed a retrospective multicenter study involving 14 Italian pediatric ERs. We compared total ER visits from 24 September 2020 to 6 November 2020 with those during the corresponding timeframe in 2019. We evaluated 17 ER specific diagnoses grouped in air communicable and non-air communicable diseases. We recognized four different triage categories: white, green, yellow and red. In 2020 total ER visits were reduced by 51% compared to 2019 (16,088 vs. 32,568, respectively). The decrease in air communicable diseases was significantly higher if compared to non-air communicable diseases (−64% vs. −42%, respectively). ER visits in each triage category decreased in 2020 compared to 2019, but in percentage, white and red codes remained stable, while yellow codes slightly increased and green codes slightly decreased. Our results suggest that preventive measures drastically reduced the circulation of air communicable diseases even during the reopening of social activities but to a lesser extent with regard to the strict lockdown period (March–May 2020)