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Abstract Context There are only a few nationwide studies on boys with central precocious puberty (CPP) and the last Italian study is a case series of 45 boys that dates back to 2000. Objective We aimed to evaluate the causes of CPP in boys diagnosed during the last 2 decades in Italy and the relative frequency of forms with associated central nervous system (CNS) abnormalities on magnetic resonance imaging (MRI) compared to idiopathic ones. Methods We performed a national multicenter retrospective study collecting data from 193 otherwise normal healthy boys with a diagnosis of CPP. Based on MRI findings, the patients were divided into: Group 1, no CNS abnormalities; Group 2, mild abnormalities (incidental findings) unrelated to CPP; and Group 3, causal pathological CNS abnormalities. Results The MRI findings show normal findings in 86%, mild abnormalities (incidental findings) in 8.3%, and causal pathological CNS abnormalities in 5.7% of the cases. In Group 3, we found a higher proportion of patients with chronological age at diagnosis < 7 years (P = .00001) and body mass index greater than +2 SDS (P < .01). Gonadotropin-releasing hormone analogue therapy was started in 183/193 subjects. The final height appeared in the range of the target height in all groups and in 9 patients in whom the therapy was not started. Conclusion In our study on a large nationwide cohort of boys referred for precocious puberty signs, the percentage of forms associated with CNS abnormalities was one of the lowest reported in the literature.

Background Foramen magnum stenosis (FMS) is a serious complication in children with achondroplasia that may necessitate cervicomedullary decompression (CMD). It is unclear how FMS and CMD influence growth in these children. This study aimed to assess the effects of FMS and CMD on the growth of children with achondroplasia. Methods Eighty-seven children (45 males, 42 females) with achondroplasia, aged 4 to 6 years, were evaluated. Height, weight, head circumference, and body mass index were expressed as standard deviation scores (SDS) according to Merker et al., while sitting height SDS was derived using Tanner’s methods. FMS was graded on magnetic resonance imaging using Fornarino’s score. Results Fifty-two patients (26 males, 26 females) underwent CMD at a median age of 0.95 years (IQR 0.52;1.50). Of these, 28 (53.8%) were under one year old at the time of CMD, with a median age of 0.6 years (0.4;0.7). The remaining 24 children had CMD after their first year of life, with a median age of 1.6 years (1.3;2.8). The median age at anthropometric assessment was 5.16 years (4.74;5.50). Children who underwent CMD showed significantly lower median height SDS, particularly among males compared to females (p=0.026). Conclusions Impaired growth in children with foramen magnum stenosis requiring cervicomedullary decompression may primarily reflect greater disease severity, while the potential contribution of surgery remains uncertain.

Abstract Context Children with congenital hypothyroidism (CH) are at risk for suboptimal neurodevelopment. Objectives To evaluate neurocognitive function and white matter microstructure in children with permanent or transient CH and to correlate these findings with disease severity. Design, participants and methods A retrospective and prospective observational study was conducted in 39 children with permanent or transient CH, and in 39 healthy children. Cognitive function was assessed by Wechsler Intelligence Scale, Fourth Edition, and by other tests; the white matter microstructure was investigated by 3 Tesla magnetic resonance imaging. Results Children with permanent CH have lower cognitive scores at a median age of 9.5 years than those with transient CH and controls. An IQ score between 71 and 84 was found in 28.6% of permanent CH and of <70 (P = 0.06) in 10.7%. The Processing Speed Index (PSI; P = 0.004), sustained visual attention (P = 0.02), reading speed (P = 0.0001), written calculations (P = 0.002), and numerical knowledge (P = 0.0001) were significantly lower than controls. Children born to mothers with Hashimoto’s thyroiditis have significantly lower IQ values (P = 0.02), Working Memory Index (P = 0.03), and PSI (P = 0.02). Significantly lower IQ and Verbal Comprehension Index values were found in children with a family history of thyroid disorders (P = 0.004 and P = 0.009, respectively). In children with permanent CH, significant correlations between abnormalities in white matter microstructural, clinical, and cognitive measures were documented. Conclusions These findings indicate that children with CH are at risk of neurocognitive impairment and white matter abnormalities despite timely and adequate treatment. The association between offspring cognitive vulnerability and maternal thyroid disorders requires careful consideration.

To evaluate the prevalence of high risk for obstructive sleep apnea syndrome (HR-OSAS) in Brazilian children with cerebral palsy (CP) using the Pediatric Obstructive Sleep Apnea Screening Tool (PosaST) and to analyze its association with demographic, clinical and functional (Gross Motor Function Classification System [GMFCS]) variables. Multicenter, cross-sectional, exploratory study. There were 312 children (median age 6.0 years, IQR 5.0–8.0) included. The prevalence of HR-OSAS in GMFCS I-V was 9.0 %. The prevalence of HR-OSAS in GMFCS V (14.7 %) was significantly higher compared to GMFCS I-IV (6.4 %) and to the frequency of OSAS in typically developing (TD) children assessed by polysomnography (5.8 %) according to literature data. Significantly higher frequencies of palatine tonsil hypertrophy, hospitalizations and outpatient antibiotic use for respiratory causes (last 12 months), gastroesophageal reflux disease, drooling and epilepsy were found in GMFCS V. Palatine tonsil hypertrophy was significantly associated with HR-OSAS. GMFCS V was significantly correlated with HR-OSAS at the expense of its significantly higher prevalence of palatine tonsil hypertrophy. The prevalence of HR-OSAS in Brazilian children with CP (GMFCS V) was higher than the frequency of OSAS in TD children assessed by polysomnography. HR-OSAS was significantly more prevalent in GMFCS V compared with GMFCS I-IV. Palatine tonsil hypertrophy was significantly associated with HR-OSAS. GMFCS V was significantly correlated with HR-OSAS due to its significantly higher prevalence of palatine tonsil hypertrophy. PosaST may be a reliable questionnaire for Brazilian children with CP, but studies are needed to define the HR-OSAS cutoff score in this population.

Abstract Context The 2019 American Association of Clinical Endocrinologists guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase. Objective The aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement. Patients and methods Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST, and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies) and 18 severe organic GHD (≥3 hormone deficiencies). Results Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis identified 7.3 μg/L as the optimal GH peak cutoff to GST [95% confidence interval (CI) 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value (PPV) 88.0%, negative predictive value (NPV) 95.7%] able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3 hormone deficiencies showed a GH peak <5 μg/L at ITT and <5.8 μg/L at GST but 1. The optimal cutoff for IGF-1 was −1.4 SD score (95% CI −1.94 to 0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population. Conclusion A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pretest probability of permanent GHD.

Craniopharyngiomas are rare solid or mixed solid and cystic tumors that arise from Rathke’s pouch remnants along the pituitary-hypothalamic axis, from the sella turcica to the brain third ventricle. Both the tumor and its treatment can lead to significant neurological and endocrinological complications. Due to the essential role of the hypothalamus in the complex neurophysiologic process of sleep, tumors involving the hypothalamic area may be responsible for disturbances in sleep–wake regulation with alterations in the circadian rhythm, sleep fragmentation, and increased daytime sleepiness. We report two cases of patients with craniopharyngioma, who came to our attention due to the occurrence of episodes characterized by psychomotor slowing and afinalistic limb movements, temporal and spatial disorientation, psychomotor agitation, and oneiric stupor like episodes. A comprehensive clinical data collection and a targeted diagnostic work-up led to a diagnosis of severe sleep disorder characterized by hypersomnia, altered sleep–wake rhythm, and sleep-related breathing disorder. In addition, the polysomnography revealed peculiar alterations in the sleep structure. The diagnostic work-up lead to an accurate differential diagnosis between epileptic seizures and episodes expressions of sleep disturbances. These clinical features can be challenging to diagnose and can lead to misdiagnosis and inappropriate treatment. Diagnosis of sleep disorders is crucial, considering the impact of sleep on general health, cognition, and neuropsychological functioning. These findings support the need to incorporate a comprehensive sleep evaluation in childhood brain tumor involving the suprasellar/hypothalamic region.

The etiology of central diabetes insipidus (CDI) in children is often unknown. Clinical and radiological features at disease onset do not allow discrimination between idiopathic forms and other conditions or to predict anterior pituitary dysfunction. To evaluate the evolution of pituitary stalk (PS) thickening and the pattern of contrast-enhancement in relation with etiological diagnosis and pituitary function. We enrolled 39 children with CDI, 29 idiopathic and 10 with Langerhans cell histiocytosis (LCH). Brain magnetic resonance images taken at admission and during follow-up (332 studies) were examined, focusing on PS thickness, contrast-enhancement pattern, and pituitary gland size; T2-DRIVE and postcontrast T1-weighted images were analyzed. Seventeen of 29 patients (58.6%) with idiopathic CDI displayed \"mismatch pattern,\" consisting in a discrepancy between PS thickness in T2-DRIVE and postcontrast T1-weighted images; neuroimaging findings became stable after its appearance, while \"mismatch\" appeared in LCH patients after chemotherapy. Patients with larger PS displayed mismatch more frequently (P = 0.003); in these patients, reduction of proximal and middle PS size was documented over time (P = 0.045 and P = 0.006). The pituitary gland was smaller in patients with mismatch (P < 0.0001). Patients with mismatch presented more frequently with at least one pituitary hormone defect, more often growth hormone deficiency (P = 0.033). The PS mismatch pattern characterizes patients with CDI, reduced pituitary gland size, and anterior pituitary dysfunction. The association of mismatch pattern with specific underlying conditions needs further investigation. As patients with mismatch show stabilization of PS size, we assume a prognostic role of this peculiar pattern, which could be used to lead follow-up.

Disclosure: N. Di Iorgi: None. D. Guglielmi: None. N. Flavia: None. A. Allegri: None. D. Fava: None. E. Casalini: None. G. Patti: None. M. Maghnie: None. Objectives: To evaluate the accuracy of the Glucagon test (GST) compared with the Insulin Tolerance test (ITT) as the gold standard in the diagnosis of Growth Hormone deficiency (GHD) in young adults with childhood-onset GHD (COGHD). Methods: Eighty-six subjects with COGHD (33F, 55M) were evaluated by ITT and GST stimulation tests and IGF-1 SDS at adult height achievement (median age of 17.5; IQR 13.9-18.4 years). Subjects were recruited from a single Center and based on the AACE 2019 Guidelines [1] classified as 1. idiopathic isolated GHD (I-GHD n=40 with normal brain MRI); 2. organic moderate GHD (omGHD with less than 3 pituitary deficiencies-PD and IGF-1<0 SDS, total n=40; n=12 midline defects, n=2 ALL, n=26 CNS tumors); 3. congenital/genetic defects/organic severe GHD (osGHD ≥3 PD and IGF-1 <-2 SDS, total n=6; n=1 midline defect, n=5 CNS tumors). ROC analyses were performed in order to analyze the Sensitivity (Se) and Specificity (Sp) of the GH peak after GST and of IGF-1 SDS compared to ITT. A peak GH value <6μg/L after ITT was suggestive of permanent GHD [2]. Results: Median GH peak to ITT (0.2; IQR 0.01-0.7 μg/L) and GST (0.1; IQR 0.01-1.4μg/L) were lower in osGHD compared to I-GHD subjects (15.0; IQR 8.6-21.9 to ITT and 12.6; IQR 10.5-18.8 μg/L to GST, P’s <0.0001); similarly, GH peak to ITT (2.1; IQR 1.1-6.8 μg/L) and GL (2.7; IQR 1.2-5.8) were lower in omGHD compared to I-GHD subjects (P’s <0.0001). Mean IGF-1 were also lower in osGHD (-3.2 SDS; IQR -7.4- -2.9, P<0.0001) and in omGHD (-2.0 SDS; IQR -2.8 - -0.7; P<0.0001) compared to I-GHD subjects (0,1; IQR -0.6-1.1SDS). A GH peak value to GST of 7.59 mcg/L (Se 92.3%, Sp of 87.2%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 89.5% of the entire cohort while an IGF-1 cut-off of -1.45 SDS (Se 73%; Sp 93.5%; AUC=0.84; 95% CI, 0.75 - 0.94) correctly classified 83,1%. A GH peak value to GST of 5.81 mcg/L (Se 96.6%, Sp of 81.8%; AUC=0.95; 95% CI, 0.88-1.02) correctly classified 92.5% of omGHD patients while an IGF-1 cut-off of -1.64 SDS (Se 72.3%, Sp of 90.9%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 77.5% omGHD patients. Median BMI SDS was higher in patients with osGHD (1.8; IQR 1,6- 2.2, P<0.001) and omGHD (0.6; IQR 0.1- 1.8, P<0.001) compared to I-GHD (0.2; IQR -0.7- 1.1). GH peak to GST correlated with BMI SDS only in the total cohort (r -0.313, P=0.0031). Conclusions: Our results suggest that a peak value <6 μg/L after GST is accurate in detecting permanent GHD during transition in a cohort of patients with organic GHD with less than 3 pituitary defects and IGF-1 values <0 SDS; the GH response to GST could be affected by BMI SDS, but further studies are needed. [1] Yuen KCJ et al. Endocr Pract 2019; 25 (11):1191-1232. [2] Maghnie M et al, EJE 2005; 152:589-596. Presentation: Thursday, June 15, 2023

Abstract Context Lumbar spine bone mineral density (BMD) rises sharply during puberty; earlier onset, as in central precocious puberty (CPP), may accelerate skeletal maturation and modify bone accrual. Objective To assess bone and body composition in girls with CPP/early puberty (EP), premature thelarche (PT), and prepubertal controls (PC). Patients and methods We analyzed 184 girls aged 5-9 years with suspected CPP/EP (108 CPP/EP, 76 PT) and 47 PC. DXA assessed L1-L4 and total body less head (TBLH) BMD, bone mineral content (BMC), and body composition. Derived measures included bone mineral apparent density (BMAD), trabecular bone score (TBS), android–gynoid fat ratio (A/G), fat mass index (FMI), and fat-free mass index (FFMI). Results Group CPP/EP showed greater height, BMI SDS, bone age (BA), FM, lean mass, and FFMI than controls, with higher L1-L4 BMD (P < .001) and a trend for higher ΔBMD L1-L4–TBLH Z-score (P = .07); L1-L4 BMAD Z-scores were similar. Versus Group PT, Group CPP/EP had higher Δheight-target height SDS (P = .005), BA (P < .001), and lean mass (P = .03); Group PT had higher A/G (P = .02) and TBS (P = .03). Within Group PT, girls with pubarche had higher height, BMI SDS, BA, FMI, A/G (P = .02) and L1-L4 BMAD Z-scores (P = .01). Conclusion Both CPP/EP and PT showed higher fat and lean mass than controls, with PT marked by greater central adiposity. Only overweight/obesity, and pubarche onset in PT, were associated with increased L1-L4 BMAD Z-scores. DXA provides additional insight into body composition and bone accrual in girls with early pubertal signs.