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Background: It has been reported that central adrenal insufficiency (CAI) in pediatric patients (pts) with Prader-Willi syndrome (PWS) may be a potential cause of their sudden death. In addition, the risk of CAI may increase during treatment with recombinant human growth hormone (rhGH)., Objective: To prevent both over- and undertreatment with hydrocortisone, we evaluated the prevalence of CAI in a large multicenter cohort of pediatric pts with PWS analyzing adrenal response in the low-dose ACTH test (LDAT) and/or the glucagon stimulation test (GST) and reviewing the literature., Methods: A total of 46 pts with PWS were enrolled to the study, including 34 treated with rhGH with a median dose of 0.21 mg/kg/week. LDAT was performed in 46 pts, and GST was carried out in 13 pts. Both tests were conducted in 11 pts. The tests began at 8:00 a.m. Hormones were measured by radioimmunoassays. Serum cortisol response >181.2 ng/mL (500 nmol/L) in LDAT and >199.3 ng/mL (550 nmol/L) in GST was considered a normal response. Additionally, cortisol response delta (the difference between baseline and baseline) >90 ng/mL and doubling/tripling of baseline cortisol were considered indicators of normal adrenal reserve., Results: Three GSTs were not diagnostic (no hypoglycemia obtained). LDAT results suggested CAI in four pts, but in two out of four pts, and CAI was excluded in GST. GST results suggested CAI in only one patient, but it was excluded in LDAT. Therefore, CAI was diagnosed in 2/46 pts (4.3%), 1 treated and 1 untreated with rhGH, with the highest cortisol values of 162 and 175 ng/dL, but only in one test. However, in one of them, the cortisol delta response was >90 ng/mL and peak cortisol was more than tripled from baseline. Finally, CAI was diagnosed in one patient treated with rhGH (2.2%)., Conclusion: We present low prevalence of CAI in pediatric pts with PWS according to the latest literature. Therefore, we do not recommend to routinely screen the function of the hypothalamic-pituitary-adrenal axis (HPAA) in all pts with PWS, both treated and untreated with rhGH. According to a review of the literature, signs and symptoms or low morning ACTH levels suggestive of CAI require urgent and appropriate diagnosis of HPAA by stimulation test. Our data indicate that the diagnosis of CAI should be confirmed by at least two tests to prevent overtreatment with hydrocortisone., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wędrychowicz, Doleżal-Ołtarzewska, Zygmunt-Górska, Kalicka-Kasperczyk, Tyrawa, Wojcik, Janus, Kot, Lecka-Ambroziak, Petriczko, Wielopolska and Starzyk.)

Objective: To assess the significance of changes in the saliva in the etiology of gingivitis and tooth wear in children and adolescents with Prader-Willi syndrome (PWS)., Materials and Methods: The study included 80 (2.8-18 years old; 39 girls and 41 boys): 40 in PWS group (mean age 8.0 ± 4.24 years) and 40 in control group (mean age 7.9 ± 4.12 years). General condition, oral para-functional habits, tooth wear (modified TWI), oral hygiene and gingival status (Plaque Index (PLI) and Gingival Index (GI)), localization of gingivitis, and salivary characteristics were assessed. The chi-square test, the Mann-Whitney U test, Spearman's rank correlation, and odds ratio based on logistic regression in a statistical analysis were applied., Results: Chances of gingivitis were increased by low PLI (odds ratio (OR) = 32.53), low resting salivary flow (OR = 3.96), increased viscosity of saliva (OR = 3.54), and mouth breathing (OR = 8.17). For gingivitis in anterior regions, low PLI (OR = 107.67), low resting (OR = 5.73) and stimulated (OR = 1.86) salivary flow, increased viscosity of saliva (OR = 5.87), mouth breathing (OR = 10.00), and low stimulated salivary flow (OR = 3.18) were observed. Tooth wear rates were increased by teeth grinding (OR = 16.20), mouth breathing (OR = 4.33), increased viscosity of saliva (OR = 11.67) and low resting (OR = 6.07), and stimulated (OR = 4.22) salivary flow., Conclusions: In PWS, reduced salivary secretion, increased viscosity, of saliva and mouth breathing increase the risk of plaque-induced gingivitis and tooth wear., Clinical Relevance: The prevention and treatment of tooth wear and gingivitis in PWS patients is necessary not only to treat bruxism and mouth breathing but also to limit the influence of negative changes of saliva.

Introduction: Sleep-related breathing disorders (SRBD) are commonly present in patients with Prader-Willi syndrome (PWS). Recombinant human growth hormone (rhGH) treatment is reported to improve breathing function in PWS, but the findings are not explicit., Material and Methods: Screening polysomnography- polygraphy (PSG), assessing nasal respiratory flow, respiratory effort, and blood oxygen saturation, was used. Group 1 - before rhGH therapy (n = 11, mean age 3.0 years); PSG was repeated after the start of rhGH therapy in a mean time of 0.9 years in six patients (Group 1a). Group 2 - on rhGH treatment, for a mean time of four years (n = 17, mean age 8.8 years). Group 3 - without rhGH therapy due to severe obesity (n = 8, mean age 13.1 years)., Results: Group 1 - mean apnoea-hypopnoea index (AHI) was 10.2, oxygen desaturation index (ODI)- 36.3, Group 1a- AHI 12.0, ODI 60.9, Group 2-AHI 9.0, ODI 25.1, Group 3- AHI 8.2, ODI 22.0. ODI was significantly higher in Group 1a than in the other groups (p < 0.005), but not strictly related to SRBD. The results in Group 2 did not differ significantly from those of Group 1., Conclusions: Our study proves the high frequency of SRBD among PWS patients, with worsening of ODI after short-term rhGH therapy.

Genotype–phenotype correlation in patients with Prader–Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start (p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID (p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 (p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age—group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start (p = 0.00), with lower body mass index (BMI) SDS (p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 (p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS.

Puberty in children with Prader-Willi syndrome (PWS) is usually delayed and/or incomplete but in some patients premature/early adrenarche is observed. We assessed the premature adrenarche (PA) in PWS patients during the recombinant human growth hormone (rhGH) therapy and influence of PA on the course of central puberty (CP), rhGH efficacy and safety, and patients’ metabolic state. Forty-nine PWS patients were treated with rhGH, 11 presented with PA (group 1) and 14 had normal course of adrenarche (group 2). PA was observed in 22.5% of the PWS children treated with rhGH. The mean time between the rhGH start and the adrenarche, the rhGH dose, the growth velocity and the insulin-like growth factor 1 SD (IGF1 SD) during the treatment, as well as the time of CP, final height SD and BMI SD were similar in both groups. There were also no significant differences in the metabolic assessment—the oral glucose tolerance test (OGTT) and lipid profile results. PA may be a part of the clinical picture of PWS, apart from hypogonadotrophic hypogonadism and it seems to have no influence on CP in PWS patients. The rhGH efficacy and safety were comparable in the patients with PA and the normal course of adrenarche.

Genotype–phenotype correlation in patients with Prader–Willi syndrome (PWS) has still not been fully described. We retrospectively analysed data of 147 patients and compared groups according to genetic diagnosis: paternal deletion of chromosome 15q11-q13 (DEL 15, n = 81), maternal uniparental disomy (UPD 15, n = 10), excluded DEL 15 (UPD 15 or imprinting centre defect, UPD/ID, n = 30). Group DEL 15 had an earlier genetic diagnosis and recombinant human growth hormone (rhGH) start (p = 0.00), with a higher insulin-like growth factor 1 (IGF1) level compared to group UPD/ID (p = 0.04). Among perinatal characteristics, there was only a tendency towards lower birth weight SDS in group UPD 15 (p = 0.06). We also compared data at rhGH start in relation to genetic diagnosis age—group 1: age ≤9 months, group 2: >9 months ≤ 2 years, group 3: > 2 years. Group 1 had the earliest rhGH start (p = 0.00), with lower body mass index (BMI) SDS (p = 0.00) and a tendency towards a higher IGF1 level compared to group 3 (p = 0.05). Genetic background in children with PWS is related to time of diagnosis and rhGH start, with a difference in IGF1 level before the therapy, but it seems to have little impact on perinatal data. Early genetic diagnosis leads to early rhGH treatment with favourable lower BMI SDS. [ABSTRACT FROM AUTHOR]

Sleep-related breathing disorders (SRBDs) can be present in children with simple obesity and with Prader–Willi syndrome (PWS) and influence an individual diagnostic and treatment approach. We compared frequency and severity of SRBDs in children with simple obesity and with PWS, both without and on recombinant human growth hormone (rhGH) treatment, and correlation of SRBDs with insulin resistance tests. A screening polysomnography-polygraphy (PSG), the oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were analysed in three groups of patients—with simple obesity (group 1, n = 30, mean age 14.2 years), patients with PWS without the rhGH therapy (group 2, n = 8, mean age 13.0 years) and during the rhGH treatment (group 3, n = 17, mean age 8.9 years). The oxygen desaturation index (ODI) was significantly higher in groups 2 and 3, compared to group 1 (p = 0.00), and hypopnea index (HI) was higher in group 1 (p = 0.03). Apnea–hypopnea index (AHI) and apnea index (AI) results positively correlated with the insulin resistance parameters in groups 1 and 3. The PSG values worsened along with the increasing insulin resistance in children with simple obesity and patients with PWS treated with rhGH that may lead to a change in the patients' care. [ABSTRACT FROM AUTHOR]

Puberty in children with Prader-Willi syndrome (PWS) is usually delayed and/or incomplete but in some patients premature/early adrenarche is observed. We assessed the premature adrenarche (PA) in PWS patients during the recombinant human growth hormone (rhGH) therapy and influence of PA on the course of central puberty (CP), rhGH efficacy and safety, and patients' metabolic state. Forty-nine PWS patients were treated with rhGH, 11 presented with PA (group 1) and 14 had normal course of adrenarche (group 2). PA was observed in 22.5% of the PWS children treated with rhGH. The mean time between the rhGH start and the adrenarche, the rhGH dose, the growth velocity and the insulin-like growth factor 1 SD (IGF1 SD) during the treatment, as well as the time of CP, final height SD and BMI SD were similar in both groups. There were also no significant differences in the metabolic assessment—the oral glucose tolerance test (OGTT) and lipid profile results. PA may be a part of the clinical picture of PWS, apart from hypogonadotrophic hypogonadism and it seems to have no influence on CP in PWS patients. The rhGH efficacy and safety were comparable in the patients with PA and the normal course of adrenarche. [ABSTRACT FROM AUTHOR]