Three years of growth hormone treatment in young adults with Prader-Willi Syndrome previously treated with growth hormone in childhood: Effects on glucose homeostasis and metabolic syndrome

Context: Growth hormone (GH) has been approved for children with Prader-Willi syndrome (PWS) and significantly improves body composition in adults with PWS. Adults with PWS are predisposed to develop impaired glucose tolerance (IGT) and diabetes mellitus type 2 (DMT2). Continuation of GH maintains body composition, but GH is known to induce insulin resistance, which might affect glucose homeostasis. Studies on long-term effects of GH treatment in adults are very limited. Objective: To investigate effects of 3 years of GH treatment on glucose homeostasis and prevalence of metabolic syndrome (MS) in adults with PWS. Design: Open-label, prospective study. Patients: 43 young adults with PWS. Setting: Dutch PWS Reference Center. Main outcome measures: Glucose and insulin during oral glucose tolerance test. Results: Estimated mean (95% CI) fasting glucose and insulin levels remained stable during 3 years of GH treatment. Glucose being 4.6 (4.4-4.8) mmol/l at start and 4.7 (4.6-4.9) mmol/l after 3 years (P =.07); insulin being 59.5 (45.2-75.8) pmol/l and 56.7 (45.2-69.6) pmol/l resp. (P =.72). Sex, ethnicity and fat mass percentage were significantly associated with fasting glucose levels, while IGF-I or GH-dose were not. Blood pressure, lipids and prevalence of MS remained stable during 3 years of GH. IGT prevalence was variable over time, six patients had IGT at start and eleven after 3 years of GH. One patient developed DMT2. However, prevalence of IGT or DMT2 was not significantly higher after 3 years than at study start. Conclusions: Three years of GH treatment in adults with PWS does not impair glucose homeostasis and does not lead to an increased prevalence of DMT2

Oxytocin in young children with Prader-Willi syndrome: Results of a randomized, double-blind, placebo-controlled, crossover trial investigating 3 months of oxytocin

Context: Prader-Willi syndrome (PWS) is characterized by hypothalamic dysfunction, hyperphagia and a typical behavioural phenotype, with characteristics of autism spectrum disorder (ASD) like stubbornness, temper tantrums and compulsivity. It has been suggested that the oxytocin system in patients with PWS is dysfunctional. In ASD, intranasal oxytocin treatment has favourable effects on behaviour. Objective: To evaluate the effects of 3 months of twice daily intranasal oxytocin (dose range 16-40 IU/day), compared to placebo, on behaviour and hyperphagia in children with PWS. Design: Randomized, double-blind, placebo-controlled, crossover study in the Dutch PWS Reference Center. Patients: Twenty-six children with PWS aged 3-11 years. Main outcome measures: (Change in) behaviour and hyperphagia measured by Oxytocin Questionnaire and Dykens hyperphagia questionnaire. Results: In the total group, no significant effects of oxytocin on social behaviour or hyperphagia were found. However, in boys, the Oxytocin Questionnaire scores improved significantly during oxytocin treatment, compared to a deterioration during placebo (4.5 (−0.8 to 15.3) vs. −4.0 (−11.3 to 0.8), P =.025). The Dykens hyperphagia questionnaire scores remain

Prevalence of growth hormone (GH) deficiency in previously GH-treated young adults with Prader-Willi syndrome

Objective: Some features of subjects with Prader-Willi syndrome (PWS) resemble those seen in growth hormone deficiency (GHD). Children with PWS are treated with growth hormone (GH), which has substantially changed their phenotype. Currently, young adults with PWS must discontinue GH after attainment of adult height when they do not fulfil the criteria of adult GHD. Limited information is available about the prevalence of GHD in adults with PWS. This study aimed to investigate the GH/insulin-like growth factor (IGF-I) axis and the prevalence of GHD in previously GH-treated young adults with PWS. Design: Cross-sectional study in 60 young adults with PWS. Measurements: Serum IGF-I and IGFBP-3 levels, GH peak during combined growth hormone-releasing hormone (GHRH)-arginine stimulation test. Results: Serum IGF-I was <−2 standard deviation scores (SDS) in 2 (3%) patients, and IGFBP-3 was within the normal range in all but one patient. Median (IQR) GH peak was 17.8 μg/L (12.2; 29.7) [~53.4 mU/L] and below 9 μg/L in 9 (15%) patients. Not one patient fulfilled the criteria for adult GHD (GH peak < 9 μg/L and IGF-I < −2 SDS), also when BMI-dependent criteria were used. A higher BMI and a higher fat mass percentage were significantly associated with a lower GH peak. There was no significant difference in GH peak between patients with a deletion or a maternal uniparental disomy (mUPD). Conclusions: In a large group of previously GH-treated young adults with PWS, approximately 1 in 7 exhibited a GH peak <9 μg/L during a GHRH-arginine test. However, none of the patients fulfilled the consensus criteria for adult GHD

Effects of 8 years of growth hormone treatment on scoliosis in children with Prader-Willi syndrome

Objective Scoliosis is frequently seen in children with Prader–Willi syndrome (PWS). There is still concern that growth hormone (GH) treatment might increase the risk of onset or progression of scoliosis. Short-term data suggested no adverse effects of GH on scoliosis, but long-term effects of GH treatment on development of scoliosis in PWS are unknown. This study investigated the effects of 8 years of GH treatment on scoliosis in children with PWS. Design Open-label, prospective cohort study in 103 children with PWS receiving GH for 8 years was analyzed. Prevalence and severity of scoliosis were compared to a group of 23 age-matched GH-untreated children with PWS. Methods Spine X-rays and DEXA-scans were performed, and Cobb angel was measured by two independent observers. Results After 8 years of GH treatment, at median age of 10.8 years, prevalence of scoliosis was 77.7%. No difference in prevalence or severity of scoliosis was found between GH-treated and age-matched untreated children with PWS (P = 0.409 and P = 0.709, respectively). Height SDS and trunkLBM were significantly higher in GH-treated children. Higher bone mineral density of the lumbar spine was found in children without scoliosis after 8 years of GH. Bone mineral apparent density of lumbar spine (BMADLS) SDS was associated with lower Cobb angle (r = −0.270, P = 0.008). Conclusions Eight years of GH treatment has no adverse effects on the prevalence and severity of scoliosis in children with PWS until 11 years of age. As BMADLS SDS is inversely associated with Cobb angle, it is pivotal to optimize the BMD status in children with PWS

Three years of growth hormone treatment in young adults with Prader-Willi syndrome: Sustained positive effects on body composition

Background: In children with Prader-Willi syndrome (PWS), the benefits of growth hormone treatment are well established. Several one-year studies have shown that growth hormone is also beneficial for adults with PWS, improving body composition. However, little is known about the longer-term effects. This study investigated the effects on body composition in adult patients with PWS during 3 years of growth hormone therapy in a dose of 0.33 mg/m2/day. Methods: Open-label, prospective study in 43 young adults with PWS with a median (IQR) age of 19.0 (17.5 to 20.7) years. Fat mass percentage SDS and lean body mass SDS were measured annually by DXA. Results: Estimated mean (95% CI) fat mass percentage SDS decreased during the three-year study from 2.1 (1.9 to 2.3) SDS at start to 1.9 (1.8 to 2.1) SDS, p = 0.012, while lean body mass SDS remained stable at - 2.1 (- 2.4 to - 1.8) SDS at start to - 1.9 (- 2.3 to - 1.6) after 3 years, p = 0.15. Fasting glucose and insulin remained similar during the three-year study, glucose being 4.6 (4.4 to 4.8) mmol/l at start and 4.6 (4.5 to 4.7) mmol/l after 3 years of growth hormone, p = 0.93 and insulin being 59.5 (42.2 to 81.5) pmol/l and 55.0 (42.4 to 69.2) pmol/l, resp., p = 0.54. There were no growth hormone-related adverse events during the study. Conclusions: Three years of growth hormone treatment in young adults with PWS maintains the positive effects on body composition attained during childhood. Thus, adults with PWS benefit from longer-term growth hormone treatment. Trial registration: EudraCT, EudraCT number 2011-001313-14. Registered 17 October 2012

Effects of childhood multidisciplinary care and growth hormone treatment on health problems in adults with prader-willi syndrome

Prader-Willi syndrome (PWS) is a complex hypothalamic disorder. Features of PWS include hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. The combination of growth hormone treatment and multidisciplinary care (GHMDc) has greatly improved the health of children with PWS. Little is known about the effects of childhood GHMDc on health outcomes in adulthood. We retrospectively collected clinical data of 109 adults with PWS. Thirty-nine had received GHMDc during childhood and adolescence (GHMDc+ group) and sixty-three had never received growth hormone treatment (GHt) nor multidisciplinary care (GHMDc− group). Our systematic screening revealed fewer undetected health problems in the GHMDc+ group (10%) than in the GHMDc− group (84%). All health problems revealed in the GHMDc+ group had developed between the last visit to the paediatric and the first visit to the adult clinic and/or did not require treatment. Mean BMI and the prevalence of diabetes mellitus type 2 were significantly lower in the GHMDc+ group compared to the GHMDc− group. As all patients who received GHt were treated in a multidisciplinary setting, it is unknown which effects are the result of GHt and which are the result of multidisciplinary care. However, our data clearly show that the combination of both has beneficial effects. Therefore, we recommend continuing GHMDc after patients with PWS have reached adult age.</p

Uterine function, pregnancy complications, and pregnancy outcomes among female childhood cancer survivors

Objective: To evaluate whether abdominal-pelvic radiotherapy for childhood cancer impairs uterine function and increases the risk of pregnancy complications and adverse pregnancy outcomes. Design: Nested cohort study. Setting: Not applicable. Patient(s): Childhood cancer survivors previously exposed to abdominal-pelvic radiotherapy (RT-exposed CCSs) as part of their treatment for childhood cancer. Intervention(s): Radiotherapy-exposed CCSs (n = 55) were age-and parity-matched to nonirradiated CCSs (non-RT-exposed CCSs; n = 110) and general population controls (n = 110). Main Outcome Measures: Uterine volume, pregnancy complications, and pregnancy outcomes. Result(s): Among nulligravidous participants, median (interquartile range) uterine volume was 41.4 (18.6-52.8) mL for RT-exposed CCSs, 48.1 (35.7-61.8) mL for non-RT-exposed CCSs, and 61.3 (49.1-75.5) mL for general population controls. Radiotherapy-exposed CCSs were at increased risk of a reduced uterine volume ( Conclusion(s): Uterine exposure to radiotherapy during childhood reduces adult uterine volume and leads to an increased risk of pregnancy complications and adverse pregnancy outcomes. Preconceptional counseling and appropriate obstetric monitoring is warranted. ((C) 2018 by American Society for Reproductive Medicine.) El resumen esta disponible en Espanol al final del articulo