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Aim: Diabetes mellitus is a major cause of death. Outpatients with diabetes have more complications than patients in general practice; mortality patterns have only been studied in the total diabetes population. This study aims to assess mortality, causes, and predictors in outpatients with diabetes. Materials and Methods: A cohort study, included people with diabetes mellitus from the nationwide Dutch Paediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics in 2016‐2020. DPARD data were linked to Statistics Netherlands (CBS), comprising data on mortality, ethnicity and education. All‐cause and cardiovascular mortality rates were estimated using Cox proportional hazard regression. Results: During a median follow‐up of 3.1 years among 12 992 people with diabetes, mortality rates per 10 000 person‐years were 67.7 in adult type 1 diabetes and 324.2 in type 2 diabetes. The major cause of non‐cardiovascular death was malignancy. During the pandemic years of influenza (2018) and COVID (2020), mortality rates peaked. Age, smoking and an estimated glomerular filtration rate of <60 ml/min were associated with all‐cause mortality. In type 2 diabetes, additional factors were male sex, body mass index <20 kg/m2, diabetes duration <1 year and hypertension. Conclusions: Mortality among Dutch outpatients with diabetes is high. Smoking and renal failure were associated with mortality in both types. Further focus on early detection and treatment of mortality‐associated factors may improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting. [ABSTRACT FROM AUTHOR]

Aims: Paediatric diabetes care has become increasingly specialised due to the multidisciplinary approach and technological developments. Guidelines recommend sufficient experience of treatment teams. This study evaluates associations between hospital volume and resource use and hospital expenditure in Dutch children with diabetes. Methods: Retrospective cohort study using hospital claims data of 5082 children treated across 44 Dutch hospitals (2019–2020). Hospitals were categorised into three categories; small (≥20–100 patients), medium (≥100–200 patients) and large (≥200 patients). All‐cause hospitalisations, consultations, technology and hospital expenditure were analysed and adjusted for age, sex, socio‐economic status (SES) and hospital of treatment. Results: Fewer hospitalisations were observed in large hospitals compared to small hospitals (OR 0.48; [95% CI 0.32–0.72]; p < 0.001). Median number of yearly paediatrician visits was 7 in large and 6 in small hospitals, the significance of which was attenuated in multilevel analysis (OR ≥7 consultations: 1.89; [95%CI 0.74–4.83]; p = 0.18). Technology use varies between individual hospitals, whereas pump usage and real‐time continuous glucose monitoring showed no significant differences between hospital volumes. Mean overall expenditure was highest in medium‐sized centres with €6434 per patient (IQR €2555–7955); the difference in diabetes care costs was not significant between hospital patient volumes. Conclusions: Care provision patterns vary by hospital patient volume. Large hospitals had the lowest hospitalisation rates. The use of diabetes technology was not different between hospital patient volumes. Medium‐sized hospitals showed the highest overall expenditure, but diabetes care costs were similar across hospital volumes. [ABSTRACT FROM AUTHOR]

Aim: Socio‐economic status (SES) influences diabetes onset, progression and treatment. In this study, the associations between SES and use of hospital care were assessed, focusing on hospitalizations, technology and cardiovascular complications. Materials and Methods: This was an observational cohort study comprising 196 695 patients with diabetes (all types and ages) treated in 65 hospitals across the Netherlands from 2019 to 2020 using reimbursement data. Patients were stratified in low, middle, or high SES based on residential areas derived from four‐digit zip codes. Results: Children and adults with low SES were hospitalized more often than patients with middle or high SES (children: 22%, 19% and 15%, respectively; p <.001, adults: 28%, 25% and 23%; p <.001). Patients with low SES used the least technology: no technology in 48% of children with low SES versus 40% with middle SES and 38% with high SES. In children, continuous subcutaneous insulin infusion (CSII) and real‐time continuous glucose monitoring (rtCGM) use was higher in high SES {CSII: odds ratio (OR) 1.54 [95% confidence interval (CI) 1.35‐1.76]; p <.001; rtCGM OR 1.39 [95% CI 1.20‐1.61]; p <.001} and middle SES [CSII: OR 1.41 (95% CI 1.24‐1.62); p <.001; rtCGM: OR 1.27 (95% CI 1.09‐1.47); p =.002] compared with low SES. Macrovascular (OR 0.78 (95% CI 0.75‐0.80); p <.001) and microvascular complications [OR 0.95 (95% CI 0.93‐0.98); p <.001] occurred less in high than in low SES. Conclusions: Socio‐economic disparities were observed in patients with diabetes treated in Dutch hospitals, where basic health care is covered. Patients with low SES were hospitalized more often, used less technology, and adults with high SES showed fewer cardiovascular complications. These inequities warrant attention to guarantee equal outcomes for all. [ABSTRACT FROM AUTHOR]

Introduction: Temple syndrome (TS14) is a rare imprinting disorder caused by maternal uniparental disomy of chromosome 14, paternal deletion of 14q32.2, or an isolated methylation defect. Most patients with TS14 develop precocious puberty. Some patients with TS14 are treated with growth hormone (GH). However, evidence for the effectiveness of GH treatment in patients with TS14 is limited. Methods: This study describes the effect of GH treatment in 13 children and provides a subgroup analysis of 5 prepubertal children with TS14. We studied height, weight, body composition by dual-energy X-ray absorptiometry, resting energy expenditure (REE), and laboratory parameters during 5 years of GH treatment. Results: In the entire group, mean (95% CI) height SDS increased significantly during 5 years of GH treatment from −1.78 (−2.52; −1.04) to 0.11 (−0.66; 0.87). Fat mass percentage SDS decreased significantly during the first year of GH, and lean body mass (LBM) SDS and LBM index increased significantly during 5 years of treatment. IGF-1 and IGF-BP3 levels rose rapidly during GH treatment, and the IGF-1/IGF-BP3 molar ratio remained relatively low. Thyroid hormone levels, fasting serum glucose, and insulin levels remained normal. In the prepubertal group, median (interquartile range [IQR]) height SDS, LBM SDS, and LBM index also increased. REE was normal at start and did not change during 1 year of treatment. Five patients reached adult height and their median (IQR) height SDS was 0.67 (−1.83; −0.01). Conclusion: GH treatment in patients with TS14 normalizes height SDS and improves body composition. There were no adverse effects or safety concerns during GH treatment. [ABSTRACT FROM AUTHOR]

Aim: To provide insight into healthcare resource utilization and hospital expenditure of patients treated for diabetes in Dutch hospitals. Materials and methods: We conducted an observational cohort study of 193 840 patients aged ≥18 years and treated for diabetes mellitus in 65 Dutch hospitals in 2019 to 2020, using real‐world reimbursement data. Consultations, hospitalizations, technology use, total hospital and diabetes care costs (encompassing all care for diabetes itself) were assessed during 1‐year follow‐up. In addition, expenditure was compared with that in the general Dutch population. Results: Total hospital costs for all patients with diabetes were €1 352 690 257 (1.35 billion) per year, and 15.9% (€214 963 703) was associated with treatment of diabetes. Mean yearly costs per patient were €6978, with diabetes care costs of €1109. Mean hospital costs of patients exceeded that of the Dutch population three‐ to sixfold. Total hospital costs increased with age, whereas diabetes expenditure decreased with age (18‐40 years, €1575; >70 years, €932). Of all patients with diabetes, 51.3% (n = 99 457) received care related to cardiovascular complications. Micro‐ and macrovascular complications, or a combination, increased hospital costs (1.4‐5.3 times higher). Conclusions: The hospital resource use of Dutch diabetes patients is high, with a large burden of cardiovascular complications. Resource use is rooted mainly in hospital care of diabetes‐related complications, not in the treatment of diabetes. Early treatment and prevention of complications remain imperative to taper future healthcare expenditure on patients with diabetes. [ABSTRACT FROM AUTHOR]

Background: Temple syndrome (TS14) is an imprinting disorder caused by a maternal uniparental disomy of chromosome 14 (UPD(14)mat), paternal deletion of 14q32 or an isolated methylation defect of the MEG3-DMR. Studies on phenotypical characteristics in TS14 are scarce and patients with TS14 often experience delay in diagnosis, which has adverse effects on their health. TS14 is often characterized as either Prader–Willi-like, Silver–Russell-like or as a Silver–Russell spectrum disorder. Methods: This study describes 15 patients with TS14 who visited the Dutch Reference Center for Prader–Willi-like from December 2018 to January 2022. Results: Eight patients had UPD(14)mat and seven a methylation defect. The most common symptoms were intra-uterine growth retardation (IUGR) (100%), hypotonia (100%), precocious puberty (89%), small for gestational age (SGA) birth (67%), tube feeding after birth (53%) and psycho-behavioral problems (53%). Median (interquartile range (IQR)) IQ was 91.5 (84.25; 100.0), whilst many patients were enrolled in special education (54%). The median (IQR) fat mass % (FM%) SDS was 2.53 (2.26; 2.90) and lean body mass (LBM) SDS −2.03 (−3.22; −1.28). There were no significant differences in clinical characteristics between patients with a UPD(14)mat and a methylation defect. Conclusions: Our patients share a distinct phenotype consisting of IUGR, SGA birth, precocious puberty, hypotonia, tube feeding after birth, psycho-behavioral problems and abnormal body composition with a high FM% and low LBM. Whilst similarities with Prader–Willi syndrome (PWS) and Silver–Russell syndrome (SRS) exist, TS14 is a discernible syndrome, deserving a tailored clinical approach. Testing for TS14 should be considered in patients with a PWS or SRS phenotype in infancy if PWS/SRS testing is negative. [ABSTRACT FROM AUTHOR]

Aims: Residual beta cell function in type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd) given in 3 intralymphatic injections with oral vitamin D has shown promising results in persons with T1D carrying the human leukocyte antigen (HLA) DR3-DQ2 haplotype in the phase 2b trial DIAGNODE-2. We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM). Methods: DIAGNODE-2 (NCT03345004) was a multicenter, randomized, placebo-controlled, double-blind trial of 109 recent-onset T1D patients aged 12 to 24 years with GAD65 antibodies and fasting C-peptide > 0.12 nmol/L, which randomized patients to 3 intralymphatic injections of 4 μg GAD-alum and oral vitamin D, or placebo. We report results for exploratory endpoints assessed by 14-day CGM at months 0, 6, and 15. Treatment arms were compared by mixed-effects models for repeated measures adjusting for baseline values. Results: We included 98 patients with CGM recordings of sufficient quality (DR3-DQ2-positive patients: 27 GAD-alum-treated and 15 placebotreated). In DR3-DQ2-positive patients, percent of time in range (TIR, 3.9-10 mmol/L) declined less between baseline and month 15 in GAD-alumtreated compared with placebo-treated patients (-5.1% and -16.7%, respectively; P = 0.0075), with reduced time > 13.9 mmol/L (P = 0.0036), and significant benefits on the glucose management indicator (P = 0.0025). No differences were detected for hypoglycemia. GAD-alum compared to placebo lowered the increase in glycemic variability (standard deviation) observed in both groups (P = 0.0219). Change in C-peptide was correlated with the change in TIR. Conclusions: Intralymphatic GAD-alum improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup.Research Design and Methods: In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12-24 years (mean ± SD 16.4 ± 4.1) with a diabetes duration of 7-193 days (88.8 ± 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 μg GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months.Results: Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845-1.408]; P = 0.5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126-2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted HbA1c ≤9; P = 0.0310). Minor transient injection site reactions were reported.Conclusion: Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach. [ABSTRACT FROM AUTHOR]

Objectives: We aim to determine the prevalence and the course of anxiety and mood disorders in Dutch adolescents (12–18 years old) with type 1 diabetes, and to examine correlates of symptom severity, including parental emotional distress. Methods: Participants were 171 adolescents and 149 parents. The Diagnostic Interview Schedule for Children‐IV was used to assess current, past year and lifetime anxiety and mood disorders in adolescents. Symptom severity and diabetes distress were measured with validated questionnaires. Correlates of these symptoms were examined using hierarchical regression analyses and included demographics (adolescent sex and age), clinical factors (diabetes duration, treatment modality, most recent glycated hemoglobin A1c; all extracted from medical charts), adolescent diabetes distress, and parent emotional distress. Results: Twenty‐four (14%) adolescents met the criteria for ≥1 disorder(s) in the previous 12 months. Anxiety disorders were more prevalent than mood disorders (13% vs. 4%). Lifetime prevalence of anxiety and mood disorders was 29% (n = 49). The presence of any of these disorders earlier in life (from 5 years old up to 12 months prior to assessment) was associated with disorders in the past 12 months (OR = 4.88, p = 0.001). Higher adolescent diabetes distress was related to higher symptoms of anxiety (b = 0.07, p = 0.001) and depression (b = 0.13, p = 0.001), while demographics, clinical characteristics, and parental emotional distress were not related. Conclusions: Anxiety and mood disorders are common among adolescents and related to earlier disorders. Higher diabetes distress was related to higher symptom severity. Clinicians are advised to address past psychological problems and remain vigilant of these problems. [ABSTRACT FROM AUTHOR]

Objective: We hypothesized that modelling catch-up growth (CUG) as developed for coeliac disease (CD), might also fit CUG in adequately treated children with juvenile hypothyroidism (JHT) or growth hormone deficiency (GHD). Methods: We used a monomolecular function for all available prepubertal data on height standard deviation score (HSDS) minus target height SDS (adjHSDS) in children with JHT (n=20) and GHD (n=18) on a conventional (CoD) or high GH dose (HD), based either on a national height reference with an age cut-off of 10 (girls) and 12 (boys) years (model 1) or prepubertal height reference values, if age (0) was =3, with no upper age limit (model 2). Results: The models could be fitted in 83-90% of cases; in other cases the HSDS decreased after several measurements, which violated the assumption of an irreversible growth process. In JHT, the rate constant (k) and adjHSDS (0) were lower than in CD (p=0.02), but adjHSDS (end) was similar. In GHD (model 1), k was lower than for CD (p=0.004) but similar to JHT, while adjHSDS (0) and adjHSDS (end) were similar to CD and JHT. Thus, the shape of CUG is similar for children with JHT and GHD, while children with CD had less growth deficit at start and a faster CUG. The differences in CUG parameters between GH dose subgroups did not reach statistical significance. Conclusion: Modelling CUG of prepubertal children with JHT and GHD can be used for assessing the adequacy of CUG and the influence of clinical treatment modalities on its speed and magnitude. [ABSTRACT FROM AUTHOR]

Background: Most girls with Turner syndrome (TS) require pubertal induction with estrogen, followed by long term replacement. However, no adequately powered prospective studies comparing transdermal with oral 17β-estradiol administration exist. This reflects the difficulty of securing funding to study a rare condition with relatively low morbidity/mortality when competing against conditions such as cancer and vascular disease. Protocol Consensus: The TS Working Group of the European Society for Paediatric Endocrinology (ESPE) has agreed to both a 3-year oral and a 3-year transdermal regimen for pubertal induction. Prerequisites include suitable 17β-estradiol tablets and matrix patches to allow the delivery of incremental doses based on body weight. Study Proposal: An international prospective cohort study with single centre analysis is proposed in which clinicians and families are invited to choose either of the agreed regimens, usually starting at 11 years. We hypothesise that pubertal induction with transdermal estradiol will result in better outcomes for some key parameters. The primary outcome measure chosen is height gain during the induction period. Analysis: Assessment of the demographics and drop-out rates of patients choosing either oral or transdermal preparations; and appropriate analysis of outcomes including pubertal height gain, final height, liver enzyme and lipid profile, adherence/acceptability, cardiovascular health, including systolic and diastolic blood pressure and aortic root diameter and bone health. Conclusion: The proposed model of prospective data collection according to internationally agreed protocols aims to break the current impasse in obtaining evidence-based management for TS and could be applied to other rare paediatric endocrine conditions. [ABSTRACT FROM AUTHOR]

Background/Aims: Growth Hormone (GH) dosage in childhood is adjusted for body size, but there is no consensus whether body weight (BW) or body surface area (BSA) should be used. We aimed at comparing the biological effect and cost-effectiveness of GH treatment dosed per m2 BSA in comparison with dosing per kg BW in girls with Turner syndrome (TS). Methods: Serum IGF-I, GH dose, and adult height gain (AHG) from girls participating in two Dutch and five Swedish studies on the efficacy of GH were analyzed, and the cumulative GH dose and costs were calculated for both dose adjustment methods. Additional medication included estrogens (if no spontaneous puberty occurred) and oxandrolone in some studies. Results: At each GH dose, the serum IGF-I standard deviation score remained stable over time after an initial increase after the start of treatment. On a high dose (at 1 m2 equivalent to 0.056-0.067 mg/kg/day), AHG was at least equal on GH dosed per m2 BSA compared with dosing per kg BW. The cumulative dose and cost were significantly lower if the GH dose was adjusted for m2 BSA. Conclusion: Dosing GH per m2 BSA is at least as efficacious as dosing per kg BW, and is more cost-effective. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Short stature is a prominent feature of Turner syndrome (TS), which is partially overcome by GH treatment. We have previously reported the results of a trial on the effect of oxandrolone (Ox) in girls with TS. Ox in a dose of 0.03 mg/kg per day (Ox 0.03) significantly increased adult height gain, whereas Ox mg/kg per day (0.06) did not, at the cost of deceleration of breast development and mild virilization. The aim of this follow-up study in adult participants of the pediatric trial was to investigate the long-term effects of previous Ox treatment. Design and methods: During the previous randomized controlled trial, 133 girls were treated with GH combined with placebo (Pl), Ox 0.03, or Ox 0.06 from 8 years of age and estrogen from 12 years. Sixtyeight women (Pl, n=23; Ox 0.03, n=27; and Ox 0.06, n=18) participated in the double-blind followup study (mean age, 24.0 years; mean time since stopping GH, 8.7 years; and mean time of Ox/Pl use, 4.9 years). We assessed height, body proportions, breast size, virilization, and body composition. Results: Height gain (final minus predicted adult height) was maintained at follow-up (Ox 0.03 10.2 ±4.9 cm, Ox 0.06 9.7±4.4 cm vs Pl 8.0±4.6 cm). Breast size, Tanner breast stage, and body composition were not different between groups. Ox-treated women reported more subjective virilization and had a lower voice frequency. Conclusion: Ox 0.03 mg/kg per day has a beneficial effect on adult height gain in TS patients. Despite previously reported deceleration of breast development during Ox 0.03 treatment, adult breast size is not affected. Mild virilization persists in only a small minority of patients. The long-term evaluation indicates that Ox 0.03 treatment is effective and safe. [ABSTRACT FROM AUTHOR]

Background: The weak androgen oxandrolone (Ox) may increase height but may also affect glucose metabolism in girls with Turner syndrome (TS). Methods: In a randomized, placebo-controlled, double-blind study, we assessed the effect of Ox at a dosage of either 0.06 or 0.03 mg/kg/day on glucose metabolism in 133 growth hormone (GH)-treated girls with TS. Patients were treated with GH (1.33 mg/m2/day) from baseline, combined with placebo (Pl) or Ox from the age of 8, and estrogens from the age of 12. Oral glucose tolerance tests (OGTT) were performed, and HbA1c levels were measured before, during, and after discontinuing Ox/Pl therapy. Results: Insulin sensitivity, assessed by the whole-body insulin sensitivity index (WBISI) decreased during GH+Ox/Pl (p = 0.003) without significant differences between the dosage groups. Values returned to pre-treatment levels after discontinuing GH+Ox/Pl. On GH+Ox, fasting glucose was less frequently impaired (Ox 0.03, p = 0.001; Ox 0.06, p = 0.02) and HbA1c levels decreased more (p = 0.03 and p = 0.001, respectively) than on GH+Pl. Conclusions: We conclude that in GH-treated girls with TS, Ox at a dosage of 0.03 or 0.06 mg/kg/day does not significantly affect insulin sensitivity. Insulin sensitivity decreases during GH therapy, to return to a pre-treatment level after discontinuing therapy. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effect of 2 growth hormone (GH) doses on adult height (AH) in GH deficiency (GHD). Methods: A multicenter, randomized, controlled dose-response trial compared attained AH minus target height (TH) between children receiving 0.7 mg/m2/day biosynthetic GH (approx. 0.025 mg/kg/day) or 1.4 mg/m2/day (approx. 0.050 mg/kg/day). The patients enrolled in the trial were 20 ‘naïve’ GHD children (had not received GH before) and 15 ‘transfer’ GHD children (already on GH for at least 1 year). Results: In the naïve group, the mean ± SD AH minus TH was –5.3 ± 6.1 and –2.2 ± 6.9 cm in patients on 0.7 and 1.4 mg/m2/day, respectively (mean ± SE difference 3.1 ± 2.9; p = 0.3). In the transfer group, the mean ± SD AH minus TH was –4.4 ± 6.4 and +0.6 ± 7.0 cm in patients on 0.7 and 1.4 mg/m2/day, respectively (mean ± SE difference 5.0 ± 3.5; p = 0.17). Spontaneous puberty started 1.1 years earlier in children on 1.4 compared to 0.7 mg/m2/day. Induction of puberty was more often delayed in transfer children on 0.7 than on 1.4 mg/m2/day. Conclusion: In our GHD patients, AH was 4–5 cm less than TH in patients on 0.7 mg/m2/day GH, while it was 0–2 cm less in patients on 1.4 mg/m2/day GH, but this difference did not reach statistical significance, probably due to limited numbers of patients, considerable variability in the growth response and earlier spontaneous puberty and pubertal induction in the children on 1.4 mg/m2/day. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In childhood the symptoms with the greatest impact on girls with Turner’s syndrome are: (1) congenital cardiac abnormalities (which can be corrected by surgical intervention); (2) short stature (mean adult height between 142 and 147 cm); and (3) ovarian failure (absent spontaneous puberty). Recent studies have shown that growth hormone (GH) treatment in young girls (8 years of age or younger) with Turner’s syndrome results in normalization of adult height in most of the girls when using the ‘standard’ GH dose of about 4 IU/m[sup 2] per day (≈0.045 mg/kg per day). Higher GH doses (6 or 8 IU/m[sup 2] per day) or the use of oxandrolone may be more effective, but their efficacy on adult height and safety in the very long term still have to be proven. If GH treatment is started early, low-dose oestrogens for induction of puberty can be given at 12 years of age without interfering with the capability of the GH treatment to normalize adult height. GH does not seem to have negative side effects on body proportions, cardiac dimensions, blood pressure, carbohydrate metabolism or bone mineral density.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In the Dutch growth hormone (GH) registration database there are currently 552 GH-deficient children being treated, subcutaneously, with recombinant human GH six to seven times per week. Of those, 112 who have been treated for at least 2 years have reached final height. Mean age at start of therapy was 11.70 years. Mean GH dose was 15.5 IU/m[sup 2] body surface per week. Mean final height was 173.2 cm (boys) and 159.7 cm (girls) and –1.36 SD of the population mean. Of the patients, 73.2% and 63.4%, respectively, reached a final height above –2 SD of the population or within target limits. FH-SDS was higher compared with the results of earlier cohorts with different treatment regimens. Target height, GH peak value at diagnosis, age at start of GH therapy, height SDS (HSDS) at start of puberty, and duration of GH therapy were significantly correlated with final height. These results, combined with those of a prospective GH dose-response study, suggest that better long-term results can be obtained with early and prolonged treatment and if the GH dose is individually adapted to the short-term growth response. In an ongoing dose-response study, 68 girls with Turner’s syndrome, aged 2–11 years, were randomized into three dosage groups with a daily GH dose of: (group A) 4 IU/m[sup 2] body surface; (group B) 4 IU/m[sup 2] in the first year of therapy and 6 IU/m[sup 2] thereafter; (group C) 4 IU/m[sup 2] in the first year, 6 IU/m[sup 2] in the second year, and 8 IU/m[sup 2] thereafter. After 4 years of GH therapy, girls aged 12 years or older started low-dose oestrogen therapy. After 7 years of GH therapy, mean HSDS in all three groups had increased to values above the third percentile for healthy girls. Mean final height and final height gain of 25 girls was 159.1 and 12.5 cm, 161.8 and 14.6 cm, and 162.7 and 16.0 cm in groups A, B and C respectively. These long-term and final height results are more favourable than the results of earlier Dutch Turner’s syndrome studies. Possible explanations are the higher GH doses and/or the younger age at start of GH therapy.Copyright © 1999 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The article presents several case studies of children who develop neuropathy following the treatment of thiamazole for Graves' disease. Topics mention including the minor side effects in children such as arthralgia and skin rashes, nerve conduction studies and blood analysis and performing thyroidectomy.