A Special, Strict, Fat-Reduced, and Carbohydrate-Modified Diet Leads to Marked Weight Reduction even in Overweight Adolescents with Prader-Willi Syndrome (PWS)

Hyperphagia is a frequent symptom in patients with Prader-Willi Syndrome (PWS) and results in marked obesity with the risk of metabolic and cardiovascular complications. Previously, we reported that our special diet for PWS patients is effective in the long run, if started early at about 2 years of age. Our objective in this study was to investigate if our special diet is also effective in PWS adolescents who are already overweight. We provided a strict, fat-reduced, and carbohydrate-modified diet, consisting of 10 kcal/cm height, to five adolescents (two female, three male) with PWS. Patients were prospectively followed at our center for 2-6 years. BMI, BMI-SDS, and Weight-for-Height Index were recorded over that period. The special diet was started at a mean age of 16 years (range: 14.1-18.9 years) and initial BMI was 41.3 kg/m2 (range: 32.4-55.5 kg/m2), corresponding to BMI-SDS +3.6 (range: +2.8 to +4.5 SDS). Weight-for-Height Index was 243% (range: 190-339%). After 2 years of the diet, BMI decreased to 33 kg/m2 (range: 26.7-38 kg/m2), as well as BMI-SDS +2.7 (range: 1.7-3.4 SDS) and Weight-for-Height Index to 191% (range: 157-232%); p < 0.01. The special diet was still effective in reducing weight after 4–6 years, with a mean BMI of 30.5 kg/m2 (range: 24.6–34.5 kg/m2) and a mean BMI-SDS of +2.1 (range: 0.7–2.9). We conclude that in a period of 2–6 years, our strict, fat-reduced, and carbohydrate-modified diet, with 10 kcal/cm height, is effective even in adolescents with PWS who are already overweight

Use of long-term microdialysis subcutaneous glucose monitoring in the management of neonatal diabetes - A first case report

In neonatal diabetes mellitus (NDM), a rare genetic disorder, insulin therapy is required but the management is difficult. Frequent blood glucose determinations are necessary in most cases. Microdialysis subcutaneous glucose monitoring (MSGM) is feasible in neonates and has been proposed to reduce painful blood sampling and blood loss. We have applied long-term MSGM to a small-fordate female newborn with transient NDM. We found a good correlation of subcutaneous and blood glucose concentration over a wide range of values. MSGM enabled a reduction in blood glucose determinations during optimization of intravenous insulin treatment and initiation of continuous subcutaneous insulin infusion. We conclude that long-term MSGM is feasible and may reduce painful blood sampling and blood loss in NDM. Furthermore, long-term MSGM may hold a potential for avoiding hypoglycemic episodes and earlier discharge. Copyright (C) 2006 S. Karger AG, Basel

Sexual difference in bone geometry of adult patients with classical congenital adrenal hyperplasia: Data using peripheral quantitative computed tomography

BACKGROUND/AIMS Glucocorticoid treatment may influence bone and muscle development in patients with congenital adrenal hyperplasia (CAH). This study evaluated bone mineral density (BMD), bone geometry and muscle mass. METHODS 73 adult patients with classical CAH were followed. BMD, bone geometry and muscle mass were measured using peripheral quantitative computed tomography (pQCT). Glucocorticoid-equivalent doses throughout life were calculated and at the time pQCT androgen levels were measured. RESULTS In males the mean standard deviation (SD) score for trabecular BMD (-0.33 ± 0.71) was reduced, whereas mean cortical BMD (1.05 ± 1.11) was elevated. Mean total (0.86 ± 1.12) and medullary cross-sectional area (CSA; 1.12 ± 1.17) were significantly increased (p < 0.001). In all patients SD scores for cortical thickness (-0.65 ± 0.91) and muscle CSA (-0.83 ± 0.91) were reduced. Treatment duration was associated with lower trabecular BMD in males (r = -0.63, p < 0.001). Suppressed androgens and simple virilizing CAH had an adverse effect on the muscle CSA SD score (OR 0.58 and 0.46, respectively, p < 0.05). CONCLUSION There was a sexual difference with enlarged total and medullary CSA in females, whereas in males trabecular BMD was reduced and cortical BMD elevated. Cortical thickness and muscle CSA were reduced in all CAH patients with a possible long-term impact on bone development and stability. Monitoring of bone and muscle development might be warranted

Hormonal control during infancy and testicular adrenal rest tumor development in males with congenital adrenal hyperplasia: a retrospective multicenter cohort study

IMPORTANCE Testicular adrenal rest tumors (TARTs), often found in male patients with congenital adrenal hyperplasia (CAH), are benign lesions causing testicular damage and infertility. We hypothesize that chronically elevated adrenocorticotropic hormone exposure during early life may promote TART development. OBJECTIVE This study aimed to examine the association between commencing adequate glucocorticoid treatment early after birth and TART development. DESIGN AND PARTICIPANTS This retrospective multicenter (n = 22) open cohort study collected longitudinal clinical and biochemical data of the first 4 years of life using the I-CAH registry and included 188 male patients (median age 13 years; interquartile range: 10-17) with 21-hydroxylase deficiency (n = 181) or 11-hydroxylase deficiency (n = 7). All patients underwent at least 1 testicular ultrasound. RESULTS TART was detected in 72 (38%) of the patients. Prevalence varied between centers. When adjusted for CAH phenotype, a delayed CAH diagnosis of >1 year, compared with a diagnosis within 1 month of life, was associated with a 2.6 times higher risk of TART diagnosis. TART onset was not predicted by biochemical disease control or bone age advancement in the first 4 years of life, but increased height standard deviation scores at the end of the 4-year study period were associated with a 27% higher risk of TART diagnosis. CONCLUSIONS AND RELEVANCE A delayed CAH diagnosis of >1 year vs CAH diagnosis within 1 month after birth was associated with a higher risk of TART development, which may be attributed to poor disease control in early life

Temporal trends in acute adrenal insufficiency events in children with congenital adrenal hyperplasia during 2019-2022

Background It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDE) and hospitalisation rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events. Aim Study temporal trends of AI related AE in the I-CAH Registry. Methods In 2022, data on the occurrence of AI-related AE in children aged &lt;18yrs with 21-hydroxylase deficiency CAH was compared to data collected in 2019. Results In 2022, a total of 513 children from 38 centres in 21 countries with a median of 8 children (range 1, 58) per centre had 2,470 visits evaluated over a 3-yr period (2019-2022). The median SDE per patient yr in 2022 was 0 (0, 2.5) compared to 0.3 (0, 6) in 2019 (p=0.01). Despite adjustment for age, CAH phenotype and duration of study period, a difference in SDE rate was still apparent between the two cohorts. Of the 38 centres in the 2022 cohort, 21 had also participated in 2019 and a reduction in SDE rate was noted in 13 (62%), an increase was noted in 3 (14%) and in 5 (24%) the rate remained the same. Of the 474 SDEs reported in the 2022 cohort, 103 (22%) led to hospitalisation compared to 299 of 1099 SDEs (27%) in the 2019 cohort (p=0.02). Conclusions The I-CAH Registry can be used for targeted monitoring of important clinical benchmarks in CAH. However, changes in reported benchmarks need careful interpretation and longer-term monitoring

Blood pressure, fludrocortisone dose and plasma renin activity in children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency followed from birth to 4 years of age.

Infants with congenital adrenal hyperplasia (CAH) require higher doses of fludrocortisone (FC) due to physiological mineralocorticoid resistance. The adequacy of mineralocorticoid replacement should be closely monitored to avoid hypertension.To evaluate blood pressure (BP) in infants with CAH due to 21-hydroxylase deficiency.Thirty-three patients (18f/15 m) diagnosed by newborn screening were followed until the age of 4 years. Mean start of HC and FC treatment was day 9·8 ± 9·2 postnatally. Mean daily HC dose ranged from 8·6 to 12·3 mg/m(2) /day.During the first year of life prevalence of systolic hypertension was up to 45·5%. At 12 and at 18 months, BP was highest. Prevalence of systolic hypertension was up to 57·6% at 18 months of age. After 24 months BP levels were lower and at 48 months prevalence of hypertension decreased to 15·2%. Systolic and diastolic BP correlated significantly with the administered fludrocortisone dose (r = 0·3, P = 0·005), but not with body mass index. Hypertensive children received significantly higher FC doses and had significantly lower plasma renin activity during the study period.High prevalence of transient, most likely FC induced hypertension was found in young children with classic CAH diagnosed by newborn screening. The changing mineralocorticoid sensitivity in infants is a risk factor for the development of hypertension in patients with CAH, who are treated with FC. Therefore suppressed plasma renin activity should be avoided to prevent arterial hypertension

Besonderheiten des Wachstumsverlaufs beim klassischen Adrenogenitalen Syndrom mit 21-Hydroxylasemangel und daraus resultierende Optimierung der Glukokortikoidtherapie

Unter dem Adrongenitalen Syndrom (AGS) werden alle Störungen der adrenalen Cortisolbiosynthesse zusammengefasst. In 95% der Fälle liegt ein 21-Hydroxylasemangel vor. Unbehandelt kommt es zu lebensbedrohlichen Salzverlust- und Addison-Krisen. Die Therapie besteht aus einer Gluko- und Mineralokortikoid-Substitutionstherapie. Sowohl Glukokrotikoidüberdosierung als auch Glukokortikoidunterdosierung führen zu einer Wachstumsstörung. Durch die Analyse des Wachstumsverlaufes eines großen AGS-Patientenkollektivs mit 21-Hydroxylasemangel konnten folgende Besonderheiten herausgearbeitet werden: 1. In den ersten sechs bis zwölf Lebensmonaten besteht eine relative Androgeninsensitivität. 2. Der pubertäre Wachstumsspurt fällt beim AGS signifikant vermindert aus und resultiert in einer leicht verminderten Endgröße. 3. Die Endgröße von Patienten, die mit Prednison behandelt wurden, ist signifikant geringer als die Endgröße von Patienten, die während der Wachstumsphase ausschließliche Hydrocortison erhielten. Daraus leiten sich folgende Konsequenzen für die Therapie ab: In den ersten sechs bis zwölf Lebensmonaten muss keine vollständige Androgensuppression vorliegen. Bezüglich des Wachstums stellt die Pubertät eine kritische Phase in der AGS-Behandlung dar. Eine Glukokortikoidüberdosierung sollte in dieser Phase unbedingt vermieden werden

Metabolic safety of growth hormone in type 1 diabetes and idiopathic growth hormone deficiency.

To evaluate metabolic consequences of growth hormone (GH) treatment in children with type 1 diabetes.This study is an analysis of metabolic changes in 37 patients with childhood-onset GH deficiency and type 1 diabetes, documented in the Diabetes Patienten Verlaufsdocumentationsystem database. Main outcome measures were changes in hemoglobin A1c and daily insulin requirements during GH therapy in children with GH deficiency and type 1 diabetes compared with a large cohort of adolescents with type 1 diabetes.Thirty-seven patients with type 1 diabetes and a diagnosis of idiopathic GH deficiency after onset of diabetes were compared with 48856 patients with type 1 diabetes. After adjustment for age, sex, duration of diabetes, and migration background, a significant difference in mean daily insulin requirement was seen between the 2 groups (1.0 IU/kg/day in subjects with GH deficiency and type 1 diabetes vs 0.85 IU/kg/day in controls; P .05).An increased daily insulin requirement should be considered in patients with type 1 diabetes treated with GH. With adequate adaptation of insulin dosage, metabolic control is not impaired during GH treatment