Management of bone disease in cystinosis: Statement from an international conference.

Cystinosis is an autosomal recessive storage disease due to impaired transport of cystine out of lysosomes. Since the accumulation of intracellular cystine affects all organs and tissues, the management of cystinosis requires a specialized multidisciplinary team consisting of pediatricians, nephrologists, nutritionists, ophthalmologists, endocrinologists, neurologists' geneticists, and orthopedic surgeons. Treatment with cysteamine can delay or prevent most clinical manifestations of cystinosis, except the renal Fanconi syndrome. Virtually all individuals with classical, nephropathic cystinosis suffer from cystinosis metabolic bone disease (CMBD), related to the renal Fanconi syndrome in infancy and progressive chronic kidney disease (CKD) later in life. Manifestations of CMBD include hypophosphatemic rickets in infancy, and renal osteodystrophy associated with CKD resulting in bone deformities, osteomalacia, osteoporosis, fractures, and short stature. Assessment of CMBD involves monitoring growth, leg deformities, blood levels of phosphate, electrolytes, bicarbonate, calcium, and alkaline phosphatase, periodically obtaining bone radiographs, determining levels of critical hormones and vitamins, such as thyroid hormone, parathyroid hormone, 25(OH) vitamin D, and testosterone in males, and surveillance for nonrenal complications of cystinosis such as myopathy. Treatment includes replacement of urinary losses, cystine depletion with oral cysteamine, vitamin D, hormone replacement, physical therapy, and corrective orthopedic surgery. The recommendations in this article came from an expert meeting on CMBD that took place in Salzburg, Austria, in December 2016.

Diabetes mellitus in pediatric solid organ recipients without and with cystic fibrosis: An analysis from the German-Austrian diabetes database (Diabetes Patienten Verlaufsdokumentation).

INTRODUCTION: Posttransplantation diabetes mellitus (PTDM) increases the risk of cardiovascular disease, graft loss, and decreased survival. Follow-up treatment after solid organ transplantation (SOT) needs to focus on, inter alia, maintaining balanced glucose metabolism. This study aimed to ascertain the prevalence of PTDM and describe patient characteristics in the large DPV (Diabetes Patienten Verlaufsdokumentation) pediatric diabetes database. METHODS: DPV data of 71 902 patients from the January 01, 1995 to January 04, 2015 period were analyzed for patients with and without cystic fibrosis (CF) after SOT (kidney, liver, heart, and lung). Multivariable analysis served to assess differences between SOT patient groups at risk for developing diabetes. RESULTS: Out of 109 SOT patients, 51 had CF; 72.5% received steroids and 62% were additionally given tacrolimus. PTDM developed in 45% of CF patients and 12% of non-CF patients. SOT patients were older at diabetes onset (mean age, 12.50 ± 3.98 years), shorter (height z-score, -1.67 ± 1.25), and lighter (weight z-score, -1.59 ± 1.57) than non-SOT diabetes patients (P < 0.01). With transplantation, glycated hemoglobin (HbA1c) was significantly lower and treatment for hypertension and dyslipidemia was increased. Among SOT patients, weight and body mass index (BMI) z-scores were significantly lower in patients with CF-related diabetes (P < 0.05). CONCLUSIONS: SOT was present in 6.6% of children with diabetes, and this might aggravate the risk of cardiovascular disease in populations with already increased rates of hypertension and dyslipidemia. Dystrophy and short stature were also present, particularly in transplant recipients with CF and diabetes. Comorbidities and long-term consequences call for multidisciplinary collaboration.

Pulse pressure in children and adolescents with type 1 diabetes mellitus in Germany and Austria.

BACKGROUND: Impaired blood pressure regulation contributes to the development of diabetic complications. The influence of systolic (SBP) vs.diastolic blood pressure (DBP) is still controversial. Peripheral pulse pressure(PP), the difference between SBP and DBP, is an indicator for arterial stiffness. Only little data are available for PP in children. Therefore, we studied PP regulation in type 1 diabetic children and adolescents.Methods: Blood pressure values of 46 737 patients with T1DM younger than 20 years are documented in the DPV database and were compared with the control populations of the '4th report on high blood pressure (4th report)' and the German KIGGS study. RESULTS: PP is increased in 63% (4th report) or 67% (KIGGS) of the patients,respectively. The rate of increased PP remains stable between 59 and 68%,irrespective of sex, age, and the control population. Absolute PP is elevated independently of the control population (PP T1DM 49.13±11.1 vs. 4th report 45.38 ± 3 vs. KIGGS 44.58 ± 4.6 mmHg; all p<0.0001, Wilcoxon test)and increases with age in both sexes. Age, male sex, diabetes duration, insulin dose, and body mass index (BMI) are independent factors contributing to elevated absolute PP levels and to the prevalence of wide PP. HbA1c is negligible negatively related to increased PP levels (multiple linear regression). CONCLUSIONS: In T1DM increased PP is a marker for accelerated arterial stiffness and aging and should be considered as an additional risk factor in the treatment of diabetic children. Elevated PP in children with T1DM may contribute to the high risk for early development of atherosclerosis.

Bone health in children and adolescents with chronic diseases that may affect the skeleton: the 2013 ISCD Pediatric Official Positions.

The aim of this Task Force was to review the use of dual-energy X-ray absorptiometry (DXA) in children and adolescents with underlying chronic diseases that pose risk factors for compromised bone health, such as inflammation, glucocorticoid therapy, or decreased mobility. The Task Force systematically analyzed more than 270 studies, with an emphasis on those published in the interval since the original 2007 Position Statements. Important developments over this period included prospective cohort studies demonstrating that DXA measures of areal bone mineral density (aBMD) predicted incident fractures and the development of robust reference data and strategies to adjust for bone size in children with growth impairment. In this report, we summarize the current literature on the relationship between DXA-based aBMD and both fracture (vertebral and non-vertebral) outcomes and non-fracture risk factors (e.g., disease characteristics, ambulatory status, and glucocorticoid exposure) in children with chronic illnesses. Most publications described the aBMD profile of children with underlying diseases, as well as the cross-sectional or longitudinal relationship between aBMD and clinically relevant non-fracture outcomes. Studies that addressed the relationship between aBMD and prevalent or incident fractures in children with chronic illnesses are now emerging. In view of these updated data, this report provides guidelines for the use of DXA-based aBMD in this setting. The initial recommendation that DXA is part of a comprehensive skeletal healthy assessment in patients with increased risk of fracture is unchanged. Although the prior guidelines recommended DXA assessment in children with chronic diseases at the time of clinical presentation with ongoing monitoring, this revised Position Statement focuses on the performance of DXA when the patient may benefit from interventions to decrease their elevated risk of a clinically significant fracture and when the DXA results will influence that management.

Growth abnormalities in children and adolescents with juvenile idiopathic arthritis.

In patients with juvenile idiopathic arthritis (JIA) growth impairment and variance in body composition are well-known long-term complications. In the active phases of the disease, particular patients with systemic and polyarticular JIA reveal growth impairment. Some experience "catch-up" growth following reduction in disease activity and lower glucocorticoid doses. Although new therapeutic options are available, there are still 10-20 % of patients with severe forms of the disease who show continuous growth disturbance. Only few studies have specifically addressed body composition in JIA. Bone mass deficits in part could be related to the deficits of muscle mass. Study data on growth hormone treatment in short children with JIA are promising in respect of growth development, final height and body composition. The major goal for physicians is optimal disease control while maintaining normal growth and body composition. Early recognition of patients who develop prolonged growth and body composition disturbances is important as these abnormalities contribute to long-term morbidity and need to be addressed both diagnostically and therapeutically.

Salivary 17-Hydroxyprogesterone Levels in Children with Congenital Adrenal Hyperplasia: A Retrospective Longitudinal Study Considering Auxological Parameters.

INTRODUCTION: Children with classical congenital adrenal hyperplasia (CAH) have an impaired steroid synthesis due to 21-hydroxylase dysfunction and require glucocorticoid replacement. Therapy management in children and adolescent is based on auxological, clinical, and laboratory monitoring. The measurement of steroid precursors in saliva is particularly suitable for patients in pediatric endocrinology. METHODS: In this retrospective and longitudinal study of 22 patients with CAH, we analyzed 546 saliva samples for 17-hydroxyprogesterone (s17-OHP) in prepubertal/pubertal patients. Additionally, we correlated them with auxological parameters such as delta-height standard deviation score. RESULTS: We analyzed a median observation period of 5.5 years per patient. No precocious pubertal development, abnormal vital signs, or Addison crises occurred. 57.1% of the samples were collected in prepubertal children. 72.5% of s17-OHP values were attributed to normal auxological development. In the total cohort, the median values for s17-OHP were 67.8 pg/mL (morning), 42.5 pg/mL (noon), and 25.0 pg/mL (evening). The difference in values between the group of normal/abnormal growing patients and between prepubertal/pubertal patients was not significant. DISCUSSION/CONCLUSION: The measurement of s17-OHP is an important sub-aspect in the overall assessment of treatment response in CAH. It can provide an indication of over-/undertreatment and allows the assessment of day profiles, especially in phases of changing (e.g., puberty) steroid requirements. We present here observational data from a larger cohort with longitudinal multiple measurements of s17-OHP. The values do not allow a significant differentiation between normal and abnormal growth or pubertal status. Thus, relying solely on s17-OHP is not advisable.

Endosteal bone storage in young adults born small for gestational age - a study using peripheral quantitative computed tomography.

OBJECTIVE: Poor growth early in life is associated with numerous adverse conditions including decreased bone mass. The aim is to investigate bone and body composition in young adults born small for gestational age (SGA). DESIGN: Observational study. PARTICIPANTS: A total of 76 young adults born SGA (34f) at a mean age of 19·68 ± 0·5 years were enrolled. METHOD: Bone mineral density (BMD), bone geometry and body composition were analysed using peripheral quantitative computed tomography. RESULTS: Adults born SGA had significantly lower z-score for height (-0.86 ± 0·87), weight (-0·61 ± 0·78) and BMI (-0·38 ± 1·04) as well as fat cross-sectional area (CSA) (-0·62 ± 0·80) compared with a healthy reference population (P < 0·05). Z-scores for trabecular and cortical BMD were normal. After correction for reduced height, z-scores for total CSA (-0·14 ± 1·11) and muscle CSA (-0·21 ± 0·99) were normal and medullary cavity (-0·71 ± 0·80) was reduced. Those with a birthweight of ≤ 1500 g had even lower height-corrected z-scores for medullary cavity (-1·12 ± 0·69) and total bone CSA (-0·58 ± 0·93) (P < 0·05). After adjustment for sex and weight, significant partial correlations were detectable between BMI at the age of 48 months and height-corrected z-scores for medullary cavity (r = 0·33, P = 0·020) and total CSA (r = 0·29, P = 0·04). CONCLUSION: Environmental factors early in life seem to influence bone geometry in adulthood. Young adults born SGA have normal total bone CSA but smaller medullary cavity. Those with very low birthweight, however, show compromised bone size development that may alter bone stability later in life.

Free triiodothyronine/free thyroxine ratio in children with congenital hypothyroidism.

Thyroid-stimulating hormone is generally regarded as a standard parameter for the evaluation of thyroid function. However, relying on this hormone alone can be misleading. Therefore, thyroxine/free-thyroxine levels are used in patients with levothyroxine substitution for the adjustment of therapy. Even with normal values for free thyroxine, decreased values for the free-triiodothyronine/free-thyroxine ratio have already been described in adults. In this study, the free-triiodothyronine/free-thyroxine ratio of 25 children with congenital hypothyroidism was compared with 470 healthy children seen for other reasons and then for thyroid dysfunction. Mean free thyroxine in congenital hypothyroidism was just below the upper limit of normal and significantly higher than in control group. Mean values for free triiodothyronine showed no significant difference between the two groups. The mean value for the free triiodothyronine/free-thyroxine ratio in control group was 3.23. Significantly lower ratios were found in the congenital hypothyroidism group with a mean value of 2.5, due to higher values for free thyroxine compared to free triiodothyronine. Furthermore, an increased free triiodothyronine/free-thyroxine ratio was found at higher thyroid-stimulating hormone values due to lower values for free thyroxine. In this study, we demonstrate that the free triiodothyronine/free-thyroxine ratio was significantly lower in children with congenital hypothyroidism compared to the control group. This is most likely due to the higher values for free thyroxine in this group compared to similar values for free triiodothyronine in both groups. Further studies with differentiated thyroid hormone therapy are needed in order to understand the role of peripheral euthyroidism.

The effect of cardiovascular risk factors on the longitudinal evolution of the carotid intima medial thickness in children with type 1 diabetes mellitus.

BACKGROUND: Type 1 diabetes mellitus is a generally accepted atherogenic risk factor. The aim of this prospective longitudinal study was to evaluate changes in carotid intima media thickness (cIMT) in children and adolescents with type 1 diabetes mellitus (T1DM) using standardized methods. METHODS: We re-evaluated cIMT in 70 (38 f) of initial 150 (80 f) patients with T1DM after 4 years. At re-evaluation, mean (±SD) age was 16.45±2.59 y, mean diabetes duration was 9.2±3.24 y and patients had a mean HbA1c of 8.14±1.06%. RESULTS: Mean cIMT z-scores increased significantly during 4 years (0.58±0.75, p<0.001) as well as BMI-z-score (0.41±0.81, p<0.01), systolic blood pressure (0.77±1.15, p<0.01) and HbA1c (0.90±1.07, <0.001). In a linear regression model systolic blood pressure z-score at first measurement (0.02, CI: 0.01, 0.04) was a significant predictor for the mean effect on cIMT z-score. In a logistic regression model significant risk factors for an increase in IMT of ≥1.5 z-scores were BMI z-scores (OR: 3.02, CI:1.11, 10.14), diabetes duration (OR:1.32, CI:1.04, 1.77) and systolic blood pressure (OR: 1.14, CI: 1.04, 1.27) at first measurement each. CONCLUSIONS: Longitudinal cIMT measurements revealed progression in subclinical atherosclerosis during a four year period in diabetic children and adolescents. Systolic blood pressure and BMI were related to cIMT increment. Control of these risk factors by lifestyle and medical intervention may prevent progression of cIMT in diabetic children.

Early changes in body composition after cessation of growth hormone therapy in childhood-onset growth hormone deficiency.

At final height, somatic maturity has not been reached yet. We investigated bone and body composition in patients, who completed pediatric growth hormone (GH) treatment at final height. After a mean period of 0.55 ± 0.17 yr off GH treatment 90 (66 m/24 f) childhood-onset growth hormone deficiency (GHD) patients were reinvestigated for GHD by insulin tolerance testing at a mean age of 17.52 ± 1.50 yr. Thirty-seven (25 m/12 f) patients remained GH deficient (persistent GHD). Bone and body composition were measured using peripheral quantitative computed tomography of the nondominant forearm. Bone mineral density (BMD) was within normal limits. Total cross-sectional bone area Z-score (0.64 ± 1.3) was significantly higher as a result of an enlarged medullary cavity Z-score (1.12 ± 1.2) leading to reduction of cortical thickness Z-score (-1.21 ± 1.0). Patients with persistent GHD had a significantly higher fat mass (13.3 ± 8.7 and 6.8 ± 4.6 cm(2), p<0.05), which was more pronounced in multiple pituitary hormone deficiency patients. Shortly after cessation of GH treatment in patients treated for childhood-onset GHD age adequate normal BMD and enlarged diaphysis was detectable. Patients with persistent GHD status had a significant higher fat mass.

Subclinical atherosclerosis in diabetic children: results of a longitudinal study.

CONTEXT: Cardiovascular disease caused by atherosclerosis is a major cause of morbidity and mortality in adult diabetic patients. In children, we detected signs of subclinical atherosclerosis in a large patient cohort. This study reports the results of a longitudinal observation in this patient group. PATIENTS AND METHODS: Of the 37/150 diabetic children in whom an increased intima-media thickness (IMT) of the carotid artery had been found, 27 (mean age 14.6 +/- 2.6 yrs) could be reevaluated 2 yrs after the initial study. Of the 27, 5 patients were on medication with angiotensin-converting enzyme (ACE) inhibitors, and all patients underwent detailed counselling of their lifestyle, sports activity, and nutritional habits. RESULTS: Mean IMT increased significantly (0.49 +/- 0.02 mm vs. 0.51 +/- 0.026 mm, p < 0.05) However, there was no significant change compared to normal values (mean IMT z-score 2.4 +/- 0.3 vs. 2.6 +/- 0.5). Of the 27, 13 patients (48%) showed a progression of the IMT whereas in 14/27 patients the IMT values remained stable. In these subgroups, patients with IMT progression showed a higher hemoglobin A1c (HbA1c) (7.5 +/- 0.8 vs. 7.1 +/- 0.7, p < 0.05) and a slightly higher systolic blood pressure (120 +/- 14.4 vs. 113.9 +/- 12.1, p = 0.08). CONCLUSIONS: In a well-selected group of diabetic children, mean IMT progression during a 2-yr period did not exceed the physiological increase. Children with a higher HbA1c and a higher systolic blood pressure showed a progression of the IMT. Control of atherogenic risk factors in diabetic children may help to avoid subclinical atherosclerosis progression.

2017 American Academy of Pediatrics Clinical Practice Guideline: Impact on Prevalence of Arterial Hypertension in Children and Adolescents With Type 1 Diabetes.

OBJECTIVE: In 2017, the American Academy of Pediatrics introduced a new guideline (2017 Clinical Practice Guideline of the American Academy of Pediatrics [AAP 2017]) to diagnose arterial hypertension (HTN) in children that included revised, lower normative blood pressure (BP) values and cut points for diagnosing high BP in adolescents. We studied the impact of the new AAP 2017 on prevalence of HTN in children with type 1 diabetes mellitus (T1DM). RESEARCH DESIGN AND METHODS: Up to September 2018, 1.4 million office BP measurements in 79,849 children and adolescents (aged 5-20 years) with T1DM were documented in the DPV (Diabetes Prospective Follow-up) registry. BP values of the most recent year were aggregated, and BP values of 74,677 patients without antihypertensive medication were analyzed (median age 16 years and diabetes duration 5.3 years, 52.8% boys). BP values were classified according to AAP 2017 and the references of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) (2011) and the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (fourth report) (2004). RESULTS: Of the patients, 44.1%, 29.5%, and 26.5% were hypertensive according to AAP 2017, KiGGS, and fourth report, respectively. Differences in prevalence of HTN were strongly age dependent: <10 years, AAP 2017 31.4%, KiGGS 30.7%, fourth report 19.6%; 10 to <15 years, AAP 2017 30.9%, KiGGS 31.2%, fourth report 22.4%; and ≥15 years, AAP 2017 53.2%, KiGGS 28.4%, fourth report 30.0%. Among teenagers ≥15 years, 59.1% of boys and only 46.3% of girls were classified as hypertensive by AAP 2017 but only 21.1%/26% of boys and 36.7%/34.4% of girls by KiGGS/fourth report, respectively. CONCLUSIONS: Classification of BP as hypertension depends strongly on the normative data used. Use of AAP 2017 results in a significant increase in HTN in teenagers ≥15 years with T1DM, particularly in boys. AAP 2017 enhances the awareness of elevated BP in children, particularly in patients with increased risk for cardiovascular disease.

Insulin sensitivity decreases in short children born small for gestational age treated with growth hormone.

OBJECTIVES: To evaluate insulin sensitivity in short children born small for gestational age (SGA) treated with growth hormone (GH), and to study the relationship between growth response and insulin levels. STUDY DESIGN: In 29 children (16 female, 13 male) who were short and SGA, an oral glucose tolerance test was performed before (mean age, 8.8 years; range, 4.5-14.3 years) and after 1 year of GH treatment (33 microg/kg/day). Insulin sensitivity was calculated with the homeostasis model assessment (HOMA) and the insulin sensitivity index (ISI) of Matsuda. RESULTS: The mean height increased from -3.1 to -2.4 SD. Insulin resistance (ISI<5) was seen in 17.2% of children before and in 48.3% (mainly pubertal) children after GH treatment. Insulin sensitivity decreased significantly: ISI fell from 12.2 to 6.1 (P= .02) and HOMA increased from 1.2 to 2.2 (P= .001). Glucose and HbA1c levels did not change significantly. ISI after 1 year did not correlate with height gain, but it did correlate with age (r= -0.469; P= .01) and body mass index (r= -0.52; P= .004). CONCLUSIONS: Insulin sensitivity is impaired in some children who are SGA already at baseline and decreases with GH treatment in most of them. Children close to puberty and children who are less underweight have the highest risk to become insulin resistant.

QTc interval prolongation in children with Turner syndrome: the results of exercise testing and 24-h ECG.

BACKGROUND: Turner syndrome (TS) is the most common sex chromosome abnormality in females. Recently, a prolongation of the rate-corrected QT (QTc) interval in the electrocardiogram (ECG) of TS patients has been reported. A prolonged QTc interval has been correlated to an increased risk for sudden cardiac death, and medical treatment is warranted in patients with congenital long QT syndrome (LQTS). Additionally, several drugs of common use are contraindicated in LQTS because of their effects on myocardial repolarization. The importance of the QTc prolongation in TS patients is not known at present. MATERIALS AND METHODS: Eighteen TS patients with a prolonged QTc interval (group 1) and 11 TS patients with a normal QTc interval (group 2) (mean age 12.6+/-3.1 vs. 11.8+/-2.1 years, respectively) were tested. The QTc interval was calculated during exercise testing and during 24-h ECG recordings. RESULTS: None of the patients experienced adverse cardiac events during the tests. The mean QTc interval decreased from 0.467 to 0.432 s in group 1 and from 0.432 to 0.412 s in group 2. During the 24-h ECG, the maximum QTc interval was significantly prolonged in group 1 (0.51 vs. 0.465 s, p<0.05, respectively). We conclude that exercise testing and 24-h ECG recording provide valuable information about the cardiac risk in the single TS patient with a prolonged QTc interval. This helps in counseling these girls, as clear therapeutic guidelines are currently lacking.

Subclinical atherosclerosis after heart and heart-lung transplantation in childhood.

Children after heart transplantation are considered as at-risk patients for extracardiac atherosclerotic complications. Noninvasive ultrasound measurement of the common carotid artery (IMT) provides valid information about the endothelial structure of the vascular system. Twenty-two patients (17 male, mean age 12.4 +/- 4.5 yr) after heart and (5.7 +/- 4.5 yr) heart-lung transplantation were enrolled. The mean IMT was measured and compared with a control group (18 children, 10 male, mean age 11.8 +/- 1.8 yr) and to normative data. Transplanted children had a higher IMT than controls (0.453 +/- 0.003 vs. 0.424 +/- 0.002 mm, p < 0.001). IMT-SDS was increased as well (1.6 +/- 0.1 vs. 0.8 +/- 0, p < 0.001). Transplanted children had a higher LDL/HDL-ratio (2.2 +/- 0.2 vs. 1.2 +/- 0.1, p < 0.001). Time after transplantation, age at the time of transplantation, or medical therapy did not influence the findings. We found evidence for subclinical atherosclerosis in children after heart and heart-lung transplantation. Even if single atherosclerotic risk factors could not be identified, transplanted children seem to be at risk for atherosclerosis. Our findings support the recently published statement of the AHA-Expert panel: after heart transplantation atherosclerotic complications may occur with increased incidence. We propose the IMT-measurement in these patients as an easy method to assess the vascular status and to guide preventive measures.

Reassessment of the optimal growth hormone cut-off level in insulin tolerance testing for growth hormone secretion in patients with childhood-onset growth hormone deficiency during transition to adulthood.

CONTEXT: Retesting of patients with childhood-onset growth hormone deficiency (CO-GHD) is recommended after completion of growth hormone (GH) treatment. AIM: To identify patients who are at risk of persistent GHD, and to evaluate the most reliable cut-off level for GH secretion using the insulin tolerance test (ITT) in the transition from childhood to adulthood. RESULTS: Ninety patients (22 female) with CO-GHD were retested using the ITT 1.1 +/- 1.1 years after discontinuation of therapy. Fifty-eight of 77 patients (75%) initially diagnosed with idiopathic GHD showed normalization of GH secretion. Thirteen patients were diagnosed with multiple pituitary hormone deficiency (MPHD) and diagnosis was reconfirmed in all of them, except for one patient. IGF-I levels of patients with persistent GHD were significantly lower (112 +/- 74 ng/ml [range 22-283] vs 245 +/- 107 ng/ml [range 31-505], p<0.01). IGF-I levels correlated positively with GH peak during ITT (r = 0.54, p <0.01), but the wide range of IGF-I levels shows that IGF-I alone cannot replace retesting in many cases. The best sensitivity and specificity scores were obtained when a GH cutoff level below 5.0 ng/ml for patients in the transition phase was used. ROC analysis demonstrates that ITT is a reliable test for evaluation of GH secretion in the transition phase (ROC-AUC 0.97). CONCLUSIONS: Patients with CO-GHD should be retested after discontinuation of therapy to identify those who may profit from further replacement therapy. Patients with organic or genetic GHD or MPHD are likely to have persistent GHD, whereas 75% of our patients with idiopathic GHD showed normalization of growth hormone secretion. IGF-I levels alone are not reliable in the diagnosis of adult GHD in many cases. The best sensitivity and specificity scores were found when a GH cut-off level below 5.0 ng/ml was used in patients with GHD in the transition from childhood to adulthood.

Reduced final height outcome in congenital adrenal hyperplasia under prednisone treatment: deceleration of growth velocity during puberty.

CONTEXT: Normal to decreased final height (FH) has been reported in patients with congenital adrenal hyperplasia (CAH). OBJECTIVE: The objective was to determine FH outcome and influences of steroid treatment. METHODS: The effects of glucocorticoid treatment for classical CAH were retrospectively studied in 125 patients (77 females). Growth pattern, FH, and pubertal development were recorded. RESULTS: Corrected FH was in the lower range of genetic potential [females with simple virilizing (SV)-CAH, -0.6 +/- 1.0 sd score (SDS) vs. females with salt-wasting (SW)-CAH, -0.6 +/- 0.9 SDS; males with SV-CAH, -1.1 +/- 0.9 SDS vs. males with SW-CAH, -0.9 +/- 0.9 SDS]. Total pubertal growth was significantly reduced in comparison with a reference population (females with SV-CAH, 11.9 +/- 6.5 cm, and females with SW-CAH, 13.8 +/- 7.6 cm vs. reference 20.3 +/- 6.8 cm, P < 0.01; and males with SV-CAH, 15.4 +/- 6.6 cm, and males with SW-CAH, 18.5 +/- 6.9 cm vs. reference 28.2 +/- 8.2 cm, P < 0.01). Thirty-three patients had been treated with prednisone, which resulted in reduced FH compared with patients (n = 92) treated with hydrocortisone (-1.0 +/- 0.9 SDS vs.-0.6 +/- 0.9 SDS; P < 0.05). FH correlated negatively with hydrocortisone dose given at the start of puberty (r = -0.3; P < 0.05). Pubertal development started early in boys [9.8 +/- 2.3 yr (SV) and 10.6 +/- 1.9 yr (SW)] and was timely in girls [9.8 +/- 1.9 yr (SV) and 10.3 +/- 1.5 yr (SW), menarche at 13.3 +/- 1.7 yr (SV) and 13.7 +/- 1.5 yr (SV)]. CONCLUSION: Patients with CAH are able to achieve adequate FH with conventional therapy. Total pubertal growth is significantly decreased, and treatment with prednisone results in decreased FH. In addition to biochemical analysis, treatment should be adjusted to normal growth velocity, especially during puberty.

Growth hormone increases final height in patients with juvenile idiopathic arthritis: data from a randomized controlled study.

BACKGROUND: GH treatment stimulates growth in short children with juvenile idiopathic arthritis (JIA). The extent to which this therapy increases final height is not known. METHODS: Thirty-one growth-retarded children with systemic and polyarticular idiopathic arthritis were enrolled in this controlled study. After a mean observational time of 8.4 yr, final height was reached in 13 patients (seven females and six males) treated with GH for a mean of 6.7 yr in a dose of 0.33 mg/kg body weight per week. Eighteen patients (12 females and six males) served as an untreated control group. RESULTS: Mean increment in height in the treatment group was 1.6 +/- 0.8 SD, whereas the patients of the control group lost 0.7 +/- 1.8 SD. Overall, mean final height in the treatment group was -1.6 SD and in the control group -3.4 SD. More GH-treated patients reached a final height within target height than untreated patients (11 of 13 vs. four of 18). Disease activity markers had a significant influence on height outcome. After adjustment for baseline and average disease activity, the difference between treatment and control group was still significant (mean 1.5 SD). Patients with a moderate overall disease activity profited most from GH treatment. No adverse events were noted throughout the study. CONCLUSION: Our data suggest that long-term GH therapy has a beneficial effect on growth and final height in the majority of growth retarded children with severe forms of JIA.

Age of onset of type 1 diabetes in children and carotid intima medial thickness.

CONTEXT: Cardiovascular disease due to atherosclerosis is a major cause of morbidity and mortality in adult diabetic patients. In children, signs of subclinical atherosclerosis such as increased intima-media thickness (IMT) of the common carotid arteries have been detected in several studies. However, concerns may arise about the different analyzing methods used because measurements in patients and controls differ significantly. PATIENTS AND METHODS: We studied 208 children [150 patients with diabetes mellitus type 1, mean age (+/-sd) 13.9 +/- 2.8 yr, 66 males, mean glycosylated hemoglobin (+/-sd) 7.8 +/- 1.4%, and 58 healthy controls, mean age (+/-sd) 14.1 +/- 3.1 yr, 32 males] and used normal IMT values published recently for comparison of the results. RESULTS: Of 150 patients, 37 had an increased IMT [mean IMT (+/-sd) 1.6 +/- 0.6], whereas healthy controls had nearly normal IMT values [mean IMT (+/-sd) 0.3 +/- 0.1; P < 0.001]. Age at onset of diabetes, mean daily insulin dosage, systolic blood pressure, and total cholesterol level were significantly related to IMT in a multilinear regression model. A total of 25 diabetic patients were hypertensive and had a significantly increased IMT (mean IMT 0.475 +/- 0.03 mm) compared to the remaining patients (mean IMT 0.459 +/- 0.02 mm; P < 0.05). CONCLUSIONS: The IMT measurement detected subclinical atherosclerosis in a large cohort of diabetic children. Systolic blood pressure, total cholesterol level, insulin dosage, and age at onset of the disease were significantly related to the IMT. Longitudinal measurements may help to identify patients at special risk for atherosclerotic changes and cardiovascular disease.

Subclinical atherosclerosis, but normal autonomic function after Kawasaki disease.

OBJECTIVE: To compare the carotid artery intima-media-thickness (IMT) of children with Kawasaki disease with normative data for Western children. STUDY DESIGN: Forty-eight children (20 patients after Kawasaki disease, mean age 12.1 +/- 4.7 years; 28 age- and sex-matched healthy controls, mean age 12.0 +/- 3.1 years) were studied. RESULTS: Mean (IMT differed significantly (0.449 +/- 0.02 vs 0.424 +/- 0.01, P < .001) as well as IMT standard deviation score (1.2 +/- 0.6 vs 0.3 +/- 0.1, P < .001). Patients with coronary arterial involvement (n = 15) showed a further increase of the IMT (0.459 +/- 0.01 vs 0.436 +/- 0.01, P < .05). There was no difference regarding short-term blood pressure regulation. CONCLUSIONS: In this small patient group, signs of subclinical atherosclerosis after Kawasaki disease have been detected. These preliminary data indicate that these patients may be at risk for cardiovascular disease even in the absence of permanent alterations of the coronary arteries.