Interaction of Pubertal Development and Metabolic Control in Adolescents with Type 1 Diabetes Mellitus.

BACKGROUND: In T1DM, delayed pubertal development and reduced final height are associated with inadequate metabolic control. OBJECTIVE: To assess whether T1DM affects pubertal growth spurt and whether metabolic control during puberty is gender-related. METHODS: Using a large multicentre database, longitudinal data from 1294 patients were analysed. Inclusion criteria: complete records of height and HbA1c from the age of seven to 16 years. Exclusion criteria: other significant chronic diseases and medications, T1DM duration less than three months, and initial BMI < 3rd or >97th percentile. RESULTS: Growth velocity (GV) was impaired with a significant reduction of peak GV by 1.2 cm in boys. HbA1c increase during male puberty was lower except for a period of 1.5 years. The highest HbA1c increase in boys coincided with maximum growth spurt. In girls, the highest HbA1c increase was observed during late puberty. Even though there is impaired GV, both sexes reach a height at 16 years of age which corresponds to the background population height. CONCLUSION: Worsening of metabolic control is sex-discordant and associated with gender-specific alterations of GV. However, the vast majority of boys and girls with T1DM seems to reach normal height at the age of 16 years.

[Pediatric hyperglycemic hyperosmolar coma diabeticum: diagnostic evaluation and therapeutic concept]. / Das hyperglykämisch-hyperosmolare Coma diabeticum im Kindesalter: Diagnostische Abgrenzung und Therapiekonzept.

Hyperglycemic hyperosmolar coma diabeticum (HHS) is a rare phenomenon in pediatric patients. It causes major morbidity and significant mortality. It is characterized by the trias of hyperglycemia, hyperosmolality and absent or mild metabolic acidosis. Major complications include cerebral edema and rhabdomyolysis. Evidence based guidelines for HHS in children are lacking. Based on a literature review we discuss treatment options in pediatric HHS und suggest a therapeutic concept. Appropriate treatment consists of adequate fluid administration and a cautious lowering of the serum glucose level. Patients should be treated on an intensive care unit and monitored closely to avoid complications. Low-dose and late insulin administration seems to be favourable.

Impact of overweight on effectiveness of treatment with human growth hormone in growth hormone deficient children: analysis of German KIGS data.

BACKGROUND: We hypothesized that overweight children with growth hormone deficiency (GHD) demonstrate a lower response to growth hormone (GH) as a result of a misclassification since obesity is associated with lower GH peaks in stimulation tests. METHODS: Anthropometric data, response, and responsiveness to GH in the first year of treatment were compared in 1.712 prepubertal children with GHD from the German KIGS database according to BMI (underweight=group A, normal weight=group B, overweight=group C) (median age: group A, B, C: 7.3, 7.28, and 8.4 years). RESULTS: Maximum GH levels to tests (median: group A, B, C: 5.8, 5.8, and 4.0 µg/ml) were significantly lower in group C. IGF-I SDS levels were not different between the groups. Growth velocity in the first year of GH treatment was significantly lower in the underweight cohort (median: group A, B, C: 8.2, 8.8, and 9.0 cm/yr), while the gain in height was not different between groups. The difference between observed and predicted growth velocity expressed as Studentized residuals was not significantly different between groups. Separating the 164 overweight children into obese children (BMI>97th centile; n=71) and moderate overweight children (BMI>90th to 97th centile, n=93) demonstrated no significant difference in any parameter. CONCLUSIONS: Overweight prepubertal children with idiopathic GHD demonstrated similar levels of responsiveness to GH treatment compared to normal weight children. Furthermore, the IGF-I levels were low in overweight children. Therefore, a misclassification of GHD in overweight prepubertal children within the KIGS database seems unlikely. The first year growth prediction models can be applied to overweight and obese GHD children.

Growth hormone secretion and long-term growth data in children with psychosocial short stature treated by different changes in environment.

OBJECTIVES: We assessed auxological and endocrine data of 65 children (32 girls) from 51 families with an average age of 6.6 years (range, 0.9 to 16.5 years, all but five prepubertal) with psychosocial short stature. METHODS: Fifty-one patients had an assessment of growth hormone (GH) secretion. Thirty-four were subjected to repeated testing with the first test being performed when the child was still in the adverse environment and the next testing after the child was removed. Twenty-five out of those 34 were repeatedly tested during one uninterrupted hospital admission with limited parental access. Thirty patients had a definite, long-term change in their environment (13 were separated from their families) and were assessed concerning their auxological data. RESULTS: Of the 34 patients who had repeated endocrine testing, 11 (32%) showed reversible GH deficiency (GHD), nine (26%) increased their previously normal peak GH concentration, and six (18%) had apparently irreversible GHD. Patients who had a change in environment increased their mean height velocity SDS from -0.9 (SD 1.5) to +1.5 (2.3) (p < 0.0001). Accordingly, height SDS increased from -2.9 (SD 0.8) before to -2.6 (SD 0.8) after the change (p < 0.001). CONCLUSION: One of the diagnostic features of psychosocial short stature is reversible GH insufficiency, which usually normalises after the child is separated from the adverse environment. Catch-up growth is always found after a positive change in the environment, and may occur within the family. However, if a change in environment is not possible, GH therapy may be an option.

Longitudinal data for intrauterine levels of fetal IGF-I and IGF-II.

OBJECTIVE: An increasing body of evidence supports a major role for the insulin-like growth factors (IGFs) in the control of human fetal growth. Individual data at various times of pregnancy suggest that IGF-I and IGF-II levels remain stable up to the 33rd week of pregnancy. Thereafter, both increase to reach values 2-3 times higher at term. In order to provide an accurate reflection of fetal IGFs in utero, we sampled fetal blood from the umbilical cord by cordocentesis. METHODS: We measured IGF-I and IGF-II in 12 fetuses longitudinally for up to 5 times between the 21st week of gestation and delivery. RESULTS: All patients showed a progressive increase in IGF-I and IGF-II levels. Data determined during different time intervals (before 29th, 29th to 32nd, after 32nd week) were compared and the main increase was found after the 32nd week. The median for IGF-I before the 29th week was 33.5 ng/ml (range 19-40.5) and increased to 41 ng/ml (32-59) between the 29th to 32nd and further to 54.1 ng/ml (range 17-70) thereafter. During the same time interval, the median for IGF-II increased from 217 ng/ml (86-326) to 349 ng/ml (227-467). In 7 patients, cord blood after delivery was available. For IGF-II a further increase was consistently found after birth (from 282 ng/ml (175-511) to 393 ng/ml (297-513)), whereas only 2 fetuses showed an increase in IGF-I. CONCLUSION: We conclude that in human fetuses, IGF-I and IGF-II levels increase longitudinally throughout pregnancy. Therefore, they may become important markers of healthy fetal development.

Final height in psychosocial short stature: is there complete catch-up?

AIM: To determine whether children with psychosocial short stature attain their genetic height potential. METHODS: We report on 18 children (10 girls, 8 boys) diagnosed by a multidisciplinary team as having psychosocial short stature. All the children had had some kind of change in their environment (9 were separated from their families), and increased their mean height velocity standard deviation score (SDS) from -0.7 (1.3) to +3.6 (4.8) (p < 0.005) as well as their height SDS from -3.0 (0.3) to -2.6 (0.9) in the first year after the change. All the patients were postpubertal and had reached their near final height (mean age, 20.0 y; range, 16.0-23.3). RESULTS: Only 3 out of 18 had a greater final height than the mid-parental target height, 14 out of 18 had a near final height within the mid-parental target range (95% tolerance limits of the mid-parental height (+/- 2 SD = +/- 10 cm). Nevertheless, mean final height expressed in height SDS for the whole group was significantly shorter with -2.4 SDS compared with the mean of the mid-parental target height of -1.5 SDS (p < 0.001). Surprisingly, initial catch-up growth did not correlate with final height attainment. CONCLUSION: The majority of patients will attain a stature within the range of mid-parental target height, although towards the lower limit of this range.

Diagnosis and management of juvenile hyperthyroidism in Germany: a retrospective multicenter study.

This retrospective multicenter study was designed to survey the management of childhood and adolescent hyperthyroidism in six pediatric endocrinological units in Germany. Fifty-six patients aged between 1.1 and 17.0 yr (median 10.5 yr) were enrolled. Data were collected retrospectively from the patients' records by a trained pediatric endocrinologist using standardized questionnaires. After the diagnosis of hyperthyroidism was established on the basis of clinical and biological findings, treatment with antithyroid drugs (carbimazole, methimazole, thiamazole, propylthiouracil) was started in all patients. In 55/56 of the patients treated with antithyroid drugs, euthyroidism was achieved (98%). However, 26 patients (47%) were still hyperthyroid after discontinuation of the medication. Eight children with continued hyperthyroidism ultimately underwent subtotal thyroidectomy 13-136 (median 28) months after the initial diagnosis. Management principles of the participating centers were heterogeneous. As a consequence, prospective multicenter studies are urgently needed to establish clear standards for the diagnosis and therapy of childhood hyperthyroidism.

Interstitial deletion in Xp22.3 is associated with X linked ichthyosis, mental retardation, and epilepsy.

We describe monozygotic male twins with an interstitial deletion of Xp22.3 including the steroid sulphatase gene (STS). The twins had X linked ichthyosis, X linked mental retardation, and epilepsy. A locus for X linked mental retardation has been assigned to a region between STS and DXS31 spanning approximately 3 Mb. Recently the locus was further refined to an approximately 1 Mb region between DXS1060 and GS1. By PCR analysis of flanking STS gene markers in our patients we succeeded in narrowing down the locus to between DXS6837 and GS1.

Recognition of children with psychosocial short stature: a spectrum of presentation.

We describe 65 children (32F, 33M) with psychosocial short stature from 51 families. Average age was 6.6 years (range 0.9-16.5) and all but five were prepubertal. 67% of the patients lived in families with three or more children, but in 73% of cases the patient was the first or the second born child. 45% of the parents were divorced and in 31% of the families the father was unemployed. In 56 children, the birth weight was known and in only 29% was it above 3000 g; 21% were premature, 29% had features of low birth-weight syndrome (including four with Russell-Silver syndrome). Average birth weight was 2786 g (range 1650-4676). In all patients, the predominant reason for referral was growth failure. In 28% an environmental aetiology was suspected and in a further 29%, social or emotional problems were known to the referring physician but not suspected as the aetiology of the growth failure, despite social services involvement in 60% at the referral to our unit. At initial presentation in our clinic, we found additional features leading to the suspicion of psychosocial short stature; 54% abnormal eating pattern, 42% behaviour problems, 26% encopresis, 18% nocturnal enuresis and 12% inappropriate urination. During the observation period of a mean of 3.7 years, 27 (41%) of our patients were found to have been sexually or physically abused. In these 27 children hyperphagia, bizarre eating habits, behaviour problems, soiling and nocturnal enuresis were more common.

Serum lipids during parenteral nutrition with a 10% lipid emulsion with reduced phopholipid emulsifier content in premature infants.

Fourteen premature infants (range 26 + 0 to 32 + 3), all but two appropriate for gestational age with a mean body weight of 1196 g (range 860 to 2770 g) received a 10% lipid emulsion. This lipid emulsion contained half of the formerly used phospholipid emulsifier concentration reducing the phospholipid/triglyceride ratio to the ratio used for the 20% lipid emulsion (0.06 instead of 0.12). Lipid emulsion was given over a 10 day period commencing at the third day of life with 0.5 g/kg/24 h which was increased daily up to a dose of 2.0-2.5 g/kg/24 h which was reached in all patients at the seventh day of the observation period. During this time mean serum concentrations of cholesterol increased non-significantly from 76.1 mg/dl (SD 33.7) before lipid emulsion to 86.1 mg/dl (SD 36.4) on day seven of the observation period. 13 of the 14 patients (97%) showed no pathological increase of their serum triglyceride concentration during lipid infusion. Mean serum triglyceride concentration increased from 65.3 mg/dl (SD 32.0 mg/dl) before the start of lipid emulsion to 102.6 mg/dl (SD 76.5) on day four (p < 0.05) but with no further significant increase. Lipid emulsions with 10% triglyceride but lower phospholipid content are tolerated without pathological increase in triglyceride or cholesterol serum concentration in the vast majority of premature newborns.