Evaluation of catch-up growth in severe pediatric Hashimoto's hypothyroidism.

BACKGROUND: We aimed to evaluate catch-up growth in children with severe Hashimoto's hypothyroidism (HH) after thyroid hormone replacement therapy (HRT). METHODS: A multicenter retrospective study was conducted including children referred for growth slowdown that led to the diagnosis of HH between 1998 and 2017. RESULTS: A total of 29 patients were included, with a median age of 9.7 years (13-172 months). Median height at diagnosis was -2.7 [-4.6; -0.1] standard deviation score (SDS), with a height loss of 2.5 [0.7; 5.4] SDS compared to height before growth deflection (p<0.0001). At diagnosis, the median TSH level was 819.5 mIU/L [100; 1844], the median FT4 level was 0 pmol/L [undetectable; 5.4], and the median anti-thyroperoxidase antibody level was 1601 UI/L [47; 25,500]. In the 20 patients treated only with HRT, there were significant differences between height at diagnosis and height at 1 year (n = 19, p<0.0001), 2 years (n = 13, p = 0.0005), 3 years (n = 9, p = 0.0039), 4 years (n = 10, p = 0.0078), and 5 years (n = 10, p = 0.0018) of treatment but not in the case of final height (n = 6, p = 0.0625). Median final height was -1.4 [-2.7; 1,5] SDS (n = 6), with a significant difference between height loss at diagnosis and total catch-up growth (p = 0.003). The other nine patients were also given growth hormone (GH). They were smaller at diagnosis (p = 0.01); however, there was no difference in final height between those two groups (p = 0.68). CONCLUSION: Severe HH can lead to a major height deficit, and catch-up growth seems to be insufficient after treatment with HRT alone. In the most severe cases, administration of GH may enhance this catch-up.

Neonatal screening for congenital hypothyroidism: Time to lower the TSH threshold in France.

Neonatal screening for congenital hypothyroidism (CH) is based on the measurement of thyroid-stimulating hormone (TSH) in whole dried blood samples on filter paper in all newborns. The objective of screening for CH is to prevent mental retardation, which is irreversible in the event of a late diagnosis, by setting up prompt treatment (before day 15) with levothyroxine. The threshold value of TSH on filter paper on day 3 is 17 mIU/L in France in the GSP method (GSP, Genetic Screening Processor, Perkin Elmer): It is one of the highest thresholds used in the world. In many countries, the TSH threshold is between 6 and 12 mIU/L. Studies have found that a threshold of > 17 mIU/L may miss as much as 30% of cases of CH, with 30-80% of these being permanent CH. Recent studies suggest that mild CH (currently missed by the French TSH threshold) is associated with cognitive consequences if left untreated. An inverse relationship between TSH at screening (below the current threshold) and cognitive development at preschool or school age has been shown. These studies advocate for the evaluation of a lowering of the threshold of TSH on filter paper in France: (a) to determine the number of CH diagnoses with the new threshold and whether these "new cases" would be transitory or permanent; and (b) to analyze the cost-effectiveness of the strategy.

Laparoscopic adjustable gastric banding in adolescents with severe obesity: Psychological aspects, decision makers of surgery, and 2-year outcomes. A case series.

BACKGROUND: The results of medical treatment of severe obesity in the adolescent population (balanced diet and physical activity) are often unsatisfactory, and bariatric surgery is questioned. The psychological determinants for requesting bariatric surgery in these adolescents are unclear. The objective of this study was to report the psychiatric and psychological aspects as well as the determinants of the medical decision for surgery in a cohort of obese adolescents requesting bariatric surgery by laparoscopic adjustable gastric banding. METHODS: Thirty-five adolescents (12.3-17.7 years of age), were recruited from January 2007 to December 2012. Semistructured interviews were conducted. RESULTS: Fifty-four percent of the adolescents had a psychiatric history and 85% had psychiatric comorbidities. In adolescents undergoing surgery, excess weight loss was 46% after 1 year and 51% after 2years. For patients not receiving surgery, excess weight loss was 0.43% after 1 year (P=0.001). Compliance with medical treatment was the only significant element contributing to the decision to perform surgery. Results in terms of satisfaction and perception 1 and 2years after surgery were encouraging. CONCLUSION: Bariatric surgery is feasible in young patients and produces good results in terms of excess weight loss. We argue that compliance with medical treatment is probably one of the most important elements for making the decision to perform bariatric surgery and in excess weight loss after surgery. We probably need to focus on the compliance of young patients and evaluate how this can be improved.

Evolution of IGF-1 in children born small for gestational age and with growth retardation, treated by growth hormone adapted to IGF-1 levels after 1 year.

AIM: This study was designed to estimate the percentage of growth hormone (GH)-treated children born small for gestational age (SGA), with serum IGF-1 >2 SDS before and after GH dose adaptation. METHODS: SGA boys aged 4-9 and girls aged 4-7 with a height <-2 SDS and an annual growth rate below the mean received a subcutaneous GH dose of 57 µg/kg/day for 2 years. The GH dose was to be decreased by 30% in children with serum IGF-1 >2 SDS at 12 months and on the previous sample. The GH dose could be reduced a second time to 35 µg/kg·day. IGF-1 and IGFBP-3 dosages were centralized. RESULTS: Among the 49 (21 boys) children included in the study, 8 (16.3%) had an IGF-1 >2 SDS consecutively at 9 and 12 months (95% CI 7.3, 29.7). The GH dose was decreased in 6/8 children. However, IGF-1 levels were elevated at several nonconsecutive determinations in 45% (95% CI 28.4, 56.6) of the patients. CONCLUSION: A high IGF-1 level is observed in 45% of the GH SGA-treated children with a relatively high dose of GH. A 30% reduction in the GH dose causes a decrease in IGF-1 below 2 SDS in most children.

Sensor-augmented pump therapy from the diagnosis of childhood type 1 diabetes: results of the Paediatric Onset Study (ONSET) after 12 months of treatment.

AIMS/HYPOTHESIS: The value of managing children with type 1 diabetes using a combination of insulin pump and continuous glucose monitoring starting from diagnosis for improving subsequent glycaemic control and preserving residual beta cell function was determined. METHODS: A total of 160 children (aged 1-16 years, mean ± SD: 8.7 ± 4.4 years; 47.5% girls) were randomised to receive insulin pump treatment with continuous glucose monitoring or conventional self-monitoring blood glucose measurements. The primary outcome was the level of HbA(1c) after 12 months. Other analyses included fasting C-peptide, glycaemic variability, sensor usage, adverse events, children's health-related quality of life and parent's wellbeing. RESULTS: HbA(1c) was not significantly different between the two groups, but patients with regular sensor use had lower values (mean 7.1%, 95% CI 6.8-7.4%) compared with the combined group with no or low sensor usage (mean 7.6%, 95% CI 7.3-7.9%; p=0.032). At 12 months, glycaemic variability was lower in the sensor group (mean amplitude of glycaemic excursions 80.2 ± 26.2 vs 92.0 ± 33.7; p=0.037). Higher C-peptide concentrations were seen in sensor-treated 12- to 16-year-old patients (0.25 ± 0.12 nmol/l) compared with those treated with insulin pump alone (0.19 ± 0.07 nmol/l; p=0.033). Severe hypoglycaemia was reported only in the group without sensors (four episodes). CONCLUSION/INTERPRETATION: Sensor-augmented pump therapy starting from the diagnosis of type 1 diabetes can be associated with less decline in fasting C-peptide particularly in older children, although regular sensor use is a prerequisite for improved glycaemic control. TRIAL REGISTRATION: ISRCTN.org ISRCTN05450731 FUNDING: Medtronic International Trading Sàrl, Tolochenaz, Switzerland.

[Acute adrenal insufficiency in the newborn]. / Insuffisance surrénale aiguë chez le nouveau-né

Neonatal acute adrenal insufficiency is a rare condition. Congenital adrenal hyperplasia with 21-hydroxylase defect appears to be the most frequent cause, but the neonatal screening has improved its potential severe outcome. The other causes and the various clinical presentations have been exposed, with a special reference to the salt-wasting syndrome. Among them, the severity of X-linked adrenal hypoplasia congenita (AHC) deserves special attention. Two other causes of adrenal hypoplasia have been recently discovered, i.e. a mutation of the SF-1 gene and the syndrome IMAGe. Adrenal insufficiency secondary to ACTH deficiency is often unrecognised despite the risk of severe seizures and hypoglycaemia with brain damage. Finally, the hormonal diagnostic testing and the main therapeutic approach by corticosteroids have been indicated. The aim of this work is to focus the attention of paediatricians who examine a newborn because the risk of delayed diagnosis and fatal outcome may be limited if the clinical symptoms are soon recognized.

[Group therapy versus individual follow-up in the management of the obese child]. / Comparaison de l'education thérapeutique collective au suivi individuel pour la prise en charge de l'obésité de l'enfant.

OBJECTIVE: To compare the 1-year outcome of obese children managed medically and dietetically in a group setting with those managed individually. PATIENTS AND METHODS: Two hundred and seventy-eight obese children [168 girls and 110 boys; body mass index (BMI) > + 2 SD] were followed by the Department of Pediatrics of the University Hospital of Angers between January 1996 and December 2002 (175 children in a group setting and 103 individually). The group program consisted of 3 monthly sessions of slide shows for groups of 10 children, followed by individual consultations once every 3 months alternating medical and dietetic concerns. The individual program consisted of successive medical and dietetic consultations on the same day once every 3 months. RESULTS: The children were 10.3 +/- 2.9 years old, and their BMI was 5.5 +/- 2.1 SD, with no difference between groups. The drop-out rate (children not returning after the 1st consultation) was 17%, with no difference between groups. The drop-out rate after 1 year was 65% in the group program and 41% in the individual program (p < 0.05). Of the children who were followed for 1 year, 88% of those treated in a group setting had stabilized or reduced their BMI, whereas 74% of the individually-treated children had done so (p < 0.05). CONCLUSION: Among obese children followed for 1 year, group treatment resulted in a greater percentage of stabilization or reduction in BMI than did individual treatment, although the drop-out rate was higher in the group setting. Psychological support and physical activity sessions adapted for obese children would help to maintain motivation in these children.

Prenatal diagnosis of absence of the septum pellucidum associated with septo-optic dysplasia.

Septo-optic dysplasia (SOD; De Morsier syndrome) is a rare congenital disorder characterized by the absence of the septum pellucidum (SP), hypoplasia of the optic chiasma and nerves, and various types of hypothalamic-pituitary dysfunction. We report on two fetuses with absence of the SP diagnosed by ultrasound examination at 29 and 30 gestational weeks. In the first case the diagnosis of SOD was suspected in utero and confirmed postnatally; to the best of our knowledge this is the first report of the prenatal diagnosis of SOD. In the second case absence of the SP appeared to be isolated and no visual or endocrine impairment were detected after birth.

West syndrome and mitochondrial diabetes: relationship or coincidence?

West syndrome occurs in infancy and in early childhood. It is characterized by intractable seizures occurring almost daily, severe psychomotor retardation, poor prognosis and EEG abnormalities, known as hypsarrhythmia. We report here the case of a 28-year-old patient, who was diagnosed with West syndrome when he was 8 months old and with diabetes mellitus when he was 25 years old. Sequencing analyses and restriction analyses were suggestive of mitochondrial diabetes. Four years after the diagnosis of diabetes, this patient's diabetes is still controlled by diet and biguanides.

Body composition, fasting leptin, and sex steroid administration determine GH sensitivity in peripubertal short children.

Serum IGF-I levels in GH-treated subjects demonstrate a wide range of responsiveness to GH. However, the factors influencing GH sensitivity are not well known. The aim of this work was 1) to test whether body composition (determined by dual energy x-ray absorptiometry) or factors related to body composition (fasting blood glucose, FFA, C-peptide, leptin, and insulin sensitivity determined by an insulin tolerance test) influence GH sensitivity; and 2) to study the effect of sex steroid priming on GH sensitivity. We measured serum IGF-I at baseline and 24 h after a single administration of GH (2 mg/m(2)) in 60 healthy prepubertal and early pubertal children (height, -2.1 +/- 1.0 SD score). GH sensitivity, as estimated by the increase in serum IGF-I after GH administration (difference between stimulated and baseline serum IGF-I = delta IGF-I), was also determined after a short-term administration of oral ethinyl E2 in girls and im T in boys. The serum IGF-I concentration was 297 +/- 114 microg/liter at baseline and increased to 429 +/- 160 microg/liter, corresponding to a 46 +/- 29% increase over the baseline value (P < 0.0001, stimulated vs. baseline serum IGF-I). delta IGF-I was not different between gender or pubertal stage. There were positive correlations (P < 0.001) between delta IGF-I and adiposity (total body fat, r = 0.62; trunk fat, r = 0.62), fasting leptin (r = 0.64), and C-peptide (r = 0.54), and a negative correlation with fasting FFA (r = -0.33; P < 0.05) even after adjustment for age, gender, and pubertal stage. These factors remained significant independent predictors of the absolute as well as the percent increase in serum IGF-I in multiple regression analyses. Priming with T and ethinyl E2 had a similar stimulating effect on the serum GH peak in response to the insulin tolerance test. In boys, serum baseline IGF-I increased by 60%, and delta IGF-I was similar after vs. before T administration. By contrast, in girls, serum baseline IGF-I was similar, and delta IGF-I was 60% less after vs. before ethinyl E2 administration. This study indicates that 1) GH sensitivity is determined by fat mass, serum fasting leptin, C-peptide, and FFA; and 2) oral ethinyl E2 and im T have divergent effects on the IGF-I response to a single administration of GH.

Growth and adult height in GH-treated children with nonacquired GH deficiency and idiopathic short stature: the influence of pituitary magnetic resonance imaging findings.

We analyzed the final height of 146 short children with either nonacquired GH deficiency or idiopathic short stature. Our purpose was 1) to assess growth according to the pituitary magnetic resonance imaging findings in the 63 GH-treated children with GH deficiency and 2) to compare the growth of the GH-deficient patients with normal magnetic resonance imaging (n = 48) to that of 32 treated and 51 untreated children with idiopathic short stature (GH peak to provocative tests >10 microg/liter). The mean GH dose was 0.44 IU/kg.wk (0.15 mg/kg.wk), given for a mean duration of 4.6 yr. Among the GH-deficient children, 15 had hypothalamic-pituitary abnormalities (stalk agenesis), all with total GH deficiency (GH peak <5 microg/liter). They were significantly shorter and younger at the time of diagnosis than those with normal magnetic resonance imaging, had better catch-up growth (+2.7 +/- 0.9 vs. +1.3 +/- 0.8 SD score; P < 0.01), and reached greater final height (-1.1 +/- 1.0 vs. -1.7 +/- 1.0 SD score; P < 0.05). Among patients with normal magnetic resonance imaging, there was no difference in catch-up growth and final height between partial and total GH deficiencies. GH-deficient subjects with normal magnetic resonance imaging and treated and untreated patients with idiopathic short stature had comparable auxological characteristics, age at evaluation, and target height. Although they had different catch-up growth (+1.3 +/- 0.8, +0.9 +/- 0.6, and +0.7 +/- 0.9 SD score, respectively; P < 0.01, by ANOVA), these patients reached a similar final height (-1.7 +/- 1.0, -2.1 +/- 0.8, and -2.1 +/- 1.0 SD score, respectively; P = 0.13). Pituitary magnetic resonance imaging findings show the heterogeneity within the group of nonacquired GH deficiency and help to predict the response to GH treatment in these patients. The similarities in growth between the GH-deficient children with normal magnetic resonance imaging and those with idiopathic short stature suggest that the short stature in the former subjects is at least partly due to factors other than GH deficiency.

Relationships between placental GH concentration and maternal smoking, newborn gender, and maternal leptin: possible implications for birth weight.

The control of fetal growth depends on multiple hormones, including both IGF-I and placental GH (PGH) in the mother, and IGF-I rather than pituitary GH (pitGH) in the fetus. Leptin, which is produced by adipocytes and syncitiotrophoblast cells, has also been thought to influence fetal growth by an as yet unknown mechanism. This study assessed the relationships between the GH-IGF-I axis in mothers and newborns, and maternal smoking, neonate gender, and maternal and fetal leptin. We collected blood in 87 mothers at the onset of labor and cord blood immediately after birth in their 87 healthy full-term newborns. GH concentrations were log(10) transformed, and data were expressed as the geometric mean (-1, +1 tolerance factor). PGH was lower in the 30 smoking mothers, as compared with the 57 nonsmoking mothers [18.2 (11.5; 28.6) vs. 27.0 (15.1; 48.2) microg/liter, P < 0.01]. Cord blood IGF-I was lower in neonates from smoking mothers (90 +/- 44 vs. 135 +/- 65 microg/liter, mean +/- SD, P < 0.01), consistent with their lower birth weight percentile (P < 0.01). A gender effect was observed for PGH, which was higher when the newborn was female, and for newborn pitGH and newborn leptin, which were, respectively, lower and higher in females, even after adjustment for birth weight and maternal smoking category (P < 0.05 for all comparisons). Multiple regression analyses identified maternal leptin as a negative predictor of PGH (P < 0.05) and newborn leptin as a positive predictor of newborn IGF-I (P < 0.05). Maternal smoking is associated to decreased maternal PGH and cord blood IGF-I concentrations. A sexual dimorphism for PGH, newborn pitGH, and newborn leptin exists at the time of birth, but its physiological significance remains to be studied. The relationships between maternal leptin and PGH and between cord blood leptin and IGF-I are consistent with the hypothesis that leptin could contribute to the control of fetal growth.