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.

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.

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.

[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.

Gonadotropin-releasing hormone agonist treatment of girls with constitutional short stature and normal pubertal development.

GnRH agonists have been proposed to improve final height in patients with constitutional short stature. We treated 31 girls, aged 11.9 +/- 1 yr (mean +/- SD), with short stature, recent pubertal onset and predicted final height of 155 cm or less with depot triptorelin. During the 23 +/- 4 months of treatment, bone age progression was 0.6 +/- 0.3 bone age yr/yr, and growth velocity declined from 7 +/- 2 to 4 +/- 0.8 cm/yr (P < 0.0001). Height prognosis, calculated by the Bayley-Pinneau method, progressed from 149.6 +/- 3.4 to 151.8 +/- 4 cm at the end of treatment (+2.2 +/- 2.6 cm; P < 0.0001). When treatment was interrupted, growth velocity slightly increased to 4.6 +/- 1.6 cm/yr, and bone age maturation was accelerated: 1.3 +/- 0.4 bone age yr/yr during the first posttreatment year. At the last visit, 26 +/- 9 months after interruption of treatment, bone age was 14.9 +/- 1.3 yr (> or = 13.5 yr in all patients), height was 149.1 +/- 4 cm, and final height prognosis was 150.6 +/- 3.6 cm. Final height prognosis was 1 +/- 2.3 cm greater than pretreatment height prognosis (P < 0.02) and 1.2 +/- 2.2 cm below the height predicted at the end of the treatment (P < 0.01). No major side-effect was observed. Height SD score decreased during treatment with GnRH agonist from -2.3 +/- 0.9 to -2.7 +/- 0.7 SD score (P < 0.0001). We conclude that 2 yr of depot triptorelin-induced pubertal delay has a limited effect on near-final height in girls with constitutional short stature and that the growth benefit observed does not currently justify the use of GnRH agonists, given their cost and potential side-effects.

Short stature associated with intrauterine growth retardation: final height of untreated and growth hormone-treated children.

Short term studies have demonstrated the acceleration of growth velocity after the administration of GH in short children born with intrauterine growth retardation (IUGR). We report the final heights of 70 IUGR children whose short stature was attributed to idiopathic GH deficiency (peak plasma GH <10 ng/mL at 2 provocative tests) and treated with GH at a mean dosage of 0.4 +/- 0.1 U/kg x week during an average of 4.6 +/- 2.5 yr. They were compared to a control group of 40 untreated short children born with IUGR, without GH deficiency. At the time of evaluation, age, auxological data, and pubertal status were similar in the 2 groups (height, -2.9 +/- 0.8 and -2.8 +/- 0.7 SD score). Final heights were comparable in both groups of children (-2 +/- 0.7 and -2.2 +/- 1.1 SD score). A multivariate analysis identified 4 independent predictors of final height, namely target height, age and body mass index at evaluation, and GH treatment. Treatment was associated with a gain of 0.6 SD score, suggesting a final height gain of about 3.4 cm. Fifty-three of 70 treated children were reevaluated after completion of growth, and 43 of 53 had a peak plasma GH level of 10 ng/mL or more. Auxological characteristics of these 53 patients were not different from those of nonreevaluated patients. We believe that the transient character of the GH deficiency in most patients and the nonstringent initial criteria used for the diagnosis of GH deficiency render the spontaneous growth potentials identical in the 2 groups of patients. Our data, therefore, suggest that GH treatment at this dosage has a limited effect on the final height of short children born with IUGR.

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.

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.

Macroorchidism due to autonomous hyperfunction of Sertoli cells and G(s)alpha gene mutation: an unusual expression of McCune-Albright syndrome in a prepubertal boy.

We report an unusual observation of a 3.8-yr-old boy with McCune-Albright syndrome (MAS) associated with abnormal prepubertal testis enlargement and no sexual precocity. Physical examination showed café-au-lait skin lesions, enlarged testes, prepubertal sized penis, and no pubic or axillary hair. Skeletal radiography disclosed fibrous dysplasia. The serum testosterone level was 0.58 nmol/L and remained below 1.4 nmol/L during the 4-yr follow-up. By contrast, serum inhibin B and anti-Mullerian hormone concentrations were abnormally increased up to 255 pg/mL (childhood range, 35--180) and 792 pmol/L (childhood range, 309--566), respectively. The LH response to a GnRH test was in the prepubertal range, whereas the FSH response was blunted. This abnormal hormone concentration profile indicates autonomous hyperfunction of Sertoli cells, with no evidence of Leydig cell activation. Testicular histology showed tubules with marked Sertoli cell hyperplasia and very rare germinal cells, and interstitial tissue containing mesenchymal cells but no mature Leydig cells. DNA sequence analysis from bone and testis tissues detected the known activating mutation in MAS that results in replacement of Arg by His at codon 201 of the G(s)alpha protein. Other endocrine tests showed excessive GH secretion and moderate adrenal androgen hypersecretion. These findings are consistent with the occurrence of an activating mutation of the G(s)alpha gene mainly expressed in Sertoli cells and weakly expressed or absent in Leydig cells. Abnormal prepubertal testicular enlargement extends the clinical spectrum of MAS, suggesting that determination of serum inhibin B and anti-Mullerian hormone should be considered in boys with this syndrome. This observation demonstrates the usefulness of detailed molecular and biological investigations in atypical cases of MAS.

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.

Circulating leptin level and growth hormone response to stimulation tests in obese and normal children.

OBJECTIVE: Growth hormone secretion is decreased in obese subjects, and their GH response to stimulation tests is blunted. The mechanisms relating excess adipose mass and GH secretion are unknown. We hypothesized that leptin might be a signal linking adipose mass to GH secretion. DESIGN: We measured serum leptin levels and the GH response to stimulation tests in 42 obese and 40 lean short normal prepubertal children. RESULTS: The mean serum leptin concentrations were 23.8+/-1.7 ng/ml and 3.6+/-0.4 ng/ml in obese and lean children respectively, and were found to be inversely related to GH peak in both groups. After adjusting for body fat data, leptin was still an independent predictor of GH peak. Multiple stepwise regression analysis identified both leptin (regression coefficient = -0.78, P = 0.001), and insulin (regression coefficient = -0.03. P = 0.009) as negative determinants of GH response to the GHRH test in obese children (multiple R = 0.64), and only leptin in lean children (r = -0.51, P = 0.001). No correlation was observed between leptin and IGF-I or IGF binding protein-3. CONCLUSION: These results are consistent with the hypothesis that leptin could contribute to the regulation of GH secretion.

Effects of prolonged administration of ultralente insulin on fasting and postbreakfast beta-cell function in normal adults.

Treatment with small doses of subcutaneous insulin is being investigated as a possible approach to prevent type 1 diabetes in humans. The mechanism of prophylactic insulin therapy could involve the inhibition of beta-cell secretory activity and/or the initiation of an active immunoregulatory process. To evaluate the pure metabolic effect of exogenous insulin, the present study assessed whether daily subcutaneous administration of ultralente insulin alters beta-cell function in normal adults. Fourteen healthy adults were randomized to receive 0.2 U/kg x d ultralente insulin (Ultratard; Novo Nordisk, Bagsvaerd, Denmark) or placebo subcutaneously once daily for 30 days. Plasma glucose, C-peptide, and insulin concentrations were measured in the fasting state and 1 hour after a standardized breakfast, during treatment and during a recovery period of 10 days. Insulin administration induced a 15% to 40% decrease of fasting plasma C-peptide. In contrast, postbreakfast plasma C-peptide increased by 40% to 90% in subjects receiving insulin. Fasting and postbreakfast C-peptide concentrations were significantly different between groups during the injection period after adjustment for baseline concentrations (P < .05, ANOVA with repeated measures). These alterations disappeared 3 days after cessation of insulin treatment. The present regimen of exogenous insulin alters endogenous insulin secretion in normal subjects. Instead of the expected beta-cell rest, the effect appeared to be dual, with insulin secretion decreasing in the basal state and increasing after meals.

Insulin and the prevention of insulin-dependent diabetes mellitus.

Insulin deficiency due to autoimmune destruction of pancreatic beta cells (insulin is an autoantigen) is responsible for insulin-dependent diabetes mellitus. Since 1923, substitutive administration of insulin has been used to treat the disease. Surprisingly, initial usage of insulin is associated with partial resumption of insulin secretion in most patients. This phenomenon is intensified by aggressive insulin therapy. When observed at a late phase of destruction, it has been interpreted as an immunomodulatory effect of insulin which is presumed to act either by masking the target of effector cells in the autoimmune reaction (beta cells at rest because of glycaemic normalisation would expose fewer antigens) or by direct action on autoreactive T lymphocytes (which are rich in insulin receptors). There could also be a direct beneficial effect on anti-apoptotic or pro-regenerative beta cells. Efficient prevention of diabetes has been achieved by administration of parenteral insulin to non-obese diabetic (NOD) mice. Certain sequences of the B chain appear to be responsible for this effect, which seems to be immunomediated. Some preliminary data from the groups of G. Eisenbarth and N. MacLaren have suggested that this effect could be obtained in man by administering small doses of subcutaneous insulin to prediabetic patients. Two trials have been under way since 1994: DPT1 (a non-randomised trial concerning children and adults at high risk) in the United States, and EPP-SCIT (a randomised trial concerning children at very high risk) in Europe. Another approach has also been attempted in diabetes as well as other diseases with an organ-specific autoimmune reaction (SEP, PR) i.e. oral administration of an antigen present at the reaction site. A positive effect has been shown by the group of H. Weiner in the NOD mouse in which islet infiltration was reduced and diabetes prevented by "oral tolerisation" with insulin. Oral insulin is easy to use in therapeutic studies and is currently being administered in two trials: DPT1 (prediabetic children and adults at moderate risk) in the United States, and DIOR (recently diabetic children and adults) in France. However, recent experimental data suggest that oral administration of an antigen in certain artificial circumstances can trigger an autoimmune reaction in the animal, which would indicate that due caution should be exercised in trials involving prediabetic patients.

[Cushing disease in children and in adolescents. Therapeutic results]. / Maladie de Cushing de l'enfant et de l'adolescent. Résultats thérapeutiques.

BACKGROUND: Trans-sphenoidal surgery is currently the treatment of choice for Cushing's disease in children. PATIENTS AND METHODS: The results obtained in 20 consecutive patients referred to the Pediatric Endocrinology Department of hôpital Saint-Vincent-de-Paul are reported. RESULTS: A remission of Cushing's disease was observed in 12/16 (75%) patients in whom surgery was the first treatment. Among these 12 patients, three relapsed (25%) 21 to 80 months after surgery. Four patients were initially treated with steroid synthesis inhibitors: three of those patients were subsequently operated on and their disease remitted. Among the seven patients in whom surgery failed (primary failure or relapse), two were reoperated and also remitted. Taken together, 21 operations were performed and resulted in four immediate failures (19%), three relapses (14%) and 14 long-term remissions (67%, follow-up 40 +/- 35 months). None of the biological, radiological or operative criteria were predictive of the therapeutic results. CONCLUSION: Our results illustrate the efficacy and limits of trans-sphenoidal surgery for Cushing's disease of children and emphasize the need for a very long follow-up of these patients. Treatment of patients in whom surgery has failed (initially or secondarily) is particularly difficult and requires a multidisciplinary approach.

[Primary hypothyroidism revealing pseudohypoparathyroidism without hypocalcemia and hyperphosphoremia]. / Hypothyroïdie compensée révélant une pseudohypoparathyroïdie en l'absence d'hypocalcémie et d'hyperphosphorémie.

BACKGROUND: Type la pseudohypoparathyroidism is due to a molecular defect causing Gs protein deficiency. It is responsible for multi-hormonal resistance and skeletal abnormalities. Parathyroid hormone resistance can be subtle so that the diagnosis can be difficult in patients with atypical manifestations. CASE REPORT: A 10-year-old boy was first referred for growth retardation (height standard deviation score: -2.8). He had short metacarpals, and scaphocephaly. Laboratory findings revealed an elevation of plasma TSH (8,8 microU/mL) with normal thyroid hormone levels. The investigations ruled out common causes of compensated hypothyroidism. Despite normal blood calcium and phosphate levels, parathyroid hormone was elevated to 358 pg/mL (normal values: 10-60) without renal failure, suggestive of hormonal resistance. The diagnosis of pseudohypoparathyroidism type la was confirmed by a 50% reduction of Gs activity. Melanodermia, associated with an elevation of ACTH was suggestive of ACTH resistance without MSH resistance. Moreover, skeletal radiography showed a narrow lumbar canal. CONCLUSION: Type la pseudoypoparathyroidism could be part of the etiological diagnosis of primary hypothyroidism, even in the absence of hypocalcemia and hyperphosphatemia. Similarly, skeletal abnormalities extend beyond the classical features of Albright's osteodystrophy.

Space Station atmospheric monitoring systems.

A technology assessment study on atmospheric monitoring systems was performed by Battelle Columbus Division for the National Aeronautics and Space Administration's John F. Kennedy Space Center under Contract No. NAS 10-11033. In this assessment, the objective was to identify, analyze, and recommend systems to sample and measure Space Station atmospheric contaminants and identify where additional research and technology advancements were required. To achieve this objective, it was necessary to define atmospheric monitoring requirements and to assess the state of the art and advanced technology and systems for technical and operational compatibility with monitoring goals. Three technical tasks were defined to support these needs: Definition of Monitoring Requirements, Assessment of Sampling and Analytical Technology, and Technology Screening and Recommendations. Based on the analysis, the principal candidates recommended for development at the Space Station's initial operational capability were: (1) long-path Fourier transform infrared for rapid detection of high-risk contamination incidences, and (2) gas chromatography/mass spectrometry utilizing mass selective detection (or ion-trap) technologies for detailed monitoring of extended crew exposure to low level (ppbv) contamination. The development of a gas chromatography/mass spectrometry/matrix isolation-Fourier transform infrared system was recommended as part of the long range program of upgrading Space Station trace-contaminant monitoring needs.