[TSH, FT4 and T3T evaluation in normal and preterm hospitalized newborns]. / Evaluation des taux de TSH, T4L, T3T des nouveau-nés prématurés et à terme hospitalisés.

UNLABELLED: Thyroid hormones are essential for foetus and newborn development. Preterm newborns present low levels for thyroid hormones. These low levels are related with disorder in psychomotor and neurological development. In the literature, several studies concerning newborns treated with thyroid hormone have been realized in different conditions; however, there is no consensus about preterm newborn supplementation benefit. OBJECTIVE: The aim of the study was to defined hormonal values used for normal and preterm newborns. MATERIAL AND METHODS: We reported TSH, T3T and T4L levels for 195 normal or preterm newborns, eutrophic or small for gestational age (SGA). RESULTS: A positive correlation was found between hormonal level and gestational age. This work allowed us to define a threshold for preterm newborn according to their gestational age. CONCLUSION: Owing to lack of consensus, those values are useful for clinical and biological follow-up of thyroid function for newborns at risk (SGA and preterm before 32 weeks) during the first year of life. Finally, it would be interesting to study systematic supplementation of thyroid hormone for those infants in a prospective study.

[Bone mineral metabolism: recent data and perspectives related to osteogenesis]. / Métabolisme minéral osseux: données récentes et perspectives relatives à l'ostéogenèse.

Important data have recently been added to our knowledge of bone mineral metabolism in children. Molecular pathophysiology of several pediatric syndromes has been clarified. Specially, the components of endocrine and metabolic regulations are tightly related with regard to the trophicity of bone. On another hand, the impact of several therapeutics of bone diseases like biphosphonates, parathormone (PTH) or growth hormone on bone anabolism is now strongly emphasized. All these points are important for the becoming of bone pediatric diseases in the adult life. Here we analyze the essential components of mineral metabolism and of its regulation in view of the recent biological data, like PTH/PTHrP (PTH-related peptide)-evoked cell signaling, the role of FGF 23 (Fibroblast growth factor 23) in hypophosphatemia and the regulation of vitamin D metabolism by 1alpha-hydroxylase. Inter-relation of these regulating elements is present in several genetic diseases and in the Mc Cune Albright syndrome. Relationships between metabolic and endocrine factors are analyzed considering their impact on PTH secretion and osteogenesis.

Evaluation of microcomputer nutritional teaching games in 1,876 children at school.

OBJECTIVE: We evaluated in a prospective study microcomputer nutritional teaching games and their contribution to the children's acquisition of nutritional knowledge and improvement of eating habits. MATERIAL AND METHODS: One thousand eight hundred seventy-six children aged 7-12 years took part in this study at school. All 16 schools of the same school district were randomized into two groups: games group and control group, both receiving conventional nutritional teaching by their teachers. The children in the games group played computer games during the conventional nutritional teaching period (2 hours a week for 5 weeks). At completion of the study, dietetic knowledge and dietary records were evaluated in both groups. RESULTS: Dietary knowledge tests results were better in the games group (p<0.001). The children in the games group had a significantly better balanced diet for an energy intake of about 1900 kilocalories: more carbohydrate (46.4 +/- 0.2% vs 45.7 +/- 0.2%, p<0.05), less fat (37.1 +/- 0.1% vs 37.6 +/- 0.2%, p<0.05), less protein (16.5 +/- 0.1% vs 16.7 +/- 0.1%, p<0.05), less saccharose (11.5 +/- 0.1% vs 12.2 +/- 0.2%, p<0.001), more calcium (p<0.001) and more fiber (p<0.05). The games group had a better snack at 10 a.m., a less copious lunch and less nibbling (p<0.001). CONCLUSION: The children in the games group had slightly but significantly better nutritional knowledge and dietary intake compared to children in the control group. Using our micro computer nutritional teaching games at school provides an additional and modern support to conventional teaching.

[Modelization of growth between 0 and 3 years of age in children born in Toulouse in 1993-1994 and comparison with Sempé's growth curves]. / Modélisation de la croissance staturale entre 0 et 3 ans d'enfants nés à Toulouse en 1993-1994 et comparaison avec les courbes de Sempé.

AIM: The growth charts usually used in France were established by Sempé et al from the study of children born in 1953-1955. The aim of our study was to construct longitudinal growth charts from 0 to 3-year-old children born in 1993-1994, and to compare those with the charts made 40 years ago. POPULATION AND METHODS: One hundred forty-five term neonates (75 boys and 70 girls) born in Toulouse in 1993-1994 were included in our study. Their heights were noted every 3 months during the first year of life, then every 6 months until the age of 3. A two-stage model to modelize growth curves was used for the available data (66 boys and 61 girls). RESULTS: Mean heights were higher in our study than in Sempé's. In each sex, the mean curve was 0.6 to 0.8 SD far from Sempé's mean curve. Standard deviations rose from 2.0 to 4.0 cm between the ages of 2 months and 3 years. At the age of 3, boys and girls were respectively 2.7 cm and 2.3 cm taller than in the Sempé's study. Differences could not be explained by sample bias. DISCUSSION: Constructions and publication of recent French growth charts seem necessary in order to be able to compare one child's growth to the growth of same age and sex children.

Heterozygous mutation in the WSXWS equivalaent motif of the growth hormone receptor in a child with poor response to growth hormone therapy.

Besides complete GH insensitivity syndrome (GHIS) described by Laron, clinical and molecular evidences have accumulated concerning partial GHIS. We studied GH receptor (GHR) gene in children who show poor response to GH treatment and detected a patient with a heterozygous mutation in exon 7 leading to the Y222H substitution. This missense mutation, located in the YGEFS motif of the GHR equivalent to the WSXWS motif highly conserved throughout all members of the cytokine receptor family, has not been described so far. Although we cannot conclude on the deleterious effect of this mutation, there are several lines of evidence suggesting that it could account for the partial GH insensitivity: (i) hormonal data including IGF-I generation test; (ii) molecular data - no other mutation was identified in the coding sequence, the father who has the same mutation is short, the brother did not inherit the mutated allele and was of normal height.

[Pituitary stalk transection syndrome]. / Syndrome d'interruption de la tige pituitaire.

BACKGROUND: Pituitary stalk transection is a non-negligible cause of growth hormone (GH) deficiency. POPULATION AND METHODS: We studied 22 children (13 boys, nine girls) aged at the first clinical manifestations from 2 days to 10 years (average = 5.33 +/- 2 years). Pituitary stalk transection was assessed by the means of magnetic resonance imaging (MRI). The children's past history showed fetal distress in 12 cases (54.5%), cranial trauma in three (13%) and a midline anomaly in three (13%). The first clinical manifestations were neonatal hypoglycemia (two cases), decreased growth velocity (18 cases) and diabetes insipidus (two cases). RESULTS: GH deficiency was complete, present from the onset in 19 of 22 cases and isolated in four. Fifteen of 22 cases had adreno-corticotrophic hormone (ACTH) and thyroid stimulating hormone (TSH) deficiency. Diabetes insipidus was present in six cases and revealed the syndrome in two. All children older than normal age of puberty (n = 10) had gonadotropin deficiency. In our study, these hormonal anomalies progressed from isolated GH deficiency to multiple hormonal deficiencies. CONCLUSION: The recently described stalk transection syndrome is relatively frequent and should be suspected after cranial trauma or fetal distress syndrome. The outcome is progressive evolution towards panhypopituitarism and these patients require regular clinical survey and hormonal controls.

[Androgen test: comparison of a low test and a high test in the development of the penis in male pseudohermaphroditism]. / Le test aux androgénes: comparaison d'un test faible et d'un test fort sur le développement du pénis dans les pseudohermaphrodismes masculins.

BACKGROUND: The androgen sensitivity test used in male pseudohermaphroditism for clinical assessment of the androgen sensitivity and prediction of penile development is an important element in choice of gender. However, there is a wide range of testosterone dosage and no standardized test. METHODS AND PATIENTS: Two doses (2.5 mg and 100 mg) of testosterone heptylate were used in six cases of male pseudohermaphrodism with sexual ambiguity and small penis (ages 6 to 18 months). The clinical results were compared with those of the study of androgen receptors. RESULTS: In two cases, both low-dose and high-dose tests resulted in only minimal changes in the penis. In two cases, the low-dose test gave a good result which was confirmed by the high-dose test; on the other hand, in two cases, the low-dose test was considered to be negative whereas the high-dose test led to the development of a normal-sized penis. In all cases except one, there was good concordance between the results of study of androgen receptors and those of the clinical test. CONCLUSION: The high-dose androgen test is thus useful in both diagnosis and treatment and facilitates the gender assignment.

[Precocious puberty and polycystic ovarian syndrome: apropos of 13 cases]. / Puberté précoce et syndrome des ovaires polykystiques: à propos de 13 observations.

BACKGROUND: Precocious puberty and polycystic ovarian syndrome are two different entities which appear at different stages of ovarian development. Their association is uncommon. POPULATION: Thirteen girls presented idiopathic central precocious puberty with sexual development before the age of 8 years; menstruations were seen at the age of 9.5 years in one patient. Nine of them were given medroxyprogesterone or cyproterone acetate and two patients LHRH analog. Menarche occurred at a mean age of 11.8 +/- 1.5 years. After a mean free interval of 22 months, these thirteen patients developed hirsutism with irregular menstruations (eight patients) and weight gain (seven patients). The diagnosis of polycystic ovarian syndrome was confirmed by increased plasma testosterone (mean 91.1 +/- 14 ng/dl) and LH levels during LHRH test and by ultrasonography or coelioscopy. The treatment included cyproterone acetate plus 17 beta oestradiol; it was discontinued in eleven cases after 2 years of treatment. Plasma testosterone levels were normal 6 months later in association with regular menstruations. But three patients presented clinical and hormonal recurrence one year later, requiring repeated treatment. CONCLUSION: This association seems to be related to the same gonadotropin dysfunction. It is necessary to regularly follow patients treated for precocious puberty.

[How to manage a symptomatic ovarian follicular cyst in a female child?]. / Que faire devant un kyste folliculaire ovarien symptomatique chez la petite fille?

BACKGROUND: --Ovarian cysts are common in childhood but most are non functioning. Treatment of those follicular cysts that develop in young children may be difficult. CASE REPORTS: Case no. 1.--A 1 1/2 month-old baby was admitted because of an acute abdominal syndrome. Ultrasonography showed a pelvic, heterogeneous mass without calcifications. Laparotomy showed right ovarian torsion with necrosis of a cyst requiring ovariectomy. At that time, there was an isolated increase in FSH after LHRH stimulation. A transitory premature thelarche without pubertal type response to LHRH was seen at the age of 3 months. Clinical and ultrasonographic controls remain normal with a follow-up of 1 year. Case no. 2.--A 4 yr 10 m-old girl was admitted because of an acute abdominal syndrome. Ovariectomy was necessary because laparotomy showed right ovarian torsion with necrosis of a cyst. Recurrent abdominal pain, 4 months later, was associated with an enlarged left ovary without sexual precocity. Gonadotropin were slightly increased after LHRH stimulation and the patient was given LHRH agonist that suppressed endogenous LHRH within 3 months. Clinical and ultrasonographic controls remain normal 1 year after cessation of treatment. Case no. 3.--A 19 month-old girl was admitted because of a genital hemorrhage with recent development of secondary sexual characteristics. Skeletal age was 2 yrs. Ultrasonography showed an enlarged uterus and a left ovarian cyst, heterogenous with calcifications. Plasma levels of estradiol were increased but gonadotropin were normal. Ovariectomy was performed, followed by disappearance of secondary sexual characteristics. However, the patient was given LHRH agonist at the age of 2 yr 7 mo because of recurrent pubertal activity. CONCLUSIONS: --These cases underline the difficulty in treating follicular cysts in young girls. The possibility of cyst recurrence with manifestations of pubertal activity after ovariectomy lead to discuss indication of LHRH agonists for an undetermined duration.

Response of fat cells to growth hormone (GH): effect of long term treatment with recombinant human GH in GH-deficient adults.

GH deficiency impairs lipid metabolism in adults, but little is known about the direct effect of GH on adipose tissue in humans. First, the in vitro response of fat cells to GH in five GH-deficient adults was studied; second, it was investigated whether 6-month recombinant human GH (rhGH) administration modifies this response. Biopsies of fat were obtained from the periumbilical region before and after rhGH administration. The response of the collagenase-isolated fat cells to various concentrations of GH was assessed by glycerol release, measured by bioluminescence. Before treatment, GH induced a lipolytic activity from the adipocytes, which became significantly higher after 6 months of treatment. Thus, this study provides evidence for an intrinsic lipolytic activity of GH in GH-deficient adults and for its improvement after long term rhGH administration.

Clinical use of the long acting somatostatin analogue octreotide in pediatrics.

Preliminary data of the use of the long-acting somatostatin analog octreotide (Sandostatin) in pediatrics are reported. In nesidioblastosis and other hyperinsulinemic conditions, timely treatment with octreotide can protect cerebral function and may reduce mortality. The acute use of octreotide produces prompt elevation of blood glucose, even in patients who fail to respond to diazoxide. In addition, it may be possible to avoid the need for partial or subtotal pancreatectomy by the long-term use of octreotide. As in adults, octreotide should find a place in the symptomatic treatment of secretory diarrhea, notably the watery diarrhea hypokalemia-achlorhydria complex and pancreatic cholera syndrome. Octreotide has been shown to be effective in the treatment of familial tall stature by reducing height velocity and final height. Responses to octreotide therapy vary and the individual responsiveness must be extensively studied.

[Statistic study of 5,473 somatotropin secretion stimulation pharmacologic tests (n=9). Proposed weighting coefficient]. / Etude statistique de 5,473 tests de stimulation pharmacologique (n = 9) de la sécrétion somatotrope. Proposition d'un indice de pondération.

A total of 5,473 pharmacological provocative growth hormone release tests were carried out in 3,143 children. Mean age was 9 years 9 months (range 3-16 years) and mean bone age was 7 years 6 months (range 2-14 years). Tests were of 9 different types: 1) arginine (n = 625); 2) clonidine (n = 339); 3) insulin (n = 198); 4) ornithine (n = 162); 5) insulin + arginine (n = 203); 6) clonidine + betaxolol (n = 2,003); 7) L-dopa (n = 685); 8) glucagon = propranolol (n = 443); 9) glucagon + betaxolol (n = 815). All growth hormone determinations were performed using the same radioimmunoassay. Distribution of values obtained with each test was gausso-logarithmic. Mean peak levels with their 95% confidence limit were as follows: 1) 10.2 and 0.45; 2) 11.5 and 0.7; 3) 11.8 and 0.8; 4) 14.2 and 1.2; 5) 14.3 and 0.9; 6) 15.7 and 1.1; 7) 19.8 and 2.1; 8) 20.8 and 2.3; 9) 21.0 and 2.5. These data indicate low specificity, with up to two-fold differences in mean peak levels from one test to another; proportions of peaks under 10 ng/ml ranged from 29% to 69%. Thus, the rate of patients diagnosed with growth hormone deficiency may vary substantially according to the test used. To reduce these discrepancies, we suggest adjustment of test results using a weighting coefficient of 1) 1.9; 2) 1.48; 3) 1.4; 4) 1.16; 5) 1.06; 6) 1.01; 7) 0.73; 8) 0.69; 9) 0.66.

Statistical study of 5473 results of nine pharmacological stimulation tests: a proposed weighting index.

A total of 5473 pharmacological stimulation tests were carried out in 3143 children and subjected to statistical analysis. The mean chronological age of the children was 9 years 9 months (range 3 years to 16 years 6 months) and mean bone age was 7 years 6 months (range 2 years to 14 years). Nine pharmacological tests were used: (1) arginine (n = 625); (2) clonidine (n = 339); (3) insulin (n = 198); (4) ornithine (n = 162); (5) insulin and arginine (n = 203); (6) clonidine and betaxolol (n = 2003); (7) L-dopa (n = 685); (8) glucagon and propranolol (n = 443); and (9) glucagon and betaxolol (n = 815). Measurement of plasma growth hormone was always performed using the same method. The distribution of values in each test was of the gausso-logarithmic type. The results of the mean peak and the 95% confidence limit were as follows: (1) 10.2, 0.45; (2) 11.5, 0.7; (3) 11.8, 0.8; (4) 14.2, 1.2; (5) 14.3, 0.9; (6) 15.7, 1.1; (7) 19.8, 2.1; (8) 20.8, 2.3; (9) 21, 2.5. These results lead to the following conclusions: the specificity of these tests is low, the mean peak may vary two-fold from one test to another, and the percentage of peaks < 10 ng/ml ranges from 69% for test 1 to 29% for tests 8 and 9. The proportion of growth hormone deficiencies thus varies considerably according to the test used.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 in children with GH deficiency.

Six children presenting with partial growth hormone (GH) deficiency (mean GH peak in two different tests, 8.0 +/- 1.3 micrograms/l) aged 8-10.3 years (mean, 2.7 +/- 0.9 years) were treated for 6 months by continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2); 24-hour GH profiles and height velocity were measured. A biphasic effect of GHRH(1-29)-NH2 infusion was observed. After an early substantial increase in the 24-hour integrated concentration of GH, from 1.6 +/- 0.1 to 3.5 +/- 0.7 micrograms/l/minute, a subsequent consistent decrease occurred by 3 months, which was more pronounced after 6 months (mean 24-hour integrated concentration of GH, 1.9 +/- 0.9 micrograms/l/minute). This effect reflects modification of both pulse amplitude and frequency of GH secretion. At the end of the study, one child had complete suppression of GH secretion and two others showed only one peak above 5 micrograms/l during a 24-hour period. No correlation was found between these changes and height velocity. Three children did not grow significantly; the other three children who had a growth response to GHRH(1-29)-NH2 were those with the lowest 24-hour integrated GH concentration at the end of the study. The possible mechanisms involved in this biphasic effect, including GHRH antibodies, changes in somatostatin levels and/or desensitization of pituitary GHRH receptors, have been investigated.

Effect of long-term rhGH administration in GH-deficient adults on fat cell epinephrine response.

Besides exerting its own lipolytic effect, growth hormone (GH) has been reported to potentiate the lipolytic response of adipose tissue to epinephrine. It was thought interesting to find out whether long-term recombinant human growth hormone (rhGH) administration modifies epinephrine-induced lipolysis in isolated adipocytes of GH-deficient adults. In a double-blind protocol, GH-deficient subjects received either 6 mo placebo (controls, n = 5) or 6 mo rhGH (treated, n = 5). Biopsies of fat were obtained from the periumbilical region before and after placebo or rhGH administration. The response of the collagenase-isolated fat cells to various concentrations of epinephrine was assessed by glycerol release, measured by bioluminescence. Epinephrine-induced lipolysis was not altered by 6 mo placebo, while it was significantly increased by 6 mo rhGH. A similar response was obtained with isoproterenol, but no significant differences occurred in either group with UK 14304, an alpha 2-adrenoreceptor agonist. Thus, in GH-deficient adults, long-term rhGH administration improves the lipolytic response of isolated adipocytes to epinephrine, essentially by increasing the efficiency of the beta-adrenergic pathway.

School achievement in children with hypothyroidism detected at birth and search for predictive factors.

Neonatal screening of hypothyroidism started in 1975, and now sufficient hindsight is gained to assess school results in children with hypothyroidism and compare them to IQ tests. From the 85 cases of hypothyroidism detected in the Midi-Pyrénées area, 40 have enrolled in or finished primary school and 18 started secondary school. School achievement was assessed by school test results in French and mathematics using specific grids for each class and by retention rates. These results were compared to control groups. The hypothyroid group obtained identical results in French to those of the control groups but scored lower in mathematics. Grade retention rated higher in hypothyroid children (20%) than in the control groups (12.5%), especially in the first primary school grade. The search for predictive severity factors revealed significant differences between the grade repeater group and the nonrepeater group: more cases of athyrosis (75 vs. 25% for ectopia), lower T4 levels at birth, lower bone surface, lower IQ at 4 and 7 years, neurological troubles of fine motricity and coordination, and lower socioeconomic level. These results should shortly be taken into consideration in order to isolate a group at risk and undertake specialized care to improve school results in this group.