[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.

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.

Effect of overnight constant infusion of human growth hormone (GH)-releasing hormone-(1-44) on 24-hour GH secretion in children with partial GH deficiency.

A continuous infusion (0.5 or 1 microgram/kg X h) of GH-releasing factor-(1-44) [GHRH-(1-44)] was administered from 2000-0800 h to 16 children with GH deficiency, defined as a maximum peak plasma GH less than 11 ng/ml in response to 2 provocative tests [first test; mean, 7.4 +/- 2.6 (+/- SD) ng/ml; second test; mean, 8.4 +/- 2.4 ng/ml]. Eight were boys and 8 girls; their average age was 10 yr, 5 months; and growth was retarded in all [mean, -3 +/- 0.6 (+/- SD)]. Polygraphic monitoring was carried out during the night, and blood samples for plasma GH measurements were drawn every 20 min during the night and the following day. A control study had been carried out in the preceding months with the same children. During GHRH infusion, a significant increase in nocturnal GH secretion occurred; the mean maximum peak increased from 17.5 +/- 3.4 (+/- SD) to 38.7 +/- 3.2 ng/ml, the mean area under the curve from 2243 +/- 459 to 5348 +/- 710 ng/ml, the mean integrated concentration from 4.2 +/- 0.8 to 9.9 +/- 1.3 ng/ml X min, and the mean number of peaks above 5 ng/ml from 2.7 +/- 0.3 to 4.7 +/- 0.4. During GHRH infusion, the 16 children had 2 peaks during the first 4 h of sleep and a third peak at the end of the night. Plasma GH levels the day after the infusions were not significantly increased. We conclude that continuous nocturnal GHRH infusion increases pulsatile sleep GH secretion throughout the night in children with partial GH deficiency.

Results of 1-year growth hormone (GH)-releasing hormone-(1-44) treatment on growth, somatomedin-C, and 24-hour GH secretion in six children with partial GH deficiency.

Six children with short stature and partial GH deficiency in response to two pharmacological tests received GHRH for 12 months (10 micrograms/kg X day, sc) each evening. Twenty-four-hour GH secretion was studied before and after 3 and 12 months of treatment, and GHRH tests (2 micrograms/kg, iv) were done before and after 6 months of treatment. Plasma somatomedin-C was measured before and after 1.5, 3, 6, 9, and 12 months of treatment. Statural growth was measured at 3-month intervals. Mean growth velocity increased from 4.2 to 8.6 cm/yr, with a good result in five children and no response in the other. The growth response was substantial during the first 3 months. It was maintained during the following 6 months, and then decreased during the last 3 months. The peak plasma GH level in response to GHRH increased from 34.5 +/- 14.2 (+/-SD) ng/mL before treatment to 47.8 +/- 3.4 ng/mL after 6 months of treatment. Twenty-four-hour GH secretion increased in all parameters at 3 months (maximum peak, area under the curve, integrated concentration, and number of peaks) and at 12 months (with the exception of the maximum peak). Nycthemeral secretory profiles became normal, with reappearance of secretory pulses in two children, slight increases in three children, and no change in one child. Plasma somatomedin-C levels rose from 0.8 +/- 0.3 U/mL before treatment to 2.0 +/- 1.0 U/mL at 3 months, then decreased to 1.3 +/- 0.6 U/mL at 12 months. These results indicate that GHRH administered by sc injection for a 1-yr period stimulated growth and GH secretion. However, a decrease in activity was noted during the last 3 months of treatment. Tests for anti-GHRH antibodies were positive in the only child who did not respond to treatment.

Long term effects of continuous subcutaneous infusion of the somatostatin analog octreotide in the treatment of acromegaly.

The marked pituitary tumor shrinkage achieved by continuous sc infusion (CSI) of the long-acting somatostatin analog octreotide in one acromegalic patient led us to treat 16 other acromegalic patients for up to 24 months by CSI. This therapy, given in doses ranging from 100-600 micrograms/day, resulted in normalization of the mean daily serum GH (mGH) and insulin-like growth factor I levels in 9 of the 17 patients (53%). In 7 patients, mean daily serum GH decreased but not to normal; 3 of these patients had hyperprolactinemia which was not influenced by octreotide. One patient was completely unresponsive. In contrast to the biochemical results, 80% of the patients had marked clinical improvement. Side-effects consisted of slightly impaired carbohydrate tolerance in 2 patients and cholelithiasis in 2 patients. Pituitary tumor size decreased in only 3 patients; in 1 of them visual field defects disappeared rapidly. These results suggest that octreotide treatment may prove beneficial before surgery in patients with macroadenomas, although its efficacy varies widely. Potential responsivity can usually be determined by a short course (24 h) of CSI of octreotide.

Shrinking of a growth hormone-producing pituitary tumor by continuous subcutaneous infusion of the somatostatin analog SMS 201-995.

SMS 201-995, a long-acting somatostatin analog, was given as the initial treatment to an acromegalic patient. SMS 201-995 (200 micrograms, sc, three times daily) reduced, but did not normalize, serum GH levels. Complete and prolonged control of GH secretion was obtained with a 600-micrograms daily continuous sc infusion (CSI), and the patient was treated in this way for 6 months. Rapid improvement of clinical signs and symptoms of acromegaly occurred, as did major tumor shrinkage. The other pituitary functions did not change. After 6 months, the daily SMS 201-995 dose was progressively reduced; GH secretion remained suppressed. After 12 months of treatment, GH secretion was controlled with a CSI of 100 micrograms SMS 201-995 daily, but not with two daily sc 100-micrograms injections. Further significant reduction in tumor size occurred. We conclude that CSI of SMS 201-995 resulted in constant GH normalization and marked clinical and morphological improvement. This form of treatment should be considered as an alternative to ablative treatment of acromegaly.

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.

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.

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.

[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.

[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.

[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.

[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.

[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.

[Comparison of nyctohemeral somatotropin secretion and response to pharmacological tests in 38 children with growth retardation]. / Comparaison de la sécrétion somatotrope nycthémérale et des réponses aux tests pharmacologiques chez 38 enfants présentant un retard statural.

We report a comparative study of the growth hormone nycthemeral secretion and the response of growth hormone secretion to pharmacological stimulation tests in 38 children with growth retardation. Two groups were separated according to the results of the nycthemeral growth hormone secretion study: a group of 26 children with normal secretion (mean maximum peak: 26.6 +/- 9.6 ng/ml and mean integrated concentration: 4.26 +/- 2.13 ng/ml/min) and a 2nd group of 12 children with hyposecretion (mean maximum peak: 6.7 +/- 2.6 ng/ml and mean integrated concentration: 1.08 +/- 0.45 ng/ml/min). There was no correlation between nycthemeral secretion and the responses to pharmacological tests. Thus, in the group with hyposecretion, 5 children had normal responses to a pharmacological test and in the group with normal secretion 13 children had intermediate responses to 2 pharmacological tests and 4 had dissociated responses. Thus, it appears mandatory to perform 2 different pharmacological tests in any investigation and to study the nycthemeral secretion in cases with intermediate or dissociated responses as well as in cases with normal responses when the clinical picture is consistent with growth hormone deficiency.

[A familial case of multiple endocrine neoplasia (MEN IIb). Diagnosis of medullary thyroid cancer]. / Un cas familial de néoplasie endocrine multiple (NEM IIb). Intérêt du dépistage du cancer médullaire de la thyroïde.

The familial observations of multiple endocrine neoplasia are rare such that there are only four known cases in France. In our family, two children and their mother are affected. Their mother, at the age of 16, was operated on a medullary thyroid cancer (MTC) and now presents with a phaeochromocytoma. Vanessa also presents with a MTC but without either phaeochromocytoma nor hyperparathyroidism. Her sister was then systematically screened and the only positive test was Pentagastrin. This allowed us to practice a thyroidectomy which will confirm the presence of a medullary thyroid cancer. In all three cases, the Marfan-like features, the abnormal facies and lingual neuromas are all features of the disease. These observations are of interest for the systemic familial screening of MTC by tumour markers (calcitonin, ACE) and by the Pentagastrin test, while awaiting for the use of specific probes on chromosome 10.