Effects of growth hormone therapy in prepubertal children with short stature secondary to intrauterine growth retardation.

A total of 130 short children were included in a French multicentre study and randomized between a control group (group A) and two groups treated with daily subcutaneous injections of GH at doses of 0.7 IU/kg/week (group B) and 1.4 IU/kg/week (group C) for 2 years. Height velocity was significantly increased (p < 0.0005) in groups B and C, with a greater increase in group C than in group B (p < 0.001). The benefit after 2 years compared with controls was 4.3 cm in group B and 5.9 cm in group C. The rate of bone maturation was not affected by GH therapy. These results led to the conclusion that 2 years of treatment with GH improves final height prognosis in children with short stature secondary to IUGR, and that this effect is dose dependent. The effect on final height has still to be demonstrated.

Growth of short normal children in puberty treated for 3 years with growth hormone alone or in association with gonadotropin-releasing hormone agonist.

GH, 0.1 IU/kg/day 6 days/week, was given to 30 early pubertal short patients for 3 years. There were 16 males, aged 14.4 +/- 0.8 years, and 14 females, aged 12.2 +/- 1.2 years, at pubertal stage 2 or 3 with slow growth (4.2 +/- 1.2 cm/year) and no detected GH insufficiency or other cause for short stature. They were randomized in 2 groups: group A with GH alone, and group B with GH and a gonadotropin-releasing hormone agonist during the first 2 years. 28 of the 30 patients completed 3 years of treatment. The annual growth rate increased during the 1st year in both groups and sexes, the increase being significant (p < 0.01) in group A only. Patients of group A kept an improved growth velocity in the 2nd year, then returned to pretreatment growth rate in the 3rd year, while completing their sexual development and bone maturation. Their height, expressed as standard deviation score (SDS) for bone age, improved in the first 2 years, but decreased thereafter. Group B patients returned to pretreatment growth velocity in the 2nd year, and had no significant improvement in growth rate in the 3rd year with GH alone. Their bone maturation, slow when on the GnRH agonist, accelerated when sexual development resumed. At the end of the 3 years, height, expressed as SDS for age, improved in group A from -2.5 +/- 0.6 to -1.5 +/- 0.4 in males (p < 0.05) and from -2.8 +/- 0.5 to -2.1 +/- 0.9 in females (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Near normalization of adolescent height with growth hormone therapy in very short children without growth hormone deficiency.

Ten prepubertal children with stature at or below the 1st percentile for height and without growth hormone deficiency received 0.3 U recombinant growth hormone per kilogram daily for 2 years before puberty. Their growth velocity increased from 4 +/- 0.3 cm/yr before treatment to 10.7 +/- 0.6 and 8.8 +/- 0.6 cm, respectively, during the first and second years of treatment, and then remained at 5.7 +/- 0.7 cm the year after the end of growth hormone administration. This resulted in a near normalization of adolescent height. Bone maturation paralleled chronologic age, and therefore the expected final height of the children increased by approximately 10 cm. Administration of growth hormone induced a reversible hyperinsulinemia, with moderate and transient changes in glucose metabolism. A prospective, randomized study, including an untreated cohort, will be needed to confirm the effects on final height and to determine the magnitude of the response in familial short stature.

Three-year results of treatment with growth hormone, alone or associated with oxandrolone, in girls with Turner syndrome. The Kabi Collaborative Study Group.

22 girls with Turner syndrome aged 10.8 +/- 2.4 years with bone age 8.58 +/- 1.32 years, randomized in two groups, were treated for 3 years with either growth hormone (GH), 0.1 U/kg daily (group A), or GH, 0.1 U/kg, plus oxandrolone, 0.06 mg/kg (group B). This resulted in a sharp increase in growth rate for the first year of treatment, followed in the second and third years by a growth rate near to the normal mean for age. The growth velocity was better in group B, the difference being significant during the first year only. After 3 years, the predicted adult height had increased by 2.1 cm as a mean in group A and by 4.5 cm in group B, with important individual variations, resulting in a gain of at least 3 cm in 3/10 patients of group A and 9/12 of group B. No metabolic or other side effects occurred. These 3-year data confirm that GH improves the predictable height in Turner girls. They suggest that it may be useful for at least 3 years and that adding a small dose of oxandrolone for 2 years in girls aged more than 8 years could be of good practice. However, earlier and more protracted treatment with GH has to be studied with the hope to better improve the predictable adult height.

Modification of 24-hour growth hormone secretion after continuous subcutaneous infusion of growth hormone-releasing hormone (GHRH (1-29)NH2) in short children with low 24-hour growth hormone secretion.

Six short children with low 24-hour growth hormone (GH) secretion were treated with continuous subcutaneous infusion of GHRH (1-29)NH2 for 3 weeks using a portable infusion pump. Restoration of pulsatile GH secretion was observed in all three children treated with 40 micrograms/kg/day of GHRH, but in only one of the three children treated with 20 micrograms/kg/day. All parameters of 24-hour GH secretion increased, but in five children the magnitude of the GH response was greater on day 1 than on day 21 of GHRH treatment. This decrease was not observed in the single child who responded to a low dose of GHRH (20 micrograms/kg/day); on the contrary, the response in this patient was greater after 21 days of GHRH treatment. Plasma levels of GHRH (1-29)NH2 were significantly higher on day 21 than on day 1 of treatment, suggesting altered pharmacokinetics over time. The effect of GHRH treatment on growth could not be determined because of the short duration of the study, but the data obtained on 24-hour GH secretion and GHRH metabolism suggest that a long-acting analogue of GHRH could be useful for the treatment of GH deficient or insufficient children.

[Early treatment of congenital hypoplasia of the penis with intramuscular delayed-action testosterone]. / Le traitement précoce des hypoplasies congénitales de la verge par la testostérone-retard intramusculaire.

Three intramuscular injections of 25 to 50 mg of testosterone hexahydrobenzoate were prescribed in 37 boys who presented with hypoplastic penis: 16 with micropenis and normally placed urethra, 21 with hypospadias. Ages ranged from 4 months to 9 years. In almost all children treated between the ages of 6 and 18 months, penis growth became normal for age. Growth and bone maturation were temporarily accelerated but in a parallel fashion, so that this very early androgen-therapy need not reduce the adult height of children thus treated.

Insulin pump therapy in young children with type 1 diabetes.

Six 17- to 53-month-old diabetic children had marked metabolic instability characterized by chronic hyperglycemia and frequent or severe hypoglycemia with conventional management that included twice daily insulin injections, diet, and home blood glucose monitoring. Because of the metabolic instability, all were given continuous subcutaneous insulin infusions (CSII) via portable externally worn infusion pump. During 6 months of CSII, there was marked improvement: hemoglobin A1 decreased from 192% +/- 8% (SD) to 152% +/- 31% of the normal mean (P less than 0.02), and hypoglycemic episodes decreased in both severity and frequency. CSII was incorporated into the children's treatment with no appreciable adverse psychologic effects or interference with normal activities. CSII, under carefully controlled clinical conditions, may be of benefit in some preschool children with unacceptable metabolic control of diabetes mellitus.

[Thyroid pathology of newborn infants of mothers with Basedow's disease]. / Pathologie thyroïdienne des nouveau-nés de mères basedowiennes.

Of 15 neonates born to mothers presenting with Graves' disease, who were admitted for presumptive thyroid disorder, 6 presented with neonatal thyrotoxicosis, 4 with goiter and/or hypothyroidism, and 5 presented with euthyroidism. In cases with thyrotoxicosis, the mothers were not or insufficiently treated. Evolution was regressive in 5 instances, there was a craniostenosis and persisting hyperthyroidism in one case. In cases with goiter and/or hypothyroidism, on the other hand, the mothers were correctly treated, and neonatal manifestations were benign and transient. This emphasizes both the importance of supervising gravidic hyperthyroidism and the complexity of materno-foetal relationship in thyroid diseases.

[Ambulatory treatment of diabetes in children by continuous subcutaneous infusion of insulin using a portable pump]. / Traitement ambulatoire du diabète de l'enfant par perfusion sous-cutanée continue d'insuline au moyen d'une pompe portable.

Six diabetic children, aged 2 to 4 years, were selected for continuous subcutaneous insulin infusion (SCII) therapy using a portable pump, because of unstable glycemic control. Under previous conventional insulin therapy, they experienced both chronic hyperglycemia (mean: 2.10 +/- 0.07 milligrams, HbA1 C: 9.02 +/- 0.2%) and frequent or severe hypoglycemic manifestations. Reduction of both glycemic level: 1.08 +/- 0.04 milligrams (p less than 0.01) and instability: M index 0.76 +/- 0.2 vs 5.5 +/- 1.4 (p less than 0.01) was obtained the first week after CSII therapy was started. The metabolic improvement was maintained over 5 to 9 months of ambulatory CSII therapy: HbA1 C decreased down to 7.6 +/- 0.6% (p less than 0.05), while hypoglycemic episodes became rare. The portable insulin delivery system was well tolerated both physically and psychologically by 5/6 of the children and their families.

Hyporeninemic hypoaldosteronism in infancy: a familial disease.

Hyporeninemic hypoaldosteronism was found in two male siblings with urinary salt wasting and low plasma sodium levels. The eldest, aged 1 yr, had growth retardation, with hyponatremia and normal plasma potassium levels. The second, aged 2 months, had low plasma sodium and high plasma potassium levels. Both were severely and repeatedly hypoaldosteronemic. Primary adrenal deficiency was excluded by ACTH testing, which showed a good aldosterone rise and normal responses of other steroids. Both children had low PRA compared to that in age-matched normal subjects. The eldest sibling also had decreased total renin, low inactive to total renin ratio, and a subnormal level of angiotensinogen. The father had low plasma angiotensinogen levels. Congenital deficiency of renin activity and/or angiotensinogen production is suggested as the primary abnormality.

[Neonatal Basedow's disease with premature craniosynostosis and stenosis of the aqueduct of Sylvius]. / Maladie de Basedow néonatale avec craniosynostose prématurée et sténose de l'aqueduc de Sylvius.

Newborn from mother with untreated Graves' disease, born with thyrotoxicosis and exophthalmia, treated with carbimazole from age 6 weeks. At age 8 months, persisting hyperthyroidism requiring the continuation of treatment, and premature craniosynostosis with dilatation of cerebral ventricles suggesting a stenosis of the aqueduct of Sylvius.

[Isolated breast prematurity in young girls]. / La prématurité mammaire isolée des fillettes.

The clinical and follow-up data of the isolated premature thelarche are reviewed in a series of 61 girls aged 6 months to 6 years. Transitory increase of plasma estrogens was observed in some cases. The results of LHRH test were similar to those from normal girls of the same age. Premature thelarche could be a normal variant in girls, related with the physiologic unsteadiness of the prepubertal female pituitary-gonadal axis.