J L Chaussain

Effect of synthetic luteinizing hormone-releasing hormone on the release of gonadotropins in hypophysogonadal disorders of children and adolescents

The effects of LH-RH on FSH and LH were studied in 39 prepuberal boys with undescended testes and in 18 normal prepuberal boys. The mean basal levels of LH and FSH and the mean peak level of FSH after administration of LH-RH did not differ significantly between the two groups but the mean peak level of LH was significantly (p≤0.01) lower in those with undescended testes. This may correlate with a delay of gonadotropic secretion in boys with undescended testes. But, as two boys among the 39 studied had undetectable LH and FSH serum levels which failed to increase after LR-RH, inclusion of hypogonadotropic patients in the group must be considered as an alternative hypothesis.

Glycemic response to 24-hour fast in normal children: III. Influence of age

A 24-hour fast was performed in 28 normal children-17 boys and 11 girls, 2 to 17 years of age. After the fast, blood was drawn for blood sugar, plasma growth hormone and cortisol, serum free fatty acids and alanine measurements. Blood sugar values ranged between 30 and 77 mg/dl and were significantly correlated to age (R = 0.68, P less than 0.001). Plasma cortisol (R = 0.73, P less than 0.001), GH (R = 0.57, P = 0.01), and FFA (R = 0.76, P less than 0.001) were negatively correlated to age. Serum alanine fasting values ranged between 10 and 36 micrometer/dl and were significantly correlated to age (R = 0.86, P less than 0.001) and to blood sugar values (R = 0.54, P less than 0.01). These data demonstrate that carbohydrate regulation during fast improves with age in children, correlating with higher levels of gluconeogenic substrates and a lower rate of lipolysis.

Simultaneous postnatal rise of plasma LH and testosterone in male infants

2. Lee RGL, and Bode HH: Stunted growth and hepatomegaly in diabetes mellitus, J PEDIATR 91:82, 1977. 3. Yde H: The growth hormone dependent sulfation factor in serum from patients with various types of diabetes, Acta Med Scand 186:293, 1969. 4. Cohen MP, Jasti K, and Rye DL: Somatomedin in insulindependent diabetes mellitus, J Clin Endocrinol Metab 45:236, 1977. 5. Van den Brande JVL, and DuCaju MVL: Plasma somatomedin activity in children with growth disorders, in Raiti S, editor: Advances in human growth hormone research, DHEW Publ. No. (NIH) 74-612-1973, p 98. 6. Phillips LS, Pennisi AJ, Belosky DC, et al: Somatomedin activity and inorganic sulfate in children undergoing hemodialysis, J Clin Endocrinol Metab 46:165, 1978. 7. Jackson RL, and Kelly HG: Growth of children with diabetes mellitus in relation to level of control of the disease, J PEDIATR 29:316, 1946. 8. Winter RJ, Phillips LS, Klein MN, et al: Somatomedin activity and diabetic control in children with insulindependent diabetes, Diabetes 28:952, 1979. 9. Phillips LS, and Orawski AT: Nutrition and somatomedin. iII. Diabetic control, somatomedin, and growth in rats, Diabetes 26:864, 1977. 10. Phillips LS, Belosky DC, Young HS, and Reichard LA: Nutrition and somatomedin. VI. Somatomedin activity and somatomedin inhibitory activity in serum from normal and diabetic rats, Endocrinology 104:1519, 1979.

Growth hormone therapy with three dosage regimens in children with idiopathic short stature

Abstract Objective: In children with idiopathic short stature (ISS) we studied the growth-promoting effect at 4 years of recombinant human growth hormone (rhGH) therapy in three dose regimens and evaluated whether increasing the dosage after the first year could prevent a decline in height velocity (HV). Design: Included were 223 patents who were treated with subcutaneous administrations of rhGH 6 days per week. They were randomized to three groups: 3 IU/m2 body surface/day, 4.5 IU/m2/day, and 3 IU/m2/day during the first year and 4.5 IU/m2/day thereafter, corresponding with dosages of 0.2 and 0.3 mg/kg body weight/week, respectively. Growth was compared with a standard of 229 untreated children with ISS [ISS standard]. Results: During the first year of treatment HV almost doubled and was higher with 4.5 IU/m2 than with 3 IU/m2. In the second year HV no longer differed among the groups, but increasing the dosage slowed the rate of the fall of HV. During 4 years of therapy the height SD score for age increased by a mean (SD) of 2.5 (1.0) [ISS standards], or 1.2 (0.7) (British standards), bone age increased by 4.8 (1.3) years, and predicted adult height SD score increased by 1.5 (0.7). After 4 years the results of the group with 4.5 IU/m2 were slightly better than those of the other groups. When dropouts were included in the analysis (assuming a stable height SD score after discontinuation of rhGH therapy), height gain was still significant. Conclusions: During 4 years of rhGH therapy, growth and final height prognosis improved, slightly more with 4.5 IU/m2 than with 3 IU/m2 or 3 to 4.5 IU/m2. However, bone age advanced on average 4.8 years during this period; therefore, any effect on final height will probably be modest. (J Pediatr 1998;132:455-60)

The Use of Luteinizing Hormone-Releasing Hormone in Pediatric Patients

Luteinizing hormone-releasing hormone (LH-RH), first synthetized in 1971; became soon available for clinical purposes and was immediately used as a diagnostic tool in children and adolescents as well as in adults. The first results of the LH-RH test in pediatrics were reported in 1972 and soon after discussed in meetings allowing comparison of the data from different groups. From this time, a great number of publications has been devoted to the diagnostic usefulness of LH-RH in the study of pubertal development and of pituitary-gonadal disorders in children and adolescents. Until recently, the theraeputic use of LH-RH has been restricted by the lack of availability of sufficient amounts, so that only few preliminary data have been reported in this field. Thus the scope of this review is mainly to present a critical survey of the data concerning LH-RH test in pediatric patients.

Glycemic response to 24-hour fast in normal children and children with ketotic hypoglycemia: II. Hormonal and metabolic changes

Metabolic and hormonal changes induced by a 24-hour fast were studied in six children with a recent history of ketotic hypoglycemia and in six control children of comparable ages. Mean blood sugar level dropped more in KH children (80-33 mg/dl) than in control subjects (86-55 mg/dl). Glycemia and plasma insulin responses to intramuscular glucagon (0.03 mg/kg) were similar in each group before fast. After fast, they were low or suppressed in KH children, still present in the controls. Plasma growth hormone and free fatty acid levels before and after fast were identical in each group. At the end of the fast, a significant (p≤0.01) correlation was demonstrated between glycemia and plasma cortisol values in children of the two groups. Serum alanine decreased significantly (p≤0.01) in KH and control children, the alanine level at the end of the fast being correlated to blood sugar value. Concentrations of serum branched-chain amino acids increased significantly (p≤0.02) during fast in KH children, but not in controls. Similar biologic data were obtained in an additional KH patient studied at the time of a spontaneous hypoglycemic seizure. It may be concluded that the inability to sustain normal concentrations of blood sugar during fast in children could be related to deficient neoglycogeneis; this feature appears to be variable from one child to another and is more marked in KH children.

Serum branched-chain amino acids in the diagnosis of hyperinsulinism in infancy

Fasting values of branched-chain amino acids (valine, leucine, and isoleucine) were measured by column chromatography in the sera of 27 normal infants and children, 15 days to 9 years of age, 14 children with documented ketotic hypoglycemia one to 7 years of age, and in 14 sera from six infants, 15 days to 2 years of age, with documented hyperinsulinism. In normal children and those with ketotic hypoglycemia, each individual branched-chain amino acid and their sum were significantly negatively correlated with blood sugar values ranging between 11 and 92 mg/dl (P < 0.001). In infants with hyperinsulinism, branched-chain amino acid concentrations were significantly lower (P < 0.001) without correlation with blood sugar values ranging between 13 and 51 mg/dl, and plasma insulin concentrations (9 to 85 microU/ML). In all the children the sum of branched-chain amino acids was positively correlated with blood beta OH butyrate concentrations measured at the same time (r = 0.75, P < 0.001). The association of low blood sugar and low branched-chain amino acid concentrations during fasting seems characteristic of hyperinsulinism, and the measurement of branched-chain amino acids in these infants offers a physiologic indicator of the diagnosis of hyperinsulinism.

Etiologies of Late Puberty

An expected lack of pubertal development can be due to an already diagnosed disease. The diagnosis of an unexpected lack of puberty is a difficult task. We have analyzed the etiologies of late puberty in 106 adolescents: 68 boys aged over 15 years and 38 phenotypic girls aged over 13 years. According to their clinical and biological (gonadotropin) data, they were classified in 3 groups. In the first group, hypergonadotropism was observed only in 19 females; pure gonadal dysgenesis was found in 2 cases with 46,XY, in 2 with 46,Xdel(Xq) karyotypes and 9 cases were 46,XX constitutions; 2 sisters had also blepharophimosis; in 3 cases the ovarian failure was due to autoimmune disease, and 1 case, genetically male, had 17 alpha-hydroxylase deficiency. The second group had gonadotropin insufficiency and consisted of 68 adolescents, 57 males and 11 females, with low gonadotropin levels: 33 were anosmic; in the boys, cryptorchism was present in 68% and micropenis in 31%; 38 had a familial history of hypogonadism, the transmission of which was matrilineal in 16, patrilineal in 13 and recessive autosomal in 7. The third group had low or low-normal gonadotropin levels: 22 cases of constitutional delay of puberty (11 cases in both sexes), demonstrated by further normal puberty during the follow-up. No clinical marker and familial history in 50% were noted.

Corticosurrénalomes de l'enfant: analyse rétrospective de 54 cas

Resume Les temeurs du cortex surrenalien sont rares chez lenfant. Leurs criteres de malignite, de meme que lefficacite des traitements melicaux, resient mal connus. Population et methodes. — Nous avouns etudie 54 (age median : 4 ans) ayant an corticosurrenalome diagnosrique entre 1973 et 1993. Resultats. — Des signes de virilisation etaient presents dans 76 % des cas, et la tameur etait palpable dans 57 %. La tumeur etait localisee (80 %), ou avait une extension locoregionale (7 %), ou metastatique (13 %). Demblee ou apres un traitement medical, 45 patients (83 %) ont beneficie dune exerese jugee macroscopiquement complete par le chirurgien. Parmi cux, 18 (40%%) ont presente une recividive 2 a 17 mois apres lintervention. Viangt-quatre enfants ont recu, demblee (tumeur inextirpable), ou secondairement pour tumeur dans un biers das cas. La survie globale a ete 49 % a 5 ans. Conclusions. — Le pronostic est donc sombre. Lefficacite des traitement medicaux est controversee et lexerese chirurgicale reste le traitement de choix. Linteret dun traitement par o.p.-DDD dans le but de prevenir la recidive apres exerese chirurgicale complete est discute. Seuls des essais multicentriques permettront devaluer les strategies therapeutiques.

Effect of synthetic luteinizing hormone-releasing hormone on the release of gonadotropins in hypophysogonadal disorders of children and adolescents: VII. Constitutional delay of puberty in males*

Serum gonadotropins (LH and FSH) were measured by radioimmunoassay before and after intravenous injection of 0.1 mg/m2 of synthetic luteinizing hormone-releasing hormone in 20 male patients, aged 15 to 18 years, with constitutional delay of puberty. Basal plasma levels of LH and FSH were in the prepubertal range. After administration of LH-RH, the increase in LH was significantly high than in prepubertal control subjects, aged 1 to 13 years; the difference between test patients and pubertal control subjects was not significant. The increase in FSH was in the prepubertal range, significantly lower than that in pubertal control subjects. This discrepancy between LH and FSH responses to LH-RH is similar to that observed in normal boys at the late prepubertal stage and suggests that an elevation of readily releasable pituitary stores of LH correlates with the first step of pubertal onset in males, even if puberty is delayed.