Human insulin induces a higher glucagon response to induced hypoglycemia in short normal children, compared to porcine insulin.

After transfer of diabetic patients from porcine to human insulin, many reports emerged supporting an increased hypoglycemia unawareness. Several studies were then undertaken in both diabetic and healthy adults to investigate counterregulatory hormone responses to both porcine and human insulin-induced hypoglycemia as a possible underlying cause for this different hypoglycemia awareness. Most studies demonstrated similar neuroendocrine responses to both insulin species in adults. However, no such studies have ever been performed in healthy children. We undertook a double-blinded study of counterregulatory hormone responses to both porcine and human insulin-induced hypoglycemia in 17 short normal children randomly assigned to two groups, one receiving human and the other porcine insulin. We found similar responses of growth hormone, cortisol, epinephrine, norepinephrine and dopamine to both porcine insulin- and human insulin- induced hypoglycemia. Interestingly, we observed a significantly higher glucagon secretion when hypoglycemia was induced by human insulin. In conclusion, human insulin induces a higher glucagon secretion in healthy children than porcine insulin. Evidently, this observation cannot be extrapolated to diabetic patients. This study, however, further underlines the importance of performing investigations in children, since results found in adults differ from those observed in children.

Evidence for a reduction of growth potential in adolescent female gymnasts.

The goal of this prospective study was to assess whether intensive physical training during puberty could alter the growth potential of adolescent female athletes. Height, sitting height, leg length, weight, body fat, and pubertal stage of 22 gymnasts aged 12.3 +/- 0.2 years (mean +/- SEM), with an average training period of 22 hr/wk, and of 21 swimmers aged 12.3 +/- 0.3 years (average training period 8 hr/wk) were recorded half-yearly for a mean period of 2.35 years (range 2.0 to 3.7 years). Adult height predictions were performed with the methods of Bayley and Pinneau; Roche, Wainer, and Thissen, and Tanner et al. Growth velocity of gymnasts was significantly lower than that of swimmers from 11 to 13 years of bone age (p < 0.05), with a mean peak height velocity of 5.48 +/- 0.32 cm/yr versus 8.0 +/- 0.50 cm/yr for swimmers. Height standard deviation score decreased significantly in gymnasts with time (r = -0.747; p < 0.001). This observation was not associated with a significant alteration of chronologic age/bone age ratio. By contrast, height standard deviation score remained unchanged in swimmers (r = -0.165; p = 0.1). A marked stunting of leg-length growth was observed in gymnasts from 12 years of bone age, resulting in a marked difference in overall sitting-height/leg-length ratio (gymnasts 1.054 +/- 0.005 vs swimmers 1.100 +/- 0.005; p < 0.001). Concomitantly, predicted height of gymnasts decreased significantly with time (Tanner et al.: r = 0.63, p < 0.001; Bayley-Pinneau: r = 0.44, p < 0.001), whereas those of swimmers did not change. We conclude that heavy training in gymnastics (> 18 hr/wk), starting before puberty and maintained throughout puberty, can alter growth rate to such an extent that full adult height will not be reached. The mechanisms underlying these observations are not settled; we suggest that prolonged inhibition of the hypothalamic-pituitary-gonadal axis by exercise, together with or because of the metabolic effects of dieting, is responsible for them.

Comparison between short- and long-term insulin-like growth factor response to recombinant human growth hormone.

Eight growth-hormone-deficient children were treated with recombinant human GH (rhGH). Results of the short-term metabolic response to rhGH performed at the start of therapy during a 5-day introduction period and long-term results on growth were analyzed. We could not find any correlation between the effects on the short-term metabolic test and the growth response during long-term therapy, namely between the urea and insulin-like growth factor-I response during the short test and the increase in growth velocity. The short-term test is not a good predictor of the long-term response.

Risks of jet injection of insulin in children.

The aim of our study was to assess whether a non-invasive insulin injector could improve the metabolic control of ten diabetic children complaining of painful injections with syringe and needle. The cumulative study period amounted to 1347 days. Whereas a non-significant rise in insulin needs was observed (from 0.98 +/- 0.03 to 1.03 +/- 0.06 units/kg per day, mean +/- sem), mean HbA1c value remained unchanged (8.9% +/- 0.4% vs 9.0% +/- 0.5%). Jet injections were felt as less painful than those using syringe and needle (nine out of ten cases). This advantage was hampered by side-effects in eight out of ten cases such as episodes of glycoketonuria (six out of ten cases) leading to hospitalization in three patients. Other side-effects included inability to adjust injection pressure (four out of ten cases) and technical failure requiring an exchange of injector in five cases. The four children with most serious problems were significantly younger (P = 0.009) than other subjects. In conclusion, this type of injector should be discouraged in young diabetic children. For older children and adolescents, it may be an alternative to syringe and needle provided repeated detailed information and tight medical supervision is available.

Eating problems and calorie intake levels in Swiss adolescent athletes.

The purpose of this study was to investigate the incidence of eating disorders (ED), calorie intake levels and body fat measures in Swiss female athletes. Thirty athletic and 34 non-athletic adolescent Swiss females were assessed for tendencies toward eating disorders and weight preoccupation using the Eating Disorders Inventory (EDI). Calorie intakes were calculated from 7-day intake records. Body compositions were determined using skin-fold measures. The athletes were divided into two groups: Those whose activities emphasize leanness (12 gymnasts, means age = 12.5 +/- 1.1 yrs), and those whose activities do not emphasize leanness (18 swimmers, mean age = 12.8 +/- 0.9 yrs). The non-athletic school-girls (mean age = 13.4 +/- 1.2 yrs) served as controls. ANOVA indicated that the gymnasts had lower body fat levels (p less than 0.01) and consumed fewer total calories (p less than 0.05) than swimmers or controls, but all groups consumed similar calories per kg/body weight. Chi square analysis indicated that similar numbers of swimmers (11%), gymnasts (1%) and controls (6%) were exceptionally preoccupied with weight (p greater than 0.05). However, more swimmers (38%) scored high on the body dissatisfaction subscale of the EDI than the gymnasts (1%) or control (9%) (p less than 0.01). In fact, more swimmers scored high on 3 subscales of the EDI compared to the other groups (p less than 0.05). It appears that disturbances in eating behaviors are not limited to sports that emphasize leanness.

Growth and pubertal development of young female gymnasts and swimmers: a correlation with parental data.

Whereas intensive and regular physical training is known to alter female reproductive function, its potential role in growth is still controversial. At the beginning of a longitudinal growth study of young elite female gymnasts (n = 34, 15-25 h/wk training) and moderately trained swimmers (n = 19, 5-15 h/wk), patterns of recalled parental growth and pubertal maturation were compared with those of parents of 25 sedentary school girls. These data were also correlated to the height, weight, pubertal development as well as adult height prognosis of their daughters. Bone age was estimated using the methods of Greulich-Pyle and Tanner (RUS score) and adult height prognosis using the methods of Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner et al. (TW2). Parents of gymnasts were significantly lighter (fathers: P = 0.027; mothers: P = 0.038) and shorter (fathers: P = 0.034; mothers: P less than 0.001) than those of swimmers and controls. Consequently, target heights of gymnasts were also significantly shorter (P less than 0.001). Recalled menarche occurred significantly later (P = 0.030) in mothers of gymnasts who, in turn, grow much alike their mothers. At the first visit, the gymnasts were shorter and lighter for age than swimmers and controls. Their bone age (11.0 +/- 1.3 years, mean +/- SD) was retarded (P less than 0.001) when compared with chronological age (12.6 +/- 1.2 years). Adult height prognosis was lower for gymnasts than for other girls (BP: P less than 0.001; RWT: P = 0.023, TW2: P less than 0.001), but adequate for target height range.(ABSTRACT TRUNCATED AT 250 WORDS)

Developmental pattern of 17 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase activities in the foreskin of boys from birth to eight years of age.

The normal developmental pattern of 17 beta-hydroxysteroid dehydrogenase (17HSD) activity in genital skin was examined using radiolabeled androstenedione as a substrate in a microassay based on high-pressure liquid chromatography separation of the metabolites. This assay allowed the simultaneous determination of 17HSD and 5 alpha-reductase (5R) activities in both individual foreskin samples and pools of tissue obtained at circumcision from birth to 8 years of age. The results show that 17HSD activity is very low at birth and increases steadily during the so-called quiescent period. Reciprocal changes were observed for 5R. The increase in 17HSD activity appears to be independent of gonadal stimulation, but the mechanisms involved remain to be elucidated. From a clinical standpoint, our results provide an alternative explanation for the relative lack of virilization observed in newborns with testicular 17HSD deficiency.

[The endocrine impact of sports]. / Retentissement endocrinien du sport.

Physical exercise triggers neurons within the central nervous system which are responsible for complex alterations of the hypothalamo-pituitary axis as well as an increase in sympathoadrenal activity. Although mechanisms controlling the release of pituitary hormones have not yet been fully understood, there is evidence that endogenous opioid peptides and catechol oestrogens probably play an important neuromodulatory role. From the clinical point of view female reproductive function is exquisitely sensitive to physical training. However, cycle disturbances disappear spontaneously when training is drastically reduced. After cessation of sports activities, fertility and pregnancy do not seem to be affected. Growth delay is observed in some types of sport. It is similar to constitutional short stature and therefore probably not related to growth hormone secretion.

Growth hormone response to thyrotropin-releasing hormone in children and adolescents: a reappraisal.

In normal subjects, thyrotropin-releasing hormone (TRH) is not involved in the control of growth hormone secretion. Paradoxical growth hormone (GH) responses to TRH have been described in acromegalic subjects and, recently, in some constitutionally tall children. To confirm this finding, we have examined the GH response to combined LHRH-TRH tests performed to assess the pituitary function of children with GH deficiency, tall stature before and during bromocriptine therapy, precocious or delayed puberty as well as in a group of patients of average height and normal bone age. Unlike prolactin, the GH "response" to TRH, in children followed longitudinally, is particularly heterogeneous with an unpredictable pattern of secretion in repeated tests. Over 90% of children display peaks of GH (greater than or equal to 5 ng/ml), of which 38% occur twice during the test period. Amplitude and frequency of GH peaks appear to be independent of height, chronological age or bromocriptine therapy. Secretory rate estimated by integrated surface area increases in parallel to sex steroids impregnation. The pattern of GH secretory episodes, the increase in mean GH secretion in parallel to the production of gonadal sex steroids and the failure of bromocriptine to affect GH secretion in constitutionally tall children allow to speculate that what is measured after TRH injection is normal spontaneous GH rhythm rather than a direct effect of TRH on GH secretion.

Hydrophobic interaction chromatography (HIC) for the separation of protein-bound and free steroids. Application to binding protein and receptor assays.

Protein-bound steroids can be separated from free steroids using microcolumns of silica gel coated with an hydrophobic (octadecyl) solid phase. The bound fraction is eluted in the assay buffer, whereas the free fraction is retained quantitatively on the column in the first step and can be recovered in methanol. Both fractions can be quantitated directly (e.g. by liquid scintillation spectrometry when using radioactive ligands) or kept for further analysis (e.g. by TLC, HPLC etc.). Separation of the bound and free fractions is rapid, accurate and reproducible; intra- and inter-assay coefficients of variation are lower than 5 and 10%, respectively. Recovery of radioactive steroids is high (usually over 85%) and can be estimated separately for each sample. Since assay blanks are very low (typically less than 0.1% of input), this new method, which could be termed "hydrophobic interaction chromatography" (HIC), should prove especially useful for the development of sensitive binding assays, particularly in the field of steroid receptors. The HIC method compared well with three methods currently used for steroid binding assays, namely adsorption of unbound steroids on dextran-coated charcoal, gel filtration on Sephadex LH-20 and adsorption of steroid-protein complexes on DEAE-cellulose filters. Examples of application described here include studies on human plasma sex hormone binding globulin (SHBG) and SP2 placental protein (saturation analysis, binding specificity etc.), the separation of antibody-bound steroids in a radioimmunoassay and the estimation of androgen binding to rat epididymal androgen binding protein (rABP). Receptor assays are illustrated by saturation analysis of the mouse uterine oestrogen receptor and of the androgen receptor in the human genital skin.

[Value of the assay of plasma steroids in the control of congenital adrenal hyperplasia]. / Intérêt du dosage des stéroïdes plasmatiques dans le contrôle de l'hyperplasie surrénale congénitale.

Twenty patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency have been followed during a mean period of 68.4 months (from 19 to 120 months). Plasma 17 alpha-hydroxyprogesterone, delta 4-androstenedione and testosterone have been measured at regular intervals and correlated to growth and bone maturation. Satisfactory growth was obtained through repeated changes in the daily dose of oral hydrocortisone which varied from 58.7 +/- 37 mg/m2/day in infants to respectively 19.3 +/- 7.0 and 25.3 +/- 7.2 mg/m2/day in prepuberty and puberty. Fludrocortisone was added in 15 cases because of evidence of salt loss. delta 4-androstenedione and 17 alpha-hydroxyprogesterone are the best markers of adequate suppression of the pituitary-adrenal axis in both sexes. Testosterone can be used in girls and prepubertal boys. In some cases with low levels of androgens suggesting oversuppression, a reduced velocity of bone maturation was observed, particularly in young subjects.

[The pediatrician and sports]. / Le pédiatre face au sport.

In contrast to recreative sports, competition should not be allowed in children without regulations and supervision. Physical handicaps should be carefully looked for through a thorough pre-participation examination and appropriate physical activities should be defined for handicapped children. Hypoactivity, fear of accident and functional deterioration cause more damage to these children than physical training which may include competition provided the underlying disease is adequately treated. Regular physical exercise appears to provide significant physical and psychological benefits which are effective beyond the period of physical activity. Stress and aggressivity linked to competition do not seem to have harmful effects on child mental health, with an exception for elite adolescent athletes for whom more information is needed. These athletes are at risk for orthopaedic lesions by overuse as well as disturbances of cardiac and endocrine functions which may disqualify them temporarily for sport events. Treatments designed to boost performance such as anabolic steroids, amphetamines or blood transfusions should be strictly forbidden.

Primary hyperparathyroidism and rickets. A case report and review of the literature.

A case of primary hyperparathyroidism with clinical signs of rickets in a 15-year-old boy of South Morocco is presented. X-ray findings include a diffusely osteoporotic skeleton with areas of subperiostal resorption, cysts and metaphyseal rachitic changes. Hypercalcaemia, hypophosphataemia, increased alkaline phosphatase are found together with low calcidiol and high calcitriol plasma levels. The surgical removal of a chief-cell adenoma of a parathyroid gland leads to very rapid bone healing as well as normalization of blood chemistry. Reviewing the literature shows that 10 similar cases have been described. However, no correlation can be established between the occurrence of rachitic lesions and the Ca X P product. When limited calcium is available from the gut, elevated calcitriol then contributes to mobilize more mineral from bone, in conjunction with parathormone. In addition, the interaction of these 2 hormones on the renal tubule maintains a phosphate leak, creating proper conditions for the development of rachitic lesions.

Prolactin and the gut: a controversy.

Previous reports suggest that prolactin could be one of the factors controlling intestinal mucosal growth. Therefore plasma levels of prolactin have been measured at the time of jejunal biopsy performed for suspicion of celiac disease. One hundred eighty-seven biopsies from 166 children have been reviewed according to histology, age, diagnosis, and plasma prolactin. No difference in the plasma prolactin could be detected among a group of 117 normal biopsies (9.4 +/- 0.4 ng/ml, mean +/- SEM), 31 biopsies with partial atrophy of various degree (9.0 +/- 0.9 ng/ml), and 39 biopsies with flat mucosa (9.1 +/- 0.7 ng/ml), nor could we demonstrate an increase in prolactin according to age and diagnosis (celiac disease before and after treatment, cow's milk protein intolerance, isolated postenteritic syndrome, selective sugar intolerance, and functional gut problems). Prolactinlike material has been detected by immunoperoxidase in the jejunal mucosa. The intracellular granules are located in the infranuclear portion of isolated epithelial cells mainly in the crypts. This material could not be correlated with the corresponding prolactinemias, whatever the histological appearance of the mucosa. These results would suggest that plasma prolactin is not a marker of jejunal regeneration in children. The nature and function(s) of this prolactinlike material remain to be established.