Isabelle Oliver

Intensive Dance Practice Repercussions on Growth and Puberty

To determine the effect of intensive sports training on growth and puberty, we studied a group of 97 young female dancers longitudinally for 5 years. We studied the changes in their heights, weights, and pubertal developments and compared these findings with those of a control group. We found that 15 (16%) dancers who started dance training had noticeably decreased growth velocity during the prepuberty stage after the beginning of ballet practice compared with the control group. This group had the same average training time compared with the other dancers, but these dancers were the slimmest and had the most inadequate nutri tional intake. Puberty in dancers was delayed com pared with the controls. We found that moderately intensive dance practice can lead to eating disorders and weight control early in childhood, with conse quences that are poorly known. Weight and height statistics of children who practice individual sports in volving body aesthetics must be monitored to detect early anomalies.

Long-term evolution of endocrine disorders and effect of GH therapy in 35 patients with pituitary stalk interruption syndrome

We report long-term evolution of endocrine functions and the results of GH treatment in 35 patients (26 male and 9 female) with pituitary stalk interruption. At diagnosis, mean chronological age was 4.8 ± 2.7 years, mean SDS for height –3.1 ± 0.8 with a bone age retardation of 2.3 ± 1.3 years and a mean SDS for growth velocity of –0.5 ± 1.1; 80% presented complete GH deficiency (GHD) and 20% partial GHD; thyroid deficiency was present in 47.1% of children with complete GHD but absent in all partial GHD. Diagnosis was made during the first months of life in only 2 patients while 23% presented with severe neonatal distress; neonatal signs were only observed in the group with pituitary height below 2 mm (45.7% of patients). GHD was isolated in 40.6% of patients below 10 years while multiple hormone deficiencies was consistent at completion of growth in all patients. Height gain was significantly higher in patients who started GH treatment before 4 years (p = 0.002). GH treatment is very effective: in 13 patients, final height was –0.4 ± 1.0, total height gain 3.2 ± 1.2 and distance to target height –0.3 ± 1.6 SDS.

Comparison of response to 2-years’ growth hormone treatment in children with isolated growth hormone deficiency, born small for gestational age, idiopathic short stature, or multiple pituitary hormone deficiency: combined results from two large observational studies

BackgroundFew studies have compared the response to growth hormone (GH) treatment between indications such as isolated growth hormone deficiency (IGHD), born small for gestational age (SGA), idiopathic short stature (ISS), and multiple pituitary hormone deficiency (MPHD). The aim of this analysis of data, collected from two large ongoing observational outcome studies, was to evaluate growth and insulin-like growth factor-I (IGF-I) response data for children of short stature with IGHD, MPHD, SGA, or ISS following two years of treatment with the recombinant GH product Norditropin® (Novo Nordisk A/S, Bagsværd, Denmark).MethodsAnalysis of auxologic data from two ongoing prospective observational studies, NordiNet® International Outcomes Study (NordiNet® IOS) and NovoNet®/American Norditropin® Studies: Web-enabled Research (ANSWER) Program®.Results4,582 children aged <18 years were included: IGHD, n = 3,298; SGA, n = 678; ISS, n = 334; and MPHD, n = 272. After two years’ GH treatment, change in height standard deviation score (SDS) was +1.03 in SGA and +0.84 in ISS vs. +0.97 in IGHD (p = 0.047; p < 0.001 vs. IGHD, respectively). Height gain was comparable between IGHD and MPHD. In pre-pubertal children vs. total population, height SDS change after two years was: IGHD, +1.24 vs. +0.97; SGA, +1.17 vs. +1.03; ISS, +1.04 vs. +0.84; and MPHD, +1.16 vs. +0.99 (all p < 0.001).ConclusionsAfter two years’ GH treatment, change in height SDS was greater in SGA and less in ISS, compared with IGHD; the discrepancy in responses may be due to the disease nature or confounders (i.e. age). Height SDS increase was greatest in pre-pubertal children, supporting early treatment initiation to optimize growth outcomes.

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 childrens 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.

Elevated Insulin-Like Growth Factor-I Values in Children with Prader-Willi Syndrome Compared with Growth Hormone (GH) Deficiency Children over Two Years of GH Treatment

BACKGROUND Children with Prader-Willi syndrome (PWS) are routinely treated with GH and have a response comparable with that observed in children with GH deficiency (GHD). OBJECTIVE The objective of the study was to compare changes in serum IGF-I, IGF binding protein 3 (IGFBP-3), IGF-I to IGFBP-3 molar ratio, and growth velocity during the first 2 yr of GH therapy in PWS and GHD children. SUBJECTS AND METHODS Thirty-three children with PWS (14 boys, 4.9 ± 3.8 yr) and 591 with GHD (351 boys, 9.6 ± 3.6 yr), all naive to GH treatment, were included in this study. Serum IGF-I and IGFBP-3 were measured at 0, 6, 12, and 24 months of GH therapy. The mean initial dose of GH was 0.9 and 1 mg/m(2) · d in the PWS and GHD groups, respectively. RESULTS Mean ± SD IGF-I sdscore (SDS) and IGFBP-3 SDS were significantly higher in PWS compared with GHD. The IGF-I to IGFBP-3 molar ratio was significantly lower at baseline and subsequently not different. Despite significantly lower GH doses in PWS children at 6, 12, and 24 months (P = 0.021, P = 0.021, P = 0.001), IGF-I reached 2.8 ± 1.2 SDS at 24 months (72% of values > 2 SDS), and remained at 0.7 ± 1.6 SDS in GHD children (17% of values > 2 SDS). IGFBP-3 did not exceed 2 SDS in either group. There was no significant change in the IGF-I to IGFBP-3 molar ratio. CONCLUSIONS IGF-I SDS increases to a greater extent in PWS than GHD. Bioavailable IGF-I is apparently not different, suggesting that any possible safety issues related to elevated IGF-I are similar in both groups.

Pituitary Stalk Interruption Syndrome from Infancy to Adulthood: Clinical, Hormonal, and Radiological Assessment According to the Initial Presentation.

Background Patients with pituitary stalk interruption syndrome (PSIS) are initially referred for hypoglycemia during the neonatal period or growth retardation during childhood. PSIS is either isolated (nonsyndromic) or associated with extra-pituitary malformations (syndromic). Objective To compare baseline characteristics and long-term evolution in patients with PSIS according to the initial presentation. Study Design Sixty-seven patients with PSIS were included. Data from subgroups were compared: neonates (n = 10) versus growth retardation patients (n = 47), and syndromic (n = 32) versus nonsyndromic patients (n = 35). Results Neonates displayed a more severe hormonal and radiological phenotype than children referred for growth retardation, with a higher incidence of multiple hormonal deficiencies (100% versus 34%; P = 0.0005) and a nonvisible anterior pituitary lobe (33% versus 2%; P = 0.0017). Regular follow-up of growth might have allowed earlier diagnosis in the children with growth retardation, as decreased growth velocity and growth retardation were present respectively 3 and 2 years before referral. We documented a progressive worsening of endocrine impairment throughout childhood in these patients. Presence of extra-pituitary malformations (found in 48%) was not associated with more severe hormonal and radiological characteristics. Growth under GH treatment was similar in the patient groups and did not vary according to the pituitary MRI findings. Conclusions PSIS diagnosed in the neonatal period has a particularly severe hormonal and radiological phenotype. The progressive worsening of endocrine impairment throughout childhood justifies periodic follow-up to check for additional hormonal deficiencies.

Gender Influences Short-Term Growth Hormone Treatment Response in Children

Background: Gender may affect growth hormone (GH) treatment outcome. This study assessed gender-related differences in change from baseline height standard deviation scores (ΔHSDS) after 2 years’ GH treatment. Methods: Data from two observational databases were analyzed – the NordiNet® International Outcome Study (NordiNet® IOS) and the American Norditropin Studies: Web Enabled Research Program (ANSWER Program®). Of all the evaluated patients (n = 5,880; age 0 to <18 years), 4,471 were diagnosed with GH deficiency (GHD), 422 with multiple pituitary hormone deficiency, and 987 were born small for gestational age (SGA). Data were analyzed by indication, gender and pubertal status (total population/prepubertal). Results: In the total population, after correcting for dose, mean baseline age and HSDS, ΔHSDS was significantly greater in boys than in girls born SGA (p = 0.0261). In the prepubertal cohort, ΔHSDS was significantly greater for boys versus girls with GHD (p = 0.0004) and SGA (p = 0.0019). No between-gender difference in ΔIGF-I SDS was found. Conclusions: A significant gender difference was found in the 2-year response to GH treatment in the total population of SGA children as well as in the prepubertal cohorts of SGA and GHD children.

Isolated Lymphocytic Infiltration of Pituitary Stalk Preceding the Diagnosis of Germinoma in 2 Prepubertal Children Treated with Growth Hormone

We report the clinical course of 2 patients with central diabetes insipidus and evolving to panyhypopituitarism which prompted the diagnosis of an isolated pituitary stalk thickening (PST). In both patients, all etiological investigations were normal and the first biopsy revealed an isolated lymphocytic infiltrate with no sign of malignancy. Close clinical follow-up accompanied by serial brain MRIs was proposed to determine a precise diagnosis and for early detection and treatment of neoplastic disease. In our first case, the diagnosis of germinoma was made 9 months after the PST diagnosis owing to tumor progression. In the second case, the time course was even longer with the diagnosis of germinoma 6 years following initial presentation. In these cases, it is speculated that the lymphocytic infiltrates represent the first sign of a host reaction to an occult germinoma. To our knowledge, this is the third case reported of lymphocytic infiltrates preceding a germinoma in a prepubertal girl, and the only case reported in a prepubertal boy. These cases underline the difficulties in establishing the diagnosis of germinoma in a patient with isolated PST.

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.

Wilms tumor, pleuropulmonary blastoma, and DICER1: case report and literature review

BackgroundPleuroblastoma (PPB) is a rare pediatric tumor which, in 30% of cases, is associated with cystic nephroma. It has been recently linked to the DICER1 mutation as part of a predisposition syndrome for various tumors. However, if DICER 1 anomalies have been reported in patients with Wilms tumor (WT), to date, no cases of PPB, WT, and DICER1 mutations have been reported in the same patient.Case presentationWe report the case of a 3-year-old patient, initially managed for metastatic WT. During his clinical course, the diagnosis of a PPB was made after detecting the DICER1 mutation and subsequent management was therefore modified.ConclusionThis case highlights that in case of simultaneous discovery of a renal tumor and a pulmonary lesion in a child, the DICER 1 mutations should be looked for as these could help adapt management and schedule the surgical procedures.