Background: Optimal dosage for growth hormone (GH) therapy in short, prepubertal children born small for gestational age (SGA) is controversial. Methods: SGA OPTIMIS (NCT00249821) is a multicenter, open-label, parallel-group, pilot study of short children born SGA who had received recombinant human GH (r-hGH) (57 µg/kg/day) for 3 years. Children were randomized 1:1 to receive either 57 or 35 µg/kg/day r-hGH during year 4. The primary endpoint was height gain during year 4. Results: 22 children were randomized (57 µg/kg/day, n = 10; 35 µg/kg/day, n = 12) and 21 completed the fourth year of therapy; 22 were included in efficacy analyses. During year 4, mean [standard deviation (SD)] height velocity was 6.4 (1.4) and 4.4 (1.2) cm/year (p = 0.001) and height velocity SD score (SDS) was 0.3 (0.3) and –0.1 (0.2) (p = 0.002) in the 57 and 35 µg/kg/day groups, respectively. The 57 µg/kg/day group continued with catch-up growth, had a significantly higher mean weight gain (p = 0.015) and significantly higher insulin-like growth factor-I levels at 12 months (p = 0.038). Five treatment-emergent adverse events were reported; none was serious or caused study withdrawal. Conclusions: Children who continued receiving 57 µg/kg/day r-hGH in year 4 had significantly greater height gain than those receiving 35 µg/kg/day r-hGH.

Présentation de 3 patients 46XX présentant une anomalie de la différenciation sexuelle (ADS), virilisation et présence de tissu testiculaire en l’absence de SRY détectable. Les 3 enfants 46XX SRY- pris en charge à l’Hôpital Debrousse à Lyon présentent un aspect clinique assez similaire : micropénis, hypos-pade périnéal, hémiscrotum bien développé d’un coté contenant une gonade (testicule en anatomie pathologique) et hypoplasie de l’autre hémiscrotum (streak gonade inguinale ou intra abdominale). Le premier patient était déclaré garçon à la naissance – le diagnostic a été réalisé à l’âge de 9 mois et l’intervention chirurgicale pour son hypos-pade postérieur (Koyanagi) a été réalisée à 17 mois. Le deuxième enfant a été déclaré garçon à la naissance mais le diagnostic a été fait rapidement (15 jours de vie). Après changement du sexe civil, la féminisation a été effectuée à l’âge de 7 mois. Le troisième enfant a été vu à la naissance, la déclaration du sexe à l’état civil a été différée pour attendre l’ensemble des résultats (caryotype, biologie, génitoscopie et génitographie, biopsie des gonades) et, après discussion avec les parents, l’orientation a été décidée dans le sexe féminin. L’intervention de féminisation est prévue vers l’âge de 5 mois. Le rôle du SRY est considéré comme primordial pour permettre la différenciation testiculaire à partir de la gonade dite indifférenciée chez les mammifères. Chez ces 3 patients, l’absence de SRY détectable soulève plusieurs hypothèses : 1) Le SRY a existé et a disparu (« Y vanishing syndrome ») ; 2) Le SRY existe mais n’a pas été détectés ; 3) la présence d’autres gènes (SOX 9, gènes répresseurs) peut être suffisante pour remplacer SRY. En cas d’ADS, l’assignement d’un genre c’est-à-dire l’attribution d’une identité sociale relève de plusieurs facteurs que sont : le sexe intérieur (gènes, gonades et hormones), le sexe extérieur (phénotype des organes génitaux externes et internes), le sexe fonctionnel (possibilités de relations sexuelles et fertilité) et enfin le sexe social et culturel (milieu d’élevage, regard de la mère etc…) Les démarches diagnostiques et la prise en charge chirurgicale sont discutées, ainsi qu’une revue de la littérature actuelle.

Children born small for gestational age may demonstrate continued growth retardation, resulting in persistent short stature. In the majority of the cases, this is linked with abnormal growth hormone secretion and also abnormal insulin-like growth factor levels. This review discusses the treatment of such children with recombinant human growth hormone. It illustrates the importance of starting therapy early, the dose-dependent response, and the advantages of continuous therapy and describes safety considerations. Copyright (c) 2007 S. Karger AG, Basel.

Partial androgen insensitivity with sex phenotype variation in two unrelated families was associated with missense mutations in the androgen receptor (AR) gene that disrupted the AR NH2-terminal/carboxy terminal interaction. Each mutation caused a single amino acid change within the region of the ligand-binding domain that forms activation function 2 (AF2). In one family, the mutation I737T was in alpha helix 4 and in the other F725L was between helices 3 and 4. Neither mutation altered androgen binding as determined by assays of mutant AR in the patient's cultured genital skin fibroblasts or of recombinant mutant receptors transfected into COS cells. In transient cotransfection assays in CV1 cells, transactivation with the AR mutants at low concentrations of DHT was reduced several fold compared with wild-type AR but increased at higher concentrations. Defects in NH2-terminal/carboxy terminal interactions were identified in mammalian two hybrid assays. In similar assays, there was reduced binding of the p160 coactivators TIF2/SRC2 and SRC1 to the mutant AR ligand binding domains (LBD). In the family with AR I737T, sex phenotype varied from severely defective masculinization in the proband to a maternal great uncle whose only manifestation of AIS was severe gynecomastia. He was fertile and passed the mutation to two daughters. The proband of the F725L family was also incompletely masculinized but was raised as a male while his half-sibling by a different father was affected more severely and reared as a female. These studies indicate that the function of an AR AF2 mutant in male development can vary greatly depending on the genetic background.

The efficacy of GH for increasing adult height (AH) in short adolescents born small for gestational age (SGA) is unclear, due to the lack of long-term controlled trials. A total of 168 short children born SGA (age, 10.5 yr for girls and 12.5 yr for boys) were randomly assigned to receive either 0.067 mg/kg.d GH until attainment of AH or no treatment. In this per-protocol analysis, 91 of 102 patients in the treated group and 33 of 47 patients in the control group were followed to AH. Mean height at inclusion was -3.2 SD score (SDS). Treatment duration was 2.7 +/- 0.6 yr. AH was -2.7 +/- 0.9 and -2.1 +/- 1.0 SDS in the control and treated groups, respectively (P < 0.005). The groups differed by 0.6 SDS units (95% confidence interval, 0.2-0.9). Height gain was 0.5 +/- 0.8 and 1.1 +/- 0.9 SDS in the control and treated groups, respectively (P = 0.002). Multivariate analyses confirmed the independent effects of treatment (0.6 SDS) and treatment duration (0.4 SDS/yr). All potential biases would tend to decrease the estimate of the treatment effect. Treatment tolerance was excellent. We concluded that the potential for spontaneous catch-up in short adolescents born SGA is limited. GH treatment increases AH by at least 0.6 SDS in this population.

BACKGROUND:The aims of the study were to characterize the relatives at high risk of progression to diabetes and to determine whether rate of progression to diabetes varied according to age, specific combination of antibodies and genetic markers of susceptibility.METHODS:Family members of type 1 diabetic patients were examined through a large medical network for the presence of specific antibodies to beta cell constituents and high risk DQB1 alleles. Antibodies to insulin, GAD and IA-2 as well as ICA were examined in 4,044 family members recruited in a large prospective family study in the Rhone-Alpes region (the GRADI study). Among them, 3,951 non diabetic first degree relatives have been tested on a median of 2.2 occasions and were followed for up to 16 years.RESULTS:Presence of antibodies to GAD (3.6%), IA-2 (4.9%), insulin (2.2%) and ICA at titers equal or above 20JDF units (1.1%) were noticed at the first determination and prevalence increased among ICA positive relatives versus ICA negative relatives. All combinations of markers resulted in specificities above 90%. The positive predictive value of antibodies was dependent on the number of positive antibodies. Combination of antibodies to GAD and IA-2 or GAD and IAA had higher predictive values and sensitivities than ICA titers above 20 JDF units. Additional positivity of IAA increased the predictive value but reduced the sensitivity of the screening procedure. Using a combi GAD/IA-2 assay increased the sensitivity of the screening up to 87.8% but reduced the predictive value to 13.8%.CONCLUSIONS:These data confirm in a large French cohort of first degree relatives of type 1 diabetic patients that combinations of antibodies to beta cell constituents can replace ICA in the first screening procedure. We report that combi GAD/IA-2 assay is well suited for screening purposes. However, time to diabetes in antibody positive relatives appears to be more heterogeneous to what has been described. The importance of genetic markers needs further evaluation.

Purpose: Various endocrine studies performed in the hypospadias population show an unsatisfactory response to the human chorionic gonadotropin (HCG) test and abnormal androgen biosynthesis with possible enzyme defects. We evaluated the incidence of disorders in androgen production in boys with isolated hypospadias.Materials and Methods: A total of 32 consecutive children (46,XY) with hypospadias were prospectively enrolled in the study. Severity of the defect was assessed with a new classification based on the location of the division of the corpus spongiosum. Endocrine evaluation consisted of measuring luteinizing hormone, follicle-stimulating hormone, anti-mullerian hormone (AMH), testosterone, dihydrotestosterone, progesterone, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate and Delta(4)-androstenedione. In all but 3 patients gonadal stimulation with 1,500 IU HCG every other day for 12 days was performed and steroid concentrations were reassessed after the test. Am adrenocorticotropic hormone test was performed in 2 patients and molecular study of the androgen receptor was performed in 28.Results: An increase to 37.37 nmol./l. progesterone (normal 0.1 to 0.5) and 17alpha-hydroxyprogesterone to 25.48 nmol./l. (normal 1.18 +/- 0.66) before HCG stimulation was noted in 1 patient. These abnormal results were not found after HCG stimulation but reappeared after the adrenocorticotropic hormone test. This result might be related to a partial mix of 17alpha-hydroxylase/17,20-lyase deficiency but no mutation was found after complete sequencing of gene CYP17. Of the 32 patients 4 had an insufficient response to HCG stimulation (testosterone less than 10 nmol./l.), including 1 with a low AMH level of 180 pmol./l. (normal 451 +/- 198) and an increased dehydroepiandrosterone sulfate level of 1,995 nmol./l. (normal 59 +/- 41) before HCG stimulation. Partial androgen insensitivity was suspected in 1 patient because he had a high testosterone response (29.96 nmol./l.) after HCG stimulation but no mutation of the gene of the androgen receptor was detected. Two patients with proximal hypospadias had isolated decreased AMH levels, which was evidence of Sertoli cell insufficiency.Conclusions: Although our series of 32 patients had several abnormal endocrine screenings, these results indicate no significant endocrine defects.

The authors report the consequence of intra-uterine growth retardation on infancy and adult disease. During infancy in 7 to 10% of cases a growth retardation less than -2 DS, is observed and subsequently needs growth hormone treatment. In adult X syndrome (hypertension, diabetes of 2 types insulino resistant and cardiovascular disease) is observed 18 times more in subjects where the birth weight was low than 2.4 kg. Finally the authors give some recommendations to follow-up of the infants born with a growth restriction.

Infants born small for gestational age (SGA) are defined as those with a birth weight and/or birth length below two standard deviations for gestational age. Postnatal catch-up growth is absent in 8-12% of children born SGA and these children achieve adult heights far below their target height. The objectives of our retrospective study were to confirm the prevalence of catch-up growth and to refine the kinetics of the catch-up process. The 'Lyon series' of patients consisted of 179 children with 'idiopathic' SGA, of whom 8% did not achieve catch-up growth (i.e. their height remained below -2 SD throughout the study). The number of days that the mother was hospitalized before delivery was found to be significantly correlated with lack of catch-up growth. Maternal hypertension, term delivery and postnatal parenteral nutrition were also associated with lack of catch-up growth, but the relationship was not significant. In addition, an oscillatory growth velocity pattern was observed in boys and girls born SGA, with alternating periods of growth acceleration and deceleration. This suggests that catch-up growth is regulated in a sophisticated way by the hypothetical 'Somatostat', although further confirmation of this process is needed.

It has become common practice to apply GH treatment in short Turner syndrome patients with the objective of promoting growth. The variability in response and the high costs of this treatment demand the individualization and optimization of therapy. Based on 686 prepubertal Turner patients from the Kabi International Growth Study (KIGS; Pharmacia & Upjohn, Inc. International Growth Database), we undertook a multiple regression analysis of height velocity (centimeters per yr) by using various parameters of potential relevance. Derived prediction models for the first 4 yr of GH treatment were validated with 76 additional KIGS patients and 81 patients from Tuebingen, Germany. Among the 6 predictors identified, the most influential variable for first year growth response was the natural log (ln) of the weekly GH dose. The first year growth response was also correlated with age and distance between height and target height (SD score; both negative) and body weight SD, number of GH injections per week, and oxandrolone treatment given additionally (positive). The first year model explains 46% of the variability, with 1 SD of 1.26 cm. For the second to fourth years, 5 predictors were identified: height velocity during previous years, weekly GH dose (ln), weight SD, oxandrolone therapy (all positive), and age (negative). These models explained 32%, 29%, and 30% of the variability, respectively, with SD scores of 1.1, 1.0, and 1.0 cm, respectively. When the models were applied to the other cohorts, no significant difference was noted between observed and predicted responses. Although the parameters used in our models do not entirely explain the variability in the growth response in Turner syndrome, the parameters themselves were clinically relevant to our present understanding and proved to be of high precision. Some of the tested markers, such as karyotype, do not contribute to the growth response. These variables make the models practical and suitable for planning beneficial and cost-effective therapy.

BACKGROUND:Growth hormone (GH) contributes to insulin resistance, but whether children treated with GH are at increased risk of diabetes has not been established. We undertook a retrospective analysis of data from an international pharmacoepidemiological survey of children treated with GH to find out the incidence of impaired glucose tolerance and types 1 and 2 diabetes mellitus.METHODS:Reports to the survey of abnormal glucose metabolism were investigated and classified. The incidence and age-distribution of type 1 diabetes were compared with values from a model of reference data. The incidence of type 2 diabetes was compared with data from two reports of children not treated with GH.FINDINGS:85 (0.36%) of 23333 children were reported with abnormal glucose metabolism. After investigation, 43 had confirmed glucose disorders (11 with type 1 diabetes, 18 with type 2 diabetes, and 14 with impaired glucose tolerance). The incidence and age at diagnosis of type 1 diabetes in children treated with GH did not differ from expected values. The incidence of type 2 diabetes was 34.4 cases per 100000 years of GH treatment which was six-fold higher than reported in children not treated with GH. Type 2 diabetes did not resolve after GH therapy was stopped.INTERPRETATION:GH treatment did not affect the incidence of type 1 diabetes mellitus in any age group. We postulate that the higher than expected incidence of type 2 diabetes mellitus with GH treatment may be an acceleration of the disorder in predisposed individuals.

Face à l’augmentation du nombre de consultations pédiatriques urgentes, deux enquêtes « un jour donné » ont été menées sur le territoire de la Communauté urbaine de Lyon, avec pour objectifs l’analyse des motifs, des circonstances et de la pertinence de la non-programmation de ces demandes de soins, et la meilleure connaissance de l’itinéraire des patients.Méthodes. – Les consultations non programmées concernant les enfants de moins de 18 ans ont été répertoriées le samedi 21 avril et le jeudi 13 décembre 2001 dans l’ensemble des structures susceptibles d’assurer des soins médicaux urgents. La collecte de l’information a été réalisée par questionnaire proposé à la famille et aux médecins (médecins généralistes tirés au sort, ou pédiatres volontaires), exerçant dans les secteurs de garde généralistes, à la garde du Groupement des pédiatres lyonnais, et dans tous les services d’accueil d’urgence hospitaliers recevant des enfants (hôpitaux publics et cliniques privées). SOS médecins n’a pas participé à l’étude, mais a communiqué son activité a posteriori. Six cent quatre-vingt-trois consultations le samedi et 1183 le jeudi ont été analysées.Résultats. – En rapportant à l’ensemble des praticiens exerçant le jour donné l’activité des praticiens participants sur un mode proportionnel, on pouvait estimer à 1813 le nombre total des actes le samedi et à 4576 le jeudi. La médecine libérale (cabinets et gardes organisées) en a assuré 82 % le samedi (généralistes 70 %, pédiatres 12 %) et 93 % le jeudi (généralistes 75 %, pédiatres 18 %), les hôpitaux publics 13 et 4 %, les cliniques 5 et 2 % respectivement. Pour les parents, les problèmes étaient jugés sérieux ou graves dans 10 à 40 % des cas selon la filière. Le motif de consultation était le plus souvent d’ordre médical (douleur, gêne physique, crainte de complications, plus rarement sentiment de gravité immédiate). Les motifs non médicaux de consultation (approche du week-end, convenance personnelle, absence ou indisponibilité du médecin traitant) ont concerné un quart des consultations le jeudi et plus de la moitié le samedi. Le recours à la consultation en urgence n’était pas justifié, selon les médecins, dans 13 % des cas. Le recours direct à une structure d’hospitalisation était motivé avant tout par l’assurance « d’avoir tout sur place ». Le samedi, l’absence du médecin traitant était le motif le plus fréquemment invoqué. Le circuit du patient avant sa prise en charge était jugé globalement satisfaisant par les médecins dans 82 % des cas.Conclusion. – Les consultations non programmées correspondent à trois situations : pratique habituelle et acceptée des cabinets médicaux (consultations sans rendez-vous) ; problème médical urgent (ou ressenti comme tel) ; résultat d’un dysfonctionnement entre l’offre de soins et son utilisation par les parents. Ce dernier point permet d’envisager deux axes d’action, l’information–éducation des familles et la mise en réseau des acteurs de l’urgence avec pour objectif la réduction de 15 à 20 % de l’afflux dans les hôpitaux.With the increasing number of emergency paediatric consultations, two surveys “on a given day” were performed in the “Communauté Urbaine de Lyon”, with the aim of analyzing the causes, circumstances, and relevance of these unplanned consultations, as well as a better understanding of the itinerary of these patients.Methods. – Unplanned consultations concerned children less than 18 years old seen in consultation on Saturday April 21, and Thursday December 13, 2001, in all medical facilities capable of delivering emergency paediatric care. Data collection was performed by filling out a questionnaire given to the family and the physicians (general practitioner who were chosen randomly, or paediatricians volunteering for the study), working in general medicine sectors, at the outpatient emergency consultation of the “Groupement des Pédiatres du Lyonnais”, and in all the emergency departments to which children could be addressed (public hospitals and private clinics). “SOS Médecins” did not participate in this study but communicated its activity a posteriori. Six hundred and eighty three consultations on the Saturday and 1183 on the Thursday were analyzed.Results. – An estimation of the total number of consultations was performed taking into account the proportion of practitioners participating in the survey, with a total number of 1813 consultations on the Saturday and 4576 on the Thursday. Consultations in the private setting (by practitioners or organized emergency centers) accounted for 82% on the Saturday (general practitioners 70%, paediatricians 12%) and 93% on the Thursday (general practitioners 75%, paediatricians 18%), public hospitals 13% and 4% and private clinics 5% and 2%, respectively. Parents considered the problem to be serious in 10–40% of the cases, depending on the setting. The reason justifying consultation was generally medical (pain or discomfort, fear of complication, less frequently feeling of imminent danger). Non-medical reasons (proximity of the week-end, personal reasons, absence or unavailability of usual practitioner) concerned a fourth of the Thursday consultations and up to half of the Saturday consultations. An urgent consultation was estimated not be justified in 13% of the cases according to the physicians. The main reason for going to a hospital was that “everything would be available on site”. On Saturday the absence of the usual practitioner was the most cited reason. The global itinerary was deemed satisfactory by the physicians in 82% of the cases.Conclusion. – Unplanned consultations are found in three situations: routine and accepted activity of medical office (consultation without an appointment), urgent medical problem (or estimated to be urgent), and the result of a dysfunction between the medical possibilities of the health care system and its use by the parents. This last point opens two possibilities of action which are the information and education of families and the networking of physicians involved in emergency consultations with the aim of reducing hospital consultations by 15–20%

Acta PaediatricaVolume 88, Issue s428 p. 180-180 Treatment of growth hormone insensitivity syndrome with insulin-like growth factor I: long-term results of the European multicentre study MB Ranke, MB Ranke Department of Paediatric EndocrinologySearch for more papers by this authorMO Savage, MO Savage University Children's Hospital, Tubingen, Germany, Paediarric Endocrinology Section St Bartholomew S Hospital, London, UKSearch for more papers by this authorP Chatelain, P Chatelain Department of Endocrinology and Diabetology', Hopital Debrousse, Lyon, FranceSearch for more papers by this authorMA Preece, MA Preece Institute of Child Health University College London Medical School, London, UKSearch for more papers by this authorRG Rosenfeld, RG Rosenfeld Department of Pediatrics, Oregon Health Sciences University, Portland, Oregon, USASearch for more papers by this authorP Wilted, P Wilted , and Peptide Hormone Outcomes Research, Pharmacia & Upjohn, Stockhol Sweden USASearch for more papers by this author MB Ranke, MB Ranke Department of Paediatric EndocrinologySearch for more papers by this authorMO Savage, MO Savage University Children's Hospital, Tubingen, Germany, Paediarric Endocrinology Section St Bartholomew S Hospital, London, UKSearch for more papers by this authorP Chatelain, P Chatelain Department of Endocrinology and Diabetology', Hopital Debrousse, Lyon, FranceSearch for more papers by this authorMA Preece, MA Preece Institute of Child Health University College London Medical School, London, UKSearch for more papers by this authorRG Rosenfeld, RG Rosenfeld Department of Pediatrics, Oregon Health Sciences University, Portland, Oregon, USASearch for more papers by this authorP Wilted, P Wilted , and Peptide Hormone Outcomes Research, Pharmacia & Upjohn, Stockhol Sweden USASearch for more papers by this author First published: 21 April 2008 https://doi.org/10.1111/j.1651-2227.1999.tb14384.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume88, Issues428February 1999Pages 180-180 RelatedInformation

Cutfield W, Lindberg A, Albertsson Wikland K, Chatelain P, Ranke MB, Wilton P, on behalf of the KIGS International Board. Final height in idiopathic growth hormone deficiency: the KIGS experience. Acta Pædiatr 1999; Suppl 428: 72–5. Stockholm. ISSN 0803–5326Final height was evaluated in 369 patients with idiopathic growth hormone deficiency (IGHD) enrolled in KIGS ‐ the Pharmacia & Upjohn International Growth Database. At the start of growth hormone (GH) therapy, the patients were 9.8 years of age, their mid‐parental height SDS was ‐0.8, and their height SDS was ‐3.1. Of the 369 patients, 50% had multiple hormone deficiencies, and puberty was induced in 31%. Patients were 18 years of age at completion of GH therapy, and had received GH at a dose of 0.49 IU/kg/week (0.16 mg/kg/week), with a mean of 5.2 injections/week for 8.1 years. Final height SDS was ‐1.5, final minus initial height SDS was 1.7 and final minus mid‐parental height SDS was ‐0.5. A Swedish subgroup (n= 69) received conventional GH therapy throughout at 0.65 IU/kg/week (0.22 mg/kg/week), with seven injections/week for a mean of 9.4 years. These patients achieved their genetic potential (final minus mid‐parental height SDS, 0.03), with a normal final height SDS of ‐0.3. For the total group, the following variables were associated with final height: mid‐parental height SDS (r= 0.62), injection frequency (r= 0.37), duration of GH treatment (r= 0.28), peak stimulated GH concentration (r= ‐0.25), age (r= ‐0.19) (all p < 0.001) and height velocity SDS in the first year of treatment (r= 0.20, p= 0.004). In conclusion, genetic potential, expressed as the mid‐parental height, is the variable with the greatest identified influence on final height during GH treatment in IGHD. Current GH regimens will lead to a normal height and attainment of mid‐parental height. However, higher dose, individualized GH regimens are likely to be necessary for patients with IGHD who are disadvantaged at the time of commencing GH therapy, such as those with short parents, those whose treatment began in late childhood or adolescence and those with less severe GHD. □Final height, growth hormone treatment, height, idiopathic growth hormone deficiency, KIGS

Postmarketing surveillance studies of recombinant human GH therapy, such as the Kabi Pharmacia International Growth Study (KIGS; Pharmacia & Upjohn, Inc., International Growth Database), have accumulated extensive data concerning the characteristics and growth outcomes of children with various causes of short stature. These data provide an opportunity to analyze the factors that determine responsiveness to GH and allow the development of disease-specific growth prediction models. We undertook a multiple regression analysis of height velocity (centimeter per yr) with various patient parameters of potential relevance using data from a cohort of 593 prepubertal children with idiopathic GH deficiency (GHD) from the KIGS database. Our aim was to produce models that would have practical utility for predicting prepubertal growth during each of the first 4 yr of GH replacement therapy. These models were validated by a prospective comparison of predicted and observed growth outcomes in an additional 3 cohorts of prepubertal children with idiopathic GHD: 237 additional KIGS patients, 29 patients from the Australian OZGROW study, and 33 patients from Tubingen, Germany. The most influential variable for first year growth response was the natural log (ln) of the maximum GH response during provocation testing, which was inversely correlated with height velocity. The first year growth response was also inversely correlated with chronological age and height SD score minus midparental height SD score. First year growth was positively correlated with body weight SD score, weekly GH dose (ln), and birth weight SD score. Two first year models were developed using these parameters, 1 including and 1 excluding the maximum GH response to provocative testing. The former model explained 61% of the response variability, with a SD of 1.46 cm; the latter model explained 45% of the variability, with a SD of 1.72 cm. The two models gave similar predictions, although the model excluding the maximum GH response to testing tended to underpredict the growth response in patients with very low GH secretory capacity. For the second, third, and fourth year growth responses, 4 predictors were identified: height velocity during the previous year (positively correlated), body weight SD score (positively correlated), chronological age (negatively correlated), and weekly GH dose (ln; positively correlated). The models for the second, third, and fourth year responses explained 40%, 37%, and 30% of the variability, respectively, with SDs of 1.19, 1.05, and 0.95 cm, respectively. When the models were applied prospectively to the other cohorts, there were no significant differences between observed and predicted responses in any of the cohorts in any year of treatment. The fourth year response model gave accurate prospective growth predictions for the fifth to the eighth prepubertal years of GH treatment in a subset of 48 KIGS patients. Analyses of Studentized residuals provided further validation of the models. The parameters used in our models do not explain all of the variability in growth response, but they have a high degree of precision (low error SDs). Moreover, the parameters used are robust and easily accessible. These properties give the models' practical utility as growth prediction tools. The availability of longitudinal, disease-specific models will be helpful in the future for enabling growth-promoting therapy to be planned at the outset, optimized for efficacy and economy, and individualized to meet treatment goals based on realistic expectations.

We studied short- and long-term responses to growth hormone (GH) treatment and adverse medical events (AE) in 488 patients with craniopharyngioma who were entered into the Kabi International Growth Study (KIGS). First-year growth response and responsiveness (n = 394) were similar to those seen in children with idiopathic GH deficiency. The growth response over 5 years (n = 152) was unaffected by the recurrence of tumour and prior tumour management, but was greater in those receiving thyroxine. Mean height standard deviation scores (SDS) at the end of GH treatment (n = 129) was –0.7 ± 1.2, and 79% achieved a height over –2 SD of target height, with evidence of further growth potential. Final height SDS correlated positively with height SDS at the start of treatment and with target height SDS, whereas gain in height SDS was inversely correlated with height SDS and bone age at the start of GH treatment. The rate of recurrence of tumour, 0.045/treatment year, was greater in those who had been treated with surgery alone compared to surgery and cranial irradiation. Other AE included headaches, fluid retention and convulsions occurring at rates of 0.025, 0.005 and 0.004/treatment year, respectively. We concluded that GH treatment is safe and effective in children with craniopharyngioma and provide data for counselling of parents about outcome during GH treatment.

La saturation de la structure des urgences (SU) est un tueur silencieux. En effet, plusieurs auteurs dans différents pays ont décrit une augmentation de la mortalité, une diminution de la qualité des soins et un séjour hospitalier prolongé associés à la saturation de la SU. Les causes de la saturation sont multiples : l'organisation de l'amont et en particulier l'accès pour la médecine de ville aux examens complémentaires et aux hospitalisations, l'organisation de la SU et les tâches inutiles ou chronophages et l'organisation de l'aval en particulier la disponibilité en lits d'hospitalisation pour les malades non programmés. La principale cause de saturation de la SU est l'attente de lits disponibles dans les unités, appelé « boarding ». Les solutions pour résoudre ce boarding sont organisationnelles et nécessitent une coopération de l'ensemble de l'établissement à travers un bed management efficace et l'implication de tous les acteurs. Les patients polypathologiques et ceux pour lesquels sont intriquées des difficultés sociales sont souvent les patients qui attendent le plus longtemps en SU. La médecine interne, de par son expérience et son savoir-faire, est la discipline idéale pour ces patients complexes qui nécessitent du temps d'observation et d'évaluation. Un partenariat entre SU et médecine interne pourrait concourir à diminuer la saturation de la SU en améliorant les parcours de soins.Emergency Department (ED) overcrowding is a silent killer. Thus, several studies in different countries have described an increase in mortality, a decrease in the quality of care and prolonged hospital stays associated with ED overcrowding. Causes are multiple: input and in particular lack of access to lab test and imaging for general practitioners, throughput and unnecessary or time-consuming tasks, and output, in particular the availability of hospital beds for unscheduled patients. The main cause of overcrowding is waiting time for available beds in hospital wards, also known as boarding. Solutions to resolve the boarding problem are mostly organisational and require the cooperation of all department and administrative levels through efficient bed management. Elderly and polypathological patients wait longer time in ED. Internal Medicine, is the ideal specialty for these complex patients who require time for observation and evaluation. A strong partnership between the ED and the internal medicine department could help to reduce ED overcrowding by improving care pathways.