Gonadotropin administration to mimic mini-puberty in hypogonadotropic males: pump or injections?

Objective: Newborns with congenital hypogonadotropic hypogonadism (CHH) have an impaired postnatal activation of the gonadotropic axis. Substitutive therapy with recombinant gonadotropins can be proposed to mimic physiological male mini-puberty during the first months of life. The aim of this study was to co mpare the clinical and biological efficacy of two treatment modalities of gonadotropins administration during mini-puberty in CHH neonates. Design: Multicenter retrospective analytical epidemiological study comparing two treatments, pump vs injection, between 2004 and 2019. Methods: Clinical (penile size, testis size, testicular descent) and biological parameters (serum concentrations of testosterone, anti-Müllerian hormone (AMH) and Inhibin B) were compared between the two groups by multivariate analyses. Results: Thirty-five patients were included. A significantly higher incre ase in penile length and testosterone level was observed in the injection group compared to the pump group (+0.16 ± 0.02 mm vs +0.10 ± 0.02 mm per day, P = 0.002; and +0.04 ± 0.007 ng/mL vs +0.01 ± 0.008 ng/mL per day, P = 0.001). In both groups, significant increases in penile length and width, testosterone, AMH, and Inhibin B levels were observed, as well as improved testicular descent (odds ratio of not being in a scrotal position at the end of treatment = 0.97 (0.96; 0.99)). Conclusions: Early postnatal administration of recombinant gonadotropins in CHH boys is effective in stimulating penile growth, Sertoli cell proliferati on, and testicular descent, with both treatment modalities

Pathogenic variants in the DEAH-box RNA helicase DHX37 are a frequent cause of 46,XY gonadal dysgenesis and 46,XY testicular regression syndrome

XY individuals with disorders/differences of sex development (DSD) are characterized by reduced androgenization caused, in some children, by gonadal dysgenesis or testis regression during fetal development. The genetic etiology for most patients with 46,XY gonadal dysgenesis and for all patients with testicular regression syndrome (TRS) is unknown

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Puberté précoce centrale et insuffisance somatotrope idiopathique (un désordre endocrinien rare associé à une anomalie de développement de la région hypothalamo-hypophysaire.)

STRASBOURG-Medecine (674822101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Sténose congénitale des orifices piriformes (prévalence de l'atteinte de l'axe hypothalamo-hypophysaire et des autres anomalies associées)

La sténose congénitale des orifices piriformes (SCOP) est une malformation rare des fosses nasales responsable d'une détresse respiratoire néonatale. Elle est considérée comme une forme clinique d'holoprosencéphalie. La SCOP peut-être sporadique ou familiale, isolée ou associée à d'autres anomalies de la ligne médiane telles l'incisive médiane unique (IMU) ou l'insuffisance hypophysaire. L'objectif de ce travail a été la description et l'étude de la prévalence des anomalies de l'axe hypothalamo-hypophysaire et des autres anomalies congénitales associées à la SCOP. Sur les 31 sujets étudiés, 24 (77%) présentaient au moins une anomalie associée à la SCOP, dont les plus fréquentes étaient l'IMU (55%) et les atteintes de l'axe hypothalamo-hypophysaire. La prévalence des anomalies endocrines était de 42%. Huit sujets (26%) avaient une insuffisance hormonale (déficit somatotrope isolé n = 2 ou multiple n = 6). Douze sujets (39%) avaient une anomalie morphologique de l'axe hypothalamo-hypophysaire avec (n = 7) ou sans (n = 5) anomalie hormonale décelable. Il existait une posthypophyse ectopique chez 9 enfants, en position infundibulaire (n = 4) ou située le long de la tige pituitaire (n = 5). De plus, des anomalies cérébrales, ophtalmologiques, rachidiennes, des extrémités, rénales et/ou cardiaques ont été mises en évidence, dont certaines n'avaient pas été décrites jusqu'à présent dans le cadre de cette malformation ORL. Enfin, une composante familiale (antécédents familiaux de malformation de la ligne médiane et/ou consanguinité parentale) a été retrouvée dans 32% des cas. En conclusion, ces résultats justifient la réalisation systématique d'une IRM cérébrale et d'une exploration hormonale chez les enfants présentant une SCOP, en particulier en période néonatale et/ou préopératoire, afin de permettre un dépistage précoce des anomalies métaboliques éventuelles et une prévention de leurs complications. La forte composante familiale et la grande diversité phénotypique de ces sujets permettent de suggérer une implication des gènes exprimés au cours du développement des structures cérébrales, crânio-faciales et hypothalamo-hypophysaires dans la genèse de la SCOPAMIENS-BU Santé (800212102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Proportion élevée de pathologies chroniques associées à l hypothyroïdie congénitale: étude chez les jeunes adultes traités dès la période néonatale en France

L étude Française sur l état de santé des jeunes adultes traités depuis la période néonatale pour hypothyroïdie congénitale (HC) a permis récemment de montrer une proportion élevée de maladies chroniques associées à l HC.L objectif principal de cette étude a été la description de ces pathologies. Population et méthodes: Parmi les 1202 participants, 68 patients ont déclaré une pathologie chronique associée à l HC (5,7% vs 2,9% ; p< 0,001). Des questionnaires ont été envoyés aux patients et médecins pour avoir des précisions sur la pathologie déclarée. La population de référence incluait 5817 sujets nés pendant la même période. Parmi l ensemble des patients avec pathologies associés (n=68), ceux avec maladies neurologiques et mentales étaient les plus fréquents (50%), et étaient significativement supérieurs au nombre observé dans la population de référence (n=34 vs n=11; p<0,001). Elles étaient isolées ou associées à un retard mental, encéphalopathie, ou baisse d audition. Les malformations congénitales associées étaient aussi plus importantes (n=13 vs 3; p<0.001). Les autres pathologies étaient comparables à la population de référence. Aucune association n a été retrouvée avec l étiologie, la sévérité ou l âge au début du traitement de l hypothyroïdie. Malgré un traitement précoce, une proportion importante de pathologies neurologiques et/ou du développement associées à l HC a été mis en évidence. Cette étude pourrait permettre dans l avenir, d identifier des anomalies syndromiques et/ou des mécanismes encore mal connus actuellement qui pourraient aider à la compréhension du développement normal et pathologique de la thyroïdePARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Congenital Hypothyroidism: Role of Nuclear Medicine

International audienceThyroid scintigraphy holds a key place in the etiologic workup of neonatal hypothyroidism. Routine screening for this disorder in maternity hospitals in industrialized countries, for nearly 40 years, has permitted early treatment and thereby helped to prevent its physical and mental complications. Neonatal hypothyroidism affects approximately 1 in 3000 births. The most common causes are abnormal thyroid gland development and defective hormone synthesis by an eutopic thyroid gland. The incidence of the latter has risen in recent years, for reasons that remain unclear. A thorough etiologic workup helps to determine the disease type. Current guidelines recommend thyroid imaging by means of ultrasound and scintigraphy. Ultrasound should be done by a practitioner trained to examine the cervical region of newborns, as the thyroid is very small and must be distinguished from the particular aspect of the “thyroid empty lodge.” Ultrasound lacks sensitivity for detecting small ectopic glands but is the gold standard for measuring thyroid dimensions. Scintigraphy provides an etiologic diagnosis in most cases. The two isotopes used in this setting are technetium-99m and iodine-123. The latter isotope gives more contrast and allows the perchlorate discharge test to be performed to detect abnormal iodide organification in the neonate with an eutopic thyroid. If scintigraphy cannot be performed during the neonatal period, a postponed procedure can be achieved after 3 years of age. Close cooperation between the nuclear medicine physician and the pediatric endocrinologist is crucial for timely and optimized scintigraphy

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome

International audienceOBJECTIVE:Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment.DESIGN:We conducted a national observational multicenter study.METHODS:Birth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%).RESULTS:Birth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3-11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0-21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome.CONCLUSION:These data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy

Supplementary data to: Algorithms to define abnormal growth in children: external validation and head-to-head 3 comparison 4 5

Suplemental Tables 1, 2 and 3. Supplemental Fig.1 and Fig.2 Article published in J Clin Endocrinol Metab. 2018 Aug 20. doi: 10.1210/jc.2018-0072