Neonatal screening for congenital primary hypothyroidism (CH) may not distinguish between transient (TCH) and permanent dysfunction (PCH), causing potential overtreatment and concerns in affected families. To specify the indication for interruption of therapy, we analysed the German registry “HypoDok” for infants with CH, which oversees 1625 patients from 49 participating centres in Germany and Austria from 1997 until today. A total of 357 patients with a thyroid gland in loco typico were identified and retrospectively grouped according to cessation (TCH, n = 24) or continuation (PCH, n = 333) of l-thyroxine (l-T₄) treatment at 2 years of age. The receiver operating characteristic (ROC) analysis was performed to identify cutoffs predicting TCH by screening TSH concentrations and l-T₄ dosages. Gestational ages, birth weights and prevalence of associated malformations were comparable in both groups. The cutoff screening TSH concentration was 73 mU/L. The cutoff daily l-T₄ dosage at 1 year was 3.1 μg/kg (90% sensitivity, 63% specificity; 36 μg/day) and at 2 years of age 2.95 μg/kg (91% sensitivity, 59% specificity; 40 μg/day). At 2 years of age, specificity (71%) increased when both of these parameters were considered together.Conclusion: The decision to continue or cease l-T₄ treatment at 2 years of age in CH patients diagnosed in neonatal screening may be based on their screening TSH concentrations and individual l-T₄ dosages at 1 and 2 years of age. Thus, TCH and PCH may be distinguished; overtreatment avoided; and affected families reassured. What is Known:• The course of congenital primary hypothyroidism may be transient, causing potential overtreatment.• The dose ofl-thyroxine at 1 or 2 years of age may predict a transient course of primary congenital hypothyroidism. What is New:• TSH screening concentration andl-thyroxine dosages at 1 and 2 years of age represent reliable predictors for transient congenital primary hypothyroidism with higher sensitivity and specificity when considered together in order to select eligible patients who qualify for treatment withdrawal.

Introduction: Diagnosis of central diabetes insipidus (CDI) remains challenging. Water deprivation testing and hypertonic saline infusion, as established diagnostic tests, are mentally and physically demanding for patients. Arginine-stimulated copeptin has been shown as a putative parameter for the differential diagnosis of CDI in adults. Methods: In this single-centre retrospective study, we identified paediatric patients with suspected pituitary disorders who underwent standard arginine testing. Patients with CDI, matched controls, and primary polydipsia (PP) were identified. Diagnoses were confirmed retrospectively using comprehensive clinical and diagnostic characteristics. Serum copeptin concentrations were measured using a commercially available automated immunofluorescence assay (B.R.A.H.M.S Copeptin-proAVP KRYPTOR®) in samples stored for a median of 4.6 years (1.3–10.84) and collected before and 60 min after arginine infusion. Cut-off analyses were performed using ROC curves. Results: Serum samples from 32 patients with CDI, 32 matched controls, and 5 patients with PP (n = 69; 51 males, 18 females) were available for analysis. Median copeptin concentrations increased from 4.47 pmol/L (interquartile range [IQR]: 3.47–8.36) to 6.96 pmol/L (IQR: 4.51–12.89; p < 0.001) in controls, from 1.46 pmol/L (IQR: 1.21–2.12) to 1.44 (IQR: 1.10–1.87; p = 0.645, ns) in CDI, and from 4.40 pmol/L (3.95–6.33) to 9.58 pmol/L (8.19–11.42; p < 0.001) in PP. The published cut-off value of 3.8 pmol/L revealed a sensitivity of 100% and a specificity of 86.5% in confirming CDI. Conclusion: Our results suggest that arginine-stimulated serum copeptin concentrations are a sensitive and specific diagnostic tool for CDI in paediatric patients, which may replace and simplify the conventional diagnostic pathway of water deprivation testing and hypertonic saline infusion.

The study objective is to evaluate the results of our surgical technique for children with congenital adrenal hyperplasia and ambiguous genitalia at the University Hospital of Heidelberg, Department of Paediatric Surgery. The records of 19 patients with congenital adrenal hyperplasia treated between 1972 and 2004 were reviewed with respect to age at surgery, operative procedures and outcome. We describe the recession clitoroplasty technique currently used in our hospital and highlight the importance of short and long-term follow-up results with respect to appearance, position and size of the clitoris and quality of the vagina. One-stage recession clitoroplasty and vaginoplasty gives very satisfactory cosmetic and functional results, with few complications and a reduced need for secondary surgical interventions. The results of this study support the assumption that total correction can be achieved through a single-stage operation, performed in infancy. Le but de cette étude est d'évaluer les résultats de notre technique chirurgicale pour les enfants avec une hyperplasie congénitale des surrénales et une ambiguïté sexuelle dans le Département de chirurgie pédiatrique de l'Hôpital Universitaire de Heidelberg. Les dossiers de 19 patients avec une hyperplasie congénitale des surrénales suivis entre 1972 et 2004 ont été étudiés. Nous décrivons la technique de clitoridoplastie couramment utilisée dans notre hôpital et insistons sur l'importance du suivi, la qualité des résultats en fonction de l'apparence, de la position, de la taille du clitoris et de la qualité du vagin. La clitoridoplastie avec vaginoplastie en un temps donne de très bons résultats cosmétiques et fonctionnels avec peu de complications et une nécessité d'intervention secondaire moindre. Les résultats de cette étude confirment la possibilité d'une correction totale qui peut être réalisée par un simple acte chirurgical effectué dans l'enfance. El objetivo de este estudio es evaluar los resultados de nuestra técnica quirúrgica en niñas con hiperplasia suprarrenal congénita y genitales ambiguos en el Hospital de la Universidad de Heidelberg. Revisamos las historias de 19 pacientes con esta enfermedad entre 1972 y 2004 con atención a la edad operatoria, las técnicas y los resultados. Describimos la técnica de clitoriplastia de recesión usada actualmente en nuestro Hospital y destacamos la importancia del seguimiento a corto y largo plazo con respecto al aspecto, la posición y el tamaño del clítoris y la calidad de la vagina. La clitoriplastia en un tiempo con vaginoplastia da resultados muy satisfactorios desde el punto de vista cosmético y funcional con pocas complicaciones y escasa necesidad de intervenciones quirúrgicas secundarias. Los resultados de este estudio apoyan que se puede realizar la corrección total en un tiempo durante la infancia. Ziel dieser Studie war es, die Ergebnisse der Korrekturoperation bei Kindern mit dem Adrenogenitalen Syndrom und intersexuellem Genitale an der Universitätsklinik Heidelberg, Abteilung für Kinderchirurgie, zu evaluieren. Die Krankenakten von 19 Kindern mit einem Adrenogenitalen Syndrom zwischen 1972 und 2004 wurden hinsichtlich Operationsalter, Operationstechnik und Operationsergebnis untersucht. Wir beschreiben die in unserer Klinik zurzeit bevorzugte Technik der Klitorisreduktionsplastik und unterstreichen die Wichtigkeit einer Kurz- und Langzeitbeobachtung in Bezug auf das kosmetische Ergebnis, die Lage und Größe der Klitoris und die Qualität der Vagina. Die einzeitige Klitorisreduktionsplastik mit Vaginaleingangsplastik zeigt sehr gute kosmetische und funktionelle Ergebnisse, verbunden mit weniger Komplikationen und Zweiteingriffen. Die Ergebnisse dieser Studie unterstützen die Annahme, dass eine einzeitige Operation im frühen Kindesalter definitiv erfolgen kann.

Background: Mosaicism with cytogenetically visible Y chromosome is found in 5–6% of Turner Syndrome (TS) patients. Additionally, occult Y-chromosome derived material is increasingly found in patients with monosomy X when using more sensitive molecular techniques. These TS patients are at risk of developing gonadoblastomas when the Y genes presumed to be involved in gonadoblastoma development (Gonadoblastoma-Y-locus; GBY) are present. Aim: To find occult Y-chromosome material in TS patients and to correlate the patient’s phenotype to Y-chromosome material. Methods: We studied 60 TS-patients for presence of the Y chromosome with focus on the Gonadoblastoma Y-locus and its extension in Yp and Yq using sensitive Y centromere and Y gene deletion PCR assays. In addition, we evaluated their individual clinical and auxological characteristics. Results: We identified presence of the GBY-locus in 7 patients (11.7%) including 4 patients without evidence for a Y chromosome in their preceding standard karyotype analyses. Clinical and auxological characteristics were similar in GBY-positive and GBY-negative patients. Conclusions: Presence of the GBY locus in Turner patients with no indication of the Y chromosome in standard cytogenetic chromosome analysis can be revealed by sensitive molecular PCR assays screening for presence of the Y centromere and the GBY-candidate-genes in proximal Yp11 and Yq11, respectively.

Background: The German study group for quality assurance in pediatric endocrinology and the University of Ulm have established a software (“Hypo Dok”) for the documentation of longitudinal data of patients with congenital primary hypothyroidism (CH). Aim of this study was to analyse the long-term follow-up of patients with CH and to compare treatment with current guidelines. Methods/Patients: Anonymised data of 1 080 patients from 46 centres were statistically analysed. Results: Newborn screening result was available at a mean age of 7.3 days. Confirmation of the diagnosis was established at 8.4 days and therapy was started at 11 days. The average screening TSH was 180.0 mIU/L. During the first 3 months mean levothyroxine (LT4) dose was 10.7 µg/kg/day or 186.0 µg/m²/day. Weight-, BMI- and height-SDS did not differ significantly from the normal population. Only 25% of the patients (n=262) underwent formal EQ/IQ-testing. Their average IQ was 98.8±13.2 points. Discussion: In Germany screening, confirmation and start of treatment of CH are within the recommended time frame of 14 days. Initial LT4-doses are adequate. The auxological longterm outcome of young CH patients is normal. The implementation of standardized IQ testing has to be improved in routine patient care. Conclusion: Longitudinal data of patients with CH was analysed and compared to current guidelines. Confirmation and start of treatment are according to the recommendations. However standardised IQ testing requires improvement. Hintergrund: Die Arbeitsgruppe Qualitätssicherung der Arbeitsgemeinschaft Pädiatrische Endokrinologie (AQUAPE) und die Universität Ulm haben eine Datenbank („Hypo Dok”) für die Langzeitdokumentation von Daten von Patienten mit primärer konnataler Hypothyreose (CH) etabliert. Ziel dieser Studie war die Auswertung des Langzeitsverlaufs von Patienten mit CH und der Vergleich mit aktuellen Leitlinien. Methoden/Patienten: Anonymisierte Daten von 1 080 Patienten aus 46 Behandlungszentren wurden einer statistischen Auswertung unterzogen. Ergebnisse: Die Ergebnisse des Neugeborenenscreenings standen durchschnittlich bei einem Lebensalter von 7,3 Tagen zur Verfügung. Die Diagnose wurde im Alter von 8,4 Tagen bestätigt und die Therapie am 11. Lebenstag begonnen. Der mittlere TSH-Wert im Neugeborenenscreening betrug 180,0 mIU/L. Die durchschnittliche Levothyroxindosis (LT4) der ersten 3 Lebensmonate war 10,7 µg/kg/d oder 186,0 µg/m²/d. Gewichts-, BMI- und Größen-SDS unterschieden sich nicht signifikant von der Normalbevölkerung. Ein EQ-/IQ-Test wurde nur bei 25% (n=262) der Patienten durchgeführt. Der Durchschnitts-IQ lag bei 98,8±13,2 Punkten. Diskussion: In Deutschland wird das Neugeborenenscreening, sowie die Konfirmationsdiagnostik und Therapieeinleitung innerhalb des empfohlenen Zeitraums von 2 Wochen durchgeführt. Initiale LT4-Dosen sind adäquat. Der auxiologische Langzeitverlauf junger CH Patienten ist normal. Die Einführung standardisierter IQ-Untersuchungen im klinischen Alltag bedarf einer Verbesserung. Zusammenfassung: Langzeitdaten von Patienten mit CH wurden analysiert und mit aktuellen Leitlinien verglichen. Der Zeitpunkt der Konfirmationsdiagnostik und der Einleitung der LT4-Therapie entspricht den Leitlinien. Jedoch sollte die standardisierte IQ-Testung noch optimiert werden. ^* joint first authors. ^** joint senior authors.