Copy number variation of two separate regulatory regions upstream of SOX9 causes isolated 46,XY or 46,XX disorder of sex development.

Background: SOX9 mutations cause the skeletal malformation syndrome campomelic dysplasia in combination with XY sex reversal. Studies in mice indicate that SOX9 acts as a testis-inducing transcription factor downstream of SRY, triggering Sertoli cell and testis differentiation. An SRY-dependent testis-specific enhancer for Sox9 has been identified only in mice.

Early detection of growth disorders with the CrescNet system at the Leipzig treatment center.

Background: Growth hormone replacement therapy is more effective the earlier it is begun. This article adresses the question whether children with growth hormone deficiency (GHD) were able to begin treatment earlier through the use of the CrescNet system in the Department of Pediatrics at the Leipzig University Hospital. CrescNet is a network of pediatricians and endocrinological treatment centers, established in Leipzig in 1998, whose aim is to improve the early detection of growth disorders.

[Selective primary obesity prevention in children].

Background And Objective: Obesity in children is characterized by a rapid gain of weight starting at an age of 4 to 5 years. We investigated whether low threshold prevention prevented a further increase of the Standard-Deviation-Score of the BMI (BMI SDS) in children with impending obesity.

Patients And Methods: The network CrescNet collected data from more than 300,000 children.

Patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency can achieve their target height: the Leipzig experience.

Background: Despite treatment, the mean final height (FH) of patients with classic congenital adrenal hyperplasia (CAH) is below the mean height of a normal population.

Aims: To show that CAH patients can achieve their target height (TH), 39 adult subjects, whose therapy had started in infancy, were studied in a retrospective analysis. All height SDS were corrected so that they related to TH SDS.

[Acrodermatitis enteropathica (AE) is caused by mutations in the zinc transporter gene SLC39A4].

Background: Acrodermatitis enteropathica (AE) is an autosomal recessively inherited disease caused by a decreased intestinal zinc resorption and characterized by severe dermatitis (preferably hands, feet, mouth, genital region), chronic diarrhoea, retardation of growth and development, alopecia and increased proneness to infections. In 2002 it was shown that mutations in the zinc transporter gene SLC39A4 is the cause of AE.

Case Report: Here we report 4 patients with typical clinical signs since early childhood.

Blood pressure in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

Background: In patients with congenital adrenal hyperplasia (CAH) recording of blood pressure (BP) must be included in monitoring treatment to detect hypertension.

Aim: To investigate the BP patterns in patients with CAH.

Methods: Twenty-three children and adolescents (age 6-17 years) and 11 adult patients (age 18-26 years) were studied (21 females, 13 males; 28 salt-wasting patients).

Feminizing reconstructive surgery for ambiguous genitalia: the Leipzig experience.

Purpose: We report the results of feminizing reconstructive surgery for ambiguous genitalia with regard to the degree of virilization according to Prader and the long-term outcome with special emphasis on sexual intercourse.

Materials And Methods: Patients 16 to 46 years old with CAH (41) and MPH (17) were followed continuously by an interdisciplinary team that provided standardized hormone substitution and reconstructive surgery. More virilized genitalia were treated using a 2-stage procedure.

Gonadoblastomas in 5 patients with 46,XY gonadal dysgenesis.

We describe five patients with 46,XY gonadal dysgenesis who developed gonadoblastomas, dysgerminomas, a mature teratoma, and a testicular intraepithelial neoplasia. The age of the patients was between 12.2 and 18.

Histologic analysis of gonadal tissue in patients with Ullrich-Turner syndrome and derivative Y chromosomes.

To identify patients who had Ullrich-Turner syndrome (UTS) and were at risk for gonadoblastoma or associated germ cell tumors, molecular genetic analysis was carried out to detect Y chromosomal sequences. From peripheral blood samples of 5 patients who had cytogenetically confirmed UTS, genomic DNA was extracted and screened for Y chromosomal sequences by polymerase chain reaction. The morphology of the gonadal tissues was compared with results from polymerase chain reaction.

Video-assisted gonadectomy in children with Ullrich Turner syndrome or 46,XY gonadal dysgenesis.

Patients with dysgenetic gonads carry a high risk for the development of gonadal neoplasia. The aim of the study is to evaluate indications and feasibility of laparoscopy and video-assisted prophylactic gonadectomy in children with Ullrich Turner syndrome (UTS) or 46,XY gonadal dysgenesis (GoDy). Between 1996 and December 2002 five girls with UTS and nine patients with 46,XY GoDy (female gender role) were explored by laparoscopy.

Applicability of the SHBG androgen sensitivity test in the differential diagnosis of 46,XY gonadal dysgenesis, true hermaphroditism, and androgen insensitivity syndrome.

The sex hormone-binding globulin (SHBG) androgen sensitivity test has been used as a simple method to assess androgen receptor function in vivo. After a short term oral administration of the anabolic-androgenic steroid stanozolol the mean nadir serum concentration of SHBG is used as a measure of androgen response. We performed this test in order to evaluate its applicability in 16 patients with intersexual genital status: eleven with 46,XY gonadal dysgenesis and three with true hermaphroditism (group I), and in two patients with androgen insensitivity syndrome (AIS, group II).

Pregnancies in patients with congenital adrenal hyperplasia with complete or almost complete impairment of 21-hydroxylase activity.

Objective: To show that, with appropriate therapy, women with classic congenital adrenal hyperplasia (CAH) can become pregnant.

Design: Observational clinical study.

Setting: University hospital.

Priming with testosterone enhances stimulated growth hormone secretion in boys with delayed puberty.

Background And Objective: Tests for growth hormone (GH) deficiency are not always helpful in the differential diagnosis of physiological delay of growth and puberty and GH deficiency.

Patients And Methods: To enhance diagnostic specificity, we used a single dose testosterone priming before repeating the arginine stimulation test in 26 boys with short stature and only early signs of puberty who failed to show an adequate response of serum GH in the first test.

Results: 77% (20/26 patients) increased their serum GH peak to more than 10 ng/ml, whereas six patients were still below this concentration.

[Long-term study of patients with coeliac disease in childhood and adolescence: latent and transient coeliac disease].

Unlabelled: Coeliac disease (CD) is known as a lifelong condition of gluten intolerance. In case of some patients, the time after which gluten exposition leads to damage of the small intestinal mucosa may be very long. In addition to the florid form of CD, there are also silent (atypical mono- and oligosymptomatic with typical damage of the small intestinal mucosa) and latent forms (often asymptomatic without clear mucosal changes, antibody titres often normal).

Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complications.

Objective: In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management.

Growth-arrest and inhomogenous echotexture of the affected testis after tumor enucleation for unilateral Leydig cell tumor.

The authors report on an 8-year-old boy with unilateral left-sided Leydig cell tumor. After enucleation of the tumor, endocrine disturbances resolved. Long-time follow-up for more than 7 years was characterized by growth-arrest of the affected gonad and the unchanged appearance of a circumscribed hypoechogenic residual lesion within the testis.

The DSL analog free testosterone assay: serum levels are not related to sex hormone-binding globulin in normative data throughout childhood and adolescence.

In this study we tested the performance of easy-to-use and rapid, commercially available immunoassays to measure free testosterone (fT) and sex hormone-binding globulin (SHBG). We asked whether fT and SHBG serum levels are age-dependent and whether or not there is a gender dependence of fT and SHBG in this age group. Finally, by measuring fT and SHBG in sera of a cohort of healthy children and adolescents using commercially available immunoassays, we established normative data for fT and SHBG in this age group: in boys fT levels increased significantly (r=0.

Anorexia nervosa in congenital adrenal hyperplasia: long-term follow-up of 4 cases.

Studies which evaluate the psychosocial development and integration of adult female congenital adrenal hyperplasia (CAH) patients are rare but show that patients with the salt wasting form are significantly more virilized and more frequently single and childless. Major complaints are irregular menstruation, hirsutism, acne, obesity, deep voice, and cushingoid features. Surprisingly, a higher prevalence of psychosomatic disorders has not yet been described.

Prediction of height velocity of prepubertal children with growth hormone deficiency in the first year of treatment with recombinant human growth hormone.

Aim: Several methods have been developed to predict the outcome of growth hormone (GH) therapy in children with growth hormone deficiency (GHD).

Methods: Over 50 factors for each of 92 prepubertal patients with GHD (26 patients with total and 45 patients with partial GHD, 21 patients with neurosecretory dysfunction) were collected and included in multiple regression analyses and other nonlinear models to predict height velocity (HV) (cm/yr) in the first year of treatment. Afterwards the model was validated by two other cohorts of patients from other universities, which followed the same treatment regime as our clinic.

Laparoscopic bilateral adrenalectomy in a child.

Laparoscopic adrenalectomy is an established technique--in adults. This report describes a bilateral laparoscopic adrenalectomy in a child. As in adults, it indicates that the technique is superior in anatomic exposure and postoperative recovery, and is well suited for children.

Reversion of the differentiated phenotype and maturation block in Sertoli cells in pathological human testis.

To study the relationship between abnormal Sertoli cell differentiation and spermatogenic impairment, we examined the expression of Sertoli cell markers normally lost at puberty, cytokeratin 18 (CK18), anti-Müllerian hormone (AMH) and M2A antigen, in three children (aged 1-2 years), 50 adults (aged 19-45 years) with obstructive or non-obstructive azoospermia or oligozoospermia, and six patients (aged 1-18 years) with 5 alpha-reductase deficiency. There was CK18 and/or AMH expression, but never M2A antigen expression, associated with spermatogonial arrest or Sertoli cell-only (SCO) syndrome in infertile men. Loss of M2A antigen suggests the transition of Sertoli cells to an adult phenotype, while CK18 and/or AMH expression may be a manifestation of de-differentiation of Sertoli cells.

Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.

Conversion of testosterone (T) to dihydrotestosterone (DHT) in genital tissue is catalysed by the enzyme 5 alpha-reductase 2, which is encoded by the SRD5A2 gene. The potent androgen DHT is required for full masculinization of the external genitalia. Mutations of the SRD5A2 gene inhibit enzyme activity, diminish DHT formation, and hence cause masculinization defects of varying degree.

[Studies on sexual development, sexual behavior and ability to experience sex of young women with Ullrich-Turner syndrome].

In this investigation 25 female patients were included with the Turner syndrome (TS). From the 25 patients 6 had spontaneous menstruations, 19 had menstruations only after a hormonal stimulation. In a semi-structured interview the patients were questioned about their sexual activities, behavior and orgastic capacity.