ABSTRACT: Homoki, J., Teller, W. M., Tschürtz, D., and Fazekas, A. T. A. (Department of Paediatrics, Division of Endocrinology and Metabolism, University of Ulm/Donau, BRD). The concentrations of total Cortisol and corticosterone in mixed cord plasma. Acta Paediatr Scand, 64:587, 1975.–Cortisol and corticosterone were determined in mixed umbilical cord plasma of 43 healthy full-term newborns. The method consisted of a combined thin-layer chromatographic-ftuorimetric procedure which proved to be specific and reliable. The mean concentration in cord plasma of Cortisol was 10.6±4.9 μ.g/100 ml, of corticosterone 1.8±0.8 μg/100 ml. The mean ratio cortisol/corticosterone F/B was 6.3±2.5. Neither the duration nor the time of day of delivery appeared to influence the concentration of Cortisol or corticosterone in umbilical cord plasma. Also, there was no significant difference between male and female infants. In 18 instances of a pathological course of gestation and/or delivery the mean Cortisol level was 9.1±4.7 μg/ml, the mean corticosterone level 2.2±9 μg/100 ml. The mean F/B ratio was slightly but not significantly decreased (4.2±1.4 μg/100 ml; p>0.05). It is speculated that the high corticosterone concentration in umbilical cord plasma reflects a defect in Cortisol biosynthesis (17-hydroxylase deficiency) in the newborn, compared with later life.
Acta Paediatrica 01/2008; 64(4):587 - 591. · 2.07 Impact Factor
ABSTRACT: Leydig cell hypoplasia is a rare autosomal recessive condition that interferes with normal development of male external genitalia in 46,XY individuals. We have studied a family with a 46,XY girl due to a new homozygous mutation (V144F) in the extracellular ligand-binding domain. HEK 293 cells transfected with the mutant LH receptor exhibited a marked impairment of human chorionic gonadotropin binding. Using Western blotting of the expressed V144F mutant LH receptor protein showed the absence of the glycosylated cell surface form. Treatment of the mutant LH receptor with N-glycosidase F or endoglycosidase-H demonstrated that the mutant receptor is retained in the endoplasmic reticulum. Expression and study of enhanced green fluorescent protein-tagged receptors confirmed that the mutant LHR-V144F receptors do not migrate to the cell surface, and the fluorescence remains intracellular and colocalizes with an endoplasmic reticulum marker, ER-tracker Blue-white DPX. Comparison of the theoretical molecular models of the extracellular domain of the wild-type and the mutant receptor suggests that the mutation LHR-V144F, located in the outer circumference in a alpha-helix of the leucine-rich repeat 4, may induce a conformational strain on the molecule. F144 of the mutant LH receptor has overlapping interactions with F119, which V144 in the wild-type receptor has not.
Journal of Clinical Endocrinology & Metabolism 11/2004; 89(10):5161-7. · 6.50 Impact Factor
ABSTRACT: ACTH stimulation test is widely used as a basic diagnostic method for non-classical congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD). However, the interpretation of this test has not been definitely established. To determine the cut-off values of basal and post-ACTH serum 17-OHP concentrations, data of patients with suspected 21-OHD has been analysed.
Two hundred and eighty-seven patients with postnatal/peripubertal virilization were investigated. Serum steroid concentrations were measured by RIA, urinary steroid profile was determined by capillary gas chromatography and mutation analysis of CYP21 gene was performed by allele specific PCR. 21-OHD was diagnosed by elevated serum 17-OHP concentrations, high level of the urinary 17-OHP metabolites and/or homozygosity for CYP21 mutations.
Twenty-one patients of the total of 287 subjects (7.3 %) were identified as having 21-OHD. The numbers of 21-OHD patients compared to total numbers of patients with different ranges of serum 17-OHP were as follows: basal values below 3.5 ng/ml (mean + 1 SD) 0/225; between 3.5 - 6.6 ng/ml 3/41; above 6.6 ng/ml (mean + 2 SD) 18/21. Post-ACTH values below 6.4 ng/ml (mean + 1 SD) 0/226, between 6.4 - 10.3 ng/ml 0/35, above 10.3 ng/ml (mean + 2 SD) 21/26.
There are patients with inappropriate peripubertal virilization who have slightly elevated 17-OHP concentrations. In this subgroup of patients more sensitive and specific methods are needed to establish the diagnosis of 21-OHD. Therefore we suggest performing an ACTH stimulation test in patients with a morning 17-OHP level above 3.5 ng/ml. Furthermore, urinary steroid profile and/or CYP21 gene analysis are needed in patients with a stimulated 17-OHP value between 10 and 30 ng/ml. These tests will distinguish between patients with non-classical 21-OHD and patients with other disorders.
Experimental and Clinical Endocrinology & Diabetes 03/2003; 111(1):27-32. · 1.69 Impact Factor
ABSTRACT: Hintergrund. Der aufwändige hyperinsulinämische euglykämische Clamp ist der Goldstandard zur Bestimmung der Insulinwirkung. Einfachere
Methoden zur Berechnung von Insulinresistenz (HOMA) und Insulinsensitivität (ISI) stehen bei Erwachsenen zur Verfügung. HOMA
und ISI wurden bei Kindern und Jugendlichen gemessen und Assoziationen zu BMI und Blutdruck bestimmt.
Patienten. 59 Kinder und Jugendliche wurden in 3 Gruppen eingeteilt: Kontrollgruppe: 23 Patienten, Alter: 9,8–17,8 Jahre; Ullrich-Turner-Syndrom:
14 Patientinnen: Alter: 5,6–19,0 Jahre; Adipositasgruppe: 22 Patienten, Alter: 9,8–17,8 Jahre.
Ergebnisse. Bei 1 Patientin betrug der Variationskoeffizient innerhalb von 4 Jahren für HOMA 30% und für ISI 26%. HOMA nahm von der Kontroll-
über die Ullrich-Turner-Syndrom- zur Adipositasgruppe zu und ISI ab. Der Zusammenhang zwischen HOMA und ISI entsprach einer
hyperbolen Funktion (R=0,88). HOMA war positiv und ISI negativ mit dem BMI und dem Blutdruck assoziiert.
Schlussfolgerung. HOMA und ISI sind möglicherweise auch bei Kindern und Jugendlichen zur Bestimmung der Insulinwirkung geeignet.
Background. The hyperinsulinimic euglycemic clamp is the gold standard to determine insulin action. In adults simpler methods to define
insulin resistance (HOMA) and -sensitivity (ISI) are available. In children/adolescents HOMA and ISI were evaluated and correlated
with BMI and blood pressure.
Patients. 59 children/adolescents of comparable age were divided into a control group: 23 patients, the Ullrich-Turner group: 14 girls,
the obese group: 22 patients.
Results. HOMA increased from controls to obesity, while ISI decreased. The association between HOMA and ISI was hyperbolic with R=0.88.
The correlation between HOMA and BMI and blood presure was positive and negative for ISI. In one patient the coefficient of
variation for HOMA was 30% and 26% for ISI.
Conclusion. It appears that in children and adolescents HOMA and ISI may be suitable methods to determine insulin action.
Monatsschrift Kinderheilkunde 01/2002; 150(9):1095-1100. · 0.27 Impact Factor
ABSTRACT: The aim of the study was to evaluate the hormonal (focusing on the urinary steroid profile) and clinical effects of chronic gonadotropin-releasing hormone (GnRH) agonist treatment in patients with polycystic ovary syndrome (PCOS) suffering from hirsutism. A long-acting GnRH agonist was administered for 6 months in eight PCOS patients. Hormonal effects were measured by determining serum luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin, testosterone and estradiol concentrations, and by profiling urinary steroids using capillary gas chromatography of 24-hour urine samples. To evaluate 5 alpha-reductase enzyme activity, the ratios of androsterone to etiocholanolone and 5 alpha-tetrahydrocortisol to tetrahydrocortisol were calculated in urine samples. The ratio of androgen to cortisol metabolites was also determined before, and 3 and 6 months after therapy. LH and estradiol levels were suppressed significantly after the first injection and testosterone after the second injection of the GnRH agonist. Thus, serum testosterone was normalized. Ratios of urinary steroids reflecting 5 alpha-reductase enzyme activity (androsterone to etiocholanolone and 5 alpha-tetrahydrocortisol to tetrahydrocortisol) and the ratio of androgen to cortisol metabolites decreased significantly after 3 months of treatment. Degree of hirsutism, assessed by Ferriman-Gallwey score, diminished after 6 months, but not significantly. In conclusion, our data show that long-acting GnRH agonist treatment of PCOS patients is effective in reducing serum and urinary androgen levels, but it is not accompanied by an effective reduction in hirsutism during a 6-month treatment period. A longer or a combined treatment would be needed to achieve significant improvement in hirsutism. Gas chromatographic profiling of urinary steroids and the use of specific ratios of the excreted metabolites seems to be a sensitive tool both in the diagnosis of PCOS and in monitoring ovarian suppression.
Gynecological Endocrinology 11/2000; 14(5):337-41. · 1.58 Impact Factor
ABSTRACT: We aimed at measuring the first plasma concentrations of 17-hydroxyprogesterone (17OH-P) determined by benchtop isotope dilution/gas chromatography-mass spectrometry (ID/GC-MS) in term neonates with or without 21-hydroxylase deficiency. Plasma samples from normal cord blood specimens (n=30), unaffected neonates (n=38) and neonatal patients with classical 21-hydroxylase deficiency (eight salt-wasters, three simple virilizers) were analyzed. Steroid profiling of random urinary specimens by GC-MS served as a confirmatory test for 21-hydroxylase deficiency. 17OH-P (nmol/l) in cord blood plasma lay between 11.66 and 75.92 (median 24.74). It declined shortly after birth. In the first 8 days of life, the time that screening for 21-hydroxylase deficiency is performed, 17OH-P ranged between undetected levels and an upper limit of 22.87 (median 4.11). Thereafter (days 9-28) its concentrations lay between 2.18 and 20.30 (median 6.22). Except one simple virilizer, all other patients with 21-hydroxylase deficiency had clearly elevated plasma 17OH-P at the time that screening for 21-hydroxylase deficiency would be performed. We suggest ID/GC-MS, which provides the highest specificity in steroid analysis, for checking suspicious concentrations of 17OH-P in neonates and underscore the potential of urinary steroid profiling by GC-MS as a rapid, non-invasive and non-selective confirmatory test for congenital adrenal hyperplasia.
Journal of Endocrinology 07/2000; 165(3):679-83. · 3.55 Impact Factor
ABSTRACT: To compare the value of blood-spot 17-hydroxyprogesterone (17-OHP) daily profiles and urinary steroid excretion in untreated and treated patients with congenital adrenal hyperplasia (CAH).
Ten patients with CAH were investigated during steroid replacement therapy (Group 1), and 11 patients were investigated without treatment (Group 2).
Capillary blood samples were collected for measurement of blood-spot 17-OHP values by non-chromatographic radioimmunoassay. Steroid profiles of 24-h urine samples were analyzed by gas chromatography.
There was a close correlation between the individual daily means of blood-spot 17-OHP measurements and the pregnanetriol/ tetrahydrocortisone ratio in both groups of patients (Group 2: r=0.839, p<0.001; Group 1: r=0.686, p<0.001). Almost the same correlation was found between the blood-spot 17-OHP value and the sum of three 17-hydroxyprogesterone metabolites/the sum of three cortisol/cortisone metabolites ratio (Group 2: r=0.918, p<0.001; Group 1: r=0.741, p<0.001).
Blood-spot 17-OHP measurements and 24-h urinary steroid profile have the same impact in identification and monitoring therapy of children with CAH.
Journal of pediatric endocrinology & metabolism: JPEM 02/2000; 13(2):205-10. · 0.88 Impact Factor
ABSTRACT: Using routine stable isotope dilution/gas chromatography-mass spectrometry, 17-hydroxyprogesterone, androstenedione, testosterone, dehydroepiandrosterone, androstanediol, and 5alpha-dihydrotestosterone have been profiled in amniotic fluid of midgestation in 77 normal fetuses and 38 untreated or dexamethasone-treated fetuses at risk for 21-hydroxylase deficiency. Dexamethasone was suspended 5-7 days before amniocentesis. In normal fetuses, amniotic fluid concentrations (median, range; nanograms per mL) of 17-hydroxyprogesterone did not reveal a sex difference (1.48, 0.21-4.96), whereas those of androstenedione were lower in females (0.53, 0.00-2.71) than in males (0.93, 0.29-1.98). Testosterone levels were higher in males (0.24, 0.00-0.50) than in females (0.00, 0.00-0.27). No sex difference was found for dehydroepiandrosterone (0.47, 0.19-1.77). Levels of androstanediol and 5alpha-dihydrotestosterone were below the detection limit of our method in most cases. Regarding prenatal diagnosis of 21-hydroxylase deficiency, 17-hydroxyprogesterone and androstenedione presented the diagnostically most valuable steroids and were of equal diagnostic potential. They permitted successful diagnosis in 36 of 37 fetuses at risk: 12 were untreated and unaffected, 13 were treated and unaffected, 4 were untreated and affected (3 salt wasters and 1 simple virilizer), and 8 were treated and affected (5 salt wasters and 3 simple virilizers). In the latter group, one simple virilizer revealed normal steroid concentrations. Isotope dilution/gas chromatography-mass spectrometry, providing the highest specificity in steroid analysis, is proposed for routine use in clinical steroid analysis whenever maximal reliability is requested. Our study provides the first mass spectrometric reference data on amniotic fluid steroid concentrations and underscores the high accuracy of prenatal hormonal diagnosis of 21-hydroxylase deficiency.
Journal of Clinical Endocrinology & Metabolism 09/1999; 84(8):2724-8. · 6.50 Impact Factor
ABSTRACT: Excess secretion of growth hormone is a rare diagnosis in children or adolescents with tall stature. An oral glucose tolerance test (OGT) with determination of growth hormone is generally recommended to exclude this disorder. In order to test the validity of this approach in pediatric subjects, OGT tests were performed in 126 tall subjects (age: 12.4 +/- 1.8 years; height: 3.1 +/- 0.8 SDS). Nonsuppression was present in 39 subjects, however, anthropometric analysis and follow-up excluded the diagnosis of eosinophilic pituitary adenoma in all patients. The lowest GH concentration was reached 90 min after ingestion of oral glucose, GH rose above baseline at 180 min. Plasma concentrations of glucose and insulin did not differ between suppressors and nonsuppressors. In conclusion, absent suppression of growth hormone by oral glucose is common in tall children and adolescents. The test is therefore not recommended as a general screening for excess growth hormone. Prolonging the test beyond 120 min does not increase the diagnostic value.
Hormone Research 02/1999; 51(1):20-4. · 2.48 Impact Factor
ABSTRACT: Type 1 diabetes is often associated with additional autoimmune phenomena. However, data reported on the frequency of thyroid autoimmunity differ vastly. Therefore, the prevalence of thyroid autoantibodies was evaluated at a large pediatric diabetes center in Southern Germany. 2,305 determinations (TPO and TG, ELISA) were performed in 495 patients with type 1 diabetes (234 boys, 261 girls; age at last measurement: 15.4 +/- 0.3 years, duration of diabetes 7. 5 +/- 0.2 years). The prevalence of elevated thyroid antibodies increased dramatically with age: from 3.7% in patients less than 5 years of age up to 25.3% in the age group 15-20 years (p < 0.0001). For children older than 10 years, girls were significantly more affected than boys (p < 0.0001). Thyroid autoimmunity tended to be more prevalent in the subgroup of patients with the HLA type DR3/DR4 compared to patients with other HLA types (p = 0.08). In children older than 10 years, basal TSH concentrations were significantly elevated in antibody-positive patients (p < 0.05). In conclusion, thyroid autoimmunity is prevalent in children and adolescents with type 1 diabetes. Adolescent girls and young women are especially affected. Yearly routine determinations of thyroid antibodies are therefore recommended.
Hormone Research 02/1999; 52(3):113-8. · 2.48 Impact Factor
ABSTRACT: A two-year-old girl presented with clitoromegaly and an abdominal mass. Diagnostic procedures including sonography, computerized tomography, scintigraphy and measurement of catecholamines in urine excluded neuroblastoma, but suspected Wilms-tumor. Before completing the steroid measurements therapy was initiated according to Wilms-tumor (preoperative cytostatic therapy followed by surgical removal of the tumor). Morphology of the tumor, the serum and urinary steroid profile proved a benign adrenocortical adenoma producing mainly delta 5-steroids including the weak androgen, dehydroepiandrosterone.
Orvosi Hetilap 10/1997; 138(37):2357-62.
ABSTRACT: Fragestellung: Das gehäufte Auftreten eines Diabetes bei Wachstumshormonüberproduktion (Akromegalie, hypophysärer Gigantismus)
ist lange bekannt. Methode: Im oralen Glukosetoleranztest (OGT) wurden Blutzucker und Insulin alle 30 min bestimmt. Zwei
Patientengruppen wurden untersucht: 9 Patienten mit komplettem oder partiellem STH-Mangel (Alter bei Therapiebeginn 9,1 ±
1,0 Jahre) sowie 11 Mädchen mit Ullrich-Turner-Syndrom (10,8 ± 0,9 Jahre). Ergebnisse: Bei den STH-Mangelpatienten zeigte
sich unter einer wöchentlichen STH-Dosis von 12,8 ± 0,9 E/m2 (Mittelwert ± SEM) kein Anstieg des Blutzuckers, die Glukosetoleranz war stets normal. Dagegen stieg die integrierte Insulinsekretion
während des OGT-Tests von 3,7 ± 0,8 U/l und min vor der Therapie auf 5,9 ± 0,6 nach 1 Jahr an (p < 0,005; Wilcoxon). Ullrich-Turner-Patientinnen erhielten eine deutlich höhere STH-Dosis (im Mittel 22,4 ± 2,0 E/m2 und Woche). Nach 1 Jahr STH-Therapie zeigte sich ein vermehrter Anstieg des Blutzuckers 30 min nach oraler Glukosegabe (167
± 6 mg/dl versus 147 ± 7 vor STH-Therapie; p = 0,05), ein Mädchen entwickelte eine gestörte Glukosetoleranz. Die Insulinsekretion stieg auf mehr als das Doppelte an (Integral:
4,1 ± 0,3 U/l und min vor Therapie, 9,5 ± 1,4 nach 1 Jahr STH-Gabe; p < 0,001). Schlußfolgerungen: Eine STH-Therapie für 1 Jahr erhöht die Insulinsekretion im OGT-Test um 59 % bei Patienten
mit STH-Mangel und um 131 % bei Ullrich-Turner-Syndrom. Langfristige Auswirkungen des Hyperinsulinismus (Hypertonie, kardiovaskuläres
Risiko) sollten in prospektiven Studien verfolgt werden.
Background: An increased incidence of diabetes mellitus in patients with hypersecretion of growth hormone (acromegaly, pituitary gigantism)
is well known. In the present study, the effect of long-term growth hormone (GH) therapy on basal as well as stimulated blood
glucose and insulin concentrations was studied in pediatric patients.
Methods: During an oral glucose tolerance test, plasma glucose and insulin were measured every 30 minutes. 2 groups of patients were
studied before and during GH therapy: 9 patients with complete or partial GH deficiency (mean age at initiation of therapy:
9.1 ± 1.0 years) as well as 11 girls with Turner syndrome (mean age: 10.8 ± 0.9 years).
Results: A weekly dose of growth hormone of 12.8 ± 0.9 units/m2 did not increase blood glucose in patients with GH deficiency, all patients displayed normal glucose tolerance. In contrast,
the integrated secretion of insulin during the OGT-test increased from 3.7 ± 0.8 U/l × min before therapy to 5.9 ± 0.6 after
1 year (p < 0.005; Wilcoxon). Hyperinsulinism was still present after 2 years of GH therapy (n = 7). In Ullrich-Turner patients,
a significantly higher dose of growth hormone was used (mean: 22.4 ± 2.0 Units/m2× week). After 1 year of GH therapy, blood glucose 30 min after the ingestion of oral glucose had increased to 167 ± 6 mg/dl
compared to 147 ± 7 mg/dl before GH administration (p = 0.05). One girl developed impaired glucose tolerance. Insulin secretion
rose by more than 100 % (AUC for insulin before therapy: 4.1 ± 0.3 U/l × min, after 1 year of therapy: 9.5 ± 1.4). In 8 Ullrich-Turner
girls, the OGT-test was repeated again after 3 years of GH therapy, insulin secretion continued to be clearly elevated (AUC:
10.8 ± 2.1 U/l × min).
Conclusions: GH therapy for 1 year increases insulin release during the OGT-test by 59 % in patients with GH deficiency and by 131 % in
Ullrich-Turner syndrome. This difference may be due to a higher dose, or due to a specific tendency for insulin resistance
in girls with gonadal dysgenesis. The long-term consequences of hyperinsulinism (hypertension, cardiovascular risk) cannot
be predicted in these patients and should be followed in prospective studies.
Monatsschrift Kinderheilkunde 05/1997; 145(3):249-254. · 0.27 Impact Factor
ABSTRACT: Hintergrund: Ob die Endmetaboliten des peripheren Androgenstoffwechsels, 5 α-Androstan-3 α, 17 β-diol und 5 α-Androstan-3
α, 17 β-diol-glukuronid, biochemische Marker bei Hirsutismus darstellen, wird kontrovers diskutiert. Über die Plasmakonzentrationen
beider Parameter gibt es ferner erhebliche Diskrepanzen bei den in der Literatur berichteten Werten. Methode: Unter Einsatz
von Isotopenverdünnungs-Gaschromatographie-Massenspektrometrie, dem Verfahren mit der höchsten Spezifität in der Steroidanalytik,
untersuchten wir gesunde Mädchen und Frauen sowie Patientinnen mit Hirsutismus unterschiedlicher Ätiologie. Ergebnisse: Bei
hirsuten Patientinnen streuten beide Parameter stark. Bei Patientinnen mit adrenalen androgenisierenden Enzymdefekten (3 β-Hydroxysteroiddehydrogenasemangel,
21-Hydroxylasemangel) waren sowohl Androstandiol als auch Androstandiolglukuronid erhöht. Hirsute Patientinnen mit Hyperandrogenämie
ohne adrenalen Enzymdefekt wiesen in 33 % normales Androstandiol und in 24 % normales Androstandiolglukuronid auf. Patientinnen
mit idiopathischem Hirsutismus hatten in 54 % Androstandiol- und in 30 % Androstandiolglukuronidkonzentrationen innerhalb
des Streubereichs gesunder Mädchen und Frauen. Schlußfolgerungen: Unsere Ergebnisse zeigen, daß weder Androstandiol noch
Androstandiolglukuronid in allen Fällen von Hirsutismus erhöht sind und daß beide Parameter nicht zwischen unterschiedlichen
Formen des Hirsutismus diskriminieren.
Background: It is still controversial, whether the end metabolites of peripheral androgen metabolism, 5 α-androstane-3 α, 17 β-diol and
5 α-androstane-3 α, 17 β-diol glucuronide, represent biochemical markers of hirsutism. Furthermore, discrepant plasma concentrations
have been reported in the literature. Method: Using stable isotope dilution/gas chromatography-mass spectrometry, the most specific method in steroid analysis, we investigated
healthy females and patients with hirsutism of various etiology. Results: Generally, both androstanediol and androstanediol-glucuronide scattered much in hirsute patients. Patients with adrenal enzyme
defects (3 β-hydroxysteroid-dehydrogenasedeficiency, 21-hydroxylase-deficiency) had elevated androstanediol and androstanediol-glucuronide.
Hirsute Patients with hyperandrogenaemia but without adrenal enzyme deficiencies had normal androstanediol in 33 % and normal
androstanediol-glucuronide in 24 % of cases. 54 % of patients with idiopathic hirsutism had normal androstanediol and 24 %
had normal androstanediol-glucuronide. Conclusion: Our results show, that neither androstanediol nor androstanediol-glucuronide are consistently elevated in hirsutism and that
both do not discriminate between the various causes of hirsutism.
Monatsschrift Kinderheilkunde 04/1997; 145(1):37-43. · 0.27 Impact Factor
ABSTRACT: Das Syndrom der persistierenden Müller-Strukturen (SPMS) ist definiert durch den Nachweis von Müller-Strukturen (Tuben, Uterus,
proximale Vagina) bei Patienten mit vollständig männlich differenziertem äußeren Genitale und normalem, männlichen Chromosomensatz.
Bei typischer Klinik – gleichzeitiges Vorliegen von Leistenhernie und kontralateralem Kryptorchismus – sollte daher eine gründliche
sonographische Untersuchung des Abdomens erfolgen. Wir berichten über 3 Patienten, bei denen im Rahmen einer Herniotomie oder
Kryptorchismusoperation Müller-Strukturen gefunden wurden. Bei einem der Patienten erfolgte die Resektion der Müller-Strukturen.
Die histologische Untersuchung zeigte, daß die Vasa deferentia unmittelbar lateral des Uterus verliefen und ebenfalls mitreseziert
wurden. Bei den anderen Patienten unterblieb die Entfernung der Müller-Strukturen. Als Hinweis auf eine Degeneration testikulären
Gewebes fanden wir bei 2 Patienten, deren Gonaden im Alter von 7 bzw. 13 Monaten biopsiert wurden, um ca. 50 % reduzierte
Spermatogonienzahlen. Diskussion: Die Therapie des SPMS besteht in der frühzeitigen, beidseitigen Orchidopexie, um eine möglichst
unbeeinträchtigte endokrine und generative Hodenfunktion zu gewährleisten und einer malignen Entartung vorzubeugen. Die Integrität
der Vasa deferentia sollte bei der Operation nicht gefährdet werden.
The persistent Müllerian duct syndrome is characterized by the presence of uterus, tubes and proximal vagina in patients with
normally virilized genitalia and a 46,XY karyotype. The clinically typical constellation of inguinal hernia and contralateral
cryptorchidism should therefore lead to a thorough sonographic evaluation of the abdomen. We report on 3 patients in whom
the abnormalities were discovered during surgery for inguinal hernia or cryptorchidism. One patient underwent resection of
the Müllerian structures. Histological examination showed resection of both vasa deferentia, which ran parallel to and within
the lateral walls of the uterus. The gonadal biopsies of two patients evidenced degeneration of testicular tissue by showing
a fifty percent reduction of spermatogonias. Discussion: Therapy of this syndrome consists in early bilateral orchidopexia, aiming at preservation of endocrine and reproductive testicular
function and prevention of malignant degeneration. The integrity of the vasa deferentia should not be endangered during surgery.
Monatsschrift Kinderheilkunde 04/1997; 145(3):230-234. · 0.27 Impact Factor
ABSTRACT: In 5-7% of all cases of congenital adrenogenital hyperplasia (AGH) there is 11 beta-hydroxylase deficiency (11 beta-HM). Its clinical picture is characterised by hyperandrogenism and, in some cases, arterial hypertension. The diagnosis of the enzyme deficiency depends on a reliable method of analysing the hormone in plasma and urine. As little is known and data often contradictory about the pattern of urinary steroid excretion in 11 beta-HM, these steroid metabolites were measured by a highly specific method.
The pattern of urinary excretion of steroids was determined by gas chromatography and mass spectrometry (GC/MS) in 16 children and adults (11 males, 5 females: mean age 9(8)/12 [2/12-20(3)/12] years) with 11 beta-HM.
In all patients there was greatly increased excretion of tetrahydrated (TH) and hexahydrated (HH) metabolites of 11-desoxycortisol (S) and desoxycorticosterone (DOC). The excretion of THS and THDOC was extremely increased in all patients. The metabolites 5 alpha-THS as well as 20 alpha- and 20 beta-isomers of HHS, not normal found in healthy persons, were present in 15 patients (94%), while the 20 alpha- and 20 beta-isomers of 5 alpha-HHS were demonstrated in 14 (88%). For the first time, 20 alpha- and 20 beta-isomers of 5 alpha-HHS were shown to be typical urinary steroid metabolites in 11-HM. The excretion of cortisol metabolites is typically decreased in 11 beta-HM. No corticosterone metabolites were found.
The urinary steroid excretion pattern, measured by GC/MS, is a noninvasive, highly specific and nonselective method in the differential diagnosis of abnormal steroid metabolism.
DMW - Deutsche Medizinische Wochenschrift 02/1997; 122(1-2):3-10; discussion 11. · 0.53 Impact Factor
ABSTRACT: Deficiency of the 17 beta-hydroxysteroid dehydrogenase (17b-HSD-d) causes female external genital phenotype in spite of 46,XY karyotype and presence of testes due to disorder in biosynthesis of testosterone. However, marked somatic and genital virilization occurs during puberty. Clinical and laboratory investigation of three cases are presented with typical elevation of the precursor steroid androstenedione, and decrease of product steroid testosterone. All the three patients were reared as girls. During puberty orchidectomy was performed in two cases and vaginoplasty in one case. Estrogen replacement therapy contributed to development of female secondary sex characteristics.
Orvosi Hetilap 05/1996; 137(15):807-10.
ABSTRACT: We investigated the developmental patterns of 5 alpha-androstane-3 alpha, 17 beta-diol (AD) and 5 alpha-androstane-3 alpha, 17 beta-diol-glucuronide (ADG) in plasma of normal children and adults of both sexes and in patients with idiopathic hirsutism using a physicochemical method: high-resolution gas chromatography/mass spectrometry (HRGC/MS). In children below the age of 11 years, AD and ADG increased with age showing no differences between sexes (mean +/- SD, nmol/l): normal subjects 3-6 years: AD in females 0.08 +/- 0.03, in males 0.07 +/- 0.03; ADG in females 0.15 +/- 0.05, in males 0.14 +/- 0.04; normal subjects 7-10 years; AD in females 0.17 +/- 0.03, in males 0.17 +/- 0.07; ADG in females 0.59 +/- 0.12, in males 0.47 +/- 0.14. Thereafter, AD and ADG showed a greater increase in males (normal subjects 11-15 years: AD in females 0.24 +/- 0.06, in males 0.41 +/- 0.14; ADG in females 1.47 +/- 0.36, in males 3.36 +/- 1.22). In adults, plasma levels did not overlap between females and males (AD in females 0.24 +/- 0.07, in males 0.99 +/- 0.31; ADG in females 2.32 +/- 0.68, in males 13.01 +/- 3.05). 5 alpha-Androstane-3 alpha, 17 beta-diol-glucuronide discriminated better between sexes than AD. In idiopathic hirsutism, mean plasma concentrations of AD and ADG were higher than those of healthy females (ages 11-15 years: AD 0.31 +/- 0.10, ADG 3.48 +/- 2.00; ages > 16 years: AD 0.44 +/- 0.27, ADG 6.46 +/- 3.11), but 54% of patients had normal plasma concentrations of AD and 29% had normal ADG values. Thus, ADG reflected androgenicity better than AD. However, both metabolites were imperfect markers of androgenicity in idiopathic hirsutism. Therefore, our findings do not support the concept of increased 5 alpha-reductase activity in all patients with idiopathic hirsutism.
European Journal of Endocrinology 01/1996; 134(1):87-92. · 3.42 Impact Factor
ABSTRACT: Using stable isotope dilution/gas chromatography-mass spectrometry (ID/GC-MS), a physicochemical method, we have profiled the plasma steroids 17 alpha-hydroxyprogesterone, 4-androstenedione, and testosterone in normal children of various age groups. Comparison of our values with those obtained by direct immunologic assays and those using an extraction or purification step showed that immunoassays in general overestimate steroid concentrations. This was especially true for plasma samples in the neonatal period and was most expressed for the concentrations of 17 alpha-hydroxyprogesterone. Our study demonstrated the applicability of ID/GC-MS to routine clinical steroid analysis. The application of ID/GC-MS is recommended whenever problems from matrix effects or cross-reactivity are likely to arise or suspicious results by immunoassays need to be rechecked.
Pediatric Research 08/1995; 38(1):76-80. · 2.70 Impact Factor
ABSTRACT: To obtain data on the correlation of serum and urinary steroids in nonclassical 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency, 9 girls with precocious pubarche and 33 adolescent girls with mild to severe hirsutism were studied. Urinary steroid profiles were analyzed by capillary gas chromatography. Serum 17-OH-pregnenolone (17-OHPreg) and 17-OH-progesterone (17-OHP) were determined by RIA after column-chromatographic separation. One out of 9 girls with precocious pubarche and 4/33 girls with hirsutism had elevated ratios of 17-OHPreg to 17-OHP after ACTH stimulation in serum and elevated urinary excretion of 5-ene steroids under basal conditions. These patients were defined to have decreased adrenal 3 beta-HSD activity. Basal and ACTH-stimulated serum 17-OHPreg levels in patients with mild 3 beta-HSD deficiency overlapped those of healthy controls and peripubertally virilized female patients without enzyme deficiency. Post-ACTH 17-OHPreg/17-OHP ratios in serum discriminated patients with and without 3 beta-HSD deficiency using a cutoff value of 13 instead of mean + 2 SD for age-related control values (6.7 and 11.6 for girls with Tanner stage II-III and IV-V, respectively). Sums of urinary 5-ene steroids in patients with 3 beta-HSD deficiency overlapped those in patients without enzyme deficiency. Results showed that an abnormal post-ACTH serum 17-OHPreg/17-OHP ratio may not be associated with elevated urinary 5-ene steroid excretion, and vica versa. In conclusion, patients with simultaneous elevation of post-ACTH serum 17-OHPreg/17-OHP ratio and basal urinary 5-ene steroid excretion are supposed to have mild 3 beta-HSD deficiency.
Hormone Research 02/1995; 44(3):133-41. · 2.48 Impact Factor
ABSTRACT: A capillary gas chromatographic-mass spectrometric method for the determination of dehydroepiandrosterone sulfate (DHEA-S) in human plasma is described. [7,7-2H2]DHEA-S is used as internal standard. After desulfation by methanolysis, heptafluorobutyryl derivatives are prepared, and selected ion monitoring of characteristic fragment ions--m/z 270 for DHEA and m/z 272 for [7,7-2H2]DHEA--carried out. Requiring small amounts of plasma, the rapid, convenient work-up and the application of bench-top GC/MS instrumentation proved our method to be suited for routine clinical use in adults and children. The method needs no complex corrections for isotope contributions and provides good accuracy and precision. Comparative values of samples assayed by our GC/MS procedure and by a direct RIA indicated that the RIA overestimates the true concentration.
Hormone Research 02/1993; 39(5-6):235-40. · 2.48 Impact Factor