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Biomedical subjects

D Knorr

Publications and source records attributed to D Knorr.

At least 73 records · Page 4Linked to original sources
PubMed1985

Different gene defects in the salt-wasting (SW), simple virilizing (SV), and nonclassical (NC) types of congenital adrenal hyperplasia (CAH).

HLA (human leucocyte antigens) alleles and plasma 17-hydroxyprogesterone levels after ACTH stimulation were studied in 134 German families of patients with salt-wasting (SW), simple virilizing (SV), and nonclassical (NC) late-onset forms of CAH. HLA typing revealed a genetic difference between the two classical disease forms. SW-CAH was strongly associated with Bw47 and SV-CAH was closely linked to B5. The nearly complete connection of NC-CAH with B14 was confirmed. Bw47 and B14 were mostly components of the normally rare haplotypes A3, Bw47, DR7 and Aw33, B14, DR1, respectively. They did not occur in the families' disease-unaffected haplotypes. The HLA linkage data were consistent with those obtained from the ACTH stimulation test which showed a higher 17-hydroxyprogesterone increase in the group of genetically defined heterozygous relatives of SW patients than in the groups of heterozygous members of SV and NC families.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Genetic differences between the salt-wasting, simple virilizing, and nonclassical types of congenital adrenal hyperplasia.

Human leukocyte antigen (HLA) alleles and plasma 17-hydroxyprogesterone levels after ACTH stimulation were studied in 134 German families of patients with the salt-wasting (SW), simple virilizing (SV), or nonclassical (NC) late-onset form of congenital adrenal hyperplasia (CAH). Unexpected hormonal evidence for CAH was found in 6 otherwise healthy members of the relatives' group, who, therefore, were considered to be NC cryptic cases. HLA typing revealed a genetic difference between the 2 classical disease forms; SW CAH was strongly associated with Bw47, whereas SV CAH was closely linked to B5(w51). It also confirmed the nearly complete connection of NC CAH with B14. These alleles, especially Bw47 and B14, are mostly components of normally rare haplotypes: A3,Bw47,DR7 and Aw33,B14,DR1, respectively. They do not occur in the families' disease-unaffected haplotypes. Thus, it may be that all or almost all individuals from the general population bearing 1 of them are in fact CAH heterozygotes. Moreover, it seems possible to predict the severity of an infant's disease from his genomic type. The HLA linkage data were consistent with those obtained from ACTH testing, which showed significantly higher 17-hydroxyprogesterone increases in the genetically defined heterozygous relatives of SW patients than in the respective members of SV families. Of the families, 2 were also informative for mapping of the CAH disease gene(s) within the HLA-B to Glo interval.

17-alpha-Hydroxyprogesterone↗
PubMed1985

Effect of iodide treatment on iodine concentration and volume of endemic non-toxic goitre in childhood.

In a total of 195 children and adolescents of both sex (mean age 12.9, range 5-17 years) with endemic non-toxic goitre the thyroidal iodine concentration (IC) was determined using X-ray fluorescent scanning on admission and during iodine (100 micrograms daily) and L-thyroxine (3 micrograms/kg body weight daily) treatment respectively. Additionally the thyroid volume was measured sonographically in a longitudinal study including 46 patients before and after 4-8 months of iodine supplementation (100 micrograms daily). The IC was 305 +/- 144 micrograms/g. It compared well with that of adult goitre patients (288 +/- 109 micrograms/g) and was significantly inferior to the value of normal controls (389 +/- 170 micrograms/g). Under L-thyroxine therapy the IC further decreased (243 +/- 144 micrograms/g), whereas patients receiving iodide showed an increase of the IC (570 +/- 197 micrograms/g). The mean TSH level fell from 2.3 +/- 0.9 microU/ml to 1.4 +/- 0.6 microU/ml. The average T4/TBG (thyroxine binding globulin) ratio showed a slight increase which, however, was not significant. The mean goitre volume decreased by 40%. It was evidenced that iodide is useful not only in the prophylaxis of non-toxic goitre but also as a more physiologic treatment than thyroid hormones, at least for young subjects with simple diffuse goitres.

Adolescent↗
PubMed1984

Etomidate: a selective adrenocortical 11 beta-hydroxylase inhibitor.

To investigate the adrenocortical suppression caused by the anesthetic etomidate, plasma levels of progesterone (P), 17-hydroxyprogesterone (17-OHP), 11-deoxycorticosterone (DOC), corticosterone (B), aldosterone (Aldo), 11-deoxycortisol (S), cortisol (F), and cortisone (E) were measured simultaneously before and after a short-term ACTH stimulation test in a 6.5-year-old boy whose convulsions could be kept under control only with constant etomidate infusions. During etomidate therapy, plasma levels of DOC and S were extremely elevated, the progestins P and 17-OHP were slightly elevated, whereas B and Aldo were in the lower normal range, and F and E were markedly decreased. A short-term ACTH stimulation test during etomidate infusion gave a blunted response of B, Aldo, F and E, whereas the level of DOC remained high and S even further increased. P and 17-OHP showed a positive response to ACTH. The ratios of B/DOC and F/S, which reflect adrenocortical 11 beta-hydroxylase activity, were extremely decreased during etomidate and did not change after ACTH stimulation. In contrast, the ratios of DOC/P and S/17-OHP, which reflect 21-hydroxylase activity, were elevated and remained elevated after ACTH stimulation. After discontinuation of etomidate therapy, all the baseline steroid levels were somewhat elevated, but responded normally to ACTH. These results demonstrate that etomidate causes a specific and reversible blockade of the 11 beta-hydroxylation of adrenal steroid synthesis.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Virilization without adrenal hyperplasia in 21-hydroxylase deficiency during fetal life.

The characteristic excess production of androgens in the cortisol 21-hydroxylase defect is generally considered to be secondary to ACTH stimulation of alternate pathways. Whenever a morphological examination of the adrenals has been possible in this disorder, adrenocortical hyperplasia was a constant finding. The availability of methods for the prenatal diagnosis of the 21-hydroxylase defect has made it possible to examine some of the manifestations of this disorder during fetal life. We studied a severely virilized 20-week-old aborted female fetus with the 21-hydroxylase defect whose adrenals were neither grossly enlarged nor microscopically hyperplastic. In a pregnancy at risk for congenital adrenal hyperplasia due to a 21-hydroxylase deficiency, amniocentesis was performed in the 18th week of gestation. The 21-hydroxylase defect was established by HLA typing and highly elevated levels of 17-hydroxyprogesterone, testosterone, and androstendione in amniotic fluid. After counselling, the parents, who already had a girl with the salt-wasting form of 21-hydroxylase deficiency, wished termination of the pregnancy. The aborted 20-week-old fetus was within the normal range for gestational age in weight and height. The external genitalia were ambiguous and extremely virilized, with an enlarged clitoris and fused labioscrotal folds. A urogenital sinus opened at the base of the clitoris. The internal organs were female, with a normal uterus and ovaries. Both adrenals were normal in size and weight for their gestational age. Histological examination of the adrenals revealed no abnormalities, and no hyperplasia was detectable. Thus, the adrenals in the 21-hydroxylase defect during fetal life secrete excessive amounts of androgens and cause virilization in the absence of adrenocortical hyperplasia.

Adrenal Hyperplasia, Congenital↗
PubMed1983

Diagnosis of homozygosity and heterozygosity in congenital adrenal hyperplasia (CAH) and control of treatment.

In congenital adrenal hyperplasia the incidence of 21-hydroxylase deficiency is very high (approximately 1:7,000), whereas other enzyme defects such as 11-hydroxylase deficiency, 17-hydroxylase deficiency and 3 beta-hydroxysteroid dehydrogenase deficiency are much less frequent. The various forms of enzyme defects can be diagnosed by determining specific plasma steroids or specific urinary steroid metabolites. A new semi-automatic capillary gas liquid chromatography method has been introduced for the diagnosis of CAH and assessment of therapy. Heterozygous carriers of 21-hydroxylase deficiency can be detected in the general population by measuring 17-hydroxyprogesterone plasma levels after ACTH stimulation; however, results overlap with the general population. In families with a CAH index case, heterozygosity and homozygosity for the 21-hydroxylase deficiency gene can be detected by HLA-typing. 21-hydroxylase deficiency can be diagnosed prenatally by HLA-typing or by determining 17 OH-progesterone levels in the amniotic fluid.

Adrenal Hyperplasia, Congenital↗
PubMed1983

Testosterone and androstenedione concentrations in human testis and epididymis during the first two years of life.

Testosterone and androstenedione were measured in testicular and epididymal tissue of 37 previously healthy infants between 1 and 24 months of age who died suddenly. In half of the patients elevated plasma levels of cortisol and androstenedione suggested preterminal stress. Plasma testosterone levels, however, did not differ from those in healthy infants. Testicular testosterone concentrations were maximal in boys from 1-3 months of age (median, 36.6 ng/g; range, 7-380 ng/g) with peak values similar to those found in pubertal or even adult testes. Thereafter testicular testosterone concentrations decreased and after the age of 6 months all values were below 12.5 ng/g, which corresponds to the low normal range of older prepubertal boys. Plasma testosterone and testicular testosterone correlated significantly (P less than 0.001). On average the testicular concentrations were 36.4 times higher than the corresponding plasma concentrations. Testicular androstenedione was low but correlated significantly with testicular testosterone (P less than 0.001). Epididymal testosterone concentrations were surprisingly high (1-3 months: median, 10.3 ng/g; range, 4-42.7 ng/g) and averaged 30% of the testicular testosterone concentration. Thus, epididymal testosterone concentrations were significantly higher than the circulating plasma testosterone levels, indicating the capacity of the infant epididymis to accumulate androgens. These findings suggest that high local testosterone concentrations during early infancy are important not only for the testis itself but particularly for the developing epididymis.

Aging↗
PubMed1983

Thyroid carcinoma in childhood.

About 50% of children with thyroid carcinoma present with regional lymph node metastases as the leading symptom. The "cold nodule" is the typical scintigraphic finding in thyroid cancer in infants. Papillary carcinoma is the predominating histologic type (80%) and has a good prognosis. Radical removal of the thyroid lobe with the primary lesion and subtotal resection of the opposite lobe, combined with selective neck dissection if necessary, seems to improve the results. Postoperative scintigraphic examinations detect remnants of malignant tissue requiring 131-iodine treatment and, finally, TSH-suppressive hormone is administered. In our own cases, the survival rate in 25 children was over 90%.

Adenocarcinoma↗
PubMed1983

Leydig cell tumours in childhood.

Two cases of Leydig cell tumours in childhood are presented. In one case, delayed diagnosis and operation led to pubertas praecox vera whereas in the other case normal growth and development occurred after early diagnosis and operation.

Child↗
PubMed1982

Development of negative feedback control of the hypothalamo-pituitary-gonadal axis in the male rat fetus.

Pregnant rats were passively immunized against testosterone by injections of rabbit antibodies against testosterone. Fetuses were studied daily starting at day 18 of gestation. Testosterone antibodies were detected in all fetal plasma samples. At day 18 of gestation testicular testosterone content - as an index of gonadotropin stimulation - was unchanged even though circulating free testosterone was reduced by antibody binding. However, at day 19 and all subsequent days of gestation testicular testosterone content was significantly higher in immunized fetuses compared to the controls. These results indicate that in the male rat the negative feedback between testes and the hypothalamopituitary system develops between days 18 and 19 of gestation.

Animals↗
PubMed1982

Urinary free and conjugated oestrone and oestradiol-17 beta in early infancy.

Conjugated and free urinary oestrone and oestradiol-17 beta were determined by radioimmunoassay in 98 urine samples of 44 normal male and female infants ranging from 7 days to 2 years of age. Both sexes excreted significantly more oestrone and oestradiol-17 beta during the first 3 months of life compared to the end of the first year. Values peaked at the beginning of the second month. During the first 7 months of life, female infants excreted significantly more conjugated oestradiol-17 beta than oestrone, whereas male infants consistently excreted equal amounts of conjugated oestradiol-17 beta and oestrone. However, both sexes excreted significantly more free unconjugated oestrone than oestradiol-17 beta during the same period.

Age Factors↗
PubMed1982

[Psychosexual behavior of females with adrenogenital syndrome].

14 female patients with congenital adrenal hyperplasia aged 18 to 30 years were interviewed on their sexual behavior and orientation. In addition they were tested on a personality questionnaire (Freiburger Persönlichkeitsinventar). The majority of the patients was not handicapped in heterosexual life. Homosexual fantasies or experiences were not reported. In the personality dimensions "sociability" and "masculinity" the patients showed a tendency to enhanced scores compared to the norms, whereas in the other dimensions no difference could be demonstrated.

Adolescent↗
PubMed1981

Concentrations of aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone determined simultaneously in human amniotic fluid throughout gestation.

Corticosteroids (CS) are essential for fetal organ maturation; yet, knowledge of endogeneous CS and precursor levels throughout fetal life is limited. Therefore, unconjugated aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone (DOC), progesterone (P), 17 alpha-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F), and cortisone (E) were simultaneously determined by RIA after automated Sephadex LH-20 chromatography in 70 control samples of amniotic fluid (AF) obtained at all gestational ages between 14-42 weeks. Levels of the progestins P and 17-OHP slowly increased from means (+/- SE) of 14.7 +/- 2.8 and 1.63 +/- 0.21 ng/ml, respectively, in early gestation to maximum levels of 32.4 +/- 3.5 and 3.80 +/- 0.74 ng/ml at 36-38 weeks (P less than 0.005), then dropped significantly (P less than 0.01) to 19.2 +/- 2.2 and 1.58 +/- 0.22 ng/ml at term. All CS levels except E rose very markedly by 3- to 12-fold (P less than 0.0001) from the weeks 14-16 (DOC, 0.44 +/- 0.08; B, 1.49 +/- 0.23; Aldo, 0.043 +/- 0.012; S, 0.51 +/- 0.10; F, 5.96 +/- 0.93 ng/ml) until the 36-38th weeks (DOC, 3.50 +/- 0.66; B, 4.60 +/- 0.78; Aldo, 0.530 +/- 0.109; S, 6.00 +/- 0.75; F, 60.8 +/- 8.9 ng/ml). Term levels were significantly reduced (P less than 0.01) in the less active CS DOC (0.51 +/- 0.07 ng/ml), B (2.35 +/- 0.35 ng/ml), and S (1.14 +/- 0.14 ng/ml), whereas those of the biologically most potent CS Aldo and F declined less markedly (0.272 +/- 0.053 and 23.0 +/- 0.75 ng/ml, respectively, at 39-42 weeks). Levels of the inactive glucocorticoid E rose from 8.83 +/- 1.08 ng/ml at 14-16 weeks to 16.8 +/- 2.6 ng/ml at 31-35 weeks (P less than 0.01), then remained rather constant around 11.5 ng/ml until term. It is concluded that after the 25th week, large amounts of biologically active CS are available in AF which probably directly induce the final epithelial maturation of fetal lungs and intestinal tract.

Adrenal Cortex Hormones↗
PubMed1980

17-hydroxyprogesterone, androstenedione, and testosterone in normal children and in prepubertal patients with congenital adrenal hyperplasia.

To determine maximal plasma levels of androstenedione (A) and testosterone (T) which still can be considered non virilizing in 21-hydroxylase deficiency, we investigated plasma levels of these steroids in unaffected children and in adults. For T we found an upper limit of the prepubertal normal range of 16 ng/dl in girls and of 20 ng/dl in boys, with the exception of boys in the first half-year of life in which T is elevated up to the low adult range with peak values in the 2nd and 3rd month. During puberty T values show a significant difference between pubic hair stage 1 and stage 2. T levels below 20 ng/dl can be considered to be non virilizing. For A we found a plasma concentration of 86 ng/dl to be the upper normal level in both sexes before the onset of puberty. A values below this limit are expected to be non virilizing. To evaluate the usefulness of 17-hydroxyprogesterone (OHP) for the prediction of A and T and to define "acceptable" OHP levels in CAH we performed simultaneous determinations of OHP, T, and A in prepubertal patients treated for CAH. From these values we calculated the 95% confidence interval for prediction of T and A on known OHP levels. On an OHP value of 1.000 ng/dl, T can be expected to be between 6 and 60 ng/dl and A between 25 and 320 ng/dl. Because of these wide ranges, OHP has to be considered an unreliable parameter for predicting androgen levels in CAH.

Adolescent↗