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Biomedical subjects

W G Sippell

Publications and source records attributed to W G Sippell.

At least 19 recordsLinked to original sources
PubMed1992

Hypothalamic-pituitary-gonadal function in two infants with Smith-Lemli-Opitz syndrome.

We report on the hypothalamic-pituitary-gonadal function in 2 male infants with the Smith-Lemli-Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20-desmolase deficiency, 17 alpha-hydroxylase deficiency, and 3 beta-hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic-pituitary-gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5 alpha-reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies.

Abnormalities, Multiple↗
PubMed1992

Growth, bone maturation and height prediction after three years of therapy with the slow release GnRH-agonist Decapeptyl-Depot in children with central precocious puberty.

More than 100 patients with central precocious puberty are participating in this international multicenter study using monthly i.m. injections of the slow-release GnRH agonist Decapeptyl-Depot. In 15 patients, Decapeptyl-Depot treatment could be discontinued after 2 years of therapy. Gonadal suppression was promptly reversible in all of them, as shown by prepubertal low gonadotrophin- and sex steroid levels. Of the remaining 90 patients, 40 have been treated for more than 3 years, including 33 girls and 7 boys. Plasma levels of LH, FSH, estradiol and testosterone dropped to the prepubertal range after one month of Decapeptyl-Depot and remained there for the whole period of therapy. At start of therapy, mean chronologic age of these 40 children was 6.6 +/- 1.4 (SD) years, mean bone age 10.2 +/- 1.9 years. Mean predicted adult height increased in the boys from 173.6 +/- 13.8 (SD) cm at start of therapy to 184.6 +/- 17.0 cm after 3 years. Predicted adult height increased in girls from 158.0 +/- 12.2 to 161.0 +/- 7.5 cm. Undue side effects were not seen, long term tolerance was good. It is concluded that Decapeptyl-Depot injected i.m. every 4 weeks suppresses the pituitary-gonadal axis in children with central precocious puberty without clinical or biochemical escapes, and leads to an increase in predicted adult height by more than 3 cm in all boys and in 53% of the girls after three years of treatment.

Adolescent↗
PubMed1992

[Prenatal diagnosis and therapy of adrenogenital syndrome with 21-hydroxylase deficiency].

Genetic counselling of the parents is prerequisite before prenatal diagnosis and prenatal therapy of CAH. Today, chorionic villous biopsy with DNA probe is the method of choice to identify homozygous CAH-fetuses. The aim of prenatal therapy is to prevent intrauterine virilization of the external genitalia in affected female fetuses. Therefore, dexamethasone (3 x 0.5 mg/d p.o.) is given to the mother immediately when pregnancy is confirmed, before prenatal diagnosis and karyotyping is possible. After the result of prenatal diagnosis, treatment is continued until term only when the fetus is affected and female. Prenatal diagnosis and effective treatment of female CAH fetuses greatly reduces the need for corrective surgery and thus helps to alleviate anxieties of prospective parents and therefore encourages further pregnancies. However, prenatal treatment of CAH to date still is an experimental therapy [corrected].

Administration, Oral↗
PubMed1991

Long-term results with a slow-release gonadotrophin-releasing hormone agonist in central precocious puberty. Dutch-German Precocious Puberty Study Group.

As part of an ongoing international multicentre study, 19 children (14 girls, 5 boys) with central precocious puberty (CPP) were treated with a slow-release gonadotrophin-releasing hormone (GnRH) agonist, triptorelin, for 4 years. After 3 years of treatment, height velocity stabilized at 4.0 cm/year. Predicted adult height (mean +/- SD) increased from 158.9 +/- 6.8 to 164.9 +/- 6.6 cm in girls (n = 14, p less than 0.01), and from 174.4 +/- 18.5 to 184.3 +/- 17.1 cm in boys (n = 4, p less than 0.05). In 12 additional girls who had started the multicentre study but discontinued triptorelin treatment after 2.2 +/- 0.5 years, menses started 9.8 +/- 3.7 months after cessation of treatment in all but one patient. Height velocity increased over the first 6 months after discontinuation of treatment, from 3.6 +/- 0.1 to 5.4 +/- 2.5 cm/year, and remained higher than pretreatment values in the second 6 months, but decreased subsequently. Bone maturation increased, and no significant improvement in predicted adult height was observed. For auxological reasons, therefore, it may be advisable to continue triptorelin treatment for as long as possible. Concomitant growth hormone (GH) therapy was initiated in three girls with CPP with height velocities of 3.2-3.6 cm/year after 3 years of treatment with triptorelin and predicted adult heights of less than the third centile for Dutch girls. Prior to the administration of GH, all patients had subnormal 24-hour GH profiles and GH responses to arginine provocation. GH treatment increased height velocity markedly in all girls, and improved predicted adult height.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1991

Growth and pubertal development during and after treatment with a slow-release gonadotropin-releasing hormone agonist in central precocious puberty.

The auxological data of 25 patients (21 girls, 4 boys) with central precocious puberty (CPP), treated for 4 years with a slow-release gonadotropin-releasing hormone agonist [Decapeptyl-controlled release (D-CR) 3.75] every 4 weeks intramuscularly, and of 6 patients (3 girls, 3 boys), treated for 5 years, are presented. After 3 years of D-CR a stabilization of height velocity (HV) at about 4 cm/year was observed. Bone maturation (ratio of change in bone age to change in chronological age; delta BA/delta CA) slowed down to a mean delta BA/delta CA ratio of 0.5 +/- 0.2 (mean +/- SD) measured over 48 months. As a result, predicted adult height (PAH) improved from 156.3 +/- 7.4 to 162.2 +/- 6.8 cm in girls (p less than 0.001) and from 174.4 +/- 18.6 to 184.3 +/- 17.1 cm in boys after 4 years. In the 5th year an ongoing improvement of PAH was observed. 20 additional girls discontinued D-CR for at least 12 months after treatment with D-CR for 2 years or more. In 11 girls menses started after 10.6 +/- 3.1 months; 9 girls had no menarche after 12-16 months. HV increased in the first and second 6 months to a level of about 6.0 cm/year, decreased in the third 6 months after cessation to the level before discontinuing D-CR and decreased further afterwards. Bone maturation (delta BA/delta CA) increased progressively in the first 18 months after discontinuation, with a stabilization at about 1.3. PAH did not change in the first 12 months after discontinuation of D-CR, but showed a decrease afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1991

The steroid hormonal milieu of the undisturbed human fetus and mother at 16-20 weeks gestation.

The interrelations of steroid hormone levels in plasma and amniotic fluid from mothers and their undisturbed fetuses at early midgestation of human pregnancy have not been defined previously. We, therefore, studied 12 healthy mothers and their fetuses undergoing termination of pregnancy for social reasons at 16-20 weeks gestation. Fetal arterial and venous blood was obtained by direct vessel puncture through a fetoscope in the conscious sedated mothers immediately before termination of pregnancy. Simultaneously, maternal peripheral venous blood and amniotic fluid were collected. Aldosterone (Aldo), corticosterone (B), 11-deoxycorticosterone, progesterone (P), 17-hydroxyprogesterone (17OHP), 11-deoxycortisol, cortisol (F), and cortisone were simultaneously determined by specific RIA after extraction and chromatography. Positive fetal arterio-venous differences were found for F, B, and Aldo, whereas arteriovenous differences were negative for P and 17OHP. In amniotic fluid, six of the eight corticosteroids showed significantly lower levels during fetoscopy than during routine amniocentesis, as reported previously using the same analytical methods. The present study demonstrates that the undisturbed human fetus at 16-20 weeks gestation actively secretes the most important gluco- and mineralocorticoids, F, B, and Aldo, independent of the mother. P and 17OHP were shown to be primarily derived from placental production and supplied to the fetus as a source of F and Aldo biosynthesis. The fetoscopy procedure with premedication seemed to give rise to less stress to the fetus than routine amniocentesis without sedation. Fetoscopy is, therefore, an ideal method to study feto-maternal steroid interrelations in human pregnancy.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Improved test to identify heterozygotes for congenital adrenal hyperplasia without index case examination.

In an attempt to improve detection of heterozygote carriers of the gene for congenital adrenal hyperplasia (21-hydroxylase deficiency; CAH) 64 families with at least 1 affected member (72 homozygotes and 191 clinically healthy subjects) were studied by HLA genotyping and by the single-dose corticotropin stimulation test. Plasma samples were drawn immediately before corticotropin and 60 min after its injection, and they were analysed simultaneously for eight adrenal steroids by radioimmunoassay after extraction and automated gel chromatography. Heterozygosity was defined as the presence of one HLA haplotype in common with the affected relative. Of the various basal and corticotropin-stimulated steroid levels and their ratios, the ratio of 17-hydroxyprogesterone to 11-deoxycorticosterone after corticotropin had the greatest power to discriminate between heterozygotes and normal relatives; that ratio was significantly higher in the heterozygotes (n = 116) than in the normal relatives (n = 75) and there was no overlap between the groups (range 12.2-214 vs 1.2-11.9). Thus, it is possible to detect all CAH heterozygotes without examining the index case by means of specific steroid analysis.

17-alpha-Hydroxyprogesterone↗
PubMed1990

Treatment of children with central precocious puberty by a slow-release gonadotropin-releasing hormone agonist.

A total of 82 patients (74 girls, 8 boys) are presently participating in an international multicentre trial for treatment of central precocious puberty (CPP) with a slow release gonadotropin-releasing hormone (GnRH) agonist depot preparation: Decapeptyl-Depot (DD). Of these patients, 53 (3 boys) were previously untreated (group 1) and 29 (5 boys) have been treated before with either a short-acting GnRH analogue or cyproterone acetate (group 2). Fifty-one patients (44 girls, 7 boys) were treated with DD for 12 months or more. Basal plasma luteinizing hormone (LH) levels decreased in both groups after 1 year of therapy. The LH response to intravenous GnRH was reduced in both groups. Basal plasma follicle stimulating hormone (FSH) levels decreased in both groups. Stimulated FSH levels were reduced in both groups after 1 year of DD treatment. Plasma oestradiol levels in the girls decreased to prepubertal levels in both groups. In all patients the clinical signs of precocious gonadarche such as breast development and menstruations (girls) and an increased testis volume (boys), did not further progress and sometimes regressed in several patients. Growth velocity decreased in the girls of group 1 from 9.0 +/- 0.72 cm/year (mean +/- SEM) in the last half-year before treatment to 6.3 +/- 0.50 in the first half-year of treatment (P less than 0.01) and to 4.5 +/- 0.23 cm/year in the second half-year (P less than 0.01). After 12 months a stabilization of growth velocity was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗
PubMed1990

Repetitive injections of growth hormone releasing hormone (GHRH1-44) to normal volunteers and patients with growth hormone deficiency.

The present study was designed to answer the following three questions: Is there any difference between the growth hormone (GH) response to i.v. injections of GHRH 1-44 by a slowly injecting hormone pump or to a s. s. or rapid i. v. injection by syringe? Do nocturnal injections of GHRH 1-44 i. v. elicit different GH levels than during daytime? Can repetitive administration of GHRH 1-44 in patient with GH deficiency induce a physiological GH pattern and thereby normalize the condition resulting from a hypothalamic defect? A rapid i. v. bolus injection of 50 micrograms GHRH 1-44 by syringe with an injection time of one second elicited in the same subject at the same time of the day a twofold greater response than a slowly injecting (60 seconds) hormone pump. In six male adult volunteers each GHRH i. v. bolus was followed by a GH secretory pulse. The GH response at night (area under the curve and peak plasma GH levels) was significantly greater than at daytime (P less than 0.05) and greater than the GH pulses measured during a spontaneous nocturnal profile (P less than 0.05). Out of six GH deficient young adult patients who had been receiving extractive GH until two years prior to the study, three responded much like the controls, the other three patients-those who lacked any spontaneous nocturnal GH peaks-had markedly lower GH levels after GHRH (P less than 0.05). However, there was a clear-cut GH release after GHRH injection in each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Infusion of low dose etomidate: correction of hypercortisolemia in patients with Cushing's syndrome and dose-response relationship in normal subjects.

To investigate the adrenostatic potential of a nonhypnotic low dose etomidate infusion, we administered 0.03 mg/kg etomidate in a bolus injection, followed by constant infusion of 0.3 mg/kg.h for 24 h to 6 patients with severe Cushing's syndrome. The dose-response relationship also was determined in 15 normal subjects. Three groups of 5 received, respectively, doses of 0.03, 0.1, and 0.3 mg/kg.h etomidate for 5 h after an initial bolus dose of 0.03 mg/kg. The response to exogenously administered ACTH [0.25 mg ACTH-(1-24)], injected after the etomidate or control infusion, was determined in all normal subjects. In the six hypercortisolemic patients, serum cortisol concentrations decreased from 1374 +/- 436 nmol/L (mean +/- SEM) to 188 +/- 91 nmol/L after 11 h of etomidate infusion and remained low until the end of the infusion. Cortisol levels returned to pretreatment concentrations by 24 h. Excretion of urinary free cortisol decreased from 1180 +/- 196 to 185 +/- 66 nmol/day. In the normal subjects, administration of etomidate led to a dose-dependent decrease in serum cortisol from about 550 to 83 nmol/L, while 11-deoxycortisol rose from low or undetectable levels up to 346 nmol/L. In response to ACTH, cortisol levels rose in inverse proportion to the etomidate dose. It was, however, significantly reduced compared to normal saline infusion even after the lowest dose. Changes in aldosterone and corticosterone concentrations were similar to those in cortisol, and 11-deoxycorticosterone changed in a pattern similar to that of 11-deoxycortisol. Two of five normal subjects reported tiredness during the highest etomidate infusion. No other side-effects were noted. We conclude that iv administered etomidate in a low nonhypnotic dose reduces serum cortisol concentrations in a dose-dependent manner in both hyper- and eucortisolemic subjects. This study suggests that etomidate at a dose of 0.1 mg/kg.h or lower may be an effective strategy for the control of severe hypercortisolemia.

Adolescent↗
PubMed1990

Definitive localization of X-linked Kallman syndrome (hypogonadotropic hypogonadism and anosmia) to Xp22.3: close linkage to the hypervariable repeat sequence CRI-S232.

Kallmann syndrome is a genetically heterogeneous disease characterized by hypogonadotropic hypogonadism and anosmia. Six families in which the disorder followed an X-linked inheritance were investigated by linkage analysis. Diagnostic criteria were uniformly applied and included tests for hypogonadotropic hypogonadism and anosmia. Close linkage was found by using the hypervariable repeated sequence CRI-S232 (DXS278) previously mapped to Xp22.3. At a maximum lod score of 6.5, the recombination fraction was calculated as .03. Of 30 fully informative meioses, one recombination between the disease locus and the loci recognized by probe CRI-S232 was observed. When an independent approach is used, these results confirm the X-linked Kallmann syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome assignment previously made by deletion mapping, and allow definitive localization of the syndrome to the Xp22.3 region. This opens the way to carrier detection and to the identification of a gene responsible for this disorder.

Chromosome Mapping↗
PubMed1990

Reference ranges of lutropin and follitropin in the luliberin test in prepubertal and pubertal children using a monoclonal immunoradiometric assay.

Reference ranges of lutropin and follitropin in the luliberin test (60 micrograms/m2 body surface) were established for the various pubertal stages in a large sample of endocrinologically healthy children using a monoclonal immunoradiometric assay (LH and FSH MAIA Clone, Serono Diagnostika, Freiburg, FRG). Qualitatively, the results for lutropin were similar to those already reported from studies using polyclonal RIA's. Lutropin increased gradually throughout pubertal development. Quantitatively, however, the immunoradiometric assay system yielded considerably lower results than polyclonal RIA's. In contrast, follitropin showed a very good linear regression between monoclonal and polyclonal assays. Therefore the former reference ranges for follitropin are still applicable.

Adolescent↗
PubMed1990

[Experiences with specific screening for early detection of congenital adrenogenital syndrome with 21-hydroxylase defect].

In Southern Bavaria over 32 months a total of 575 newborn babies was selectively screened for CAH due to 21-hydroxylase deficiency. Whenever one of the 3 key symptoms "failure to thrive", "ambiguous or atypical genitalia" and/or "positive family history" were present, a small plasma sample was drawn for the rapid and centralized radioimmunologic determination of 17-hydroxyprogesterone (17-OHP) and cortisol. Pathologically elevated 17-OHP plasma levels were found in 9 babies with CAH in whom adequate replacement therapy with gluco- and mineralocorticoids could be initiated without delay. On the basis of a mean birth rate of 60 000 per year a relatively low prevalence of 1:20 000 was calculated. It is likely that this is due to the fact that such a selective newborn screening program fails to detect the clinically normal male infants with simple virilizing CAH.

Adrenal Hyperplasia, Congenital↗
PubMed1989

Further analysis of the disturbed adrenocortical function in the cerebro-hepato-renal syndrome of Zellweger.

Plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-desoxycortisol, cortisol and cortisone were determined simultaneously in small plasma samples obtained during an i.v. ACTH (Synacthen) stimulation test in five patients (age 4-7 years) with Zellweger syndrome. The response of all ACTH-dependent steroids to Synacthen was severely impaired in all patients, despite normal basal levels. It can be concluded that the biochemical defect in adrenal steroidogenesis causing the inadequate response to ACTH injection is located proximal to progesterone. We propose that the lack of responsiveness to ACTH is secondary to an abnormality of ACTH receptors on the adrenocortical cell. The extremely low levels of non-specific lipid transfer protein may be a contributing factor.

Adrenal Cortex↗
PubMed1989

Hypothalamic hypogonadism in congenital adrenal hypoplasia.

Congenital adrenal hypoplasia (CAHP) in its X-linked form is associated with hypogonadotropic hypogonadism (HH). A 23 year old man with this disorder received substitution therapy with gluco- and mineralocorticoids starting one week after birth and, recently, pulsatile subcutaneous GnRH treatment via a miniature infusion pump with stepwise increasing doses from 50 to 200 ng/kg body weight/2 hours for a total of 394 days. Testosterone levels increased from prepubertal levels to 409 ng/dl after 2 weeks and to 626 ng/dl after 3 months of treatment. The results of pulsatile GnRH therapy in our patient prove the hypogonadotropic hypogonadism to be of hypothalamic origin. Pulsatile GnRH substitution is a successful therapeutic regimen in patients with CAHP leading to pituitary and gonadal maturation.

Adrenal Glands↗
PubMed1989

Growth, bone maturation and pubertal development in children with the EMG-syndrome.

In 7 patients (5 girls, 2 boys) with the EMG or Wiedemann-Beckwith syndrome, statural growth, bone age (BA), weight and pubertal development were studied longitudinally. Height was above the 90th percentile (%) for chronological age (CA) after age 2 years, reaching an average of 2.5 SD above the mean at or after puberty. Adult or attained height also exceeded significantly (P less than 0.015) parental (genetic) target height by 13.2 cm on the average. In one girl, adult height prognosis (190 cm) could be reduced to an adult height of 183 cm by high-dose estrogen treatment. In most children, growth velocity remained above the 90th % up to 4-6 years of age and normalized thereafter. In all patients studied, bone age was markedly advanced and particularly so during the first 4 years after birth. Weight was above the 90th-97th % during infancy and early childhood and remained there, appropriate or slightly subnormal for height, until adulthood, except for 3 girls who reached and maintained the 50th % during or after puberty. Spontaneous pubertal development occurred within normal limits for CA and around the 50th % for BA. Except for the marked bone age acceleration, the reason for the increased statural growth and adult height in patients with the EMG syndrome is still unknown.

Adolescent↗