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Biomedical subjects

M Zachmann

Publications and source records attributed to M Zachmann.

At least 55 records · Page 3Linked to original sources
PubMed1992

Conversion from pure 17,20-desmolase- to combined 17,20-desmolase/17 alpha-hydroxylase deficiency with age.

A previously described phenotypically female 46,XY-individual with 17,20-desmolase deficiency was followed from adolescence to adulthood. While at age 16.9 years her 17 alpha-hydroxylating capacity was normal and steroids not hydroxylated in position 17 low, decreasing 17 alpha-hydroxylated and increasing unhydroxylated steroids were observed thereafter up to the age of 25.2 years. Simultaneously with the steroid changes, previously normal blood pressure (110/80 mmHg) increased (180/130 mmHg). Since 17 alpha-hydroxylation and 17,20-desmolase activity are regulated by one cytochrome P450-17 alpha, it is concluded that, in this same patient, 17 alpha-hydroxylase activity was normal during childhood and adolescence, but decreased in the young adult. 17,20-desmolase activity, by contrast, was completely absent already in the fetus, causing absence of masculinization. The factors modulating this difference in cytochrome P450-17 alpha activity with age are as yet unknown.

Adrenal Hyperplasia, Congenital↗
PubMed1991

Recombinant human insulin-like growth factor I (rhIGF I) reduces hyperglycaemia in patients with extreme insulin resistance.

The syndrome of type A insulin resistance is encountered in young women and is characterized by glucose intolerance or frank diabetes mellitus, endogenous hyperinsulinism, insensitivity to insulin administration, acanthosis nigricans and virilization. The insulin resistance is due to reduced cellular insulin binding because of a lack of or defective binding sites and/or because the interaction with the tyrosine kinase of the beta-subunit is hindered. This study was undertaken to find out whether hyperglycaemia in these patients may be influenced by the administration of recombinant human insulin-like growth factor I which exerts insulin-like effects through the insulin receptor as well as the type 1 insulin-like growth factor I receptor. Recombinant human insulin-like growth factor I was intravenously administered in two subsequent doses of 100 micrograms/kg body weight to three women with type A insulin resistance. An immediate but slow fall of blood glucose was observed. The glucose disappearance rate was 28.0 mumol/min, i.e. considerably lower than that seen in healthy subjects. The markedly elevated insulin and C-peptide levels fell in a parallel manner to blood glucose but not to normal levels. The results show that recombinant human insulin-like growth factor I, presumably by reacting with the type 1 insulin-like growth factor receptor, can normalize serum glucose levels in patients with severe insulin resistance at least for several hours. We suggest that the potential or recombinant human insulin-like growth factor I to control hyperglycaemia in type A insulin resistant patients should be explored in more depth.

Adolescent↗
PubMed1991

Testicular adrenal-like tissue (TALT) in congenital adrenal hyperplasia: detection by ultrasonography.

In a consecutive series of 15 male adolescents and young adults with congenital adrenal hyperplasia (CAH), the size, shape, firmness and echostructure of the testes were assessed. The latter was abnormal in 7 patients under long standing treatment with glucocorticoids (group I). In 8, 5 under and 3 off treatment for several years, ultrasonography (US) was normal (group II). On the basis of the US findings the patients were placed in two groups. In group I, the testes had a heterogeneous ultrasonographic pattern; clinically, most felt hard and irregular, although their volume was normal. Sperm count in 3 patients was 5.0 to 14.4 x 10(6)/ml. Five patients have 21-hydroxylase deficiency that was diagnosed in early infancy and had salt-wasting; two have 11-beta-hydroxylase deficiency that was diagnosed late and had no salt-wasting. In group II, testicular volume, shape, firmness and echostructure were normal. All have 21-hydroxylase deficiency, no history of salt-wasting and were diagnosed late. Sperm counts in 3 patients off treatment were 10.5 to 66.0 x 10(6)/ml. In severe cases with a history of salt loss, TALT with deficient spermiogenesis seems likely despite treatment. In mild cases, TALT is absent and spermiogenesis may be normal even without treatment. US is much more accurate in assessing the testes than palpation.

Adolescent↗
PubMed1991

Results of transsphenoidal extirpation of craniopharyngiomas and Rathke's cysts.

Fourteen patients undergoing transsphenoidal extirpation of craniopharyngiomas or Rathke's cysts underwent endocrinological evaluation before and after surgery. One patient died during the procedure because of uncontrollable arterial bleeding. The other patients were followed for up to 16 years (average, 8.5 years). One patient had recurrence of tumor 12 years after surgery. Another patient, the only one operated on because of a recurrent craniopharyngioma after previous radiation therapy, died 2 years after the transsphenoidal operation. No patient recovered pituitary functions that had been lost before surgery. One patient, who had an isolated growth hormone deficiency, and another, who had panhypopituitarism with sustained antidiuretic hormone secretion, had no change postoperatively from their preoperative endocrine status. The other 11 patients lost pituitary function and required pharmacological replacement of one to four pituitary hormones.

Adolescent↗
PubMed1991

Gonadal agenesis in a 46,XY female with multiple malformations and positive testing for the sex-determining region of the Y chromosome.

A full-term 46,XY female newborn presented with respiratory failure due to a right-sided diaphragmatic hernia. During surgical repair, exploration revealed isolated dextrocardia and hypoplasia of the right lung. Neither gonads nor wolffian or müllerian structures could be palpated. Cardiac catheterization demonstrated defects of the ventricular septum, hypoplasia of the right pulmonary artery, persistence of the left vena cava superior and a patent ductus arteriosus. Anthropometric data were normal at birth, but fell below the 3rd percentile during follow-up. Body proportions displayed a predominance of the upper compared to the lower segment. Endocrine studies indicated no defect of steroid biosynthesis and no functional gonadal tissue. Using genetic analyses of various loci within the testis-determining region of the Y chromosome, a mutation could not be detected. The patient died from pneumonia at the age of 19 months. Postmortem examination confirmed the diagnosis of gonadal agenesis.

Abnormalities, Multiple↗
PubMed1991

Therapeutic indications for delayed puberty and hypogonadism in adolescent boys.

Testosterone and synthetic androgens have formerly been used indiscriminately, but are now applied more selectively. They are the only treatment of primary hypogonadism, but are also useful in gonadotropin deficiency and constitutional delay. 17-Alkylated androgens are no longer used. Oral testosterone undecanoate is not suitable for adolescents because of unreliable absorption. The prototype disorder where replacement is necessary is congenital anorchia. As a physiological replacement, an initial dose of 35 mg/m2 per month for 6 months, followed by 70 mg/m2 for 1 year, and 150 mg/m2 thereafter, is recommended. No general rules can be given for other types of primary hypogonadism. In testicular atrophy after cryptorchidism, defects of testosterone biosynthesis, galactosemia or other causes, it is advisable to carry out periodic testosterone determinations and to wait until the levels drop below normal. Progress has been made in the treatment of gonadotropin deficiency, and pulsatile gonadotropin-releasing hormone (GnRH) has been shown to be effective in the hypothalamic type. Nevertheless, androgens still have a temporary place in this condition. In constitutional delay of growth and adolescence, treatment is not necessary somatically, but there are often psychosocial reasons. Gonadotropins, GnRH or growth hormone (GH)-releasing hormone have been used. Also treatment with human GH is successful in accelerating height velocity. The most simple and economic treatment is still testosterone in a physiological dose for 3-6 months. Oxandrolone or other synthetic androgens have no advantages.

Adolescent↗
PubMed1991

Salivary testosterone concentrations in prepubertal and pubertal males: comparison with total and free plasma testosterone.

Salivary testosterone (T) levels in male children and adolescents were measured and compared with plasma T. Salivary concentrations correlated well with plasma total T (r = 0.72) and even better with free plasma T (r = 0.89) in subjects with plasma T levels of pubertal or adult levels (greater than 1.0 nmol/l). In subjects with prepubertal or low plasma T (less than 1.0 nmol/l), there was neither a correlation with plasma total, nor with free T. In hCG tests (responder and nonresponder), salivary T reflected plasma levels faithfully. The results suggest that salivary T, which is suitable for repeated sampling, is a good marker of T secretion in pubertal males.

Adolescent↗
PubMed1991

[Reconstruction of external genitalia of the girl with adrenogenital syndrome].

Congenital adrenal hyperplasia (CAH) is the most common cause for female pseudohermaphroditism. In these patients uterus and Fallopian tubes are present and also in severe cases the clitoris cannot function as penis later in life. Therefore, a neonate with ambiguous genitalia due to CAH should be raised as female. To assess the degree of masculinization, a modification of Prader's classification was used. In 23 girls with ambiguous genitalia reduction clitoroplasty preserving the neurovascular bundle and creating a dorsal preputial skin flap and vaginoplasty with a perineal skin flap were performed. The phallic skin was used to create the labia minora and the anterior vaginal wall. The patients were reevaluated 1 to 14 years after the operation. The cosmetic and functional results have been excellent.

Adolescent↗
PubMed1990

Isolated dehydroepiandrosterone sulphate hypersecretion: a case report.

The case of a 17-year-old male with isolated hypersecretion of dehydroepiandrosterone sulphate (DHEAS) is described. Cushing syndrome, congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency, an androgen producing adrenal tumour, and elevated plasma DHEAS due to an increased renal threshold were excluded. Selective renal vein catheterization confirmed bilateral, isolated adrenal DHEAS hypersecretion. The dexamethasone suppression suggests a functional nature of this alteration. This condition has to be considered in the differential diagnosis of excessive adrenal androgen production in males, or of hirsutism in females.

Adolescent↗
PubMed1990

Growth hormone requirement for a normal human adipocyte glucose carrier function.

One of the most prominent actions of insulin is stimulation of the glucose carrier in different cell types, especially adipose cells. However, the exact mechanism of the mode of action of insulin, between receptor binding and stimulation of glucose transport, is not understood in detail. We have shown earlier, that GH plays an important role in the control of the insulin-sensitive glucose carrier system in rat fat cells. In this study, we measured glucose transport in fat cells of normal probands, GH-deficient (GHD) and GH-treated GHD patients. From sc fat tissue biopsies of three GHD patients, fat cells were isolated after digestion with collagenase. In normal fat cells, basal glucose transport was slow (t/2 = 2.5 min) and stimulated by insulin (t/2 = 0.8 min), as expected. In fat cells of GHD patients glucose transport was maximal already in the basal state (t/2 = 0.8 min) without an additional effect of insulin. After GH administration during several months to GHD patients, glucose transport was again slow in the basal state (t/2 = 3.2 min) and could be stimulated by insulin (t/2 = 0.7 min). These results confirm our earlier findings in rat adipocytes for human adipocytes: GH in vivo is responsible for a glucose transport-limiting factor in the plasma membrane that restricts basal glucose transport and is acutely inhibited by insulin resulting in enhanced glucose transport. These results demonstrate the physiological importance of GH for a normal function of the insulin transmembrane signaling system in fat tissue and indicate a possible benefit of GH administration in adult GHD patients.

Adipose Tissue↗
PubMed1990

Serum bone Gla protein: a potential marker of growth hormone (GH) deficiency and the response to GH therapy.

Serum bone Gla protein (BGP), a sensitive and specific biochemical marker of bone formation, was measured in 66 children deficient in GH before and after 3, 6, 9, and 12 months of treatment with biosynthetic human GH. Initial serum BGP levels were significantly lower than those of normal age-matched children. After 3 months of treatment, the mean serum BGP level had increased to normal. There was no relation between baseline serum BGP and the growth response, but the GH-induced increment in serum BGP levels at 3 months was highly significantly related to growth response after 12 months of therapy. The study shows that serum BGP could be a helpful biochemical marker in prediction of the growth response to long term GH therapy.

Adolescent↗
PubMed1990

Assessment of growth hormone secretion in children.

Growth hormone (GH) is secreted in a pulsatile way during the whole life under the reciprocal influence of somatostatin and GH-releasing hormone (GHRH). It mediates many effects by stimulating production of insulin like growth factor I (IGF I) in liver and other tissues, but IGF I is also regulated by the nutritional state. Women secrete more GH than men, and older men and women less than young women. This suggests importance of estradiol in regulating secretion. Sex hormone effects are also demonstrated by the increment of GH and IGF I at puberty, which is an amplitude-modulated phenomenon. Classic metabolic studies have shown that patients with GH-deficiency retain more nitrogen in response to a given dose of exogenous hGH than normal subjects. The use of the stable isotope 15N has simplified such studies. In GH-deficient patients, there was with this technique a marked positive hGH-induced balance change. In girls with Turner syndrome (as example of subjects with normal GH-secretion), balance change was less marked with the same dose. Girls with Turner syndrome, who were given a double hGH-dose showed a response in the same range as that in the GH-deficient patients with the lower dose. A conclusion from this is that patients with normal GH-secretion need higher doses to obtain a similar response, than patients with GH-deficiency. The dosage in such patients will have to be selected individually, and needs to be about twice or three times as high as in GH-deficient patients.

Adolescent↗
PubMed1989

Neurohypophyseal ectopy in growth hormone insufficiency.

Nuclear magnetic resonance imaging of the hypothalamohypophyseal tract allows the detection and identification of ectopic posterior pituitary lobe tissue by its characteristic high signal intensity. We found this anomaly in 2 boys with growth hormone insufficiency. Neurohypophyseal ectopy may be misdiagnosed as subhypothalamic tumor and such patients risk to be subjected to unnecessary neurosurgery.

Child↗
PubMed1989

Effect of recombinant human growth hormone on urinary 15N-nitrogen balance in girls with Turner syndrome as compared to children with growth hormone deficiency.

15N-nitrogen balances before and on human growth hormone (hGH) were studied in 13 girls with Turner syndrome (TS) aged 4.4-16 (median 13.2) years (45,X0 or equivalent, no X0/XX mosaicism, no estrogen replacement). The results were compared with those reported from 9 patients with growth hormone deficiency (GHD). The TS patients received subcutaneous hGH doses of 2 x 3 (group A, n = 6), 3 x 2 (group B, n = 3), or 2 x 6 (group C, n = 4) IU/m2 on consecutive days. The mean 15N dose given to the patients of groups A and C was higher (13.6 mg/kg) than that given to those of group B (2.7 mg/kg). The lower hGH doses in the first two groups induced small positive mean 15N balance changes (+0.6 +/- 0.6 mg/kg 15N, group A; +0.03 mg/kg, group B). The higher hGH dose in group C caused a more marked mean balance change (+3.0 mg/kg 15N) comparable to that in GHD patients (+3.2 mg/kg). Individual variation of response, however, was larger in patients with TS than in those with GHD. With low and high hGH doses, there were responders and nonresponders. It is concluded from this pilot study in a small number of cases that 15N balance studies might be potentially useful to choose the appropriate hGH dose for long-term treatment in TS patients.

Adolescent↗
PubMed1989

Authentic recombinant human growth hormone. Results of a multicenter clinical trial in patients with growth hormone deficiency.

197 patients with growth hormone deficiency (144 boys, 53 girls, age 1.5-19.5 [mean 11 +/- 3.6], bone age 0.3-15 [mean 8.9 +/- 3.5] years) were treated for one year with authentic recombinant human growth hormone (r-hGH, Norditropin] in several European paediatric centers. 107 patients were newly treated (group A), and 90 transferred from pituitary or methionine hGH (groups B and C). In 19 of the latter, treatment was interrupted for 6 months (group B), in the others, it was changed without interruption (group C). The dosage was 0.45 +/- 0.2 IU/kg/week given s.c. 6-7 times a week. Height velocity increased from 4.1 +/- 2.4 to 8.3 +/- 2.5 (group A), 2.6 +/- 1.8 to 8.3 +/- 2.3 (group B), and 6.2 +/- 2.7 to 6.8 +/- 2.2 cm/year (group C). Few patients complained of local discomfort at the injection site, but this disappeared after changing metacresol in the solvent to 0.9% benzyl alcohol. Only 3 patients developed antibodies to hGH in low titers, which did not interfere with growth. No changes in E. coli protein antibodies were observed. It is concluded that r-hGH is an efficient and safe treatment for children with growth hormone deficiency.

Adolescent↗
PubMed1988

Dexamethasone therapy and endogenous cortisol production in severe pediatric head injury.

A prospective randomised study was performed on 25 children aged 1.4 to 15.8 years with severe head injury (Glasgow Coma Scale less than or equal to 7) to determine the clinical effectiveness and the impact on endogenous cortisol production of high-dose steroid therapy. Thirteen patients (group 1) received dexamethasone 1 mg/kg/day during the first 3 days and 12 (group 2) not. All patients were treated with a standardized regimen. Urinary free cortisol was measured by radioimmunoassay, and the clinical data were recorded at hourly intervals. Outcome was assessed 6 months later using the Glasgow Outcome Scale. We found a higher frequency of bacterial pneumonias in the dexamethasone-treated patients (7/13 versus 2/12). Group 1 showed a suppression of endogenous cortisol production from day 1 to day 6. In group 2, mean free cortisol was up to 5-fold higher than under basal conditions. The results in group 2 showed that the endogenous steroid production reacts adequately to the stress of severe head injury. It probably is sufficient to elicit maximum glucocorticoid effects. There was no other statistically significant difference in the clinical and laboratory data between the two groups. We conclude that dexamethasone in high doses suppresses endogenous cortisol production up to 6 days and may increase the risk of bacterial infection without affecting the outcome or the clinical and laboratory data.

Adolescent↗