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Biomedical subjects

A Häger

Publications and source records attributed to A Häger.

At least 19 recordsLinked to original sources

Final height after combined growth hormone and GnRH analogue treatment in adopted girls with early puberty.

BACKGROUND: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin-releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent. AIM: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty. METHODS: Forty-six girls with early or precocious puberty (age < or =9.5 y) adopted from developing countries were randomized for treatment for 2-4 y with GnRH analogue, or with a combination of GH and GnRH analogue. RESULTS: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below -2 standard deviation scores (SDS). CONCLUSION: The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators.

Adoption↗

Prevalence of coeliac disease in Turner syndrome.

This study was undertaken to investigate the prevalence of coeliac disease in children and adolescents with Turner syndrome. Eighty-seven children and adolescents with Turner syndrome were screened for IgA-antiendomysium antibodies (EMA) and IgA-antigliadin antibodies (AGA), 5% (4/87) being found to be EMA-positive, and 15% (13/87) to have AGA levels above normal. Of the 10 patients who were either AGA- or EMA-positive and further investigated with intestinal biopsy, four manifested villous atrophy (i.e. all three of the EMA-positive patients, but only one of the seven AGA-positive patients). The results suggest EMA-positivity to be a good immunological marker for use in screening for coeliac disease, and such screening to be justified in patients with Turner syndrome.

Adolescent↗

Effect of growth hormone (GH) during puberty in GH-deficient children: preliminary results from an ongoing randomized trial with different dose regimens.

This paper reports results from an ongoing, randomized, multicentre national trial. The aim is to elucidate whether a dose of growth hormone (GH) of 0.2 IU/kg (0.07 mg/kg), given either as once-daily or twice-daily injections during puberty, is more effective than a once-daily dose of 0.1 IU/kg/day (0.03 mg/kg/day) in improving final height in children with GH deficiency (GHD). The twice-daily regimen comes closer to the spontaneous GH secretion pattern in puberty. Ninety-two children with GHD who had been receiving GH therapy for at least 1 year, and with spontaneous puberty or who were prepubertal and due to be started on replacement therapy to induce puberty, were randomly assigned to receive GH as follows: group A, 0.1 IU/kg/day (0.03 mg/kg/day), administered once daily; group B, 0.2 IU/kg/day (0.07 mg/kg/day), administered once daily; and group C, 0.2 IU/kg/day (0.07 mg/kg/day), divided into two equal injections given at 12-hour intervals. Pubertal height gain was 0.7, 0.7 and 1.3 SDS for groups A, B and C, respectively. The gain in height during puberty was thus most marked in group C. Mean final height, when corrected for parental height, was between 0 and 1 SDS in all treatment groups. All but seven children reached a final height within +/- 2 SD of the general population. There was a wide range of final heights in all three treatment groups. This variation in response suggests the need to individualize treatment in order to achieve an appropriate final height for most individuals.

Adolescent↗

Urinary excretion of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid in children.

5-S-Cysteinyldopa (5SCD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) are formed during biosynthesis of melanins. They are used as indicators of pigment formation and markers of melanoma progression in adults and could possibly be used as markers of activity, growth and even malignant transformation in large pigmented naevi in children. We investigated the urinary excretion of these pigment precursor metabolites from 136 children, 5 to 15 years of age. The mean 5SCD excretion was 38.1 mumol/mol creatinine. A significant age-related decrease from a mean of 60.4 mumol/mol creatinine at 5 years of age to 28.0 mumol/mol creatinine at age 15 was found. In a reference group (29 adults, 20-33 years of age) the mean excretion was 48.9 mumol/mol creatinine. The mean excretion of 6H5MI2C was 42.8 mumol/mol creatinine at 5 years of age and 26.1 mumol/mol creatinine at the age of 15. The mean value for the young adults was 33.4 mumol/mol creatinine. No correlation between the mean excretion of 5SCD and 6H5MI2C was demonstrated. We suggest an upper reference level of 90 mumol/mol creatinine for the excretion of 5SCD in the age group 5-11 years and of 60 mumol/mol creatinine in the age group 13-15 years. Corresponding figures for the indole 6H5MI2C are 70 and 60 mumol/mol creatinine. The establishment of reference values in children will make it possible to use 5SCD and 6H5MI2C measurements as diagnostic tools, indicating growth or malignant transformation in giant melanocytic naevi during childhood.

Adolescent↗

Improved final height in girls with Turner's syndrome treated with growth hormone and oxandrolone.

The spontaneous growth process in Turner's syndrome is characterized by a progressive decline in height velocity during childhood and no pubertal growth spurt. Therefore, therapy aimed at improving height during childhood as well as increasing final height is desirable for most girls with Turner's syndrome. Forty-five girls with Turner's syndrome, 9-16 yr of age (mean age, 12.2 yr), were allocated to three study groups. Group 1 (n = 13) was initially treated with oxandrolone alone; after 1 yr of treatment, GH without (group 1a; n = 6) or with (group 1b; n = 7) ethinyl estradiol was added. Group 2 (n = 17) was treated with GH plus oxandrolone. Group 3 (n = 15) was treated with GH, oxandrolone, and ethinyl estradiol. The dosage were: GH, 0.1 IU/kg.day; oxandrolone, 0.05 mg/kg.day; and ethinyl estradiol, 100 ng/kg.day. A height of 150 cm or more was achieved in 61%, 75%, and 60% of the girls in groups 1, 2, and 3, respectively. The most impressive increase in height was seen in group 2. In this group the mean final height was 154.2 cm (SD = 6.6), which is equivalent to a mean net gain of 8.5 cm (SD = 4.6) over the projected final height. In group 3, in which ethinyl estradiol was included from the start of therapy, the initially good height velocity decelerated after 1-2 yr of treatment. Their mean final height was 151.1 (SD = 4.6) cm, equivalent to a mean net gain of 3.0 cm (SD = 3.8). A similar growth-decelerating effect of ethinyl estradiol was seen in group 1b. We conclude that in girls with Turner's syndrome who are older than 9 yr of age, treatment with GH in combination with oxandrolone results in significant growth acceleration, imitating that in normal puberty, leading to a more favorable height during childhood. This mode of treatment also results in a significantly increased final height, permitting a great number of the girls to attain a final height of more than 150 cm. However, early addition of estrogen decelerates the height velocity and reduces the gain in height.

Adolescent↗

Thyroid autoantibodies, Turner's syndrome and growth hormone therapy.

The prevalence of thyroid autoantibodies, i.e. thyroglobulin antibodies and antibodies to thyroid peroxidase, was analyzed in 89 girls, aged 3-16 years (mean age 10 years), with Turner's syndrome. The analyses were performed before the start of growth-promoting treatment and during a follow-up period of 1-5 years. The patients were divided into four groups according to karyotype as follows: group 1, 45, X (n = 63); group 2 with structural abnormalities of the X chromosome (n = 10); group 3 with mosaicism but no structural abnormalities of the X chromosome (n = 10); and group 4, with isochromosome X of the long arm (n = 12): 199 healthy girls aged 12 years, served as controls. Thyroid autoantibodies were demonstrated in 46 of 89 (52%) patients with Turner's syndrome compared with 34 of 199 (17%) age-matched control girls (p < 0.001), thus confirming the relationship between thyroid abnormalities and Turner's syndrome. There was also an increase in the prevalence of thyroid antibodies with age. Simultaneous presence of both autoantibodies was significantly more frequent in group 1 (45, X) and group 4 (isochromosome X of the long arm) than in group 3 (mosaicism) (p = 0.04 and p < 0.002, respectively) and significantly more frequent in group 4 than in group 1 (p < 0.05). During 12-60 months of growth-promoting treatment, no increase in the prevalence of thyroid antibodies was observed. The findings demonstrate the importance of continuous monitoring of thyroid function in girls with Turner's syndrome.

Adolescent↗

Serum osteocalcin and bone and liver alkaline phosphatase isoforms in healthy children and adolescents.

We report reference values for osteocalcin and bone and liver alkaline phosphatase (ALP) isoforms in serum from 114 healthy children and adolescents, age 7-16 y. The bone and liver ALP isoforms were measured by high performance liquid chromatography (HPLC). Six ALP isoforms were separated and quantified in all samples: one bone/intestinal (B/I), two bone (B1 and B2), and three liver ALP isoforms (L1, L2, and L3). It is especially important to make distinctions between ages and gender during puberty in the interpretation of biochemical markers of bone. We observed that girls reached adult levels for osteocalcin, total ALP, and bone ALP isoforms, B/I, B1, and B2, earlier than boys. Girls in the oldest age group (15-16 y) and in the pubertal stage groups IV-V, reached higher levels than boys for the calculated ratio B1/B2 due to a more rapid decline of B2 compared with B1. This observation might indicate that B2, to a higher extent than the B1 isoform, represent a more mature expression of osteoblast differentiation during matrix mineralization in growing bone. Serial measurements of these new bone ALP isoforms could provide new insights into bone and mineral metabolism.

Adolescent↗

Effects of age, obesity and growth-hormone on adipogenic activity in human plasma.

The potential was examined for insulin, growth hormone and insulin-like growth factor (IGF-1) alone or in combinations to stimulate glycerophosphate dehydrogenase (GPDH) activity, a sensitive marker of differentiation of adipose precursor cells in primary culture. Insulin, but not growth hormone or IGF-1, stimulated GPDH in the presence of fetal calf serum and cat serum. The content of growth hormone in adult rat heparinised plasma seemed, however, important for such stimulation, but was also dependent on feeding status of the plasma donor, and was abolished by hypophysectomy of the cell donor. GPDH activity was then analysed in heparinised plasma in the over-night fasting state in humans to examine a potential influence of age, obesity and pregnancy. In comparison with non-obese adults, GPDH-stimulatory activity was higher in plasma from infants and small children. A similar trend was seen in plasma from teenagers. This activity was probably partly dependent on growth hormone, because this increase of activity could be inhibited by excess of anti-human growth hormone antiserum. Obesity in adulthood or among teenagers was not associated with any difference in plasma activity to stimulate cellular differentiation, and plasma from women during late pregnancy had a low stimulating capacity. Simultaneous analyses of the potential of plasma to stimulate lipid accumulation in adipose precursor cells was proportional to the triglyceride concentration. Overall, the inhibitory effect of antihuman growth hormone antiserum on the differentiating capacity of human plasma was small or non-existing. It is therefore suggested that in human plasma, factors other than growth hormone might be important for the differentiation of adipocyte precursor cells.

Adipose Tissue↗

Pancreatic B-cell function and abnormal urinary peptides in a boy with lipoatrophic diabetes and stenosis of the aqueduct of Sylvius.

A boy with the classical clinical manifestations of acquired lipoatrophic diabetes has been studied for 5 years from the onset of diabetes at age 13. At the age of 15 a ventriculo-cisternal shunt operation was performed because of stenosis of the aqueduct of Sylvius, followed by a dramatic improvement in his diabetic state with a decrease of the 24 hr insulin requirement from 130 to 32 units. After 12 months there was a relapse with increased insulin requirement up to the preoperative level. Pimozide treatment was given for 7 months with no effect on the metabolic derangements. Extremely high basal levels of serum C-peptide and pro-insulin were found throughout the period of observation. A further increase occurred after i.v. arginine infusion tests, indicating hyperfunctioning B-cells. Repeated screenings of peptides in the urine by sephadex chromatography revealed pathological patterns similar to those observed in patients with other hypothalamic disorders, but different from that found in the urine of patients with congenital generalized lipodystrophy. Injection into mice of peptides extracted from the preoperative urine produced an acute hyperglycemia. The mechanisms behind this hypothalamic syndrome are unknown, but it is postulated that the abnormal urinary polypeptides originate from disorganized hypothalamic centres and that these peptides may be responsible for the disturbed carbohydrate and lipid metabolism.

Adolescent↗

Sensory nerve conduction velocity and vibratory sensibility in juvenile diabetics. Relationship to endogenous insulin.

Sensory nerve conduction velocity (NCV) and the vibratory sense (biothesiometry) were determined in 67 children and adolescents with insulin dependent diabetes. Age at onset of diabetes varied between 1-14 years (mean +/- S.D. 6.5 +/- 3.6) and the duration of diabetes between 4-17 years (7.7 +/- 3.4). Within +/- 3 months of the nerve function tests blood was drawn for determination of C-peptide and insulin antibodies (IgG and IRI). A low NCV (less than 50 m/s) in the sural nerve and/or an abnormal vibratory sense (greater than or equal to 1.0 microns) were found in 34 patients (50.7%). Measurable fasting serum C-peptide 0.04-0.60 pmol/ml (0.17 +/- 0.15) was found in 16 patients (23.9%). All but one patients had insulin antibodies with IgG 0.130-11.029 mU/ml (2.957 +/- 2.509) and total IRI 10-9120 muU/ml (1204 +/- 1723). In multiple regression analysis we did not find any correlation between nerve function and sex, age, or age at onset of diabetes, and there was only a weak relationship between NCV and duration. However, there was a positive correlation between NCV and C-peptide (p less than 0.001). Vibration sense was also better among patients with C-peptide (p less than 0.05). The results support the view that insulin deficiency contributes to peripheral diabetic neuropathy.

Adolescent↗

Insulin secretion and peripheral insulin sensitivity in obese children. Evidence of deficient glucose-stimulated early insulin release despite hyperinsulinemia.

Insulin secretion and peripheral insulin sensitivity were studied in 19 grossly-obese girls and 17 age-matched non-obese girls by means of the intravenous glucose tolerance test (IVGTT) and the simulated early insulin response test (SERT) respectively. SERT measures the fall in fasting blood glucose after a short infusion of insulin, performed so as to simulate the early phase of insulin release to the acute stimulus of an intravenous glucose load (ERex). In the IVGTT, the obese girls showed significantly increased early insulin response (ERend) in comparison with the non-obese girls. The glucose disappearance rate (KG) was similar in the two groups, although four obese girls had borderline low values. In the SERT, the rise in plasma insulin caused a much smaller decrease in blood glucose in the obese girls, than in the reference girls over the whole range of insulin levels studied. The relationship between insulin sensitivity and insulin secretion of each subject was evaluated from the plot of the ERex/ERend ratio vs blood glucose decrement. This showed that the hyperinsulinemia of the obese girls did not match the degree of peripheral resistance.

Blood Glucose↗