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Biomedical subjects

M B Ranke

Publications and source records attributed to M B Ranke.

At least 163 records · Page 9Linked to original sources
PubMed1994

Adult height in Turner syndrome: results of a multinational survey 1993.

Under the auspices of ESPE/LWPES, a survey on spontaneous adult height in patients with Turner syndrome was conducted in 12 European countries. A total of 661 patients (45,X = 51%) with a median age of 23.6 years (range: 16-63) who had never received any growth-promoting treatment until the age of 14 had reached a mean height of 144.3 +/- 6.7 cm. There was no height difference between those (n = 220) who had received oxandrolone and/or estrogen after the age of 14 years and those (n = 441) who never received any treatment until the age of 20. On average, there was no major gain in height after an age of 16 years. The height achieved was positively associated with the height of normal women in the underlying population. There was a high positive correlation (r = 0.436; p < 0.0001) between adult height and target height in adults never treated. A positive correlation of these parameters was present irrespective of karyotype (45,X vs. 'others') or treatment with oxandrolone/estrogen. The findings strengthen the observations on height development from national studies.

Adolescent↗
PubMed1993

Serpentine fibula--polycystic kidney syndrome and Melnick-Needles syndrome are different disorders.

We report on the third patient with serpentine fibula-polycystic kidney syndrome. Main features in the three reported cases were growth retardation, abnormal face, hirsutism, short neck, bowed forearms and lower legs due to bowed radii and elongated serpentine fibulae, and metatarsus adductus. Two patients including our own were deaf. All were mentally normal, all were female and sporadic. In addition, we report on a girl with Melnick-Needles syndrome and illustrate the similarities and differences between these syndromes.

Child↗
PubMed1993

Decreased serum levels of insulin-like growth factors and IGF binding protein 3 in osteoporosis.

OBJECTIVES: The aim of the study was to investigate endogenous growth hormone (GH) secretion in patients with osteoporosis and in patients with degenerative bone diseases or no spinal disease by measuring serum insulin-like growth factors 1 and 2 (IGFs) and their major binding protein 3 (BP-3) as an indirect parameter of GH secretion. DESIGN: A cross-sectional study. SETTING: All patients were seen as out-patients of the Endocrinology Department of the University of Heidelberg where all bone parameters were measured. IGFs and BP-3 serum levels were measured at the Children's Hospital of the University of Tübingen. SUBJECTS: A total number of 310 patients were studied. The group with primary osteoporosis and vertebral fractures (OPO) consisted of 141 patients (98 females, 43 males). Spinal degenerative bone disease or osteoarthritis (DEG) was present in 108 patients (91 females, 17 males). Sixty-one control patients (56 females, 5 males) had no spinal disease on X-ray, but presented with lower back pain. MAIN OUTCOME MEASURES: Serum levels of IGFs, BP-3, PTH and 25-vitamin D3 were measured by radioimmunoassay. Bone mineral density (BMD) was determined using absorptiometry; anthropometric parameters and menopausal status were recorded. RESULTS: There was no difference in age and years after menopause between OPO and DEG, but control individuals were younger. Mean IGFs and BP-3 serum levels in patients with OPO were lower (P < 0.001) than those in patients with DEG or in controls. Patients with DEG had significantly higher BP-3 levels than controls (P < 0.001). There was a significant (P < 0.05) negative correlation of BP-3 with age in females with OPO, but not in controls or in DEG patients. The IGFs did not decrease with age in any of the three groups. Binding protein 3 was positively correlated (P < 0.05) with BMD in postmenopausal women with OPO but not in controls or DEG patients. CONCLUSION: We conclude that systemic IGFs and IGF binding protein 3 are decreased in patients with osteoporosis. Further studies are needed to investigate whether this is as a result of diminished secretion of endogenous GH and whether this reflects the local circumstances of IGFs and IGF binding proteins in bone.

Adult↗
PubMed1993

Growth hormone insensitivity syndromes: a preliminary report on changes in insulin-like growth factors and their binding proteins during treatment with recombinant insulin-like growth factor I. Kabi Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes.

Serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with growth hormone (GH) insensitivity syndromes (GHIS) before and during treatment with IGF-I. As in normal subjects, there was a highly significant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-third of the total IGFBP concentration. In 6 patients with GH deficiency and in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentration. A slight but significant increase in IGFBP-3 was observed coincident with the IGF-I peak, whereas IGFBP-2 increased after a delay of about 10 hours. In the patients with GHIS, chronic IGF-I treatment, with twice-daily injections for 6 months, caused a significant steady decline of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 and IGFBP-3 levels. During IGF-I treatment, an inverse relationship between baseline IGF-I and GH levels was observed. The data suggest that total IGF-I and IGF-II serum levels are determined mainly by IGFBP-3, even in extreme situations such as GHIS, while other IGFBPs are less important. The IGFBP-3 concentration seems to be a major regulator of the pharmacokinetics of exogenous IGF-I, which, in turn, influences IGFBP-3 levels. This effect of IGF-I on IGFBP-3 is not through induction of IGFBP-3 synthesis, but possibly by reduction of IGFBP-3 clearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Prediction of the growth response in children with various growth disorders treated with growth hormone: analyses of data from the Kabi Pharmacia International Growth Study. International Board of the Kabi Pharmacia International Growth Study.

Analyses to predict the growth response to recombinant human growth hormone (GH) in prepubertal children during the first year of treatment were performed on data from 472 patients with idiopathic GH deficiency (IGHD), 202 children with Turner's syndrome, 327 children with idiopathic short stature (ISS) and 135 children with intrauterine growth retardation (IUGR). In IGHD, 56% of the variability of the response could be predicted from a model based on six variables. These variables could be ranked in order of importance as follows: target height SDS minus height SDS, chronological age, frequency of GH injections, dose of GH, weight-for-height index, and birth weight SDS. When the model for IGHD was applied to Turner's syndrome, ISS and IUGR, there was a high degree of similarity between the predicted and achieved growth response in ISS and IUGR. However, an uneven distribution within the plot of Studentized residuals in ISS and IUGR suggested heterogeneity within these populations. Prediction of growth in Turner's syndrome was greatly exaggerated by the model for IGHD, suggesting a different pathogenesis as the basis of the growth disorder. Specific prediction models were therefore developed for Turner's syndrome, ISS and IUGR. In all three disorders, the dose of GH was found to be the most important predictor, suggesting that, in contrast to IGHD, first-year growth is governed less by the difference between height and the presumed genetically determined target height. Again, in contrast to IGHD, this suggests that catch-up phenomena are not involved.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight↗
PubMed1993

Effects of growth hormone on the metabolism of lipids and water and their potential in causing adverse events during growth hormone treatment.

GH effects certain changes in the metabolism of lipids and body water in humans. The effects of GH, such as high blood pressure, an increase in cholesterol and triglycerides, and lipoatrophy, among others, must, however, be seen in the context of the diverse disorders being treated. The risks faced in acromegaly, for instance, are not necessarily shared by Turner's syndrome patients treated with GH. The various metabolic effects of GH could thus be said to lead to adverse events in certain risk groups, which makes the monitoring of relevant parameters essential during treatment with GH.

Growth Hormone↗
PubMed1993

Serum levels of insulin-like growth factor I (IGF-I) and IGF binding protein 3 reflect spontaneous growth hormone secretion.

The relationship between 24-h GH secretion, insulin-like growth factor (IGF) I serum levels, IGF-binding protein 3 (IGFBP-3) levels and height was studied in 114 healthy children and adolescents (147 tests). A significant correlation was found between the spontaneous GH secretion expressed as the area under the curve above baseline (AUCb) or the calculated 24-h GH secretion rate (GHb) and IGF-I (n = 147, r = 0.65, or 0.78, respectively, P < 0.001) or IGFBP-3 levels (r = 0.48 or 0.62, P < 0.001). Correlations were also significant within the various subgroups [females (n = 51), males (n = 96), prepubertal children (n = 75), pubertal children (n = 72)]. The slopes of the regression lines of IGF-I levels vs. AUCb or GHb were clearly steeper in pubertal children than in prepubertal ones; this was not as evident with IGFBP-3. In prepubertal children, a significant correlation was found between height (compared to Swedish reference values) standard deviation scores (SDS) and IGF-I SDS (n = 75, r = 0.66, P < 0.001) or IGFBP-3 SDS (r = 0.61, P < 0.001). The reproducibility during repeated testing (19 individuals, 6 prepubertal) was best with IGFBP-3 as compared to AUCb, GHb, or IGF-I which showed considerable variability. The data suggest: 1) that IGF-I and IGFBP-3 serum levels reflect spontaneous GH secretion in healthy individuals; 2) IGF-I levels are more sensitive to GH regulation than IGFBP-3; 3) in puberty, there may be increased sensitivity of IGF-I regulation by GH as compared to the prepubertal stage; 4) short children have low IGF-I and IGFBP-3 levels, whereas tall children have high levels, a fact which is likely to contribute to the understanding of height variability in a healthy population; 5) the good reproducibility of IGFBP-3 on repeated testing makes it an interesting parameter for the evaluation of the GH-IGF-axis. IGFBP-3 measurements may substitute for GH profiles in many cases, when the goal is an estimation of the GH secretion rate.

Adolescent↗
PubMed1993

Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome).

Twenty-seven patients with GH insensitivity were identified from 44 possible cases, using a scoring system based on height standard deviation score (SDS), basal GH, insulin-like growth factor-I (IGF-I), IGF-I response to IGF-I generation test, and GH-binding protein (GH-BP) determinations. The 27 cases were from 8 European countries and Australia. Clinical features were as follows: age 2.8-22.6 yr; 12 male, 15 female, 19 prepubertal. Birth weight was median -0.72 SDS (1.75(-)-3.29) and birth length, median -1.59 SDS (0.63(-)-3.63). Hypoglycemia had been documented in 33% of the cases, and micropenis was present in 58% of the males. At assessment, height was median -6.1 SDS (-3.8(-)-10.2), weight was median -3.2 SDS (-0.1 to -5.2), and percentage weight for height, median 111.3 (72-271). Puberty was absent in 2 boys aged 15 yr and in 3 girls aged 13 yr. Bone age was delayed in 19 of the 27 patients. Endocrine investigations showed basal serum GH median 17 micrograms/L (0.5-79), IGF-I values less than 5th percentile, and all except 2, age less than 8 yr, less than 0.1 percentile for age. Percentage increment of IGF-I during IGF-I generation test (hGH 0.1 U/kg body weight daily x 4) did not exceed twice the intraassay coefficient of variation, being less than 0.1 percentile for age. IGF-II was median 135.0 micrograms/L (62-232), all values being less than 5th percentile for age. Insulin-like growth factor binding protein-3 (IGFBP-3) values were median 0.53 mg/L (0.10-1.17 mg/L), all being less than 5th percentile for age. IGFBP-3 values after hGH remained less than 5th percentile. IGFBP-1 values showed the normal fall with age, some being above the normal range; IGFBP-2 values were normal. There was a positive correlation between height SDS and IGF-II SDS (r = 0.66, P < 0.001) and IGFBP-3 (r = 0.64, P < 0.001). Specific binding of [125I]hGH to GH-BP was undetectable in 18 patients and extremely low (< or = 5.6%) in 2. GH-BP was normal (14.2-45.9% radioactivity) in 7 subjects, all female, demonstrating that normal GH-BP does not exclude GH insensitivity.

Adolescent↗
PubMed1993

Insulin-like growth factors (IGF) I and II and IGF binding proteins 1, 2 and 3 during low-dose growth hormone (GH) infusion and sequential euglycemic and hypoglycemic glucose clamps: studies in GH-deficient patients.

To evaluate the short-term effects of growth hormone (GH), insulin and different levels of glycemia on insulin-like growth factors (IGF) I and II and IGF binding proteins (IGFBP) 1, 2 and 3, we studied six GH-deficient adolescents during a night and the following day in the postabsorptive (basal) state followed by sequential euglycemic (5 mmol/l) and hypoglycemic (3 mmol/l) glucose clamps concomitant with an intravenous infusion (starting at 24.00 h) of GH (35 micrograms/h) or saline. Current GH therapy was withdrawn 24 h prior to each study. Nocturnal levels of IGF-I, IGF-II, IGFBP-2 and IGFBP-3 remained stable during both studies. Nocturnal serum IGFBP-1 increased and correlated inversely with insulin in both studies. Regression analysis revealed a significant inverse correlation between mean nocturnal IGFBP-2 and IGFBP-3 levels. During the daytime, serum IGF-I declined slowly during saline infusion, whereas serum IGF-II remained stable in both studies. Serum IGFBP-1 displayed a gradual significant decline during the basal state and the euglycemic and hypoglycemic clamps seemed to be unaffected by GH levels. By contrast, serum IGFBP-2 remained stable during the same period in both the GH and the saline study. Serum IGFBP-3 declined insignificantly during the daytime in the saline study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Clinical studies of IGFBP-2 by radioimmunoassay.

A specific radioimmunoassay for human IGFBP-2 was developed using a polyclonal antiserum directed against a partial sequence (hIGFBP-2(176-190)). The tracer was prepared by radioiodination of a [Tyr]o-hIGFBP-2(176-190) derivative. The assay was used to study IGFBP-2 levels in numerous clinical and experimental situations. There was little circadian fluctuations of serum level which showed a marked age-dependence with high levels at birth and senescence and low levels during puberty. Decreased IGFBP-2 levels were present in untreated insulin-dependent diabetes mellitus (IDDM), in acromegaly and during dexamethasone suppression test. GH deficiency, fasting, IGF-I administration to patients with GH receptor deficiency, hepatic failure and insulinomas caused a moderate increase of serum IGFBP-2. Markedly elevated levels were found in chronic renal failure, non-islet cell tumour induced hypoglycemia and leukaemias. The fact that all possible relationships between insulin secretion and IGFBP-2 levels could be identified suggests that insulin is not a major regulator. In general, there was an inverse relationship with serum IGFBP-3 (except IDDM) and IGFBP-2 levels were high in situations where free IGF-II should be expected to be high. The tentative conclusion would therefore be that free IGF-II is a major regulator of circulating IGFBP-2.

Animals↗
PubMed1992

Increased insulin-like growth factor-II tissue concentrations during compensatory kidney growth in infantile rats.

Insulin-like growth factor (IGF)-I and IGF-II serum and kidney tissue concentrations were measured in compensatory kidney growth in infantile and adult rats. We hypothesized that the known switch from IGF-II in fetal life to IGF-I in adult life may be responsible for the different modes of compensatory kidney growth, which are mainly characterized by hyperplasia in infantile rats and hypertrophy in adult rats. While IGF-I serum concentrations increased with age in infantile rats, kidney tissue concentrations of IGF-I showed a similar increase in both age groups after uninephrectomy. In adult rats, serum and kidney tissue concentrations of IGF-II were unchanged by uninephrectomy. In infantile rats, however, a significant increase in both serum and kidney concentrations of IGF-II was observed with a maximum at day 5 after uninephrectomy. To investigate if compensatory kidney growth is dependent on hyperperfusion of the remnant kidney, the left renal artery was clipped in infantile rats. The clipped kidney showed growth retardation despite normal kidney tissue concentrations of IGF-I and IGF-II. The contralateral kidney was enlarged and IGF-II kidney concentrations were elevated. However, animals with one clipped kidney and nephrectomy of the contralateral kidney showed compensatory kidney growth of the clipped kidney combined with increased IGF-II kidney tissue concentrations. We conclude that IGF-II mainly promotes compensatory kidney growth in infantile rats by hyperplasia. Hyperperfusion of the remnant kidney seems to be unnecessary for initiation of compensatory kidney growth.

Aging↗
PubMed1992

IGF binding protein 3 in patients with Laron type dwarfism: effect of exogenous rIGF-I.

OBJECTIVE: The aim of the study was to investigate the serum levels of IGFBP-3, the major IGF-I binding protein, in patients with Laron type dwarfism (LTD) before and after IGF-I treatment. DESIGN AND PATIENTS: Eight Laron type dwarfism patients (four children and four adults) were treated for 7 days by one daily s.c. injection of biosynthetic IGF-I in doses of 120 or 150 micrograms/kg/day. MEASUREMENTS: Blood was sampled in the fasting state before and 1 and 7 days after the last injection. RESULTS: It was found that IGF-I administration significantly reduced plasma hGH levels with recovery after one week of no treatment. Serum IGFBP-3 was abnormally low (0.70 +/- 0.37 mg/l) and decreased significantly further during IGF-I treatment (to 0.48 +/- 0.28 mg/l) (P less than 0.065). CONCLUSIONS: The finding that serum IGFBP-3 is low in Laron type dwarfism, a disease due to molecular defects in the GH receptor, is compatible with the hypothesis that this IGF binding protein is GH-dependent. On the other hand the decrease during IGF-I administration and concomitant suppression of GH secretion may denote either that GH activity is not completely blocked in this syndrome or that there are additional mechanisms regulating IGFBP-3 synthesis.

Adolescent↗
PubMed1991

Growth hormone resistance and inhibition of somatomedin activity by excess of insulin-like growth factor binding protein in uraemia.

Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) were studied in children with end-stage renal failure (ESRF, n = 31) and chronic renal failure (n = 11) with residual glomerular filtration. Somatomedin bioactivity in patient sera was found to be decreased while IGF-I and IGF-II levels by radio-immunoassay (RIA) were normal. In contrast, IGFBP-1 and IGFBP-3 levels (measured by RIA) were markedly increased in uraemia. Excess IGFBP was shown to be able to bind IGF by determination of the free IGF binding capacity. Using high-performance liquid chromatography a shift of the IGFBP-3 profile to low molecular weight components could be demonstrated in ESRF. Affinity cross-linking experiments showed that these low molecular weight IGFBP-3 immunoreactive forms are biologically active. In normal urine only IGFBP-3 forms smaller than 60 kDa were detected with a major peak at 12-20 kDa. Removal of excessive IGFBP from patient sera by affinity chromatography on an IGF-II Sepharose column resulted in a significant increase in somatomedin bioactivity. Model calculations on the interaction of IGF and IGFBP using empirical data suggested a reduction of IGF secretion in uraemia by an order of magnitude. It is concluded: (1) that renal failure causes an accumulation of low molecular weight IGFBP, (2) that the resulting excess of IGFBP acts as a somatomedin inhibitor, and (3) that in uraemia there is a relative growth hormone resistance with respect to IGF production.

Adolescent↗
PubMed1991

Insulin-like growth factors and their binding proteins in human follicular fluid.

Increasing evidence suggests that insulin-like growth factors I and II (IGF-I, IGF-II) have a regulatory role in animal granulosa cells. This study was undertaken to investigate the presence of IGF-I and IGF-II, as well as that of their binding proteins (BP), IGFBP-1 and IGFBP-3 in human serum and follicular fluid (FF). Preovulatory FF was obtained from 51 patients undergoing in-vitro fertilization. The IGFBP-1 level was found to be significantly higher (P less than 0.01) in FF than in serum, whereas IGF-I and IGFBP-3 values remained markedly lower (P less than 0.01) in FF. Serum IGF-II levels were slightly but not significantly elevated compared to values obtained in the FF of patients. A positive correlation (P less than 0.001) between individual serum and FF levels was observed only for IGF-I. When a group of poor responders was compared to patients with normal stimulation characteristics, no significant difference was found in either IGF or IGFBP levels in the FF. It is concluded that IGFBP-1 is produced locally, whereas the serum may possibly be the major source of IGF-I. No clear conclusions can be drawn regarding the source of FF IGF-II and IGFBP-3. Neither the absolute level nor the relationship of IGFs to their transport proteins could explain the poor response to ovarian stimulation.

Body Fluids↗
PubMed1991

Clinical spectrum of the syndrome of growth hormone insensitivity. Advisory Committee on Growth Hormone Insensitivity.

A survey of 46 patients with suspected growth hormone (GH) insensitivity is presented. Clinical details and plasma samples from these patients were analysed centrally. A diagnostic score based on basal levels of GH and insulin-like growth factor I (IGF-I), IGF-I response to GH (0.1 U/kg daily for 4 days) and height SDS was determined for all patients to identify those with GH insensitivity. A total of 29 such patients was identified (14 males and 15 females; age range, 3.2-22.6 years). Their mean height SDS was -6.0 (range, -8.9 to -2.6), mean weight SDS was -2.9 (range, -5.2 to 1.2). Pubertal development was delayed in three out of three boys and two out of six girls of pubertal age. Their basal GH level was 32.4 mU/l (range, 0.8-158.2 mU/l) and mean basal IGF-I level was 33.6 ng/ml (range, 20-97 ng/ml). None of the 29 patients showed a significant serum IGF-I response to injections of GH.

Adolescent↗