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C Hagen

Publications and source records attributed to C Hagen.

At least 37 records · Page 2Linked to original sources
PubMed2000

Growth hormone treatment in adults with adult-onset growth hormone deficiency increases iliac crest trabecular bone turnover: a 1-year, double-blind, randomized, placebo-controlled study.

The effects of growth hormone (GH) substitution on bone metabolism were evaluated by dynamic histomorphometry on iliac crest bone biopsies. Twenty-nine patients, aged 21-61 years (mean 45.5 years), with adult-onset GH deficiency (GHD) were randomized to receive subcutaneous injections with GH (2 IU/m2/day = 0.67 mg/m2/day) or placebo for 12 months. Serum insulin-like growth factor I (IGF-I) levels increased 263 +/- 98% (mean +/- SD) during GH treatment (p < 0.0001). In the GH group, osteoid surface increased during treatment from 11% (3-15%) (median [25-75 percentiles]) to 21% (10-27%) (p = 0.01) and mineralizing surface from 4% (1-8%) to 11%(7-16%) (p = 0.04). Moreover, erosion surface tended to increase in the GH group from 2% (1-3%) to 4% (3-5%) (p = 0.07). The quiescent surface decreased in the GH group from 87% (83-96%) to 74% (68-87%) (p = 0.01). The adjusted appositional rate, mineral apposition rate, bone formation rate, bone erosion rate, mineralization lag time, and osteoid thickness remained unchanged during treatment. Erosion depth showed a trend toward increase in the GH group (p = 0.09), whereas wall thickness was unchanged. Bone balance at the remodeling unit level and activation frequency were unchanged. At the tissue level, bone erosion rate increased significantly from 26% (17-36%)/year to 39% (23-72%)/year (p = 0.03). Similarly, the bone formation rate at the tissue level tended to increase, from 24% (15-31%)/year to 36% (17%-63%)%/year (p = 0.06). Finally, bone balance at the tissue level decreased significantly from 1% (-2-2%)/year to -5% (-13-1%)/year (p = 0.01). No significant difference in change was seen in the cancellous bone volume. We conclude that 12 months of GH substitution therapy increases trabecular bone turnover. Moreover, our data suggest that bone balance at the bone multicellular unit level is not changed to positive.

Adult↗
PubMed1999

Posterior distal cement extrusion during primary total hip arthroplasty: a cause for concern?

Manually operated injection systems are routinely used to deliver polymethyl methacrylate during cemented femoral component primary total hip arthroplasty (THA). The goal of cement delivery is to achieve sufficient intrusion of cement into the trabecular bone of the prepared femur so that the femoral component is securely bonded to the femur. We have observed posterior distal cement extrusion (PDCE), which appears to be secondary to too-successful pressurization. We sought to quantify and offer a possible explanation for this phenomenon. Eight patients with PDCE were identified, with an estimated incidence range of 0.90%, to 1.6% of primary cemented femoral component THA. All occurred in female patients of small stature. Endosteal canal diameters were also small, averaging 11 mm, 10 cm from the lesser trochanter. The PDCE occurred at an average distance of 9.8 cm from the midpoint of the lesser trochanter, and was most easily visualized on the lateral radiograph where it resided in the posterior soft tissues. Examination of 49 human femora showed 1 or more vascular channels in the posterior aspect of the femur in all specimens. The most proximal vascular channel averaged 10.1 cm distal to the lesser trochanter and had an average lumen diameter of 1 mm. The vascular channel contained an artery and 2 veins by histologic examination. We postulate that PDCE represents the escape of low-viscosity cement out of the vascular channel, and laboratory simulation supports this possibility. Because this finding has not previously been reported, we hoped that other centers will look closely for this phenomenon.

Aged↗
PubMed1999

Low serum levels of free and total insulin-like growth factor I (IGF-I) in patients with anorexia nervosa are not associated with increased IGF-binding protein-3 proteolysis.

Patients with anorexia nervosa (AN) are GH resistant, with elevated GH levels and low serum levels of total insulin-like growth factor I (IGF-I). IGF-I action is modulated by IGF-binding proteins (IGFBPs), and a variety of catabolic states has been characterized by the presence of increased IGFBP-3 proteolysis. The present study was performed to examine the levels of free IGFs in AN and to clarify whether AN is associated with increased IGFBP-3 proteolytic activity. In 24 patients and 10 age-matched controls, the fasting serum concentrations of free IGF-I and -II were measured using ultrafiltration by centrifugation. In addition, GH, GH-binding protein, total IGFs, IGFBP-1 to -4, and IGFBP-3 proteolytic activity were measured. The IGFBPs were measured by both immunoassays and Western ligand blotting. Twelve of the patients were restudied 3 months after a minor increase in body mass index. In AN, the levels of GH-binding protein, free and total IGF-I, free IGF-II, and IGFBP-3 were significantly reduced; total IGF-II, IGFBP-2, and IGFBP-4 levels were unchanged; and IGFBP-1 was increased. No increased IGFBP-3 proteolytic activity could be detected in AN. In conclusion, the mechanisms responsible for the adaption of the GH-IGF-IGFBP axis in AN may be different from other catabolic conditions, because the low levels of free and total IGF-I in AN are not associated with increased IGFBP-3 proteolysis.

Adult↗
PubMed1999

The effects of endogenous opioids and cortisol on thyrotropin and prolactin secretion in patients with Addison's disease.

This study assessed the controversial role of endogenous opioids and cortisol in the regulation of TSH and PRL secretion in humans. Seven euthyroid male patients with Addison's disease were studied four times, with an interval of 1-3 months, as follows: 1) during normocortisolism [graduated infusion of hydrocortisone, 0.4 mg/kg, over 19.5 h]; 2) normocortisolism and coadministration of naloxone, at 25 microg/kg x h during the last 6.5 h; 3) hypocortisolism (24 h withdrawal of hydrocortisone, followed by 19.5 h saline infusion); and 4) hypocortisolism plus naloxone administration. The TSH and PRL levels were measured every 15 min, from 0800-1530 h. A TRH test was performed at 1300 h and 1400 h (10 microg and 200 microg of TRH, respectively). The mean TSH level increased significantly during hypocortisolism, compared with normocortisolism (1.78 +/- 0.04 vs. 0.84 +/- 0.02 mU/L; P < 0.001). The administration of naloxone suppressed the TSH levels during hypo- and normocortisolism (1.78 +/- 0.04 vs. 1.50 +/- 0.03 and 0.84 +/- 0.02 vs. 0.61 +/- 0.02 mU/L, respectively; P < 0.001). During hypocortisolism, the TSH responses to small and high doses of TRH were significantly higher than during normocortisolism (P < 0.02). Naloxone had no effect on the TSH responses to TRH, neither during hypo- nor during normocortisolism. The mean PRL level increased significantly during hypocortisolism, compared with normocortisolism (5.8 +/- 0.4 vs. 3.6 +/- 0.2 microg/L; P < 0.001), and naloxone induced an increase in PRL levels both during hypo- and normocortisolism (7.1 +/- 0.7 vs. 4.7 +/- 0.5 microg/L, respectively; P < 0.01). The PRL responses to TRH were similar during hypo- and normocortisolism and without any change during opioid receptor blockade. In conclusion, cortisol suppressed basal TSH and PRL secretion and reduced the sensitivity of the thyrotrophs to TRH, without affecting the PRL response to TRH. Our results suggest that endogenous opioids act at the hypothalamic level to stimulate TSH secretion and to suppress the PRL secretion, but these results argue against an essential role of endogenous opioids in the physiological regulation of TSH and PRL secretion in humans.

Addison Disease↗
PubMed1999

Jointly amplified basal and pulsatile growth hormone (GH) secretion and increased process irregularity in women with anorexia nervosa: indirect evidence for disruption of feedback regulation within the GH-insulin-like growth factor I axis.

Anorexia nervosa (AN) is associated with multiple endocrine alterations. In the majority of AN patients, basal and GHRH-stimulated serum GH levels are increased. The metabolic effects of GH are known to be related to its pulsatile secretory pattern. The present study was performed to examine GH pulsatility in AN using the techniques of deconvolution analysis and approximate entropy, which quantify secretory activity and serial irregularity of underlying hormone release not reflected in peak occurrence or amplitudes. To this end, 24-h GH profiles were obtained by continuous blood sampling aliquoted at 20-min intervals in 8 nonfasting patients with AN [body mass index (BMI), 14.2 +/- 0.8 kg/m2; mean +/- SEM) and in 11 age-matched healthy women (BMI, 20.3 +/- 0.5 kg/m2). The deconvolution-estimated half-life of GH was not altered in the AN patients. The pituitary GH secretory burst frequency, burst mass, and burst duration were each significantly increased in women with AN compared to those in normal weight women. A 4-fold increase in daily pulsatile GH secretion was accompanied by a 20-fold increase in basal (nonpulsatile) GH secretion. There were significant negative correlations between BMI and the basal as well as pulsatile GH secretion rates. Moreover, AN patients exhibited significantly greater GH approximate entropy scores than the controls, denoting marked irregularity of the GH release process. In contrast to previous reports in healthy fasting subjects, cortisol levels in AN patients were positively correlated to GH secretion rates. Leptin levels were significantly inversely correlated to the pulsatile, but not the basal, GH secretion rate. The present data demonstrate augmented basal as well as pulsatile GH secretion with disruption of the orderliness of the GH release process in AN. Accordingly, GH secretion in AN probably reflects altered neuroendocrine feedback regulation, e.g. associated with increased hypothalamic GHRH discharge superimposed on reduced hypothalamic somatostatinergic tone.

Activity Cycles↗
PubMed1998

Lack of effect of the dopamine D1 antagonist, NNC 01-0687, on unstimulated and stimulated release of anterior pituitary hormones in males.

Dopamine in humans inhibits the secretion of luteinizing hormone (LH), follicular stimulating hormone (FSH), thyroid stimulating hormone (TSH) and prolactin (PRL), and is a stimulator of growth hormone (GH) secretion. Dopamine-D1 receptor stimulation with fenoldopam increases basal PRL levels, suppresses TSH, and increases gonadotropin releasing hormone (LHRH) induced LH release. We have investigated the effect of a dopamine D1-receptor antagonist, NNC 01-0687, on the secretion of anterior pituitary hormones. In 8 healthy males NNC 01-0687 and placebo were administered orally in a double-blind placebo controlled cross-over study for three days with a wash-out period of 14 days. Hormonal responses (PRL, LH, FSH, GH, TSH, thyroid hormones and testosterone), unstimulated and LHRH/TRH stimulated, were studied on days 1 and 3. No significant difference (p > 0.05) between placebo and active periods was found neither in unstimulated nor in stimulated hormone concentrations expressed in absolute values, percent change of before, incremental values and area under the curve. These results suggest that the neuronal DA-D1 activity is not activated during basal conditions in healthy male subjects.

Adult↗
PubMed1998

Growth hormone (GH) substitution for one year normalizes elevated GH-binding protein levels in GH-deficient adults secondary to a reduction in body fat. A placebo-controlled trial.

The high affinity growth hormone binding protein (GHBP) in human serum derives from the extracellular domain of the GH receptor. It is well known that fat mass correlates positively to GHBP levels, but it is uncertain whether GH secretory status influences GHBP levels. Since body composition is known to change during GH substitution in adult GHD patients, we determined the relation between GHBP and body composition during GH substitution in GHD adults. Twenty-five GHD adults aged 45.0 +/- 1.8 years, were examined before and after 12 months of placebo-controlled GH substitution (2 IU/m2) in a parallel design. A group of 27 healthy age- and gender-matched normal-weight adults provided reference data. The participants underwent anthropometric measurements [body mass index (BMI), waist/hip ratio (W/H)], computer-tomography (CT-scan) of femoral and abdominal regions, dual-energy X-ray absorptiometry (DEXA-scan), and bioimpedance (BIA), as well as blood sampling. At baseline, the GHBP levels were increased compared to controls (1.63 +/- 0.14 nmol/l vs 1.12 +/- 0.1 nmol/l, P = 0.01). During 12 months of GH substitution, GHBP levels decreased to the levels of the control subjects. GHBP correlated positively to indices of adiposity in GHD patients at baseline: intra-abdominal fat (r = 0.54, P = 0.005), subcutaneous abdominal fat (r = 0.59, P < 0.002), body fat (BIA) (r= 0.41, P= 0.044), BMI (r= 0.58, P = 0.002), and total body fat (DEXA scan) (r= 0.61, P < 0.001). After 12 months of GH substitution, different estimates of body fat were significantly decreased in the GH treated group, but the positive relationship between GHBP and these estimates of body fat was maintained. In multiple linear regression analyses, fasting insulin levels were also a significant determinant of GHBP levels. We conclude that GHBP levels are increased in GHD patients and decrease to normal levels during 12 months of GH substitution. Furthermore, GHBP is predominantly correlated to indices of adiposity also in GHD patients.

Adipose Tissue↗
PubMed1998

The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study.

OBJECTIVE: To investigate whether the changes in lipoproteins following growth hormone (GH) substitution in GH deficient (GHD) adults are determined by the concomitant changes in body composition and physical fitness in a controlled long-term study. DESIGN: A randomized, double-blind, placebo-controlled trial with GH (2 IU/m2) or placebo given for 12 months. SUBJECTS: Twenty-seven patients (18 male, 9 female, aged 21-61 y) with adult onset GH deficiency. Comparisons were made with age- and gender-matched healthy adults. MEASUREMENTS: Serum triglycerides (TG) and lipoproteins, body composition (Dual-Energy X-ray Absorptiometry and computerized tomography), and exercise capacity (VO2-max measured by bicycle ergometry) were measured at baseline and after 12 months. RESULTS: Baseline values of total cholesterol, low-density lipoprotein (LDL) and serum triglycerides were significantly higher in GHD adults compared to normal subjects (P < 0.001, P < 0.001, P= 0.004, respectively) whereas no difference in high-density lipoprotein (HDL) or lipoprotein (a) (Lp(a)) was found. After one year of GH treatment total cholesterol decreased significantly (P = 0.02). Serum LDL decreased after GH and increased after placebo, but the difference in delta values was not significant (P=0.12). Serum HDL and TG concentrations were unchanged. Lp(a) increased but not significantly. Serum total and LDL cholesterol remained significantly elevated after one year of GH treatment. Significant reductions in total and visceral adiposity, and improved exercise capacity were also recorded after GH treatment. In normal subjects, serum total cholesterol and TG correlated positively with age, subcutaneous fat and intraabdominal fat, and negatively with VO2-max. Serum LDL correlated positively with age. In GHD patients, baseline values of serum TG correlated positively with subcutaneous fat and serum insulin. During treatment, no significant correlations were found between the changes in lipoproteins and in body composition. CONCLUSION: The cholesterol lowering effect of GH is not determined by the concomitant decrease in adiposity, which supports the concept of a direct effect of GH on lipoprotein metabolism.

Adipose Tissue↗
PubMed1998

Determinants of serum insulin-like growth factor I in growth hormone deficient adults as compared to healthy subjects.

OBJECTIVE: Growth hormone status is an important determinant of serum IGF-I but it is well known that hypopituitary adults with pronounced GH-deficiency (GHDA) may exhibit normal IGF-I levels. To elucidate possible causes of this apparent paradox we compared the significance of putative IGF-I predictors in GHDA and normal subjects. DESIGN: A cross-sectional study. SUBJECTS: Twenty-seven GHDA (9 females, 18 males, mean +/- SE age 44 +/- 1 years) and 27 healthy control subjects (9 females, 18 males, mean +/- SE age 43 +/- 2 years). RESULTS: Serum IGF-I and IGFBP-3 were significantly lower in GHDAs, but a considerable overlap existed (IGF-I (microgram/l) 87 +/- 12 (GHDA) vs 177 +/- 10 (Control) (P < 0.001)). In both Controls and GHDA, IGF-I was higher in males than females (Control: 196 +/- 12 vs 138 +/- (P = 0.004); GHDA: 97 +/- 16 vs 56 +/- 11 (P = 0.05)). In GHDA, males on testosterone substitution had the highest IGF-I concentrations. The molar IGF-I:IGFBP-3 ratio was significantly lower in GHDAs (0.18 +/- 0.01 vs 0.23 +/- 0.02 (P = 0.002)). IGFBP-1 (microgram/l) was significantly elevated in GHDAs (6.28 +/- 1.11 vs 3.07 +/- 0.32 (P < 0.001)) despite comparable fasting insulin levels. Percentage total body fat (TBF, DEXA, waist/hip ratio, and intra-abdominal fat (CT) were all elevated in GHDAs. IGF-I correlated positively with lean body mass (DEXA) and negatively with TBF and IGFBP-1 in both groups. IGF-I correlated negatively with age in CON but not in GHDAs, whereas IGF-I correlated positively with IGFBP-3 only in GHDAs. Multiple regression analysis revealed that age and IGFBP-1 were the only significant predictors of IGF-I in CON, whereas IGFBP-3 and, to a lesser extent TBF, were the only independent predictors of IGF-I in GHDAs. Neither peak stimulated GH, nor physical fitness contributed in any equations in the two groups. CONCLUSIONS: 1) IGF-I levels are regulated by several variables in addition to GH status 2) age per se is an independent negative determinant in healthy subjects but not in GHDA 3) it is probable that some cases of paradoxically high IGF-I levels in GHDA are secondary to inappropriately elevated IGFBP-3 levels. 4) in mid-adulthood males have higher IGF-I levels than females and it is likely that testosterone directly stimulates IGF-I. The influence of gender and sex steroids must therefore be accounted for when comparing IGF-I levels between hypopituitary and healthy subjects.

Adult↗
PubMed1998

Diurnal variation of the serum leptin concentration in patients with anorexia nervosa.

OBJECTIVE: In rodents, leptin is involved in regulating eating behaviour, fat storage, and reproductive function. In humans, the serum leptin concentration in obese and normal weight subjects correlates with body mass index, reflecting the body fat store. The serum leptin exhibit diurnal variation, however, this has been reported to be absent in normal weighted amenorrheic athletes. Anorexia nervosa is associated with multiple endocrine abnormalities. Hypothalamic amenorrhoea often precedes the weight loss and may persist after weight recovery. We hypothesized that leptin could be involved in the regulation of eating behaviour and gonadal function in anorexia nervosa. DESIGN: We measured the concentration of leptin in serum samples taken after an overnight fast in 18 female anorexia nervosa patients and 11 controls. To study diurnal variation, eight patients and 11 controls were hospitalized for 24 h and had a standardized diet at regular times. Seven blood samples were obtained at 4 h intervals from each subject. PATIENTS: The patients fulfilled the DSM-IV criteria for anorexia nervosa. The mean body mass index for the patients was 14.2 +/- 2.3 kg/m2 and for controls 20.3 +/- 1.7 kg/m2. RESULTS: The mean fasting leptin concentration as well as the 24 h mean concentration were significantly lower in the anorectic group than in the control group (2.5 +/- 0.9 vs 10.1 +/- 6.1 micrograms/l, P < 0.01 and 2.7 +/- 1.5 vs 10.6 +/- 7.1 micrograms/l, P < 0.01 respectively). In the whole group of subjects (n = 28) a significant positive correlation between the leptin level and body mass index was found (r = 0.63, P < 0.001). In the anorectic group it was found that the leptin level correlated better with body fat percentage than with body mass index. In normalized data the time course of the mean leptin levels showed a monophasic variation with nadir and zenith at about 0900 and 0100 h respectively. However, the individual coefficients of variance were significantly lower in the anorectic group compared to the group of healthy women. CONCLUSION: In patients with anorexia nervosa the leptin level is low, reflecting the low body fat mass, and the relative diurnal variation is strikingly reduced. The similarity to that of normal weighted women with hypothalamic amenorrhoea suggest that altered leptin oscillations may be of particular significance in the hypothalamic regulation of reproductive function.

Adolescent↗
PubMed1998

The effect of short-term cortisol changes on growth hormone responses to the pyridostigmine-growth-hormone-releasing-hormone test in healthy adults and patients with suspected growth hormone deficiency.

BACKGROUND AND AIMS: The interaction between cortisol and growth hormone (GH)-levels may significantly influence GH-responses to a stimulation test. In order to systematically analyse the interaction in a paired design, it is necessary to use a test, which has been proven safe and reliable such as the pyridostigmine-growth-hormone-releasing-hormone (PD-GHRH) test. Three groups of subjects with a different GH-secretory capacity were included. STUDY A: Eight healthy adults were tested seven times, once with placebo throughout the examination and six times with the PD-GHRH test following no glucocorticoid pretreatment, pretreatment with hydrocortisone (HC) (30 mg/day and 80 mg/day for 1 and 3 days) or pretreatment with 15 mg prednisolone for 1 day. HC (80 mg/day for 1 day) in combination with PD significantly stimulated GH-levels compared to PD alone, 18.9 mU/l +/- 6.1 vs 3.0 mU/l +/- 0.8 (P < 0.05). However, peak GH-responses to PD in combination with GHRH were reduced during HC (80 mg/day for 1 day) compared to no glucocorticoid pretreatment in all healthy adults. Conventional HC therapy (30 mg/day for 1 and 3 days) did not significantly affect peak GH-responses. STUDY B: 16 patients with suspected GH-deficiency (GHD) (seven with known ACTH-deficiency and nine with an intact pituitary-adrenal axis) were tested five times with the PD-GHRH test following no pretreatment or pretreatment with HC (30 mg/day and 80 mg/day for 1 and 3 days). Peak GH-responses were not significantly affected by conventional HC therapy (30 mg/day for 1 and 3 days). However, peak GH-responses to PD in combination with GHRH were reduced during HC (80 mg/day for 1 day) compared to no glucocorticoid pretreatment in all patients. Short-term hypocortisolism did not significantly affect peak GH-responses. CONCLUSION: The GH-responses to a PD-GHRH test were reduced in all individuals during acute stress-appropriate cortisol levels and the percentage reduction in GH-levels was independent of the GH-secretory capacity. Clinically, we found that peak GH-responses were not significantly affected by a short break in conventional HC therapy nor by conventional HC therapy itself. However, our results also demonstrated that a GH-stimulation test should not be performed on patients, suffering from acute stress.

Adrenocorticotropic Hormone↗
PubMed1998

Pulsatile luteinizing hormone secretion in patients with Addison's disease. Impact of glucocorticoid substitution.

The physiological and pathophysiological role of cortisol in pulsatile LH release was investigated in 14 patients (5 men, 6 premenopausal women, and 3 postmenopausal women) with Addison's disease. The explicit effect of cortisol in relation to the effect of corticotropin-releasing factor (CRF), ACTH, and opioids was ensured by hypo-, normo-, and hypercortisolism. Hypocortisolism was obtained by 24-h discontinuation of hydrocortisone (HC) followed by 23-h saline infusion. Eucortisolism was secured by infusion of HC (0.5 mg/kg) over 23 h. Stress-appropriate hypercortisolism was obtained by infusion of HC (2.0 mg/kg) over 23 h, preceded by treatment for 5 days with dexamethasone (1.5 mg/day). To imitate the normal diurnal rhythm for serum cortisol, HC was infused in graduated doses. Blood sampling was performed every 10 min during the last 10 h of the study period, followed by a LH-releasing hormone test (5 microg, i.v.) and a TRH test (10 microg, i.v.). In pre- and postmenopausal women, the mean LH level and the LH pulsatility pattern were similar on the 3 occasions. In contrast, the mean LH level in men was significantly reduced during hypocortisolism compared to that during eucortisolism (3.26 +/- 0.68 vs. 4.49 +/- 0.83 U/L; P < 0.05) and was associated with a clear decrease in LH pulse amplitude (1.09 +/- 0.33 vs. 1.96 +/- 0.53 U/L; P < 0.05). During high doses of glucocorticoids, the mean LH level in men was significantly lower than that during eucortisolism (3.81 +/- 0.88 vs. 4.49 +/- 0.83 U/L; P < 0.05). In both men and women, the mean PRL levels increased significantly (P < 0.05) during hypocortisolism, whereas high glucocorticoid doses suppressed the mean PRL level (P < 0.05). The LH and PRL responses to LH-releasing hormone and TRH were, however, similar during low, medium, and high cortisol levels in both men and women. In conclusion, our data suggest that the attenuation of pulsatile LH secretion in men during hypo- and hypercortisolism is due to variations in the hypothalamic opioid activity secondary to alterations in serum cortisol levels. A higher level of opioid receptor activity in men than in low estrogen women may explain the gender differences.

Addison Disease↗
PubMed1998

Evaluation of growth hormone assays using ratio plots.

To permit comparison between growth hormone (GH) results obtained using the Pharmacia polyclonal assay and the Delfia monoclonal assay, we used both methods to measure GH concentrations in peak GH responses to the pyridostigmine-growth-hormone-releasing-hormone (PD-GHRH) test and in unstimulated samples from 40 healthy adults and 31 patients with suspected GH deficiency. Ratio plots were used for the comparison, and acceptability criteria were based on inherent analytical imprecision and on analytical quality specifications. The mean ratio (r; Pharmacia/Delfia) for the peak GH responses in 40 healthy adults was calculated to be 1.59, and the 95% prediction interval for ratios fulfilling the imprecision criterion was applied. For GH values >1 mIU/L, the peak and unstimulated GH ratios in healthy adults and patients were within the 95% prediction interval, and fulfilled the biological criterion as well. Therefore, the conversion factor of 1.59 is applicable for the evaluation of GH-stimulation tests.

Adolescent↗
PubMed1997

[Soft tissue changes in adults with acquired growth hormone deficiency during substitution treatment. A double-blind, randomized, placebo-controlled study after a year of treatment].

The aim of the study was to assess the influence of growth hormone (GH) on body composition in 29 adult persons with acquired growth hormone deficiency (GHD). The study was a double-blind placebo-controlled study of one year's duration. The treatment consisted of daily subcutaneous injections of GH (2.0 IU/m2, Norditropin) or placebo. Before and after one year's treatment, the patients were hospitalized for measurement of Dual-Energy X-ray Absorptiometry (DXA) in order to assess body composition (Fat mass (FM) + Lean Body Mass (LBM). In addition, fasting serum Insulin-like Growth Factor (IGF-I) was collected. The study showed a 200% increase in serum IGF-I. Regarding LBM a 5.7% increase was seen, and this was primarily due to an increase in LBM of the extremities, whereas FM was reduced by 21.5% mainly located truncally. Our data demonstrate that favorable changes in body composition are maintained during long-term, controlled GH treatment, which loads support to the concept of GH substitution in GH-deficient adults.

Absorptiometry, Photon↗
PubMed1997

Serum leptin is increased in growth hormone-deficient adults: relationship to body composition and effects of placebo-controlled growth hormone therapy for 1 year.

The gene product from the ob gene, leptin, has recently been characterized in humans. The circulating level of leptin is related to body mass index (BMI) and more closely to estimates of total body fat, whereas visceral fat has been reported to be of minor importance. However, it is unknown if leptin is directly regulated by hormones that influence substrate metabolism and body composition. We studied leptin in adult growth hormone (GH)-deficient (GHD) patients substituted with GH treatment for 12 months in a parallel double-blind, placebo-controlled study. Twenty-seven GHD adults aged 44.9 +/- 1.9 years underwent anthropometric measurements for determination of regional and total body fat (BMI, waist to hip ratio [WHR], computed tomographic [CT] scan, dual-energy x-ray absorptiometry [DEXA] scan, and bioimpedance analysis [BIA]) before and after 12 months of placebo-controlled GH substitution (2 IU/m2) in a parallel design. The same measurements were performed in 42 healthy adults aged 39.1 +/- 1.7 years. The logarithm of serum leptin levels correlated positively with abdominal subcutaneous fat and total body fat (BIA and DEXA) in untreated GHD patients and healthy subjects. Fasting insulin did not correlate with leptin levels in either of the groups. After 12 months of GH administration, the body composition of GHD patients was significantly changed with respect to a marked decrease in body fat. The relations of leptin to the estimates of body fat were maintained, and leptin was furthermore related to BMI and fasting insulin. In multiple linear regression analyses, additional estimates of visceral adiposity (intraabdominal fat and maximal anterior-posterior diameter determined by CT scan) were significant determinants of leptin in the healthy subjects. The increase in fasting insulin levels during GH substitution correlated negatively with the reduction in leptin levels (r = -.823, P = .003). At baseline, leptin levels were increased in the patients compared with controls in both sexes (women, 21.8 +/- 3.3 v 11.3 +/- 1.4 ng/mL, P = .002; men, 8.1 +/- 1.2 v 4.7 +/- 0.7 ng/mL, P = .008). Leptin levels were similar in GHD patients treated for 12 months compared with healthy controls for both women and men (women, 15.9 +/- 2.3 and 11.3 +/- 1.4 ng/mL, P = .163; men, 7.1 +/- 2.8 and 4.7 +/- 0.7 ng/mL, P = .759). In healthy adults and in GHD patients, leptin levels were significantly higher in women than in men (11.3 +/- 1.4 v 4.7 +/- 0.7 ng/mL, P < .001; 21.8 +/- 3.3 v 8.1 +/- 1.2 ng/mL, P < .001). Gender remained a significant determinant of leptin levels in several models of multiple linear regression analysis also including age, estradiol levels, insulin, and estimates of body fat. We conclude that leptin is increased but not differently regulated in GHD patients compared with normal subjects, and that leptin levels are closely related to estimates of body fat. This relationship is maintained during a decrease in body fat due to GH substitution.

Absorptiometry, Photon↗
PubMed1997

Serum free insulin-like growth factor-I in growth hormone-deficient adults before and after growth hormone replacement.

The objective of the present study was to compare fasting levels of free IGF-I in serum from patients with adult onset growth hormone deficiency (GHD) and from healthy volunteers, and to examine the effect of GH replacement therapy in GHD on serum free IGF-I. Free IGF-I was measured using separation of free IGF-I by ultrafiltration in serum samples from 42 healthy volunteers and 27 patients with GHD, in the latter before and after 1 year of treatment with GH (2 IU/m2) (n = 13) or placebo (n = 14). Free IGF-I was significantly decreased in patients with GHD (700 +/- 100 ng/l (mean +/- S.E.M.), range 55-2618 ng/l) compared with controls (1010 +/- 70 ng/l, range 231-2431 ng/l; P = 0.0016). Total IGF-I was 85 +/- 10 micrograms/l (GHD) and 160 +/- 10 micrograms/l (controls) (P < 0.0001). The ratio of free over total IGF-I was increased in GHD to 0.85 +/- 0.08% compared with 0.66 +/- 0.05% in controls (P = 0.04). In both GHD and controls, free IGF-I correlated significantly (P < 0.05) with total IGF-I (GHD r = 0.78; controls r = 0.42), IGFBP-1 (GHD r = -0.67; controls r = -0.46) and the molar ratio of total IGF-I over IGFBP-3 (GHD r = 0.58; controls r = 0.62). After 1 year of GH treatment, free IGF-I was increased to 2780 +/- 320 ng/l (P = 0.003) and total IGF-I was increased to 270 +/- 30 micrograms/l (P = 0.006) both of which values were greater than those in healthy volunteers. There were no changes in free or total IGF-I in the placebo-treated group. In conclusion, levels of free IGF-I are decreased in GHD, but measurements of free IGF-I in a single, fasting serum sample do not offer a better separation of patients with GHD from individuals with normal GH status than can be achieved by measurement of total IGF-I. One year of treatment with 2IU/m2 GH caused an increase of serum free IGF-I to supraphysiological levels.

Adult↗
PubMed1997

Elevated levels of sex hormones and sex hormone binding globulin in male patients with insulin dependent diabetes mellitus. Effect of improved blood glucose regulation.

In a prospective study we have measured serum levels of sex hormone-binding globulin (SHBG), androgens, oestrogens and gonadotropins in 20 male IDDM patients with the aim of evaluating the effect of improved glycaemic control on these levels and to compare the IDDM patients with an age- and weight-matched healthy non-diabetic control group. The patients were chosen from the male IDDM patients attending the outpatient clinic at the Department of Endocrinology, Odense University Hospital. Glycaemic control was optimized by a trained diabetologist according to the patients' measurements of home blood glucose concentrations and reported hypoglycaemic episodes during a three month period. Prior to regulation the patients, compared to healthy control subjects, had significantly higher serum levels of oestrone (0.29 +/- 0.02 vs 0.16 +/- 0.01 nmol/l (Mean +/- SEM), p < 0.01), 17 beta-oestradiol (0.12 +/- 0.01 vs 0.08 +/- 0.01 nmol/l, p < 0.01), dihydrotestosterone (4.20 +/- 0.18 vs 1.66 +/- 0.09 nmol/l, p < 0.01), total testosterone (20.7 +/- 0.9 vs 17.8 +/- 1.1 nmol/l, p < 0.05) and SHBG (42.3 +/- 2.9 vs 15.5 +/- 3.5 nmol/l, p < 0.05), while the calculated free-testosterone was lower (0.34 +/- 0.02 vs 0.40 +/- 0.02 nmol/l, p = 0.068). After regulation, the patients obtained significantly lower levels of glycosylated haemoglobin (10.4 +/- 0.3 vs 8.9 +/- 0.2%, p < 0.005) and serum fructosamine (1.50 +/- 0.05 vs 1.34 +/- 0.04 nmol/l, p < 0.005) on a higher 24 hour insulin dose (52.7 +/- 4.4 vs 59.2 +/- 4.6 IU/24 h, p < 0.005). Levels of free-testosterone (0.41 +/- 0.04 nmol/l), oestrone (0.33 +/- 0.03 nmol/l), oestradiol (0.14 +/- 0.01 nmol/l), delta 4-androstenedione (4.44 +/- 0.43 vs 3.85 +/- 0.42 nmol/l), and prolactin (249 +/- 24 vs 200 +/- 19 mIU/l) increased compared to values obtained before regulation (all p < 0.05). We conclude that SHBG, testosterone, dihydrotestosterone and oestrogen levels are increased in male IDDM patients. High SHBG levels tend to keep the free fractions of sex hormones within normal limits. During improvement of glycaemic control with insulin, levels of free-testosterone and its bioprecursors and metabolites rise. This may partly be due to the increased daily insulin dose and/or to the improvement in glycaemic control itself.

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