Biomedical subjects

N Vahl

Publications and source records attributed to N Vahl.

At least 19 recordsLinked to original sources

PubMed2004

Dose-, IGF-I- and sex-dependent changes in lipid profile and body composition during GH replacement therapy in adult onset GH deficiency.

OBJECTIVE: Patients with GH deficiency of adult onset (GHDA) exhibit dyslipidaemia and increased cardiovascular morbidity. GH replacement potently reduces body fat and serum lipids in GHDA. In recent years, lower GH doses have been introduced. The purpose of this analysis was to explore the response relationship between GH doses, lipids and body composition. DESIGN: Two consecutive, randomized 12-month GH replacement studies covering placebo and three different doses of GH (0.5, 1.0 and 1.7 IU/m(2) per day). Low and intermediate doses were IGF-I titrated. PATIENTS: Fifty-eight patients with severe GHDA, not previously treated with GH and stably substituted for other endocrine deficiencies, were included in the study. METHODS: Serum lipoproteins, serum IGF-I and body composition analysis by dual energy X-ray absorptiometry (DXA) were used. RESULTS: Fifty-seven percent of patients exhibited low density lipoprotein (LDL) cholesterol levels above 4.16 mmol/l, corresponding to the American Heart Association threshold of 160 mg/dl. GH treatment resulted in significant decreases in total and LDL cholesterol, with no significant change in high density lipoprotein cholesterol or triglycerides. The low dose induced no significant changes in lipid levels, whereas the medium dose reduced LDL cholesterol and the high dose decreased both LDL and total cholesterol. The effects depended significantly on the GH dose and the level of IGF-I obtained, but not on gender. GH replacement induced dose-dependent reductions in fat mass and sex-dependent increases in lean mass. CONCLUSIONS: GH given for 1 year at a dosage between 0.5 and 1.7 IU/m(2) per day reduced fat mass in a dose-dependent manner, increased lean body mass and lowered total and LDL cholesterol in patients with severe GHDA. Low dose GH treatment with normal IGF-I levels induced smaller changes compared with high dose therapy, and may need a longer treatment time.

Adipose Tissue↗

PubMed2002

Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult-onset GH deficiency: results from two 12-month randomized studies.

OBJECTIVE: To establish the optimum GH dose for restoring bone mineral density (BMD) in adult-onset GH deficiency (GHDA). DESIGN: Two separate randomized, controlled clinical trials. PATIENTS: Fifty-eight adults aged 45.1 (20-64) years with severe GHDA were followed in two 12-month studies. In the first study, patients were randomized to placebo or GH 1.7 IU/m2/day and in the second study GH 0.5 IU/m2/day or 1.0 IU/m2/day. MEASUREMENTS: BMD of the spine, hip, forearm and whole body was measured at 0 and 12 months. Alkaline phosphatase (AP) and collagen markers serum C-terminal propeptide of type I collagen (PICP), type I collagen telopeptide (ICTP) and N-terminal propeptide of type III collagen (PIIINP) were measured at baseline and every 3 months. RESULTS: Biochemical markers of skeletal and soft tissue collagen increased significantly and remained elevated throughout the study period. BMD changes depended on site, dose and gender. In placebo-treated patients, spinal BMD declined by 2.5%. At the low and medium doses, BMD increased by 2.4 and 3.1%, respectively, while a nonsignificant 0.2% decrease was seen with high dose. Forearm BMD decreased by 4.9% (P < 0.05) with high-dose treatment but remained unchanged at lower doses. Males showed larger gains in BMD, but the dose-response relationship was similar in males and females. CONCLUSION: A GH dose of 0.5-1.0 IU/m2/day (4-9 micro g/kg/day) stimulated bone remodelling and increased BMD over 12 months in patients with severe GHDA, irrespective of gender. A higher dose (1.7 IU/m2/day congruent with 15 micro g/kg/day) was associated with initial declines in forearm and whole-body BMD.

Adenoma↗

PubMed2002

Effects of 12 months of GH treatment on cortical and trabecular bone content of IGFs and OPG in adults with acquired GH deficiency: a double-blind, randomized, placebo-controlled study.

To investigate the effects of 12 months of GH treatment on cortical and trabecular bone content of IGFs, iliac crest bone biopsies were obtained from 25 patients with GH deficiency (9 women and 16 men; ages, 21-61 yr; mean, 46 yr) who were randomized to sc injections with GH (2 IU/m(2).d) or placebo for 12 months. Levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, osteocalcin, OPG, RANKL, and total protein were determined in extracts obtained after EDTA and guanidine hydrochloride extraction. Calcium was determined after HCl hydrolysis. Comparing changes during GH or placebo treatment, significant increases were observed during GH substitution for cortical and trabecular bone content of IGF-I [mean difference vs. placebo (mean +/- SEM), 97 +/- 30 and 72 +/- 38%] and OPG (mean difference vs. placebo, 109 +/- 59 and 51 +/- 19%). Also, a significant decline was found for cortical osteocalcin (mean difference vs. placebo, -49 +/- 22%) during GH treatment. In conclusion, our results indicate that long-term GH treatment increases the accumulation of IGF-I and OPG in cortical and trabecular bone in patients with GH deficiency, and this may in turn lead to an increase in bone mass and improved skeletal biomechanical competence.

Adult↗

PubMed2001

Growth hormone treatment in adults: is there a true gender difference?

The importance of growth hormone (GH) deficiency in adults became evident at the end of the 1980s, when the first clinical studies on GH replacement therapy in adults were published. Since then, accumulated experience has shown a great individual variability in the response to GH replacement, including a potential difference in responsiveness between genders. The aim of this paper is to review the data regarding the effects of gender differences on GH pharmacokinetics, pharmacodynamics, and efficacy of replacement. In addition, we start with a short review of the possible role of GH in sexual development and sexual life.

Adult↗

PubMed2001

Short-term tools to measure responsiveness to growth hormone replacement.

Growth hormone (GH) replacement is a prolonged and expensive treatment modality which involves daily subcutaneous injections in children and adults. Efforts have been made, therefore, to develop short-term tests to predict long-term clinical response. The so-called insulin-like growth factor I (IGF-I) generation test was originally introduced in order to select responders to GH among short children without classical GH deficiency. A positive correlation between short-term increase in serum IGF-I and linear growth has, however, only been reported in a minority of studies. There is no single outcome measure available in GH-deficient adults, and no evidence of a correlation between IGF-I and the effects of GH replacement on factors such as body composition or physical fitness. In conclusion, no reliable short-term test to predict long-term response to GH replacement is available in either children or adults. For safety reasons, however, measurement of serum IGF-I concentrations in GH-deficient patients remains an important means of monitoring during GH replacement.

Endocrinology↗

PubMed2001

Skin morphological changes in growth hormone deficiency and acromegaly.

OBJECTIVE: To evaluate the histomorphology of skin and its appendages, especially eccrine sweat glands, in patients with GH disorders, because reduced sweating ability in patients with growth hormone deficiency (GHD) is associated with increased risk of hyperthermia under stressed conditions. DESIGN AND METHODS: A skin biopsy was obtained from 17 patients with GHD treated with GH, five patients with untreated GHD, 10 patients with active acromegaly and 13 healthy controls. RESULTS: The sweat secretion rate (SSR) was significantly decreased in both the untreated (median 41 mg/30 min, range 9-79 mg/30 min) and the GH-treated (median 98 mg/30 min, range 28-147 mg/30 min) patients with GHD compared with that in controls (median 119 mg/30 min, range 90-189 mg/30 min; P=0.001 and 0.01 respectively). Epidermal thickness was significantly decreased in both untreated (median 39 microm, range 28-55 microm) and GH-treated patients with GHD (median 53 microm, range 37-100 microm), compared with that in controls (median 66 microm, range 40-111 microm; P<0.02). A statistically non-significant tendency towards thinner epidermis (median 59 microm, range 33-83 microm) was recorded in acromegalic patients (P=0.08) compared with controls. There was no significant difference in the area of the sebaceous glands in the biopsies between the three groups and the controls. The area of eccrine sweat gland glomeruli was significantly decreased in the untreated patients with GHD (median 16407 microm2, range 12758-43976 microm2) compared with that in controls (median 29446 microm2, range 13511-128661 microm2; P=0.03), but there was no significant difference between the GH-treated patients with GHD and controls. CONCLUSIONS: We conclude that GH, either directly or via IGF-I, may have both a structural and a functional effect on human skin and its appendages, and that patients with GHD have histomorphological changes in skin compared with controls. Importantly, these changes are not fully reversed despite long-term and adequate GH treatment in patients with childhood onset GHD.

Acromegaly↗

PubMed2000

Continuation of growth hormone (GH) replacement in GH-deficient patients during transition from childhood to adulthood: a two-year placebo-controlled study.

Previous studies have demonstrated beneficial effects of GH replacement, in adults with GH deficiency (GHD), on body composition, physical fitness, and quality of life. These studies, however, concern patients with adult-onset GHD or childhood-onset (CO) patients enrolled several years after withdrawal of initial therapy. So far, the effects of continuation of GH-administration in patients with CO-GHD have not been examined. We studied a group of nineteen young adults (13 males + 6 females; 16-26 yr old; mean age, 20.2 +/- 0.65 yr) with CO-GHD, in a randomized, parallel, double-blind, placebo-controlled trial for 1 yr, followed by an open phase with GH for 1 yr. All patients received GH therapy at the start of study, and trial medication (GH/placebo) was given in a similar dose. Patients randomized to continued GH treatment exhibited no significant changes in any parameters tested, but intra- and interindividual variations in insulin-like growth factor (IGF)-I levels could suggest compliance problems. Discontinuation of GH for 1 yr resulted in a decrease in serum IGF-I, from 422.0 +/- 56.8 to 147.8 +/- 33.4 microg/L, in the placebo group (P = 0.003). After discontinuation of GH for 1 yr, an increase in total body fat (TBF, kg), measured by dual-energy x-ray absorptiometry scan, was seen [placebo: 22.7 +/- 2.7 to 26.5 +/- 2.5 (P = 0.01); GH: 16.2 +/- 2.1 to 17.2 +/- 2.1 (not significant)]. Resumption of GH after placebo was followed by increments in serum IGF-I (microg/L) [from 147.8 +/- 33.4 to 452 +/- 76 (P = 0.001)] and IGF-binding protein 3, as well as in fasting glucose (mmol/L) [4.9 +/- 0.2 vs. 5.3 +/- 0.2 (P = 0.03)]. After resumption of GH lean body mass (kg) increased [52.4 +/- 4.9 vs. 60.7 +/- 5.6 (P = 0.006)]. Likewise, resumption of GH therapy increased thigh muscle volume and thigh muscle/fat ratio, as assessed by computed tomography [muscle volume (cm2/10 mm): 118.2 +/- 11.7 vs. 130.0 +/- 10.9 (P = 0.002); muscle/fat ratio: 1.33 +/- 0.24 vs. 1.69 +/- 0.36 (P = 0.02)]. In conclusion, discontinuation of GH treatment in GHD patients, during the transition from childhood to adulthood, induces significant and potentially unfavorable changes in IGF-I and body composition, both of which are reversed after resumption of GH treatment. By contrast, continuation of GH therapy results in unaltered IGF-I and body composition. We recommend continuation of GH therapy in these patients, to be undertaken in collaboration between pediatricians and adult endocrinologists.

Adolescent↗

PubMed2000

Continuation of growth hormone (GH) therapy in GH-deficient patients during transition from childhood to adulthood: impact on insulin sensitivity and substrate metabolism.

The appropriate management of GH-deficient patients during transition from childhood to adulthood has not been reported in controlled trials, even though there is evidence to suggest that this phase is associated with specific problems in relation to GH sensitivity. An issue of particular interest is the impact of GH substitution on insulin sensitivity, which normally declines during puberty. We, therefore, evaluated insulin sensitivity (euglycemic glucose clamp) and substrate metabolism in 18 GH-deficient patients (6 females and 12 males; age, 20 +/- 1 yr; body mass index, 25 +/- 1 kg/m2) in a placebo-controlled, parallel study. Measurements were made at baseline, where all patients were on their regular GH replacement, after 12 months of either continued GH (0.018 +/- 0.001 mg/kg day) or placebo, and finally after 12 months of open phase GH therapy (0.016 mg/kg x day). Before study entry GH deficiency was reconfirmed by a stimulation test. During the double-blind phase, insulin sensitivity and fat mass tended to increase in the placebo group [deltaM-value (mg/kg x min), -0.7 +/- 1.1 (GH) vs. 1.3 +/- 0.8 (placebo), P = 0.18; deltaTBF (kg), 0.9 +/- 1.2 (GH) vs. 4.4 +/- 1.6 (placebo), P = 0.1]. Rates of lipid oxidation decreased [delta lipid oxidation (mg/kg x min), 0.02 +/- 0.14 (GH) vs. -0.32 +/- 0.13 (placebo), P < 0.05], whereas glucose oxidation increased in the placebo-treated group (P < 0.05). In the open phase, a decrease in insulin sensitivity was found in the former placebo group, although they lost body fat and increased fat-free mass [M-value (mg/kg x min), 5.1 +/- 0.7 (placebo) vs. 3.4 +/- 1.0 (open), P = 0.09]. In the group randomized to continued GH treatment almost all hormonal and metabolic parameters remained unchanged during the study. In conclusion, 1) discontinuation of GH therapy for 1 yr in adolescent patients induces fat accumulation without compromising insulin sensitivity; and 2) the beneficial effects of continued GH treatment on body composition in terms of decrease in fat mass and increase in fat-free mass does not fully balance the direct insulin antagonistic effects.

3-Hydroxybutyric Acid↗

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↗

PubMed2000

Evidence-based approach to growth hormone replacement therapy in adults, with special emphasis on body composition.

In the past decade, a large number of controlled clinical trials have reported positive effects of growth hormone (GH) replacement therapy in GH-deficient adults. The majority of these studies have been carried out in accordance with the guidelines for Good Clinical Practice. The data thus accumulated offer a solid baseline for practicing evidence-based medicine within this area of endocrinology.

Adipose Tissue↗

PubMed1999

Growth hormone (GH) status is an independent determinant of serum levels of cholesterol and triglycerides in healthy adults.

OBJECTIVE: Both severe growth hormone (GH) deficiency in hypopituitary adults and physiological ageing are associated with an increase in fat mass, dyslipidaemia, and an increased incidence of cardiovascular disease. Ageing is also associated with a physiological decrease in spontaneous as well as stimulated GH secretion. We wished to evaluate the effects of endogenous GH status on circulating lipoproteins. DESIGN: A cross-sectional study. SUBJECTS: Forty-two healthy nonobese adults of both sexes (20 M + 22 F) aged 27-59 years. MEASUREMENTS: Twenty-four hour GH secretion, arginine-stimulated GH secretion, and fasting values of lipoproteins and triglycerides. Body composition was measured by CT-scan and whole body DXA-scan. VO2-max was measured on an ergometer bicycle. RESULTS: GH secretion decreased with age and was lower in males. Older subjects had more total body fat, subcutaneous abdominal fat, and intra-abdominal fat than younger ones, and their VO2-max was decreased. Men had more intra-abdominal and subcutaneous abdominal fat but less total body fat than women. There was no sex difference in VO2-max. Total cholesterol (TC) and LDL-C (mmol/l) were higher in older than in the younger subjects (TC: 5.32 (95% CI = 0.49) vs. 4. 17 (95% CI = 0.28), P < 0.001; LDL-C: 3.66 (95% CI = 0.52) vs. 2.54 (95% CI = 0.37), P = 0.001) without sex differences. HDL-C did not show any difference with age or between sexes. Triglycerides (mmol/l) were higher in older subjects and in males (older: 1.36 (95% CI = 0.19) vs. younger: 1.02 (95% CI = 0.20), P = 0.015; M: 1. 34 (95% CI = 0.24) vs. F: 1.03 (95% CI = 0.16), P = 0.03). There was no age-difference in lipoprotein (a), but concentrations were higher in women (M: 4.35 (2.95-8.30) vs. F: 19.40 (4.10-32.80), P = 0.03). TC, LDL-C, and triglycerides correlated positively with age and indices of adiposity, and inversely with VO2-max. TC, LDL-C, and triglycerides also correlated significantly and negatively with arginine-stimulated GH secretion (peak GH) (TC vs. peak GH (r = - 0. 395, P = 0.01); LDL-C vs. peak GH (r = - 0.365, P = 0.017); triglycerides vs. peak GH (r = - 0.386, P = 0.01)). Multiple linear regression analysis showed GH status to be an independent predictor of both TC, LDL-C, and triglycerides. CONCLUSION: We hypothesize that GH may exert direct effects on lipid metabolism.

Adult↗

PubMed1999

Evidence supporting a direct suppressive effect of growth hormone on serum IGFBP-1 levels. Experimental studies in normal, obese and GH-deficient adults.

It has occasionally been suggested that GH directly suppresses circulating IGFBP-1 levels, although it is generally believed that such an effect is secondary to a GH-induced increase in insulin levels. We present data from several experiments in which the effects of GH on IGFBP-1 could be studied more extensively. In normal subjects (n = 36), an i.v. GH bolus caused a small but significant decrease in plasma IGFBP-1 concentrations without changes in insulin [IGFBP-1 (microgram/l): 2.6 +/- 0.3 (GH) vs 3.2 +/- 0.4 (placebo), P < 0.05]. Conversely, a 28-h somatostatin infusion with and without GH administration during fasting in normal subjects yielded higher IGFBP-1 levels in the non-GH substituted study [50.5 +/- 5.3 (GH-suppression) vs 22.6 +/- 5.6 (GH-substitution), P < 0.01], comparable with an increased concentration of IGFBP-1 during fasting in GH-deficient patients without usual GH substitution [23.4 +/- 7.6 (GH pause) vs 14.1 +/- 4.9 (GH substitution), P < 0.01]. In both fasting studies insulin levels remained stable. During a hypocaloric diet, long-term GH treatment in obesity lead to a significant decline in IGFBP-1 level (2.3 +/- 0.6 vs 1.2 +/- 0.2, P < 0.01), while no changes were found in the placebo group. Again, insulin levels remained equally low in both studies. Finally, a significant rebound increase in IGFBP-1 level in response to insulin induced hypoglycemia was only observed among GH-deficient patients, but not in control subjects, the latter of whom responded to hypoglycemia with a significant increase in serum GH levels [23.2 +/- 7.2 (GHDA) vs 2.5 +/- 0.3 (controls), P < 0.01]. In conclusion, a suppressive effect of GH on IGFBP-1 appears to be unmasked in the presence of low or suppressed insulin levels, making GH a potential regulator of IGF-1 bioactivity in a hitherto unrecognized way.

Adult↗

PubMed1999

Impact of gender and androgen status on IGF-I levels in normal and GH-deficient adults.

OBJECTIVE: The regulation of IGF-I levels is complex and not only dependent on GH status, as the diagnostic sensitivity of serum IGF-I levels for GH deficiency (GHD) in adults is low. Other GH-related parameters have so far not proven to be of additional diagnostic value in GHD adults. In the present study we evaluated the impact of gender and androgen status on IGF-I levels and the diagnostic value of IGF-I and GH-related parameters in a population of adult hypopituitary patients and age- and gender-matched healthy subjects. DESIGN: A cross-sectional study. SUBJECTS: Fifty-nine GHD patients (40 males, mean age 39.3+/-1.7 (s.e.m.) years, and 19 females, mean age 41.9+/-2.6 years) and 69 healthy subjects (42 males, mean age 36. 7+/-1.5 years, and 27 females, mean age 38.9+/-2.1 years). RESULTS: IGF-I levels were low in the GHD patients (91+/-7 vs 173+/-7 microgram/l, P<0.001), and lower in female patients than in male (68+/-10 vs 100+/-8 microgram/l, P=0.03). In the control group there was no gender-related difference in IGF-I levels (males: 178+/-8, females: 164+/-12 microgram/l, P=0.23). IGF-II and IGF-binding protein-3 (IGFBP-3) were also decreased in GHD without any gender-related differences. GH-binding protein (GHBP) levels were increased in the patient group. The diagnostic sensitivity (%) of IGF-I, IGF-I/GHBP, IGF-I/IGFBP-3, and of the combination of IGF-I plus IGF-II (both low or one normal and one low), was higher in female patients than in male (IGF-I: 57.8 vs 22.0, P<0.0001; IGF-I/GHBP: 84.2 vs 48.8, P=0. 002; IGF-I/IGFBP-3: 36.8 vs 7.3 P=0.001; IGF-I+IGF-II: 77.8 vs 52.6, P=0.01). Testosterone levels were reduced in the female patients compared with female controls (0.5+/-0.3 vs 2.1+/-0.2nmol/l, P<0.001). Forward regression analyses revealed that IGFBP-3 was a significant predictor of IGF-I levels in both patients and healthy subjects. In a combined analysis of both patients and controls, sex hormone-binding globulin (SHBG) level was the main contributor as an explanatory variable. Gender and prolactin also predicted IGF-I in patients, whereas SHBG and estradiol were significant predictors only in the control group. CONCLUSION: (i) Levels of IGF-I, and of IGF-I/IGFBP-3 and IGF-I/GHBP ratios are lower in females compared with male adult GHD patients. (ii) IGF-I/GHBP has a high diagnostic sensitivity of adult GHD, in particular in women. (iii) We hypothesize that the gender difference in IGF-I levels among adult GHD patients are causally related to the very low androgen levels observed among females.

Adult↗

PubMed1998

Resting metabolic rate in healthy adults: relation to growth hormone status and leptin levels.

Studies in patients with acromegaly and growth hormone (GH) deficiency, and administration of GH in normal and obese subjects and in patients with GH deficiency, suggest that GH increases resting metabolic rate (RMR) independently of changes in body composition. To test whether endogenous GH status determines RMR, we studied 38 healthy adults (18 women and 18 men) in two age groups (young, 30+/-0 years (n=18); older, 51+/-1 years [n=18]) with indirect calorimetry, deconvolution analysis of 24-hour GH secretion, arginin stimulation test, insulin-like growth factor-I (IGF-I) measurement, lean and fat tissue distribution (computed tomography [CT] and dual-energy x-ray absorptiometry), assessment of physical fitness (maximal oxygen consumption [VO2max]), thyroid status, and serum leptin levels. RMR was higher in men compared with women, whereas RMR per lean body mass (LBM) (kcal x 24 h(-1) x kg(-1)) was higher in women (30.0+/-0.5 v 33.0 2/3 0.8; P=.003). GH secretion was higher in women and in young people. Total-body fat (TBF) was higher in women, whereas LBM and abdominal fat were higher in men. Older people had significantly more TBF and abdominal fat as compared with younger people. VO2max was higher in younger people. Leptin levels were higher in women and in older people. Thyroid status was narrowly within the normal range in all subjects. RMR was strongly correlated with LBM (r=.90, P < .001). RMR/LBM correlated strongly with TBF (r=.49, P < .01) and leptin (r=.56, P < .001), but not with GH status. By multiple regression analysis, sex and TBF were the strongest predictors of RMR/LBM. However, in the young subgroup, GH production rate was a positive determinant of RMR/LBM. In the male subgroup, leptin was a stronger predictor than TBF of RMR/LBM (P < .001). Neither age, physical fitness, nor thyroid status contributed independently to predict RMR/LBM. In conclusion, (1) LBM was the most important determinant of RMR; (2) RMR/LBM was higher in women and depended strongly on TBF; (3) GH status in healthy adults was only weakly associated with RMR; and (4) in men, serum leptin levels were a strong positive determinant of RMR.

Adult↗

PubMed1998

Consequences of stopping growth hormone (GH) therapy in young GH deficient patients with childhood onset disease.

Many studies have shown the beneficial, anabolic effects of growth hormone (GH) replacement therapy in GH deficient adults with childhood onset or adult onset disease. It is becoming increasingly evident, however, that these two groups of patients differ in many respects. Patients with adult onset GH deficiency represent fully developed individuals who have various organic, cerebral defects. By contrast, patients with childhood onset disease represent a heterogenous group comprising individuals with conditions, such as idiopathic isolated GH deficiency, genetic defects and organic defects. It is generally accepted that all children treated with GH should be retested in adulthood before adult replacement is started, as around 40% have a normal retest. It is unclear whether continued treatment with GH in childhood onset GH deficiency will yield results as positive as those seen in trials where GH is re-instituted after longer periods without treatment. Similarly, it is unknown at what timepoint cessation of GH treatment will cause a worsening in the physical state of the patient. In our placebo-controlled trial where GH was discontinued in 19 patients treated with GH during childhood, we determined exercise capacity, body composition, muscle mass and strength, cardiac function, sweating capacity, thyroid function and glucose metabolism before and after 12 months of continued treatment with GH.

Adolescent↗

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.

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