Biomedical subjects

N Vahl

Publications and source records attributed to N Vahl.

At least 37 records · Page 2Linked to original sources

PubMed1998

No effect of growth hormone on serum insulin-like growth factor binding protein-3 proteolysis.

Increased proteolysis of insulin-like growth factor binding protein (IGFBP)-3 is seen in several pathophysiological conditions and may represent an important mechanism for the regulation of insulin-like growth factor bioavailability. It has previously been suggested that proteolysis of IGFBP-3 is dependent on the GH status. To investigate this, IGFBP-3 proteolysis was measured in three groups of subjects: 1) GH-deficient patients before and after GH replacement (n = 14); 2) healthy subjects before and after 14 days of GH administration (n = 7); and 3) acromegalic patients before and after treatment with a long-acting SRIH analogue (octreotide; n = 14). In vivo IGFBP-3 proteolysis was investigated by Western immunoblotting. No difference was detected in pretreatment samples, and GH treatment in GH-deficient subjects or octreotide treatment in acromegalic subjects had no impact on in vivo proteolysis. In contrast, GH administration to healthy subjects caused a 21% increase in in vivo proteolysis (P = 0.0008). In vitro IGFBP-3 proteolysis was investigated by incubation of serum with 125I-rhIGFBP-3, followed by SDS-PAGE. In pretreatment samples, the percentage of proteolyzed 125I-rhIGFBP-3 was 13 +/- 1% (acromegalic subjects), 11 +/- 1% (healthy subjects), and 9 +/- 1% (GH-deficient subjects) (P < 0.009, GH-deficient vs. acromegalic subjects). Treatment had no effect on in vitro proteolysis. We conclude that GH status has no major impact on IGFBP-3 protease activity in serum.

Acromegaly↗

PubMed1998

Increased pulsatile, but not basal, growth hormone secretion rates and plasma insulin-like growth factor I levels during the periovulatory interval in normal women.

The secretion of GH changes during the menstrual cycle, exhibiting high levels during the periovulatory phase (PO). Previous studies have not investigated whether this difference in GH status is due to increased secretion or reduced clearance of pituitary GH and amplified pulsatile vs. basal GH secretion. It is also unclear whether the PO phase is accompanied by changes in circulating insulin-like growth factor I (IGF-I). In this study we investigated the 24-h GH release patterns in the early follicular (EF) vs. the periovulatory menstrual phase in the same individuals. Ten young (aged 24-34 yr) healthy women with regular menses were studied with deconvolution analysis of GH profiles obtained by blood sampling every 20 min for 24 h, followed by an arginine stimulation test. A high sensitivity immunofluorometric GH assay was used. All women were studied in both the EF and PO phases in random order. There were no differences in the basal GH secretion rate or GH half-life during the two phases. The number of GH secretory bursts identified during the 24-h sampling period was significantly increased during the PO (13.3 +/- 0.5) compared to the EF (10.3 +/- 0.6) phase (P = 0.002); conversely, the mean interburst interval was shorter in the PO (107 +/- 5 min) than in the EF (134 +/- 8 min) phase (P = 0.004). There was no difference in GH pulse mass (P = 0.13) or amplitude (P = 0.21) between the two phases. The pulsatile GH production rate (milligrams per L/24 h) was significantly elevated during the PO (61 +/- 6) compared to that during the EF (37 +/- 8; P = 0.004). Increased total GH pulse area was confirmed by Cluster analysis (P = 0.027). Furthermore, the 24-h mean serum GH concentration was significantly increased in the PO (1.4 +/- 0.1 mg/L) vs. that in the EF (0.9 +/- 0.1 mg/L; P = 0.002). There was a positive correlation between estradiol (E2) and GH secretory pulse amplitude, frequency, and mean 24-h serum GH concentration in the PO cycle phase, indicating E2 to be a major statistical determinant of GH secretion. Serum GH increased significantly after arginine infusion in both phases (P < 0.001), whereas there was no difference between the two cycle phases (P = 0.20). Serum IGF-I levels were increased during the PO phase (253 +/- 20 mg/L) compared to those during the EF phase (210 +/- 16 mg/L; P = 0.03), whereas serum IGF-binding protein-3, IGF-II, and GH-binding protein were similar during the two phases. This study unequivocally documents elevated GH levels during the PO phase of the menstrual cycle, mediated by increased GH production rate and burst frequency. The concomitant increase in serum IGF-I suggests a central stimulation of the GH-IGF-I axis, which may be mediated by endogenous E2 levels.

Adult↗

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

Abdominal adiposity rather than age and sex predicts mass and regularity of GH secretion in healthy adults.

We tested the hypothesis that body composition is the major predictor of growth hormone (GH) secretion in nonobese adults. We measured lean and fat tissue distribution (computerized tomography and dual-energy X-ray absorptiometry scan) and physical fitness [maximal oxygen consumption (Vo2max)] in 42 healthy nonobese adults (22 women and 20 men, age range 27-59 yr, mean +/- SE body mass index = 24 +/- 0.5 kg/m2). Deconvolution analysis was used to estimate specific features of 24-h GH secretion and clearance. Approximate entropy was used to quantify the regularity of GH release. Older subjects exhibited decreased estimates of GH secretion compared with younger subjects. Females had higher estimates of GH secretion, a longer GH half-life, and displayed more irregularity in GH release than males. Mean 24-h serum GH concentrations correlated inversely with intra-abdominal fat and waist-to-hip ratio and positively with Vo2max. Multiple linear regression analysis revealed intra-abdominal fat as the dominant determinant of estimates of GH secretion. Vo2max was more important than sex and age in predicting GH secretion. We conclude that abdominal fat is the major determinant of GH secretion in healthy nonobese adults. Although the underlying mechanisms remain elusive, our findings extend the clinical implications of visceral adiposity to include hyposomatotropism.

Abdomen↗

PubMed1997

Somatopause and adiposity.

Mobilization of lipids is the pivotal action of growth hormone (GH) in both children and adults. The temporal association between declining GH levels and accumulation of body fat with ageing is, therefore, interesting although the cause-effect relationship remains unknown. Recent cross-sectional data suggest that both stimulated and spontaneous GH release is predominantly predicted by the amount of abdominal fat in both men and women. The same study also shows that ageing is associated with an increased metabolic clearance rate and apparent distribution volume, both of which correlate positively with fat mass and negatively with age. Furthermore, the acute lipolytic response to a GH bolus is somewhat lower in older adults (and in women). It is, therefore, proposed that changes in life style and dietary habits, perhaps together with an age-determined reduced lipolytic responsiveness to GH, initiates fat accumulation. The increased fat mass, in turn, inhibits the release and promotes the clearance of GH thus establishing a vicious circle.

Adipose Tissue↗

PubMed1997

Abdominal fat determines growth hormone-binding protein levels in healthy nonobese adults.

The circulating high affinity GH-binding protein (GHBP), which derives from the extracellular domain of the hepatic GH receptor, correlates inversely to GH levels and directly to body mass index (BMI) in healthy adults. As GH secretion and adiposity are also interrelated, we tested the hypothesis that body composition more than GH, determines GHBP levels in healthy adults. Forty-two healthy adults [21 females and 21 males; mean age, 39.4 yr range, 27-59 yr); mean BMI, 23.9 kg/m2 (range, 18.9-34.7 kg/m2)], underwent anthropometric measurements (BMI, W/H ratio, computed tomography scan, dual energy x-ray absortiometry (DEXA) scan, and bioimpedance) in addition to two GH stimulation tests (arginine and clonidine) and a 24-h GH profile. By simple linear regression, serum GHBP correlated positively to several indices of adiposity: intraabdominal fat (r = 0.537; P = 0.001), sc abdominal fat (r = 0.680; P < 0.001), BMI (r = 0.483; P = 0.001), W/H ratio (r = 0.452; P = 0.003), total body fat (DEXA scanning; r = 0.503; P = 0.002), and body fat (bioimpedance; r = 0.354; P = 0.023). Lean body mass estimated by DEXA scan was negatively associated with GHBP (r = 0.541; P < 0.001). GHBP was inversely proportional to arginine-stimulated GH release (r = -0.346; P = 0.027) and negatively associated with several measures of spontaneous GH release as estimated by deconvolution analysis (GH mass, GH production rate, and mean GH; r = -0.371; P = 0.017, r = -0.393; P = 0.011, and r = -0.343; P = 0.028, respectively)). With multiple linear regression analyses, indices of adiposity were significant determinants of GHBP levels, whereas GH status did not contribute independently to the prediction of GHBP. Neither insulin-like growth factor I nor fasting insulin levels correlated to GHBP levels. In conclusion, GHBP levels in normal adults seem to be determined by abdominal fat mass rather than GH secretion.

Abdomen↗

PubMed1997

Metabolic effects and pharmacokinetics of a growth hormone pulse in healthy adults: relation to age, sex, and body composition.

The acute effects of a single GH pulse have previously been studied in young males. It is, however, likely that both the metabolic effects and the pharmacokinetics of GH may differ between age groups and sexes. We studied 36 healthy, clinically nonobese adults of both sexes, who were divided into a young group (mean age, 29.6 yr) and an older group (mean age, 51.0 yr). On 2 separate occasions, they received an i.v. bolus of either GH (200 micrograms) or saline followed by blood sampling for 5 h. Glucose turnover was estimated by infusion of [3-3H]glucose, and indirect calorimetry was performed before and 2 h after the bolus infusions. Body composition (computed tomography scan and dual energy x-ray absorptiometry) was performed at baseline. Baseline levels of serum insulin-like growth factor I (IGF-I) was lower in older subjects, whereas circulating IGF-binding protein-1 and lipid intermediates were lower in males than in females. The area under the GH curve was lower in older subjects (young, 3978 +/- 1532 micrograms/L.24 h; older, 1144 +/- 79; P = 0.001), whereas the elimination half-life did not differ with age (young, 18.1 +/- 0.9 min; older, 16.4 +/- 0.8; P = NS). The MCR and apparent distribution volume of GH were higher in older subjects [MCR: young, 0.11 +/- 0.02 min/L; older, 0.19 +/- 0.01; P = 0.001; apparent distribution volume: young, 2.5 +/- 0.4 L; older, 4.5 +/- 0.3; P < 0.001). Both MCR and Vd correlated inversely with age and positively with indexes of adiposity. GH significantly increased lipid intermediates, but the response was higher in young subjects and males. By contrast, the ability of GH to acutely suppress IGF-binding protein-1 was more pronounced in older subjects and females. Serum levels of insulin and IGF-I did not differ significantly between GH and saline treatment groups. GH decreased the respiratory exchange ratio and increased resting energy expenditure, with no age or gender differences. A gradual decline over time in plasma levels and rate of turnover of glucose was recorded after both GH and saline. The following conclusions were reached. 1) The MCR and Vd of GH increase with age and correlate positively with fat mass. 2) Older subjects are responsive to the acute lipolytic effects of GH, but the response is higher in young subjects and in males. 3) Adipose tissue may be actively involved in the distribution and clearance of GH. 4) Age, sex, and body composition interact with GH in a complex manner, involving clearance, distribution, and metabolic actions of the hormone.

Adult↗

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↗

PubMed1996

Growth hormone versus placebo treatment for one year in growth hormone deficient adults: increase in exercise capacity and normalization of body composition.

OBJECTIVE: Studies with GH substitution in GH-deficient (GHD) adults lasting more than 6 months have so far been uncontrolled. End-points such as physical fitness and body composition may be subject to a considerable placebo effect which weakens the validity of open studies. We therefore tested GH (2 IU/m2 per day) versus placebo treatment for 12 months. DESIGN: Twenty-nine patients (mean age 45.5 +/- 2.0 years) with adult-onset GHD were studied in a double-blind, parallel design. Measurements of body composition by means of conventional anthropometry, bioelectrical impedance (BIA), CT scan and DEXA scan, exercise capacity, and isometric muscle strength were performed at baseline and after 12 months treatment. For body composition measurements a control group of 39 healthy, age and sex-matched subjects was included. RESULTS: Sum of skinfolds (SKF) at 4 sites decreased significantly after GH treatment. Total body fat (TBF) as assessed by DEXA and BIA was elevated at baseline but normalized after GH. TBF assessed by SKF revealed significantly higher levels compared to DEXA and BIA, although all estimates intercorrelated closely. Visceral and subcutaneous abdominal fat decreased by 25 and 17%, respectively after GH (P < 0.01) to levels no longer different from the control group. CT of the mid thigh revealed a significant reduction in fat tissue and a significant increase in muscle volume after GH treatment, both of which resulted in a normalization of the muscle: fat ratio (%) (placebo: 58:42 (baseline) vs 58:42 (12 months); GH: 66:34 (baseline) vs 72:28 (12 months) (P = 0.002); normal subjects: 67:33 (P < 0.05 when compared to 12 months placebo data)). Total body resistance and resistance relative to muscle volume decreased significantly after GH treatment suggesting over-hydration as compared to normal subjects. Exercise capacity (kJ) increased significantly after GH treatment (placebo: 54.7 +/- 9.8 (baseline) vs 51.6 +/- 8.2 (12 months); GH: 64.9 +/- 13.3 (baseline) vs 73.5 +/- 13.6 (12 months) (P < 0.05)). Isometric quadriceps strength increased after GH but no treatment effect could be detected owing to a small increase in the placebo group. Serum IGF-I levels (microgram/l) were low baseline and increased markedly after GH treatment to a level exceeding that of normal subjects (270 +/- 31 (12 months GH) vs 156 +/- 8 (normal subjects (P < 0.01)). The levels of serum electrolytes and HbA1c remained unchanged. The number of adverse effects were higher in the GH group after 3 months, but not after 6 and 12 months. CONCLUSIONS: (1) The reduction in excess visceral fat during GH substitution is pronounced and sustained; (2) beneficial effects on total body fat, muscle volume and physical fitness can be reproduced during prolonged placebo-controlled conditions; (3) uncontrolled data on muscle strength must be interpreted with caution; (4) a daily GH substitution dose of 2 IU/m2 seems too high in many adult patients.

Abdomen↗

PubMed1996

Bioavailability of recombinant human growth hormone in different concentrations and formulations.

Whether the bioavailability of growth hormone depends on the concentration or formulation of the preparation was evaluated in 18 growth hormone-deficient patients. The design was a single-blinded, randomized cross-over study, where the patients were given a single, fixed dose subcutaneous injection of growth homrone (3 IU/m2) of 3 different preparations: (1) 4 IU/ml in a bicarbonate buffer dissolved in 0.9% benzyl alcohol (approximately 1.37 mg/ml), (2) 5.9 IU/ml in a phosphate buffer dissolved in 1.5% benzyl alcohol (approximately 2 mg/ml) and (3) 11 7 IU/ml in a phosphate buffer dissolved in 1.5% benzyl alcohol (approximately 4 mg/ml). Conventional growth hormone-therapy was withdrawn 2 days before each study period. Blood samples were drawn over a 24-hr period and assessed for growth hormone, serum insulin-like growth factor I (IGF-I), insulin and glucose. The geometric mean values (+/- geometric S.D) of the relative absorption fractions were F5.9 IU/4 IU = AUC5.9 IU/AUC4 IU = (+/- 1.139) (P = 0.66), F11.7 IU/AUC4 IU = AUC11.7 IU/AUC4 IU (1.14 +/- 1.21) (P = 0.009) AND F11.7 IU/5.9 IU = AUC11.7 IU/AUC5.9 IU = 1.12 (+/- 1.17) (P = 0.005), respectively. The 90% confidence intervals were contained within the limits of 0.80-1.25 accepted for bioequivalence. Geometric mean values (+/- geometric S.D.) of the relative observed maximum concentration, Cmax was for Cmax 5.9 IU/Cmax 4 IU = 1.04 (+/- 1.19) (P = 0.32), Cmax 11.7 IU/Cmax 4 IU = 1.24 (+/- 1.21) (P = 0.0002) and Cmax 11.7 IU/Cmax 5.9 IU = 1.19 (+/- 1.29) (P = 0.012). The median and the range values for the observed time to reach Cmax was tmax 5.9 IU/tmax 4 IU = 0.63 (0.04-1.00), tmax 11.7 IU/tmax 4 IU = 0.59 (0.06-1.0) and tmax 11.7 IU/tmax 5.9 IU = 0.90 (0.51-18.00). There were no significant differences in IGF-I, glucose and insulin profiles. Based on the upper limits of the 90% confidence intervals for relative AUC's the conclusion is that the three different preparations were bioequivalent.

Absorption↗

PubMed1996

Influence of growth hormone and androgens on body composition in adults.

The secretion of both growth hormone (GH) and androgens declines with age which may play a role in the senescent changes in body composition and organ function. Among healthy adults abdominal adiposity is an important negative determinant of GH secretion. Surprisingly, abdominal or android obesity seems inversely correlated with testosterone levels in males but not in females. The ability of GH to promote lipolysis and preserve or increase lean body mass has been reappraised in substitution studies in GH-deficient adults. By comparison, adequately controlled studies of androgen replacement in hypogonadal and/or elderly males are few. In view of the physiological and clinical relevance of obtaining information about the aging process, there is a need for controlled experiments addressing similarities and differences between the action of GH and sex steroids in adults.

Adult↗

PubMed1996

Abdominal adiposity and physical fitness are major determinants of the age associated decline in stimulated GH secretion in healthy adults.

Growth hormone (GH) secretion is reduced with age in normal subjects. Aging is furthermore associated with a decline in lean body mass and an increase in relative adiposity, and overt obesity is a negative determinant of GH secretion in all age groups. We tested the hypothesis that differences in body composition and physical fitness rather than age determine stimulated GH secretion in healthy adults. Forty-two clinically nonobese adults [22 women and 20 men, mean age 39.4 yr (range 27-59), mean +/- SE body mass index (BMI) = 23.9 +/- 0.5 kg/m2] underwent 2 GH stimulation tests (arginine and clonidine), determination of maximal oxygen consumption (VO2-max), and a number of anthropometric measurements: body mass index (BMI), waist to hip (W/H)-ratio, intraabdominal fat and thigh muscle to fat (M/F)-ratio (computed tomography scan), total body fat, and lean body mass (DEXA scan). Peak GH levels were lower with clonidine [mean +/- SE (micrograms/L): 9.79 +/- 1.29 (arginine) vs. 3.56 +/- 0.57 (clonidine) (P < 0.001)]. Arginine-stimulated GH peak levels correlated negatively with indices of adiposity and age [intraabdominal fat: r = -0.72, P < 0.001; W/H-ratio: r = -0.58, P < 0.001; age: r = -0.54, P < 0.001], and positively with VO2-max [r = 0.60, P < 0.001]. Clonidine-stimulated GH peak correlated negatively with intraabdominal fat [r = -0.60, P < 0.001] and age [r = -0.46, P = 0.008]. Multiple linear regression revealed multicollinearity among several of the independent variables. In all equations abdominal adiposity and physical fitness, rather than age, contributed significantly to predict changes in arginine stimulated GH secretion. Intraabdominal fat was a more important determinant of the clonidine evoked GH response than age. In clinically nonobese, healthy adults relative adiposity, in particular in the abdominal region, is a major negative determinant of stimulated GH secretion, and physical fitness is an important positive predictor. The cause-effect relationship of these observations remains to be elucidated, but our findings may have clinical implications in the diagnosing of GH-deficiency in adults.

Abdomen↗

PubMed1996

Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study.

The effects of GH substitution on skeletal mass, bone turnover, and calcium metabolism were investigated in 29 patients with GH deficiency who were randomized to sc injections with GH (2 IU/m2 day) or placebo for 12 months. During GH treatment, serum insulin-like growth factor I increased 263 +/- 98% (P < 0.001). Serum osteocalcin, bone a alkaline phosphatase, and procollagen type I C-terminal propeptide increased by 376 +/- 78% (P < 0.005), 128 +/- 17% (P < 0.005), and 100 +/- 17% (P < 0.005), respectively. Serum type I collagen telopeptide and urinary levels of pyridinoline, deoxypyridinoline, and hydroxyproline rose by 158 +/- 39% (P < 0.005), 170 +/- 48% (P < 0.005), 156 +/- 78% (P < 0.005), and 161 +/- 50% (P < 0.005), respectively. Serum ionized calcium rose by 1.7 +/- 0.6% (P < 0.05), whereas serum PTH decreased insignificantly. Vitamin D metabolites remained unaltered. Urinary calcium/creatinine increased and phosphate/creatinine decreased transiently, returning to baseline values at 9 months. When measured by dual energy x-ray absorptiometry, whole body bone mineral density (BMD) and (BMD) of the radius decreased 2.4 +/- 0.6% (P < 0.05) and 3.5 +/- 1.0% (P < 0.005), respectively, whereas no significant changes were observed in BMD of the femur or spine. Our results indicate that long term GH treatment activates bone remodeling in patients with GH deficiency. The observed slight decrease in BMD may be explained by expansion of the remodeling space and reduced mean age of bone tissue. IT remains unclear whether long term treatment with GH will lead to an increase in bone mass and improved skeletal biomechanical competence.

Adult↗

PubMed1995

Fuel metabolism in growth hormone-deficient adults.

Apart from being a stimulator of longitudinal growth, growth hormone (GH) regulates fuel metabolism in children and adults. A halfmark is mobilization of lipids, which involves an inhibition of lipoprotein lipase activity in adipose tissue and activation of the hormone sensitive lipase. Suppression of basal glucose oxidation and resistance to insulin are other important effects. This may cause concern during GH substitution in GH-deficient adults, some of whom may present with insulin resistance due to concomitant abdominal obesity. However, there are data to suggest that the GH-induced reduction in fat mass and increase in lean body mass may offset the insulin antagonistic actions of the hormone. The nitrogen-retaining effects of GH seem to involve a direct stimulation of protein synthesis in addition to secondary effects such as generation of insulin-like growth factor-I (IGF-I), hyperinsulinemia, and promotion of lipolysis. Thus, during periods of substrate affluence, GH acts in concert with insulin and IGF-I to promote protein anabolism. Postabsorptively, GH is primarily lipolytic and thereby indirectly protein-sparing. This effect becomes further accentuated with more prolonged fasting. In that sense, GH is unique by its preservation of protein during both feast and famine. These fuel metabolic effects add merit to the principle of GH substitution in hypopituitary adults.

Adult↗

PubMed1995

Whole body and regional soft tissue changes in growth hormone deficient adults after one year of growth hormone treatment: a double-blind, randomized, placebo-controlled study.

OBJECTIVE: Adults with GH deficiency (GHD) exhibit changes in body composition. Studies of the effects of GH substitution on body composition have been short-term or not adequately controlled. The purpose of this study was to evaluate the long-term effects of GH on soft tissue using dual-energy X-ray absorptiometry (DEXA). This technique enables assessment of whole body as well as regional soft tissue composition. DESIGN: A double-blind, randomized, placebo-controlled study in patients with acquired GHD. The therapeutic regime consisted of biosynthetic human GH (2.0 IU/m2 per day) or placebo, given as a daily subcutaneous injection at 2000 h for 12 months. PATIENTS: Twenty-nine patients with acquired GHD (GH < 10 micrograms/l (< 20 mU/l) following standard provocative tests) in whom additional hormone replacement was maintained. MEASUREMENTS: Soft tissue determinations by DEXA scan, height, weight, foot volume and finger circumference were recorded together with serum IGF-I at baseline and after 12 months. RESULTS: Twelve months of GH therapy induced a total fat mass (FM) reduction of (mean +/- SEM) 4.88 +/- 0.58 kg (P < 0.002) (n = 13) corresponding to 21.5% of the total FM. The reduction in fat was most marked in the trunk, i.e. 3.07 +/- 0.29 kg (P < 0.002) corresponding to 61% of the total FM reduction. Total lean soft tissue mass (LSTM) increased by 3.31 +/- 0.81 kg (P < 0.001). Regional changes for arm and leg in the GH group amounted to 0.32 +/- 0.08 kg (P < 0.002) and 0.71 +/- 0.14 kg (P < 0.002), respectively, without accompanying significant changes in truncal LSTM between the groups. The foot volume was increased by 55.8 +/- 15.7 ml (P < 0.007) and the finger circumference by 2.67 +/- 0.5 mm (P < 0.005) on active treatment with no significant changes in the placebo group. CONCLUSIONS: Twelve months of GH therapy induced marked changes in soft tissue; fat mass was reduced, particularly in the trunk (61% of total fat mass reduction) whereas lean soft tissue mass increased more in the extremities. The data imply that GH-induced changes in body composition are maintained with long-term therapy.

Absorptiometry, Photon↗

PubMed1995

Growth hormone deficiency and hyperthermia during exercise: a controlled study of sixteen GH-deficient patients.

Sweat secretion is often disturbed in patients with GH secretory disorders. Hyperhidrosis is a classic feature of acromegaly, and it has recently been shown that GH-deficient patients exhibit decreased sweating capacity after pilocarpine stimulation of the skin. Thus, patients with GH-deficiency may be at risk for developing hyperthermia. To pursue this, we performed a controlled study on sweating and body temperature regulation during exercise in the heat in 16 GH-treated GH-deficient patients with normalized insulin-like growth factor-I and insulin-like growth factor/binding protein-3 serum levels [11 with multiple pituitary deficiency (MPD) and 5 with isolated GH deficiency] and in 10 healthy subjects as controls (CTs). Each subject exercised on a bicycle ergometer for 60 min at a workload corresponding to 45% of their individual maximal oxygen consumption (VO2max), in a room maintained at 35 C. GH serum concentrations increased significantly after approximately 10 min of exercise in the CTs (P < 0.001) but remained low in the patients. Body heat storage was significantly higher in the patients compared with the CTs [89 (SE +/- 10) watts (MPD) vs. 37 (SE +/- 8) watts (CTs), P < 0.001]. Consequently, the core temperatures of the patients increased significantly after exercise compared with those of the CTs [38.3 C (0.10 C) (MPD) and 38.1 C (0.06 C) (isolated GH deficiency) vs. 37.5 C (0.2 C) (CTs) (P < 0.004)]. Skin temperature increased significantly during exercise in the patients but remained unaltered in the CTs. Sweat secretion rates, as determined by the pilocarpine method, were significantly lower in the MPD patients [77 (SE +/- 10) mg/30 min] than in the CTs [115 (SE +/- 7) mg/30 min] (P < 0.005). Total body sweating was lower in the patients than in the CTs, although the difference did not reach statistical significance. Significantly reduced estimated evaporative heat loss was demonstrated in the patients compared with the CTs (P < 0.001). In conclusion, 1) decreased sweating, decreased sensitivity of the sweat gland, and impaired thermoregulation are part of the adult GH-deficiency syndrome, and 2) GH-deficient patients are at risk for developing hyperthermia during physical activity in hot environments.

Adolescent↗

PubMed1994

Short and long-term cardiovascular effects of growth hormone therapy in growth hormone deficient adults.

OBJECTIVE: Since GH substitution therapy is now available for adult GH deficient patients, information on the cardiovascular effects of GH substitution has assumed major clinical interest. We have therefore assessed cardiovascular effects of short and long-term growth hormone substitution therapy in these patients. PATIENTS AND MEASUREMENTS: Doppler echocardiography was performed in 21 GH deficient patients after 4 months placebo and 4 months GH therapy, in a double blind cross-over study. In an open design study, 13 patients were reinvestigated following 16 months and 9 patients following 38 months of GH therapy. Twenty-one age and sex-matched normal control subjects were also investigated. RESULTS: Heart rate was increased in placebo treated patients as compared to controls. After 4 months of GH treatment, heart rate showed a further increase (10%, P < 0.01) and seemed to remain elevated after 16 months of GH therapy. Systolic and diastolic blood pressures were significantly lower in placebo treated patients than in controls, and did not change significantly after GH treatment. The left ventricular diastolic diameter was reduced in patients as compared to controls, but increased after 4 months GH therapy (P > 0.05) and seemed to increase further during prolonged GH treatment. Cardiac index was at the same level in controls and in placebo-treated patients, but increased by 20% following GH therapy and remained elevated after 16 and 38 months (P < 0.05) of GH substitution. CONCLUSION: Following GH substitution in GH deficient adult patients, left ventricular diastolic dimensions increased and seemed to normalize, while heart rate and cardiac output were found to be increased to supranormal levels.

Adult↗