Childhood-onset Growth Hormone Deficiency Research Articles

Adults with childhood-onset growth hormone deficiency: effects of growth hormone treatment on cardiac structure.

To evaluate the effects of growth hormone deficiency (GHD) and of growth hormone (GH) therapy on cardiac structure in adults with childhood-onset GHD. Out-patient clinic in the Italian Institute for Auxology, Milan. Eight adults with childhood-onset GHD and eight healthy controls, matched for sex, age, exercise and body mass index. Recombinant GH (Saizen Serono, Italy), administered in a conventional dose of 0.5 IU kg-1 week-1 for 6 months. Cardiac structure parameters, evaluated by two-dimensional, M-mode and Doppler echocardiograms, and stress test, by means of a modified Bruce protocol with a bicycle ergometer, were determined before and after 6 months GH therapy. Before treatment, mean (+/- SE) intraventricular septal thickness (IVST: 7.1 +/- 0.2 mm), LV posterior wall thickness (LVPT: 5.2 +/- 0.1 mm), LV mass (LVM: 94.6 +/- 5.0 g), LV mass index (LVM/body surface area, LVMI: 65.1 +/- 3.0 g m-2) and left ventricular end-diastolic diameter (LVED: 41.4 +/- 0.6 mm) of patients were significantly lower (P < 0.01) than in controls, whilst LV end-systolic diameter (LVES) of patients (25.5 +/- 0.7 mm) was similar to controls (27.5 +/- 0.7). GH treatment significantly (P < 0.01) increased LVPT (6.8 +/- 0.2 mm), LVM (111.6 +/- 4.6 g) and LVMI (80.5 +/- 3.5 g m-2); no significant changes were observed in LVED, LVES and IVST values. The stress test showed a significant improvement of cardiac performance, as demonstrated by the reduction of blood pressure x heart rate product at the same workload (basal: 32,722.5 +/- 897.4 vs. after: 25,574.6 +/- 439.7). GH plays a role in the maintenance of a normal cardiac structure in adulthood. The present study suggests that GH treatment might be able to improve the cardiac structure of patients with childhood-onset GHD.

Increased Arterial Intima-Media Thickness in Childhood-Onset Growth Hormone Deficiency

Very little is known about the atherosclerotic risk in patients with childhood-onset growth hormone deficiency (GHD). Such data may be relevant to reconstructing the natural course of the cardiovascular abnormalities associated with GHD. To this end, the intima-media thickness (IMT) of the carotid arteries and the vascular risk factors were evaluated in 14 childhood-onset GHD patients (age 25 +/- 1 yr, BMI 22 +/- 0.6 Kg/m2) and in 14 age-, sex-, and BMI-matched control subjects. IMT was greater in GHD patients (0.83 +/- 0.06 and 0.81 +/- 0.06 mmol/L for the right and left carotid artery) than in controls (0.64 +/- 0.03 and 0.64 +/- 0.04 mmol/L, P < 0.01 and P < 0.02, respectively). Serum total and lipoprotein cholesterol, and serum total triglycerides did not differ between the two groups. However, a significant increase in low density lipid triglycerides was present in GHD patients (0.27 +/- 0.02 mmol/L) compared with controls (0.19 +/- 0.01; P = 0.007). No difference was found in plasma fibrinogen and serum Lp(a) levels. Plasma glucose and insulin concentrations were similar in GHD and control subjects both in the fasted state and after an oral glucose load. In conclusion, young patients with childhood-onset GHD show an increased IMT in the absence of clear-cut abnormalities of the classic vascular risk factors. This suggests a role for GH deficiency per se in increasing the atherosclerotic risk.

Increased Arterial Intima-Media Thickness in Childhood-Onset Growth Hormone Deficiency

Increased Arterial Intima-Media Thickness in Childhood-Onset Growth Hormone Deficiency

Elderly patients with adult-onset growth hormone deficiency are not osteopenic.

The age-related decline in GH secretion has been implicated in the development of osteoporosis. GH-deficient adults show a significant reduction in bone mineral density (BMD), which is greater in those with childhood-onset GH deficiency than in those with GH deficiency occurring in adult life. To determine whether GH deficiency in late adult life causes a reduction in BMD beyond the decline observed with increasing age, we studied 21 patients over the age of 60 yr with GH deficiency caused by organic pituitary disease and 23 controls of similar age and sex distribution and BMI. Dual energy x-ray absorptiometry was used to determine total bone mass and BMD at the hip and in the lumbar spine. Serum osteocalcin was determined in all subjects and urinary deoxypyridinoline/creatinine ratio in 19 patients and 21 controls. The median (range) known duration of GH deficiency in the patients was 8 yr (range, 4-41 yr). The median (range) total bone mass was 2774 g (range, 1534-3734) in the patients and 2717 g (range, 1235-3549) in the controls (P = 0.42). Specific measurements of BMD made at L2-L4, the right femoral neck, the right femoral trochanter, and Ward's triangle were 1.234 (range, 0.778-1.507) vs. 1.144 g/cm2 (range, 0.809-1.466; P = 0.48), 0.921 (range, 0.605-1.372) vs. 0.96 g/cm2 (range, 0.534-1.315; P = 0.62), 0.92 (range, 0.523-1.229) vs. 0.915 g/cm2 (range, 0.353-1.313; P = 0.68), and 0.773 (range, 0.408-1.289) vs. 0.806 g/cm2 (range, 0.353-1.154; P = 0.81) in the patients and controls, respectively. The median (range) serum osteocalcin was 11.5 (range, 3.6-23.0) vs. 15.1 ng/mL (range, 0.7-40.5; P = 0.019) in the patients and controls, respectively. The median (range) deoxypyridinoline cross-links/creatinine ratio was 3.5 micromol/mol (range, 0.8-8.3) in the patients and 4.9 micromol/mol (range, 3.0-9.7) in the controls (P 0.038). There was a significant correlation between serum insulin-like growth factor I and total bone mass in the controls, but not in the patients. These data demonstrate that BMD is not significantly altered in GH-deficient adults over the age of 60 yr. Markers of bone formation and resorption are decreased, however, suggesting that bone turnover is reduced. Further studies are required to determine whether the reduction in bone turnover in these patients is of benefit.

Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3.

Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children and exhibit little diurnal variation, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some controversy still exists. In adults, the diagnostic value of IGF-I and IGFBP-3 suspected of GHD has been reported in only a few studies. We performed a GH provocative test, using oral clonidine, in 108 patients who had previously been treated with GH during childhood (73 men and 35 women). Basal IGF-I and IGFBP-3 levels were compared to those in 1237 healthy controls (312 controls > 18 yr) as well as to peak GH levels. Seventy-nine patients had peak GH values below a cut-off value of 7.5 micrograms/L (34 with isolated GHD), whereas 29 patients had a normal GH response (28 with previous isolated GHD), i.e. 45% of patients treated with GH during childhood because of isolated GHD had a normal GH response when retested in adulthood. Multiple regression analysis revealed that peak GH levels were dependent on the degree of hypopituitarism, body mass index, and duration of disease. IGF-I levels were below -2 SD in 60 of 79 GHD patients and above -2 SD in 21 of 29 patients with a normal GH response. IGFBP-3 levels were below -2 SD in 54 of 79 GHD patients and above -2 SD in 23 of 29 patients with a normal GH response. Multiple linear regression analysis demonstrated that IGF-I and IGFBP-3 were significantly dependent on peak GH levels and the number of other pituitary axes affected. In this analysis, duration of disease was significantly associated with both IGF-I and IGFBP-3, whereas body mass index was significantly associated with IGFBP-3, but not with IGF-I. We conclude that IGF-I and IGFBP-3 determinations predict the outcome of a GH provocative test in adults suspected of GHD and believe that IGF-I as well as IGFBP-3 serum concentrations are valuable diagnostic parameters in the evaluation of GHD in adults with childhood-onset disease. We suggest that children who have been treated with GH should undergo reassessment of their GH secretory status as young adults by provocative testing as well as by IGF-related peptides before continued adult GH replacement therapy is considered. However, our data suggest that it is not necessary to reconfirm GH deficiency by GH provocative testing in young adults who have two or more pituitary hormone deficiencies in addition to GHD.

Growth Hormone (GH) Provocative Retesting of 108 Young Adults with Childhood-Onset GH Deficiency and the Diagnostic Value of Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-3

Growth Hormone (GH) Provocative Retesting of 108 Young Adults with Childhood-Onset GH Deficiency and the Diagnostic Value of Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-3

Changes in bone mineral density, body composition, and lipid metabolism during growth hormone (GH) treatment in children with GH deficiency.

Adults with childhood onset GH deficiency (GHD) have reduced bone mass, increased fat mass, and disorders of lipid metabolism. The aim of the present study was to evaluate bone mineral density (BMD), bone metabolism, body composition, and lipid metabolism in GHD children before and during 2-3 yr of GH treatment (GHRx). Forty children with GHD, mean age 7.9 yr, participated in the study of bone metabolism and body composition; and an additional group of 17 GHD children, in the study of lipid metabolism. Lumbar spine BMD, total body BMD, and body composition were measured with dual-energy x-ray absorptiometry. Volumetric BMD (bone mineral apparent density, BMAD) was calculated to correct for bone size. BMD, BMAD, lean tissue mass, bone mineral content, fat mass, and percentage body fat were expressed as SD scores (SDS), in comparison with normative data of the same population. Lumbar spine BMD and BMAD and total body BMD were all decreased at baseline. All BMD variables increased significantly during GHRx, lumbar spine BMD SDS, already after 6 months of treatment. Lean tissue mass SDS increased continuously. Bone mineral content SDS started to increase after 6 months GHRx. Fat mass SDS decreased during the first 6 months of GHRx and remained stable thereafter. Biochemical parameters of bone formation and bone resorption did not differ from normal at baseline and increased during the first 6 months of GHRx. Serum 1,25 dihydroxyvitamin D increased continuously during GHRx, whereas PTH and serum calcium remained stable. Lipid profile was normal at baseline: Atherogenic index had decreased and apolipoprotein A1(Apo-A1) had increased after 3 yr of treatment. In conclusion, children with GHD have decreased bone mass. BMD, together with height and lean tissue mass, increased during GHRx. GHRx had a beneficial effect on lipid metabolism.

Lung volumes and respiratory muscle strength in adult patients with childhood- or adult-onset growth hormone deficiency: effect of 12 months' growth hormone replacement therapy.

We have described impairment of the respiratory function in adult patients with childhood-onset growth hormone (GH) deficiency. The aim of the present study was to evaluate lung volumes and respiratory muscle strength in patients diagnosed as GH deficient before and after 6 and 12 months of recombinant GH treatment. Ten adults diagnosed as GH deficient in childhood, ten adults diagnosed as GH deficient in adulthood and ten healthy subjects entered the study. For each subject, evaluation of respiratory function followed the same standard approach, consisting of respiratory muscle strength assessment, record of flow-volume curves, measurement of static lung volumes and lung diffusing capacity. Childhood-onset GH-deficient patients had a significant reduction of maximal inspiratory (p < 0.01) and maximal expiratory (p < 0.05) mouth pressures. Total lung capacity, vital capacity and functional residual capacity were significantly reduced compared to healthy subjects (p < 0.05). Conversely, residual volume and diffusing lung capacity did not show any significant change. No significant change of the ratio between the percentage forced expiratory volume in 1 s and the forced vital capacity was observed. The decrease of respiratory mouth pressures was not correlated to the decrease of lung volumes. Adult-onset GH-deficient patients had only a significant reduction of maximal expiratory pressure compared to healthy subjects (p < 0.05). After 6 months of treatment no significant differences in any of the evaluated parameters were found. After 12 months of treatment patients with childhood-onset GH deficiency show a significant improvement of lung volumes (p < 0.01) and maximal respiratory mouth pressures (p < 0.005), whereas adult-onset GH-deficient patients show a significant improvement of maximal expiratory pressure (p < 0.05). In conclusion, the results of this study showed that adult patients affected with childhood-onset GH deficiency suffer from an impairment of the ventilatory function due to a reduction of lung volumes and a decrease of respiratory pressures probably due to a reduction of respiratory muscle strength. This impairment was reversed after 12 months of treatment with recombinant GH. Conversely, adult-onset GH-deficient patients had only an impairment of the maximal expiratory pressure, probably due to respiratory muscle weakness re-established after 12 months of GH therapy.

Improved left ventricular function after growth hormone replacement in patients with hypopituitarism: Assessment with radionuclide angiography

Prolonged growth hormone deficiency (GHD) leads to marked cardiac dysfunction; however, whether reversal of this abnormality may be achieved after specific replacement therapy has not yet been completely clarified. Fourteen patients with childhood-onset GHD (nine men and five women, mean age 27+/-4 years) and 12 normal control subjects underwent equilibrium radionuclide angiography under control conditions at rest. Patients with GHD were also studied 6 months after recombinant human (rh) GH treatment (0.05 IU/kg per day). Normal control subjects and patients with GHD did not differ with respect to age, gender and heart rate. In contrast, left ventricular ejection fraction (53%+/-9% vs 66%+/-6%, P <0.001), stroke volume index (41+/-11 vs 51+/-8 ml/m2, P <0.01) and cardiac index (2.8+/-0.6 vs 3.+/-0.5 l/min/m2, P <0.001) were significantly lower in GHD patients than in normal control subjects. None of the GHD patients showed adverse or side-effects during rhGH therapy; thus none required a reduction in GH dose during the treatment period. Heart rate and arterial blood pressure were not significantly modified by rhGH treatment. After 6 months of rhGH therapy a significant improvement in left ventricular ejection fraction (from 53%+/-9% to 59%+/-9%, P <0.01), stroke volume index (from 41+/-11 to 47+/-13 ml/m2, P <0.05) and cardiac index (from 2.8+/-0.6 to 3.3+/-0.8 l/min/m2, P <0.01) was observed in GHD patients. In conclusion, prolonged lack of GH leads to impaired left ventricular function at rest. Reversal of this abnormality may be observed after 6 months of specific replacement therapy in patients with childhood-onset GHD.

Impairment of lung volumes and respiratory muscle strength in adult patients with growth hormone deficiency

Little is known of the respiratory function in patients with growth hormone (GH) deficiency. The aim of the present study was to evaluate lung volumes and respiratory muscle strength in patients diagnosed as GH deficient in childhood. Ten patients diagnosed as GH deficient in childhood and ten healthy subjects entered the study. For each subject the evaluation of respiratory function followed the same standard approach, consisting of respiratory muscle strength assessment, recording of flow-volume curves, measurement of static lung volumes and lung diffusing capacity. Both maximal inspiratory and expiratory mouth pressures were decreased in GH deficiency. Vital capacity, N2 functional residual capacity and total lung capacity were significantly reduced when compared to healthy subjects. Conversely, the residual volume and diffusing lung capacity to CO did not show any significant change. No significant change of percentage forced expiratory volume in 1 s/forced vital capacity ratio was observed. The decrease of respiratory mouth pressures was not correlated to the decrease of lung volumes. In conclusion, the results of this study show that adult patients affected with childhood onset GH deficiency suffer from impairment of ventilatory function and a decrease of respiratory muscle pressures, probably due to reduction of respiratory muscle strength.

Reduced bone mineral density in adults with growth hormone (GH) deficiency: increased bone turnover during 12 months of GH substitution therapy

To evaluate the consequences of growth hormone (GH) deficiency on bone mineral density and to evaluate the effects of GH substitution therapy, 68 adults (25 females and 43 males) aged 22-61 (mean 44.2 +/- 1.2) years with GH deficiency (GHD) were studied. Fifty-eight patients had panhypopituitarism, three had isolated GHD and in seven patients at least one additional pituitary function was affected. Twenty-one patients had childhood onset GHD. The patients were randomized to receive either GH in daily injections (0.125 IU.kg-1. week-1 for the first 4 weeks and subsequently 0.25 IU.kg-1. week-1) or placebo for 6 months. The trial continued as an open study with GH treatment for 6 to 12 months, with data presented as compiled data of 12 months of GH treatment in 64 patients. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry and bone turnover was assessed by serum markers of bone metabolism (osteocalcin, procollagen I peptide, cross-linked telopeptide of type I collagen and alkaline phosphatase activity), In women with adult onset GHD (N = 19) and in men with childhood onset GHD (N = 15), total body, spine and hip BMD was significantly reduced at baseline compared to Swedish age- and sex-matched control material. In men with adult onset of GHD (N = 28), BMD did not differ from male controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone treatment in adults with childhood onset growth hormone deficiency: effects on psychological capabilities.

The psychological aspects (personal traits, way of relating to the surrounding environment, perception of body image, degree of self-esteem) of eight adults with childhood onset growth hormone (GH) deficiency (GHD) were studied before and after 6 months of recombinant GH therapy. Each subject was evaluated using the following tests: the Bem Sex Role test, the non-verbal scales of the WAIS test for adults, the State-Trait Anxiety Inventory, the Experiential-World Inventory, the Image-Marking Method and the Draw-a-Person test; a psychoneurophysiological profile was also evaluated in order to monitor, by means of four neurophysiological variables (muscular tension, galvanic resistance, skin temperature and heart rate), the reactions to specific and aspecific stress. Before treatment, adults with GHD tended to underestimate their body size by an average of 30%, with peaks of 47% for the head area; furthermore, they showed a low level of self-esteem, a closed attitude towards social relationships, a pessimistic attitude with a tendency towards depression and a strong sense of detachment from the outside world. After 6 months of GH treatment, patients presented an overall improvement in relation to intellectual tasks, accompanied by a lower level of stress during their performance. A clear improvement was also observed in terms of emotional control during specific and aspecific stress, which might contribute a positive effect on their interrelationships. As expected, the treatment was not able to reduce the subjects' highly distorted perception of body image, due to the fact that GH treatment, despite a clear amelioration of lean/fat body mass ratio, did not change their body proportions.(ABSTRACT TRUNCATED AT 250 WORDS)

Quadriceps and hand-grip strength in adults with childhood-onset growth hormone deficiency

The effects of chronic growth hormone (GH) deficiency on muscle size and strength of postural (quadriceps) and non-postural (hand-grip) muscle groups, as well as on vertical jump capacity, were evaluated in six adults with childhood-onset GH deficiency. Data obtained were compared to those recorded in an age-, sex- and exercise-matched healthy control group. Thigh muscle plus bone cross-sectional area (CSAM+B) of the dominant quadriceps was significantly lower (p < 0.001) than in controls, while the CSAM+B/(Body height)2 ratio was similar to that of controls. The maximum voluntary contraction (MVC) of the quadriceps of patients was significantly lower (p < 0.002) than in controls, while no differences existed in the quadriceps force expressed per unit area (MVC/CSA) between patients and controls. As far as hand-grip was concerned, the CSAM+B of the dominant forearm was significantly lower (p < 0.003) than in controls, while the CSAM+B/(Body height)2 ratio was no different. The hand-grip MVC of patients was significantly lower (p < 0.004) than in controls, while no differences existed in the MVC/CSA ratio. It is noteworthy also that no difference existed in the hand-grip to quadriceps MVC ratio of the two groups. Furthermore, no differences were found in the vertical jump capacity, because both delta Height and delta Height/Body weight of patients were not significantly different from those of controls. In conclusion, our study suggests that GH deficiency seems to reduce the size and strength of postural and non-postural muscle groups to the same extent.(ABSTRACT TRUNCATED AT 250 WORDS)

Further increase in forearm cortical bone mineral content after discontinuation of growth hormone replacement

Growth hormone replacement of adults with childhood onset GH deficiency results in an increase in bone mineral density (BMD) after 6-12 months of GH replacement. By measuring BMD 12 months after discontinuation of GH replacement we aimed to investigate whether there is an effect of GH replacement on BMD persisting after GH has been withdrawn. BMD was measured 13 +/- 1 (mean +/- SE, range 11-16) months after discontinuation of GH replacement. Ten adults, age 23.2 +/- 1.4 (range 18.8-32.4) years, with childhood onset isolated GH deficiency (2 idiopathic, 8 irradiation induced) who had previously completed a study of the effect of 12 months of GH replacement on BMD. Forearm cortical bone mineral content (BMC) was measured using single-photon absorptiometry at the proximal site of the distal forearm. Forearm integral BMC at the ultradistal site of the forearm and bone width at both proximal and ultradistal sites of the distal forearm were measured by the same technique. Vertebral trabecular BMD was measured using quantitative computed tomography. Forearm cortical BMC was significantly greater than that measured at the time of discontinuation of GH (1.48 +/- 0.04 vs 1.44 +/- 0.05 g/cm). There was no significant change in forearm integral BMC or in vertebral trabecular BMD after discontinuation of GH. There was no significant change in bone width at proximal and ultradistal sites of the distal forearm after discontinuation of GH. After discontinuation of GH replacement the further increase in forearm cortical bone mineral content without a significant increase in forearm bone width suggests that the increase in cortical bone mineral content is due to a persisting effect of previous GH replacement, and not to further spontaneous attainment of bone mass before peak bone mass is reached. These findings emphasize the importance of continuing to monitor bone mass after the stimulus to increase bone turnover has been withdrawn.

Growth hormone (GH) treatment in GH‐deficient adults: effects on muscle size, strength and neural activation

The effects of 6 months of recombinant growth hormone (GH) treatment (0.5 IU kg-1 per week) on muscle size, strength and neural activation (EMG) was studied in eight adults with childhood onset GH deficiency (GHD). Before treatment, height, body mass (BM) and lean body mass (LBM) of the GHD subjects were significantly lower (P < 0.01) from those recorded in eight healthy controls, while no significant differences were found between the body mass index (BMI) of the two populations. Thigh muscle + bone cross-sectional area (CSAM+B) and lower limb muscle plus bone volume (LLVM+B) of the GHD patients were 66.1 +/- 13.7% and 47.6 +/- 6.8% of those recorded in the controls (P < 0.01), whereas no difference in CSA/height2 was found between the two groups. By contrast, LLVM+B/height3 was 82.0 +/- 19.0% that of the controls (P < 0.05). Similarly, quadriceps muscle strength (MVC) of the GHD patients was 63.2 +/- 12.4% that of controls (P < 0.01), while no significant differences in the force per unit area (F/CSA) and per body mass (F/BM) were found. After 6 months of GH treatment LBM increased by 6.0 +/- 4.2% (P < 0.02), CSAM+B by 14.5 +/- 12.7% (P < 0.01) and LLVM+B by 10.1 +/- 7.3% (P < 0.01), absolute differences from the normals still persisting. However, the LLVM+B/height3 of the GHD patients after treatment was no longer significantly different from that of the controls. Quadriceps MVC increased by 9.8 +/- 12.0% (P < 0.02), differences from the controls being still significant, whereas the F/CSA and F/BM did not change. A right shift of the integrated EMG/Force relation, with no change in the maximal integrated EMG (iEMG) activity, was observed in the patients after treatment. In conclusion, the current study shows that adults with childhood onset GHD have a reduced skeletal muscle mass and strength which seem to be positively influenced by 6 months of GH treatment.

Consequences of childhood-onset growth hormone deficiency for adult bone mass.

To assess the implications of prolonged growth hormone deficiency (GHD) for the acquisition and maintenance of bone mass, bone mineral density (BMD) was measured in 70 adult males (mean age 26.7 +/- 4.5 years) with childhood-onset GHD, 7.4 +/- 4.2 years after discontinuation of previous GH therapy. Because most of these patients were short (mean height 165.8 +/- 6.6 cm), the influence of body height on standard BMD measurements, conventionally reported as the areal density (BMDarea, expressed in g/cm2), was analyzed in a group of age-matched healthy males. In GHD patients, BMDarea was significantly reduced at the lumbar spine (Z score -1.59 +/- 1.08, p < 0.001) as well as at the nondominant hip (Z score -1.18 +/- 0.95, p < 0.001). The reduction in BMDarea was similar for patients with isolated GHD (N = 25) and those with combined deficiencies of GH and luteinizing hormone (N = 40). In patients and controls, BMDarea was positively correlated with body height, a relation that was attributed to skeletal size. Bone dimensions were significantly smaller in patients than in controls, and therefore it was hypothesized that the difference in areal density between patients and controls might be confounded by differences in bone size. Measured bone mineral content corrected for the estimated bone volume (BMDvolume, expressed in g/cm3) remained significantly reduced (Z score: lumbar spine, -0.90 +/- 1.08, p < 0.001; femoral neck, -0.74 +/- 1.00, p < 0.001), but the differences between GHD patients and controls were less than indicated by BMDarea (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired cardiac performance in GH-deficient adults and its improvement after GH replacement

Cardiac performance was investigated by radionuclide angiography in 11 patients with childhood-onset growth hormone (GH) deficiency and in 12 control subjects. Both at rest and during maximal physical exercise, systolic function was markedly depressed in GH-deficient patients. Ejection fraction rose from 66 +/- 6 to 76 +/- 7% during exercise in control subjects, whereas in GH-deficient patients it remained unchanged or even decreased (55 +/- 6 and 54 +/- 9% at rest and after exercise, respectively; P < 0.01 vs. controls). Cardiac index was significantly lower in GH-deficient patients than in controls, both at rest (2.7 +/- 0.6 vs. 3.7 +/- 0.5 l.min-1.m-2; P < 0.001) and during exercise (8 +/- 1.2 vs. 10 +/- 1.5 l.min-1.m-2; P < 0.01). Five GH-deficient patients were treated with recombinant human (rh) GH for 6 mo at a dose of 0.05 IU.kg-1.day-1. Cardiac index at rest improved from 2.8 +/- 0.6 to 3.3 +/- 0.8 l.min-1.m-2 (P < 0.01) after rhGH. Also, cardiac index response to exercise improved markedly and became similar to that of controls (7.5 +/- 1.2 and 10.1 +/- 1.1 l.min-1.m-2 before and after rhGH, respectively; P < 0.005). Exercise tolerance was impaired in GH-deficient patients and was restored by rhGH treatment. The data support the hypothesis that GH plays an important role in the maintenance of a normal cardiac performance in humans.

Reduced bone mineral density in patients with adult onset growth hormone deficiency.

We have demonstrated previously that adults with isolated GH deficiency of childhood onset have a reduced bone mineral density (BMD) of vertebral trabecular bone [quantitative computed tomography (QCT): median Z score -1.3, P < 0.01, n = 12] and of cortical bone in the forearm [single photon absorptiometry (SPA): median Z score -2.9, P = 0.001, n = 7]. We have now examined BMD in 26 patients (13 men, 13 women), aged between 23.6 and 59.5 (mean 42.4) yr, with adult onset GH deficiency, defined as a GH response of less than 5 micrograms/L to provocative testing, of at least two years duration. BMD was measured using QCT for vertebral trabecular bone, dual energy x-ray absorptiometry (DXA) in the lumbar spine and femoral neck, and SPA in the forearm. There was a highly significant reduction in QCT (median Z score -1.07, P < 0.00005), in DXA of the lumbar spine (median Z score -0.76, P = 0.0001) and in SPA of the forearm (median Z score -0.86, P = 0.0001) but not in DXA of the femoral neck (median Z score -0.38, P = 0.35). There were no significant differences in Z scores between those patients with isolated GH deficiency and those with GH and gonadotrophin deficiency. There was a significant positive correlation between age at which BMD was measured and Z score (the older the patient, the higher the Z score) for QCT (r = 0.38, P < 0.05) and SPA (r = 0.48, P < 0.01) with a trend to a positive correlation for DXA of the lumbar spine and femoral neck. Patients were grouped according to estimated duration of GH deficiency (less than 5 yr, n = 7; 5-10 yr, n = 10; greater than 10 yr, n = 9). These groups did not show a significant difference in BMD at any site. We conclude that patients with adult onset GH deficiency (isolated or in conjunction with other pituitary hormone deficiencies) have a reduced BMD. Age at development of GH deficiency may be more important than duration of GH deficiency in determining the degree of reduction in bone mass. The impact of GH treatment on BMD in adults with adult onset GH deficiency requires investigation.

Growth hormone treatment in adults with GH deficiency: Effects on new biochemical markers of bone and collagen turnover

Serum bone Gla protein (BGP) and bone alkaline phosphatase (B-AP), markers of bone formation, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), marker of bone resorption, and aminoterminal propeptide of type III procollagen (PIIINP) levels, index of collagen synthesis, were determined in 8 adults (mean age +/- SE: 29.6 +/- 1.2 yr) with childhood onset GHD before and after 3 and 6 months of recombinant GH treatment (0.5 IU/kg/week). Before treatment, mean BGP (3.8 +/- .5 ng/ml) and B-AP (44.9 +/- 6.9 IU/L) were significantly (P < 0.001 and p < 0.05, respectively) lower than those recorded in normals (5.4 +/- 0.1 ng/ml and 61.8 +/- 1.9 IU/L, respectively), while serum ICTP and PIIINP levels were similar to those found in controls (ICTP: 4.7 +/- 0.8 vs 4.1 +/- 0.3 ng/ml; PIIINP: 3.7 +/- 0.6 vs 3.2 +/- 0.2 ng/ml). BGP and ICTP levels significantly (p < 0.005) increased after 3 (28.4 +/- 5.3 ng/ml and 17.5 +/- 2.8 ng/ml, respectively) and 6 months (25.1 +/- 5.0 ng/ml and 15.0 +/- 1.9 ng/ml, respectively) of recombinant GH treatment. B-AP levels significantly (p < 0.01) increased during the treatment (basal: 44.9 +/- 6.9 IU/L, 3rd month: 173.6 +/- 40 IU/L, 6th month: 194.4 +/- 40 IU/L), while non B-AP levels remained similar to those recorded in basal condition. Serum PIIINP levels significantly (p < 0.0001) rose up after 3 (12.5 +/- 1.4 ng/ml) and 6 months (10.2 +/- 0.8 ng/ml). Serum BGP and ICTP levels were directly (r = 0.85, p < 0.001; r = 0.53, p < 0.01) correlated with serum IGF-I levels.(ABSTRACT TRUNCATED AT 250 WORDS)