Influence of growth hormone (GH) receptor deletion of exon 3 and full-length isoforms on GH response and final height in patients with severe GH deficiency

CONTEXT: A polymorphism of the GH receptor (GHR) gene resulting in genomic deletion of exon 3 (GHR-d3) has been associated with responsiveness to GH therapy. However, the data reported so far do vary according to the underlying condition, replacement dose, and duration of the treatment. OBJECTIVE, DESIGN: The aim of this study was to analyze the impact of the GHR genotypes in terms of the initial height velocity (HV) resulting from treatment and the impact upon adult height in patients suffering from severe isolated GH deficiency. CONTROLS, PATIENTS, SETTING: A total of 181 subjects (peak stimulated GH相似文献   

Dynamics of bone turnover in children with GH deficiency treated with GH until final height

OBJECTIVE: To examine the dynamics of bone turnover in children with growth hormone deficiency (GHD) during long-term treatment. DESIGN: We longitudinally measured growth velocity and serum concentrations of osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP), and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in 24 patients with GHD during long-term GH treatment until final height (age: 7.7+/-0.7 and 16.9+/-0.5 years at baseline and at final height respectively). RESULTS: At baseline, OC, PICP, and ICTP levels were significantly (P<0.0001) reduced in comparison with prepubertal bone age-matched controls (10.2+/-2.3 microgram/l and 22.5+/-7.6 microgram/l; 187.8+/-26.2 microgram/l and 328. 4+/-74.3 microgram/l; 7.7+/-2.0 microgram/l and 14.2+/-1.3 microgram/l respectively). During the first year of treatment mean levels of the bone markers increased significantly (P<0.0001) with a peak at 12 months. After the first year of treatment, OC and PICP levels progressively declined, whereas ICTP levels remained stable until the final height; in any case, bone marker levels remained significantly higher (P<0.03-P<0.0001) than baseline. The change in bone marker levels at 6 and 12 months of treatment with respect to the baseline values was not related to growth rate during long-term treatment or final height. CONCLUSIONS: The results show that children with GHD have reduced bone turnover at baseline, and that long-term GH treatment is associated with a stimulation of bone turnover. OC, PICP, and ICTP do not predict growth rate during long-term treatment or final height in children with GHD.     

Growth hormone (GH) pharmacogenetics: influence of GH receptor exon 3 retention or deletion on first-year growth response and final height in patients with severe GH deficiency

CONTEXT: A polymorphism in GHR gene, the presence or absence of exon 3, has been shown to influence the 1- and 2-yr growth responses to human recombinant GH (hGH) therapy in children without GH deficiency (GHD). OBJECTIVE: The objective of this study was to assess the influence of GHR-exon-3 genotype on the short and long-term response to hGH therapy in children with GHD. SETTING: The study was conducted in the university hospital. DESIGN AND PATIENTS: Genotype and retrospective analysis was performed on data of 75 children with GHD. Intervention: Intervention consisted of hGH treatment at a mean dose of 33 mug/kg.d and GHR-exon-3 genotype by multiplex PCR. MAIN OUTCOME MEASURES: The main outcome measures were GHR genotype: full-length (fl) and exon 3-deleted (d3) alleles, growth velocity in 58 children who remained prepubertal during the first year, and adult height in 44 patients with GHD after 7.5 +/- 3.0 yr of treatment. RESULTS: Clinical and laboratory data at the start of treatment and hGH doses were indistinguishable among patients with different GHR-exon-3 genotypes (fl/fl vs. fl/d3 or d3/d3). Patients carrying at least one GHRd3 allele had a significantly better growth velocity in the first year of hGH replacement (12.3 +/- 2.6 vs. 10.6 +/- 2.3 cm/yr; P < 0.05) and achieved a taller adult height (final height sd score, -0.8 +/- 1.1 vs. -1.7 +/- 1.2; P < 0.05) when compared with patients homozygous for GHRfl alleles. CONCLUSIONS: Patients with GHD who are homozygous for GHR exon 3 fl were less responsive to short- and long-term hGH therapy. Approximately half of the population is homozygous for GHRfl, and future studies adjusting hGH therapy to genotype may improve outcome.     

Linear growth and final height after treatment for Cushing's disease in childhood

Cushing's disease is associated with growth failure in childhood and adolescence. Growth and final height were analyzed in 10 patients who were cured or in remission after treatment of Cushing's disease. Seven males and 3 females, aged 6.8-17.6 yr (bone age, 3.3-15.4 yr), had transsphenoidal surgery, which was combined with pituitary irradiation (4,500 cGy in 25 fractions) in 5 patients. At presentation, 5 patients were prepubertal (males), and 5 were pubertal (2 males and 3 females). The mean height SD score was -2.15 +/-1.26 (range, -0.21 to -4.32) compared with mean target height SD score of -0.43 +/- 0.58. Height velocity in 6 patients was subnormal (0.9-3.8 cm/yr). After treatment, short-term height velocity, over a mean interval of 0.57 yr, in 8 patients not receiving human GH (hGH) therapy, was variable (range, 0.8-7.6 cm/yr). GH stimulation tests (insulin tolerance test/glucagon) in 9 subjects showed peak GH levels of 0.5-20.9 mU/L. Eight were treated with hGH (14 IU/m2 wk), combined in 2 girls and 1 boy with a GnRH analog. After 1 yr of hGH, the mean height SD score had increased from -2.45 +/- 1.0 at initiation of hGH to -2.07 +/- 1.2 (P = 0.01). GH therapy was continued until final height or latest assessment. The mean final height SD score (n = 6) was - 1.24 +/- 1.38, and at the latest assessment the mean height SD score (n = 4) was - 1.52 +/- 1.33. Combining these 2 groups, the mean height so score was -1.36 +/- 1.29. The difference between final or latest height SD score and target height SD score was 0.93 +/- 1.13, i.e. less (P = 0.005) than the difference between height and target height SD score of 1.72 +/- 1.26 at presentation. In conclusion, catch-up and favorable long-term growth was seen after treatment for Cushing's disease. Posttreatment GH deficiency was frequent, and early hGH replacement may have contributed to the encouraging outcome.     

Lumbar bone mineral density at final height and prevalence of fractures in treated children with GH deficiency

Lumbar bone mineral density (BMD) by dual energy x-ray absorptiometry was assessed in 46 (29 boys, 17 girls) treated patients with growth hormone deficiency (GHD) at final height, comparing the BMD results with normative data. Prevalence of fractures in patients during treatment and healthy controls (n = 100) during the corresponding time period was assessed. Lumbar BMD values at final height of fractured and fracture-free patients were compared between them. Lumbar BMD corrected for bone area was significantly (P < 0.01) reduced (boys, -0.4 +/- 0.8 Z score; girls, -0.5 +/- 0.7 Z score), but lumbar BMD corrected for bone size (BMDvolume) did not differ [P = not significant (NS); boys -0.2 +/- 1.0 Z score; girls, -0.3 +/- 1.0 Z score] from normal mean. Approximately 22% of patients had reduced lumbar BMD (Z score, -1 to -2). The fact that patients had a complete or partial GHD did not influence lumbar BMD. The prevalence of fractured patients did not differ (P = NS) from that of controls [n = 7 (15.2%) and n = 24 (24.0%), respectively; odds ratio, 1.837]. Lumbar BMDvolume of fractured patients was significantly (P < 0.02) lower than that of fracture-free (n = 39) patients (boys, 0.310 +/- 0.005 and 0.351 +/- 0.032 g/cm(3), respectively; girls, 0.326 +/- 0.027 and 0.382 +/- 0.036 g/cm(3), respectively). The percentage of the fractured patients with lumbar BMDvolume less than 1 SD of normal mean was significantly (P < 0.0001) higher than that of fracture-free patients [n = 6 (85.7%) and n = 4 (10.3%), respectively; odds ratio, 26.092). The fractured patients also showed reduced lumbar BMD corrected for bone area and BMDvolume at the time of fractures (-1.6 +/- 0.4 and -1.5 +/- 0.2 Z score, respectively). The results show that treated patients with GHD have normal mean values of lumbar BMDvolume at final height, but some patients have reduced lumbar BMD (Z score <1) with an increased susceptibility to fractures.     

Improvements in final height over 25 years in growth hormone (GH)-deficient childhood survivors of brain tumors receiving GH replacement

Final height (FH) outcome is important in survivors of childhood brain tumors. GH replacement is indicated in those found to be GH deficient (GHD). More recently, GnRH analogs (GnRHa) have been introduced to delay early or rapidly progressing puberty to allow more time for linear growth. Studies to FH are important to determine the effectiveness of growth-promoting strategies. Our aim was to assess whether evolving endocrine strategies have improved FH outcome and to determine whether GnRHa therapy has contributed auxologically. FH data were examined in 58 children (31 males and 27 females) with radiation-induced GHD who had been treated with GH. All had received a combination of cranial (CI; n = 17) or craniospinal (CSI; n = 41) irradiation with or without chemotherapy for a brain tumor. Eleven patients received GnRHa therapy. Throughout the 25 yr of the study patients came closer to achieving target height (i.e. a reduction in height loss), both those receiving CI (r = 0.5; P = 0.03) and those receiving CSI (r = 0.6; P < 0.001). The patients receiving GH therapy before 1988 compared with from 1988 onward had a similar age at irradiation [mean (+/-SD), 5.8 (3.0) vs. 6.2 (2.9) yr; P = 0.6], but experienced a more prolonged time interval from completing irradiation to starting GH [5.4 (2.4) vs. 3.3 (1.6) yr; P < 0.001]. Forward stepwise regression analysis revealed that height loss is affected by age at irradiation (P < 0.001), previous spinal irradiation (P = 0.02), chemotherapy (P < 0.001), and exposure to GnRHa therapy (P < 0.001). In the 11 patients treated with GnRHa therapy FH SD scores were improved compared with FH predictions calculated from a model derived from the patients not treated with GnRHa [-0.8 (1.6) vs. -2.4 (0.8) SD score; P < 0.001]. We have demonstrated an overall improvement in FH in children treated with GH for GHD after therapy for brain tumors over the last 25 yr. In the subset of children in whom the growth prognosis was adversely affected by early puberty, the combination of GnRHa and GH improved their prospects of achieving target height. The improved auxological outcome may reflect 1) the use of more standardized GH schedules and better dosing regimens, 2) a reduction in the time interval between finishing radiotherapy and receiving GH replacement, and 3) the use of GnRHa in addition to GH replacement in carefully selected patients.     

A prospective investigation of quality of life and psychological well-being after the discontinuation of GH treatment in adolescent patients who had GH deficiency during childhood

Some patients given growth-promoting therapy for GH deficiency in childhood will remain GH deficient in their adult lives and hence could benefit from continued GH replacement therapy. This longitudinal study sought to assess whether quality of life declines after GH discontinuation in late adolescence, and whether differences can be discerned in quality of life in patients whose GH deficiency persists into adulthood and those whose GH secretory capacity falls within normal ranges. Forty patients, aged 16-21 yr at baseline, were assessed over a 2-yr period commencing with discontinuation of GH therapy. Twenty-one patients were assigned to a GH deficiency group, and 19 were assigned to a GH-sufficient group. Quality of life assessments were made using the Nottingham Health Profile, Psychological General Well-Being Index, and Mood Adjective Check List Measures. Visual analog assessment of personality and affect and cognitive function tests were performed. The Mood Adjective Check List and visual analog assessments identified between-group and temporal changes in a limited number of the various personality domains assessed. The Psychological General Well-Being Index assessment indicated greater baseline impairment in the GH deficiency group than in the GH-sufficient group in overall score and in the domains of depression and general health. There was also a between-group difference in anxiety score at the 2-yr assessment, with the GH deficiency group having greater anxiety. Measurement of cognitive factors failed to reveal differences between groups. These results indicate that the discontinuation of GH therapy in late adolescence does not risk an immediate decline in the perceived quality of life detectable with the Nottingham Health Profile and Psychological General Well-Being Index measures. However, differences detected with the Mood Adjective Check List and visual analog assessments hint at clinically significant changes in the life experiences of adolescents discontinued from GH for which traditional measures may lack sensitivity.     

Birth weight affects final height in patients treated for growth hormone deficiency

OBJECTIVE: Birth weight influences both postnatal growth and the initial response to GH therapy in GH-deficient subjects, but its relationship to final height is uncertain. Therefore, we examined final height results in a group of subjects treated for GH deficiency who were born small, appropriate or large for gestational age (GA). DESIGN: Retrospective study. PATIENTS: 108 GH-treated patients (age at diagnosis 11.1 +/- 2.0 years) affected by idiopathic and isolated GH deficiency (peak < 8 microg/l after pharmacological and/or nocturnal mean GH concentration 相似文献   

Continued growth hormone (GH) treatment after final height is necessary to complete somatic development in childhood-onset GH-deficient patients

Lean body mass (LBM), fat mass (FM), and total bone mineral content are significantly reduced in adult GHD subjects who had received pediatric GH. To test the hypothesis that continued GH therapy after final height is necessary to attain adult body composition, we performed a prospective, multinational, randomized, controlled, 2-yr study in patients who completed pediatric GH treatment at final height. Patients were randomized to GH at 25.0 microg/kg x d (pediatric dose; n = 58) or 12.5 microg/kg x d (adult dose; n = 59) or no GH treatment (control; n = 32). LBM and FM were measured by dual energy x-ray absorptiometry and were centrally evaluated. IGF-I, IGF-binding protein-3, and lipid concentrations were also measured centrally. During the 2 yr, GH-treated patients gained a significant amount of LBM compared with controls (P < 0.001), but the change with the higher pediatric dose (14.2 +/- 11.7%) was not different from that seen with the lower adult dose (12.7 +/- 9.4%; P = 0.970). Similarly, the decrease in FM was significantly (P = 0.029) influenced by treatment, but with no dose effect (adult dose, -7.1 +/- 22.8%; pediatric dose, -6.0 +/- 26.6%; P = 0.950). When the GH treatment effect was analyzed by gender, males gained 15.6 +/- 9.8% and 14.3 +/- 11.7% LBM (P = 0.711) and lost 12.4 +/- 22.2% and 11.0 +/- 27.1% FM (P = 0.921) with the low and high doses, respectively. Females gained 8.3 +/- 7.3% and 12.5 +/- 12.8% LBM with the two doses (P = 0.630), but increased their FM by 3.5 +/- 16.2% with the lower dose and lost only 1.2 +/- 23.2% FM with the higher dose (P = 0.325). A similar pattern was seen in IGF-I sd score; the 2-yr GH dose response was significantly higher with the pediatric than with the adult dose in females (P = 0.008), but not males (P = 0.790). The divergent pattern of change in LBM and FM in males and females is consistent with normal developmental sexual dimorphism and indicates that GH-dependent progress to target body composition continues after the age at which GH treatment is usually terminated. Dose requirements may have to be adjusted by gender, with females requiring a higher dose than males.     

Serum growth hormone (GH) profiles after nasally administered GH in normal subjects and GH deficient patients

OBJECTIVE GH-deficient patients are at present treated with daily subcutaneous GH injections. Further improvements in patient compliance and effects of treatment may occur with nasal administration. We have examined the absorption of nasally administered GH in healthy subjects and In GH deficient patients in two separate studies. DESIGN Healthy subjects and GH deficient patient were examined in the morning after an overnight fast. Twelve IU of GH in a powder containing didecanoyl-l -α-phosphatidylcholine as enhancer were administered in the nostrils (6 IU in each nostril) at the beginning of the study in the healthy subjects. The GH deficient subjects received a total of 6 IU GH/m² intranasally. Blood was frequently sampled for up to 4 hours. Before and after nasal application anterior rhinoscopy was performed. PATIENTS Eight normal subjects and 7 GH deficient patients. MEASUREMENTS Serum GH. RESULTS (mean ± SD) Mean maximum concentration (C_max) in the normal group was 57.6 mU/l ± 36.9 with a mean time to obtain C^max(T_max) of 65 ± 47 min. In the GH deficient group C^max was 56.1 ± 26.1 mU/l with a mean T_max of 45 ± 15 min. The subjects did not report any major inconvenience during the study. Anterior rhinoscopy did not reveal changes. CONCLUSION Nasally administered GH is absorbed to a significant degree from the nasal mucosa without obvious untoward effects in the short term. These data encourage further studies with nasal GH administration.     

Longitudinal changes of lumbar bone mineral density (BMD) in patients with GH deficiency after discontinuation of treatment at final height; timing and peak values for lumbar BMD

OBJECTIVE: GH treatment has an important role in the acquisition of bone mass in children and adolescents with GH deficiency (GHD). However, there is no information concerning the timing and value of peak bone mass in treated patients with GHD. In adolescents with GHD we longitudinally measured lumbar bone mineral density (BMD) after discontinuation of GH treatment at final height until they achieved lumbar peak BMD (pBMD). Moreover, the changes of lumbar BMD after the attainment of the peak were assessed for a period of 2 years. The results of patients were compared with those obtained in age- and sex-matched healthy controls. PATIENTS AND MEASUREMENTS: Lumbar BMDarea [bone mineral content (BMC) corrected by the vertebral surface area scanned] and lumbar BMDvolume (BMC corrected by vertebral volume estimated by a mathematical model), by dual energy X-ray absorptiometry, were assessed in 16 patients (nine males, seven females; aged 14.9-18.8 years) with isolated GHD and 157 healthy subjects (78 males, aged 16.2-24.9 years; 79 females, aged 14.1-22.8 years) as controls. In patients, lumbar BMDarea and lumbar BMDvolume were measured at final height and approximately every year up to 21-24 years and 19-22 years in males and females, respectively; BMD values of the patients were plotted on the reference curves for age and sex obtained in controls. RESULTS: At final height, seven male (78%) and five female (71%) patients had a value for lumbar BMDarea below 2SD of normal mean, whereas all patients had a value of lumbar BMDvolume between 0 and -2SD of normal mean. In patients, lumbar pBMDarea and lumbar pBMDvolume were achieved approximately 1-3 years after final height. The timing of lumbar pBMDarea and lumbar pBMDvolume was significantly (P < 0.0001) delayed in patients in comparison with controls (pBMDarea: males, 19.8 +/- 0.6 years and 18.4 +/- 0.6 years; females, 18.0 +/- 0.3 years and 16.7 +/- 0.6 years, respectively; pBMDvolume: males, 19.8 +/- 0.7 years and 18.6 +/- 0.6 years; females, 18.0 +/- 0.4 years and 16.7 +/- 0.6 years, respectively). In addition, mean values for lumbar pBMDarea and lumbar pBMDvolume were significantly (P < 0.01 to P < 0.0001) reduced in patients compared with controls (pBMDarea: males, 1.129 +/- 0.055 g/cm2 and 1.225 +/- 0.048 g/cm2; females, 1.122 +/- 0.053 g/cm2 and 1.227 +/- 0.060 g/cm2, respectively; pBMDvolume: males, 0.326 +/- 0.010 g/cm3 and 0.352 +/- 0.036 g/cm3; females, 0.348 +/- 0.010 g/cm3 and 0.388 +/- 0.039 g/cm3, respectively). In patients, mean values of lumbar BMDvolume declined significantly (P < 0.03 to P < 0.01) 2 years after its peak. At any rate, mean values of lumbar BMDarea and lumbar BMDvolume of patients one and two years after their peak remained significantly lower (P < 0.01 to P < 0.0001) than those of controls. CONCLUSIONS: The results show that treated adolescents with GHD have an increase of lumbar BMDarea and lumbar BMDvolume after discontinuation of GH treatment at final height, but they have delayed timing and reduced mean values of lumbar pBMDarea and lumbar pBMDvolume in comparison with controls. In patients, mean values of lumbar BMDvolume declined 2 years after its peak. Although the number of the patients was small, the results seem to indicate that GH has a role in the acquisition of lumbar BMD after final height in patients with GHD, suggesting that GH treatment should be continued up to the achievement of lumbar pBMD.     

Upregulation of GH receptor and GH binding protein during pregnancy in the GH deficient rat

During pregnancy there are dramatic changes in the endocrine and metabolic status of the mother: growth hormone (GH) is an important regulator of growth and development. A proportion of GH is bound by specific GH binding proteins (GHBP) that closely resemble the GH receptor (GHR). In the rodent both GHBP and the GHR are considered to be GH dependent, and consequently during pregnancy the increase in serum GH is associated with an increase in GHBP. To examine whether an increase in maternal GH is obligatory for elevation of maternal GHBP or GHR during pregnancy, we used a unique GH-deficient (GHD) strain of rats, to avoid the methodological complications of hypophysectomy and assessed serum GH, GHBP and hepatic GHR binding during the course of pregnancy. In GH normal rats, serum GH concentrations increased twofold and GHBP levels increased threefold; there was no change in hepatic GHR binding. In GHD rats, serum GH concentrations were low and did not increase during pregnancy. Nonetheless, levels of both serum GHBP and hepatic GHR binding increased to that measured in normal rats. Thus, an increase in maternal GH concentration is not required for the gestational upregulation of maternal GHBP or hepatic GHR binding, suggesting that other hormones may be essential in modulating the GH axis during pregnancy.     

Pitfalls in diagnosing impaired growth hormone (GH) secretion: retesting after replacement therapy of 63 patients defined as GH deficient.

Possible causes of error in the diagnosis of isolated GH deficiency are the variability of GH response to repeated tests, the existence of transient GH deficiencies, and the low GH levels found in short statured children with delayed puberty. Sixty-three patients with variously expressed GH deficiency were retested (1 sleep test and 2 pharmacological tests) after 1-3.9 yr of GH therapy (dose, 15 U/m2.week). Forty-eight subjects had arginine, L-dopa, and sleep tests (mean serum GH concentration) twice, while 15 had only arginine and L-dopa tests. All patients were retested 1 month after withdrawal from therapy. The criteria used to subdivide the patients were pubertal development and response to pharmacological and sleep tests at first diagnosis and on retesting. The initial diagnosis in 33 subjects (52.4%) was not confirmed, and 13 (20.6%) were no longer deficient on retesting. The percentage of normalization was high for the sleep test (43.9%), lower for the pharmacological test (24.5%), and lower still (12.9%) for pharmacological and sleep tests considered together. While none of the 28 subjects who remained prepubertal at retesting normalized in any of the tests, 13 of the 35 subjects retested during puberty did. When normalization was observed in pubertal subjects, it occurred predominantly in the sleep test. Growth velocity and height age/bone age increment ratio after the first year of therapy were no different for the groups of subjects classified according to GH secretion on retesting. Our study demonstrates that a number of children diagnosed as GH deficient do not have a true deficiency. However, such a diagnostic error seems to have little effect, at least in the first year of therapy, on the effectiveness of GH treatment.     

Management of the growth hormone (GH)-treated patients with diagnosis of GH deficiency (DGH) during transition from childhood to adulthood

Growth hormone (GH) has many beneficial effects in patients with childhood-onset GH deficiency (GHD) in addition to its promotion of linear growth. The discontinuation of GH treatment in GHD patients, during the transition from childhood to adulthood, induces significant unfavorable changes in body composition, skeletal integrity, exercise capacity, and an adverse cardiovascular risk profile. These changes are reversed after the resumption of GH treatment. As the benefits of continuing GH therapy into adulthood has been well established, it is possible that GH replacement therapy will not be stopped once growth has been completed, but it will continue into adult life. Considering that a high proportion of patients with diagnosis of DGH in childhood are no longer GHD in adolescence, the GH status must be retested when growth is completed. Other factors such as clinical history, GH response in childhood, hipotalamic-pituitary MRI and IGF-1 concentration must be considered. Reconfirmation of GHD diagnosis through stimulation testing is usually required, unless there is a proven genetic or structural lesion persistent from childhood.     

The influence of growth hormone (GH) therapy on cardiac performance in patients with childhood onset GH deficiency.

OBJECTIVE: There is accumulating evidence that growth hormone (GH) plays an important role in the maintenance of normal cardiac growth and function. Abnormalities in left ventricular diastolic function and impairment of systolic function have also been reported in patients with GHD. In this study, we investigated the effects of 12 months GH replacement therapy on cardiac functional indices measured by echocardiography, the ECG stress test and SPECT imaging. DESIGN: Sixteen patients with childhood onset GHD (age 42.3+/-13.1 years, 10 males) were investigated before, and after, 12 months of GH treatment at a dosage of 0.02 IU/kg/day (7 microg/kg/day). The GH administration resulted in serum IGF-I levels within the normal range in all the patients. The following investigations were performed initially and after 12 months: electrocardiography, systolic and diastolic blood pressure, heart rate measurement, a complete Doppler-echocardiographic examination, treadmill exercise test and Technetium-99m sestamibi single-photon emission computer tomography (SPECT) imaging at rest and after exercise. RESULTS: Echocardiography showed improvement in left ventricular systolic function after GH treatment. End-systolic volume fell from 29.9+/-12.4 to 24.4+/-6.9 ml (p<0.05) and the ejection fraction increased from 56.2+/-7.2% to 63.2+/-6,1% (p<0.01). Left ventricular diameter and wall thickness did not change after GH treatment, although systolic increase in interventricular septum thickness (IVS%) and systolic increase in posterior wall thickness (PWT%) increased significantly (IVS% 52.2+/-31.9% vs. 67.3+/-30.4% and PWT% 48.7+/-20.2% vs. 58.0+/-17.7%, p<0.01, p<0.01, respectively). Contractile function, measured at midwall level, improved as left ventricular midwall fractional shortening (MWS) increased (16.11+/-6.55 vs. 23.30+/-5.89 %, p<0.01) and stress-corrected MWS increased between the examinations performed before and after 12 months of GH treatment (90.97+/-36.66 vs. 133.10+/-32.84 %, p<0.01). Diastolic function did not change, as assessed by early diastolic flow (E), diastolic flow secondary to atrial contraction (A), or the E/A ratio. The LV-mass index did not change significantly after GH treatment (78.4+/-22.1 vs. 81.9+/-21.1g/m(2)). After 12 months of GH treatment the myocardial performance index (MPI) decreased significantly from 0.483+/-0.146 at baseline to 0.410+/-0.086 at the end of the study (p<0.05). There was a trend towards an increase in exercise duration and capacity after GH treatment but the differences did not reach levels of statistical significance. SPECT imaging basally and after 12 months showed normal myocardial perfusion at rest and after exercise in all the patients. In conclusion, GH replacement therapy in adults with GHD demonstrated the beneficial effects on cardiac functions.