Seven years of growth hormone (GH) replacement improves quality of life in hypopituitary patients with adult-onset GH deficiency.

OBJECTIVE: Few studies have determined the effects of long-term growth hormone (GH) replacement on quality of life (QoL). This study investigated the effects of 7 years of GH replacement on QoL. DESIGN: A prospective, single-center, open-label study of 95 adults (mean age 52.8 years; 46 men) with adult-onset GH deficiency (GHD). METHODS: QoL was measured using Quality of Life-Assessment for Growth Hormone Deficiency in Adults (QoL-AGHDA) and Psychological General Well-Being (PGWB) scores. RESULTS: The GH dose was gradually increased from 0.13 mg/day to 0.42 mg/day. IGF-I SD score increased from -1.49 at baseline to 0.35 at study end. The GH replacement induced sustained improvements in total QoL-AGHDA and PGWB scores. GHD women had a more marked improvement in total QoL-AGHDA score than GHD men after 5 and 7 years. Most of the improvement in QoL was seen during the first year, but there was a small further improvement also after one year as measured using QoL-AGHDA. All QoL-AGHDA dimensions improved, but the improvement in memory and concentration as well as tenseness occurred later than that of other dimensions. Correlation analysis demonstrated that the patients with the lowest baseline QoL had the greatest improvement in QoL. CONCLUSIONS: Seven years of GH replacement improved QoL with the most marked improvements in GHD women and in patients with low baseline QoL. Most, but not all, of the improvement in QoL was seen during the first year. Some QoL-AGHDA dimensions (memory and concentration, tenseness) responded at a slower rate than other dimensions.

Baseline characteristics and effects of ten years of growth hormone (GH) replacement therapy in adults previously treated with pituitary irradiation.

CONTEXT: Little is known of the importance of previous irradiation therapy for baseline characteristics and responsiveness to GH replacement in GH deficient (GHD) adults. OBJECTIVE/DESIGN/PATIENTS: In this prospective, single-centre, open-label study, the effects of 10-year GH replacement were determined in 18 GHD adults that had previously received conventional external fractionated pituitary irradiation therapy (IRR group) and 18 non-irradiated GHD patients (non-IRR group). All patients had adult onset disease and complete deficiency of anterior pituitary hormones and both groups were comparable in terms of age, gender, body mass index (BMI), and waist:hip ratio. RESULTS: At baseline, IRR patients had higher serum triglyceride (TG) and insulin levels and lower high density lipoprotein (HDL)-cholesterol (HDL-C) level than non-IRR patients (all p<0.05). The 10-year GH replacement improved body composition, bone mass and serum lipid profile without any between-group differences, except for a marginally more beneficial response in serum TG level in the IRR patients. After 10 years, there was no between-group difference in any variable after correction for a higher replacement dose of glucocorticoids in the IRR patients at study end using an analysis of covariance. During the 10-year GH replacement, 5 IRR patients suffered from vascular events (2 fatal) whereas only one non-fatal vascular event occurred in the non-IRR patients. CONCLUSIONS: IRR patients with GHD display a more severely impaired cardiovascular risk profile at baseline, which was reversed by the 10-year GH replacement after correction for the higher glucocorticoid dose at study end. However, vascular events occurred more frequently in the IRR patients.

Fifteen years of GH replacement improves body composition and cardiovascular risk factors.

OBJECTIVE: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on body composition and cardiovascular risk factors. DESIGN/PATIENTS: In this prospective, single-center, open-label study, the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults (93 men) with adult-onset GH deficiency (GHD). Mean age was 50.5 (range 22-74) years at study start. Body composition was measured using dual-energy X-ray absorptiometry. RESULTS: The mean initial GH dose of 0.55 (S.E.M. 0.03) mg/day was gradually lowered to 0.40 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.53 (0.10) at baseline to 0.74 (0.13) at study end (P<0.001 vs baseline). Lean soft tissue (LST) increased to 3% above the baseline level at study end (P<0.001). After a 9% decrease during the first year of treatment (P<0.001 vs baseline), body fat (BF) started to increase and had returned to the baseline level after 15 years. Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased. Fasting plasma glucose increased from 4.4 (0.1) at baseline to 4.8 (0.1) mmol/l at study end (P<0.001). However, blood HbA1c decreased from 5.0 (0.1) to 4.6 (0.1) % (P<0.001). CONCLUSIONS: Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile. Fasting plasma glucose increased whereas blood HbA1c was reduced.

Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency.

OBJECTIVE: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on bone mineral content (BMC) and bone mineral density (BMD). DESIGN/PATIENTS: In this prospective, single-centre, open-label study, the effects of 15 years of GH replacement on BMC and BMD, measured using dual-energy X-ray absorptiometry, were determined in 126 hypopituitary adults (72 men) with adult-onset GH deficiency (GHD). Mean age was 49.4 (range 22-74) years at the initiation of the study. RESULTS: The mean initial GH dose of 0.63 (s.e.m. 0.03) mg/day was gradually lowered to 0.41 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.69 (0.11) at baseline to 0.63 (0.16) at the study end (P<0.001 vs baseline). The 15 years of GH replacement induced a sustained increase in total body BMC (+5%, P<0.001) and BMD (+2%, P<0.001). Lumbar (L2-L4) spine BMC increased by 9% (P<0.001) and BMD by 5% (P<0.001). In femur neck, a peak increase in BMC and BMD of 7 and 3%, respectively, was observed after 7 years (both P<0.001). After 15 years, femur neck BMC was 5% above the baseline value (P<0.01), whereas femur neck BMD had returned to the baseline level. In most variables, men had a more marked response to GH replacement than women. CONCLUSIONS: Fifteen-year GH replacement in GHD adults induced a sustained increase in total body and lumbar (L2-L4) spine BMC and BMD. In femur neck, BMC and BMD peaked at 7 years and then decreased towards baseline values.

Effects of 3-year GH replacement therapy on bone mineral density in younger and elderly adults with adult-onset GH deficiency.

OBJECTIVE: Little is known of the effects of long-term GH replacement on bone mineral content (BMC) and bone mineral density (BMD) in elderly GH-deficient (GHD) adults. DESIGN/PATIENTS/METHODS: In this prospective, single-center, open-label study, the effects of 3-year GH replacement were determined in 45 GHD patients >65 years and in 45 younger control GHD patients with a mean age of 39.5 (S.E.M. 1.1) years. All patients had adult-onset disease and both groups were comparable in terms of number of anterior pituitary hormonal deficiencies, gender, body mass index, and waist:hip ratio. RESULTS: The mean maintenance dose of GH was 0.24 (0.02) mg/day in the elderly patients and 0.33 (0.02) mg/day in the younger GHD patients (P<0.01). The 3 years of GH replacement induced a marginal effect on total body BMC and BMD, whereas femur neck and lumbar (L2-L4) spine BMC and BMD increased in both the elderly and the younger patients. The treatment response in femur neck BMC was less marked in the elderly patients (P<0.05 vs younger group). However, this difference disappeared after correction for the lower dose of GH in the elderly patients using an analysis of covariance. There were no between-group differences in responsiveness in BMC or BMD at other skeletal locations. CONCLUSIONS: This study shows that GH replacement increases lumbar (L2-L4) spine and femur neck BMD and BMC in younger as well as elderly GHD patients. This supports the notion that long-term GH replacement is also useful in elderly GHD patients.

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement.

CONTEXT: Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency (GHD). OBJECTIVE, DESIGN, AND PATIENTS: In this prospective open-labeled study, the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults (mean age of 65.2 years; range 61-74 years). Muscle strength was compared with reference values obtained from the background population. RESULTS: The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day. The mean IGF1 SDS increased from -1.10 at baseline to 1.17 at study end. GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength. Isometric knee extensor strength was reduced after 10 years. However, after correction for age and gender, using observed/predicted value ratios, there was sustained and even progressive increase in most variables reflecting muscle strength. Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years. CONCLUSIONS: Ten years of GH replacement therapy in elderly GHD adults resulted in a transient increase in isometric knee flexor strength, and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function.

Ten years of growth hormone (GH) replacement normalizes muscle strength in GH-deficient adults.

CONTEXT: GH replacement for 1-5 yr improves, but does not fully normalize, muscle strength. OBJECTIVE, DESIGN, AND PATIENTS: In this single-center, open-labeled, prospective study, the effects of 10 yr of GH replacement on muscle strength and neuromuscular function were followed in 109 consecutive adults (61 men; mean age 50.0 yr; range 22-74 yr) with adult-onset GH deficiency. RESULTS: The mean initial GH dose of 0.88 mg/d was gradually lowered to 0.47 mg/d. The mean IGF-I sd score increased from -1.54 at baseline to 1.12 at study end. GH replacement induced a sustained increase in lean mass and isometric knee flexor strength (60 degrees). In most other measures of upper leg and handgrip strength, there were transient increases during the first half of the study (0-5 yr), whereas during the second half (5-10 yr), the absolute values of muscle strength decreased and returned to or even below the baseline values. However, after correction for age and gender using observed/predicted value ratios, there were sustained and, until 7 yr, even progressive increases in the measures of muscle strength. At study end, knee flexor strength had increased to 104-110% of predicted, knee extensor strength to 93-108%, and handgrip strength to 88-93%. Measurements of neuromuscular function showed reduced voluntary motor unit activation after 10 yr. CONCLUSIONS: Ten years of GH replacement therapy increased muscle strength during the first half of the study and thereafter partly protected against the normal age-related decline in muscle strength and neuromuscular function, resulting in approximately normalized muscle strength after 10 yr.