GH replacement therapy has proved its efficacy and safety in short-term trials and in a few long-term trials with limited number of subjects. In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined. The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from -1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A(1c) were reduced compared with baseline values. The treatment responses in IGF-I SD score, body fat as estimated by four- and five-compartment body composition models, total body protein and nitrogen, and lumbar bone mineral content and BMD were more marked in men than in women. One patient died during the period, four patients discontinued the study due to adverse events, and one dropped out due to lack of compliance. Four patients were lost to follow-up. However, all patients were retained in the statistical analysis according to the intention to treat approach used. In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A(1c) were first observed after years of treatment.

The effect on the absolute amount of body fat was seen early and was transient, which could be due to the normal aging of the patients. The effects on metabolic indices were detected later, but they were sustained and even progressive throughout the study period.

GH replacement therapy has proved its efficacy and safety in short-term trials and in a few long-term trials with limited number of subjects. In this 1-center study, including 118 consecutive adults (70 men and 48 women; mean age, 49.3 yr; range, 22-74 yr) with adult-onset GH deficiency, the effects of 5 yr of GH replacement on body composition, bone mass, and metabolic indices were determined.The mean initial GH dose was 0.98 mg/d. The dose was gradually lowered, and after 5 yr the mean dose was 0.48 mg/d. The mean IGF-I SD score increased from ؊1.73 at baseline to 1.66 at study end. A sustained increase in lean body mass and a decrease in body fat were observed. The GH treatment increased total body bone mineral content as well as lumbar (L2-L4) and femur neck bone mineral contents. BMD in lumbar spine (L2-L4) and femur neck were increased and normalized at study end. Total cholesterol and low density lipoprotein cholesterol decreased, and high density lipoprotein cholesterol increased. At 5 yr, serum concentrations of triglycerides and hemoglobin A 1c were reduced compared with baseline values. The treatment responses in IGF-I SD score, body fat as estimated by four-and five-compartment body composition models, total body protein and nitrogen, and lumbar bone mineral content and BMD were more marked in men than in women.One patient died during the period, four patients discontinued the study due to adverse events, and one dropped out due to lack of compliance. Four patients were lost to follow-up. However, all patients were retained in the statistical analysis according to the intention to treat approach used.In conclusion, 5 yr of GH substitution in GH-deficient adults is safe and well tolerated. The effects on body composition, bone mass, and metabolic indices were sustained. The effects on body composition and low density lipoprotein cholesterol were seen after 1 yr, whereas the effects on bone mass, triglycerides, and hemoglobin A 1c were first observed after years of treatment. (J Clin Endocrinol Metab 86: 4657-4665, 2001)

ObjectiveFew studies have determined the effects of more than 5–10 years of GH replacement in adults on body composition and cardiovascular risk factors.Design/patientsIn 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.ResultsThe 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).ConclusionsFifteen-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.

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.

ObjectiveFew 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/patientsIn 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.ResultsThe 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.ConclusionsFifteen-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.

There are few studies that have determined the effects of long-term GH replacement on bone mineral density (BMD) in GH-deficient (GHD) adults. In this study, the effects of 10 years of GH replacement on BMD were assessed in 87 GHD adults using dual energy X-ray absorptiometry (DEXA). The results show that GH replacement induced a sustained increase in BMD at all the skeletal sites measured. Introduction: Little is known of the effect of more than 5 years of GH replacement therapy on bone metabolism in GHD adults. Patients and methods: In this prospective, open-label, single-center study, which included 87 consecutive adults (52 men and 35 women; mean age of 44.1 (range 22-74) years) with adulthood onset GHD, the effect of 10 years of GH replacement on BMD was determined. Results: The mean initial dose of GH was 0.98 mg/day. The dose was gradually lowered and after 10 years the mean dose was 0.47 mg/day. The mean insulin-like growth factor-I (IGF-I) SDS increased from 1.81 at baseline to 1.29 at study end. The GH replacement induced a sustained increase in total, lumbar (L2-L4) and femur neck BMD, and bone mineral content (BMC) as measured by DEXA. The treatment response in IGF-I SDS was more marked in men, whereas women had a more marked increase in the total body BMC and the total body z-score. There was a tendency for women on estrogen treatment to have a larger increase in bone mass and density compared with women without estrogen replacement. Conclusions: Ten years of GH replacement in hypopituitary adults induced a sustained, and in some variables even a progressive, increase in bone mass and bone density. The study results also suggest that adequate estrogen replacement is needed in order to have an optimal response in BMD in GHD women.European Journal of Endocrinology 156 55-64

adrenal lesions are under-reported in clinical practice. Prevalence figures for adrenal incidentalomas should therefore be interpreted with caution, especially in multi-center settings.