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)

The consequences of GH deficiency may differ if the disease is childhood onset or adulthood onset. In this single-center, prospective study, 21 consecutive adults with childhood onset GH deficiency and 21 adults with adulthood onset GH deficiency, matched for age, gender, body mass index, and number of anterior pituitary hormonal deficiencies, were included. Baseline differences and differences in the responses in body composition, muscle strength, bone mass, and metabolic indices during 5-yr GH replacement were determined. The duration of GH deficiency was longer and serum IGF-I level and body height were lower in the childhood onset patients than in the adulthood onset patients. Body fat (observed/predicted ratio) was increased, and lean mass and muscle strength were decreased, in the childhood onset patients. Total body and lumbar (L2-L4) bone mineral content and bone mineral density were lower in the childhood onset patients. Serum total cholesterol level was higher in the adulthood onset patients. The childhood onset and adulthood onset patients received a similar dose of GH. After adjustment for body weight, however, the dose of GH was higher in the childhood onset patients. The treatment responses were more marked in the childhood onset patients in lean mass, knee extensor strength, left-hand grip strength, and in total body and lumbar (L2-L4) bone mineral content and bone mineral density. The reduction in serum total cholesterol concentration was more marked in the adulthood onset patients. At study end, no differences remained between the two study groups after the correction for body height in the statistical analysis. In conclusion, the baseline analysis suggests more decreased lean mass, muscle strength, and bone mass in the childhood onset patients whereas the lipid profile was more disturbed in the adulthood onset patients. A DULT GH DEFICIENCY (GHD) IS not a homogenous condition. The clinical presentation may differ depending on the underlying pituitary disease, the severity of GHD, and the presence of other anterior hormonal deficiencies (1, 2). Furthermore, the clinical presentation may differ whether the pituitary disease was acquired in childhood or in adult life. In a study by Attanasio et al. (3), patients with childhood onset (CO) GHD had lower serum IGF-I level, lower body mass index (BMI), higher serum high-density lipoprotein cholesterol (HDL-C) level, and superior quality of life than patients with adulthood onset (AO) GHD. Lower muscle mass (4) and bone mass (5) and enhanced quality of life (6) have been observed in CO patients. Little is known whether the responsiveness to GH treatment differs between CO and AO patients.The differences between CO and AO patients may be owing to the fact that GH replacement in CO patients was discontinued when final height was reached, whereas peak bone mass and peak muscle strength had still not been attained. Furthermore, baseline differences may also be an effect of lower age and reduced body height in the CO group (7). In a study in which these two...

The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD.

Objective: Clinical response to GH therapy in GH-deficient (GHD) adults varies widely. Good predictors of treatment response are lacking. The aim of the study was to develop mathematical models to predict changes in serum IGF1 and body composition (BC) in response to GH therapy in GHD adults. Design and methods: One hundred and sixty-seven GHD patients (103 men, median age 50 years) were studied before and after 12 months of GH treatment. GH dose was tailored according to serum IGF1 concentrations. Good responders (GR) and poor responders (PR) to GH therapy were defined as patients with a response O60th and !40th percentile respectively, for changes in serum IGF1 levels (adjusted for GH cumulative dose) and in BC (lean body mass (LBM) and body fat determined using dual-energy X-ray absorptiometry). A logistic regression model was used to predict the probability of being a GR or PR. Results: In the IGF1 prediction model, men (odds ratio (OR) 5.62: 95% confidence interval 2.59-12.18) and patients with higher insulin levels (OR 1.06: 1.00-1.12) were more likely to be GR. The accuracy of the prediction model was 70%. In the BC model, men ) and GHD patients with lower LBM (OR 0.82: 0.73-0.92) and greater height (OR 1.23: 1.08-1.40) at baseline were more likely to be GR. The accuracy of the prediction model was 80%. Conclusion: Accurate mathematical models to predict GH responsiveness in GHD adults were developed using gender, body height, baseline LBM, and serum insulin levels as the major clinical predictors.

Objective: Men with growth hormone deficiency (GHD) may be more sensitive to GH treatment than women in terms of changes in body composition. We have studied whether age, body-mass index (BMI) and the different types of methodology used to assess body composition may explain these differences. Design: Forty-four men and forty-four women with GHD, closely matched for age and BMI, were studied before and after 6 months of GH replacement. The dose of GH was individually adjusted. Body composition was assessed by measurements of potassium-40, total body nitrogen (TBN), tritiated water dilution, dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA). Four-and five-compartment models for body composition were also calculated. Results: The total daily dose of GH was similar in men and women at 6 months. Serum insulin-like growth factor-I (IGF-I) was higher in men than women at baseline and after 6 months of treatment (P ¼ 0.01, paired t-test). The increment was, however, similar. In women, GH treatment reduced body weight and increased TBN. In both men and women, total body water and body cell mass increased, while total body fat (BF) mass decreased. At baseline, mean total BF varied considerably depending on the methodology used, with the highest value obtained from DXA. The changes in BF were, however, less dependent on the methodology, but DXA and BIA demonstrated the largest inconsistency between men and women. Conclusions: These results suggest that gender differences in body composition in response to GH treatment are small, if adjustments are made for baseline factors such as age, BMI and dose of GH. Different methods of body composition measurements produce different results, but changes in response to GH administration are less inconsistent.European Journal of Endocrinology 154 545-553