Long-term effects of growth hormone replacement therapy in growth hormone deficient adults

Sammanfattning: Deficiency of growth hormone (GHD) in adults results in abnormal body composition, reduced bone mass and muscle strength, deteriorated cardiovascular risk factors. Short-term GH replacement reverses many of the symptoms associated with adult GHD. The aim of this thesis was to investigate the efficacy and safety of 5-10-year GH replacement in a large group of patients with adult onset (AO) GHD. Gender differences and responsiveness to GH replacement in subgroups of GHD adults were also determined. GH replacement for 5-10 years induced a reduction in body fat that was transient as measured using dual energy X-ray absorptiometry (DEXA). There were sustained increases in lean and bone mass and serum lipid concentrations improved. Men had a more marked treatment response in serum insulin-like growth factor-I (IGF-1) concentration and total body fat. The increase in BMC and BMD was detected later in women but was of a similar potency as that in men. Patients with childhood onset (CO) GHD had lower baseline serum IGF-I concentration, lean mass, knee flexor- and extensor strength, BMC and BMD in total body and lumbar (L2-L4) spine as compared with matched AO GHD patients. Baseline serum total cholesterol concentration was higher in AO GHD patients. GH replacement reversed all the baseline abnormalities and after 5 years no differences remained between the two groups.Baseline knee flexor, knee extensor, and hand-grip strength was reduced in elderly (>60 years of age) GHD patients. Five-year GH replacement resulted in increased isometric (60 a) knee flexor strength. After correction for age and sex using observed/predicted values ratios, an increase in isokinetic knee flexor and extensor strength and right-hand grip strength was also observed.In conclusion, GH replacement therapy for 5-10 years was safe and well-tolerated and induced beneficial effects on body composition, bone mass, and metabolic indices in GHD adults. Improvement of the features of GHD was observed in all subgroups of patients. GH replacement therapy should therefore be given in adult GHD patients irrespective of gender, age or onset of disease.