A positive effect of GH treatment on CVD and fracture risk could be concluded , but study design limitations have to be considered .
Stroke and secondary brain tumours remained more prevalent .
Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment .
All fatal and nonfatal malignancies were not more prevalent in  GH-treated adults compared to the general population .
Due to the positive effects demonstrated in r and omized clinical trials on cardiovascular surrogate markers and bone metabolism , a positive effect of growth hormone ( GH ) treatment on clinical ly relevant end-points seems feasible .
In this review , we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency ( GHD ) with emphasis on morbidity : fatal and nonfatal cardiovascular disease ( CVD ) and stroke , fractures , fatal and nonfatal malignancies and recurrences , and diabetes mellitus .
The optimal growth hormone replacement dose in adults, derived from bioimpedance analysis.
The prevalence of clinical signs and symptoms related to fluid retention is high in most studies evaluating the efficacy of GH treatment in GH-deficient ( GHD ) adults . This may be a consequence of supraphysiological GH replacement . To examine whether fluid retention is a dose-related phenomenon , we evaluated the impact of various GH substitution doses on body fluid status in 46 GHD men participating in a 1-yr , double blind , and placebo-controlled study . The patients were r and omized to receive either placebo ( n = 13 ) or GH in a dose of 1 ( n = 11 ) , 2 ( n = 10 ) , or 3 ( n = 12 ) IU/m2.day , respectively . Treatment was started at one third of the predetermined dose and was subsequently increased by another third every month until the maintenance dose was reached . Tissue hydration was assessed by means of electrical impedance measurements . Normal values were obtained from 128 age- and sex-matched controls . In the untreated GHD state , whole body resistance was abnormally high ( observed , 642 + /- 82 omega ; predicted , 550 + /- 31 omega ; P < 0.001 ) . This was mainly caused by an increase in specific resistance of the lean body as a consequence of a reduction in extracellular water ( ECW ) . The first month of GH treatment was associated with a sharp decline in electrical resistance that was attributed to an increase in ECW . Whole body resistance reached its nadir after 3 months of treatment ( 517 + /- 72 omega , i.e. 19.6 + /- 6.5 % lower than before treatment ; P < 0.001 ) and did not change significantly thereafter . The GH-induced changes in body resistance were dose dependent . A significant decrease was observed with a dose as low as 0.33 IU/m2.day ( P < 0.005 ) . However , whole body resistance remained higher than normal in patients receiving less than 0.67 IU/m2.day ( P = 0.05 ) . Abnormally low resistance values , indicative of overhydration , were observed in patients receiving doses equal to or higher than 2 IU/m2.day ( P < 0.005 ) . Regression analysis of the pooled data showed that GH replacement in a dose of 1.10 IU/m2.day ( 95 % confidence interval , 0.85 - 1.45 IU/m2.day ) result ed in a normalization of whole body resistance . In conclusion , GH replacement therapy in adults rapidly corrects the preexisting deficit in ECW . This rehydration process is dose dependent and may result in a substantial weight gain . ( ABSTRACT TRUNCATED AT 400 WORDS
A positive effect of GH treatment on CVD and fracture risk could be concluded , but study design limitations have to be considered .
Stroke and secondary brain tumours remained more prevalent .
Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment .
All fatal and nonfatal malignancies were not more prevalent in  GH-treated adults compared to the general population .
Due to the positive effects demonstrated in r and omized clinical trials on cardiovascular surrogate markers and bone metabolism , a positive effect of growth hormone ( GH ) treatment on clinical ly relevant end-points seems feasible .
In this review , we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency ( GHD ) with emphasis on morbidity : fatal and nonfatal cardiovascular disease ( CVD ) and stroke , fractures , fatal and nonfatal malignancies and recurrences , and diabetes mellitus .