Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society vol:11 issue:3 pages:166-72
The consequences of "pharmacological" growth hormone administration have been studied in a number of conditions, including those characterized by high rates of catabolism. The majority of studies have reported favourable effects on metabolism but recent reports indicate that GH treatment results in increased mortality in critically ill humans. The objective of the study was to assess the safety of large doses of rhGH therapy in human adults. Original trials were identified by searching MEDLINE (1966-March 2000) and the Cochrane database (2000). References of all identified trials were also inspected for more studies. All relevant trials in which GH had been administered to non-GH-deficient (GHD) adult humans were selected from. Outcomes such as death, clinically significant change in function, change in length of hospital stay or need for treatment, and adverse effects were sought. Studies were selected, quality-assessed and passed suitable for inclusion by two independent reviewers. Those studies that were placebo-controlled with satisfactory randomization were considered for inclusion. Twenty-one reports were included in the review. A wide range of patient groups were studied by a variety of investigators, employing a range of doses and duration of GH treatment. The study protocols differed markedly. The majority of studies were small and were designed and/or powered to enable identification of specific effects on nutritional status, protein metabolism, level of function or quality of life. Only two studies were designed to assess safety issues and mortality. In these, GH treatment was associated with a marked increase in mortality in critically ill ICU patients, with a range of diagnoses. Multi-organ failure and the effects of sepsis/infection accounted for most of the excess mortality. In addition morbidity, in terms of length of ICU stay, was increased by GH administration. Other less marked effects were increased fluid retention and hyperglycaemia as a consequence of GH administration. Functional improvement following GH therapy was documented in some studies. There have been few studies assessing the safety aspects of "pharmacological" GH treatment in adult humans. Two well-designed reports indicate that GH administration results in increased morbidity and mortality in a wide variety of critically ill subjects across a spectrum of age ranges. The mechanism(s) of the GH-associated mortality remain poorly understood. Based on current trial evidence, pharmacological GH treatment cannot be recommended for widespread use in critically ill subjects. Well-conducted and reported randomized trials are still needed to inform practice as to whether GH administration will be safe in specific illness categories.