Hardin and colleagues studied the effects of recombinant GH (0.3 mg/kg/wk) in 10 children with cystic fibrosis (ages 7-12, Tanner stage I) as compared to a control group of 9 similar children. All children recruited for the study were <10^th percentile for both height and weight and had adequate caloric intake as determined on 2 evaluations.  Only one had an abnormal growth hormone stimulation test.  Children were excluded from the study if they had been hospitalized within 6 weeks or had been treated with systemic or oral steroids within 6 weeks.  Evaluations were made of pulmonary functions including forced vital capacity (FVC) and forced expiratory volume at 1 second (FEV₁).  In addition, peak expiratory pressure (PEP) and peak inspiratory pressure (PIP) were measured.  Resting energy expenditure, was determined using indirect calorimetry, and lean body mass was determined by whole body dual energy x-ray absorptiometry.  Studies were made at baseline and every 3 months.  Data were collected with regard to the number of hospitalizations and antibiotic therapy.  All data for both the treatment group and the control group were similar at baseline.

The height and weight Z scores were significantly greater in the treatment group after one year than in the control group; furthermore the treatment group had a significant increase in lean body mass.  Additionally, at 12 months the treatment group had a significant improvement in percent FVC, PIP, and PEP.  There was no significant change in percent FEV_{1 .}  The GH treated group had a significant decrease in the number of hospitalizations, although outpatient antibiotic therapy was not different between the two groups.  There was no significant change in resting energy expenditure  or nutritional intake during the study and carbohydrate intolerance did not develop in either groups.  The advancement in bone age over the 12 months was not different between the two groups.

The authors conclude that growth hormone therapy is of significant benefit to pre-pubertal children with CF in terms of their height, weight, body composition, pulmonary function, and number of hospitalizations.

First Editor’s Comment:  This study by Hardin and associates is the first randomized, controlled trial of growth hormone therapy in children with cystic fibrosis.  The findings are highly significant, although they have only been collected for a single year.  Many questions remain unresolved.  It would be important for studies to be undertaken to determine whether or not the change in lean body mass was due to an improved use of ingested calories and protein as suggested by the authors.  In addition, the long-term benefits of treatment need to be evaluated, and the optimal dose needs to be determined.  Furthermore, it will be important to follow these children to determine whether or not they are at increased risk for glucose tolerance over time.  Hardin and associates have provided the preliminary data necessary to undertake a much larger scale study of the use of growth hormone in these children.

William L. Clarke, MD

Second Editor’s Comment:  Growth Hormone treatment in patients with cystic fibrosis has been shown to be of benefit in various short-term trials.^1,2  However this is the first randomized controlled trial of GH treatment in patients with this disease. Growth hormone resulted in improved clinical status and increased growth.  In CF, malnutrition develops as a result of unfavorable energy balance caused by a combination of poor intake, malabsorption of nutrients, chronic pulmonary disease and increased energy expenditures.  Malnutrition adversely affects the course of the disease as well as the survival of the patients.  Therefore any means to improve the anabolic state of CF patients may be of benefit. In this study GH treatment also improved the quality of life.  Nonetheless, detrimental effects of GH treatment could occur in patients with CF, as diabetes is prevalent among this population.³ Although in this study no patient developed this problem, the data cannot be extended to other patients or to those who would undergo a longer-term treatment.  It should also be kept in mind that improvements in growth and nutrition status of CF patients may be accomplished with aggressive nutritional supplementation without GH treatment.⁴

Fima Lifshitz, MD