A therapeutic trial of growth hormone in hypopituitary adults and its influence upon continued prescription by general practitioners.
OBJECTIVES: Adult GH deficiency (GHD) is associated with profound alterations in body composition, lipid profiles and quality of life which frequently improve after GH therapy. However, the beneficial effects of treatment are not derived by all and consequently some scepticism persists with regard to the use of GH therapy in adults. We assessed whether a 3-month therapeutic assessment with GH therapy could be used to determine which GHD adults should be treated over the longer term. We also assessed the continued prescription of GH by general practitioners (GPs) following the initial therapeutic assessment. DESIGN: A three month open therapeutic trial of GH in GHD adults. Patients were treated with GH at an initial dose of 0.01 iU/kg/d, increased after 1 month to 0.015 iU/kg/d for males and 0.02 iU/kg/d for females. After completion of the three months the continued prescription of GH by the GPs was assessed. PATIENTS: All adult GHD patients were considered for GH therapy. Thirty-nine GHD adults wanted GH therapy (group 1) and their baseline characteristics such as age, duration of GHD, and IGF-1 concentration were compared with 24 subjects who declined to receive GH (group 2). MEASUREMENTS: Measurements of body composition using bioelectrical impedance analysis, lipids and quality of life measured using a dedicated questionnaire were made before and after GH therapy. The response of the general practitioners to continued GH therapy after the initial therapeutic assessment was also noted. RESULTS: Compared with subjects who declined GH therapy (group 2), subjects of group 1 were younger (46.4 +/- 14.4 vs. 54.2 +/- 15.7 years, P < 0.05) and had lower peak GH responses to provocative testing (1.4 +/- 2.1 vs. 2.9 +/- 2.7 mU/l, P < 0.001), though there were no differences between IGF-1 concentration (11.7 +/- 6.2 vs. 14. 2 +/- 7.9 nmol/l). Following three months of GH therapy, there were significant improvements in all measured parameters including increased free fat mass (50.2 vs. 52.4 kg, P < 0.005) and total body water (37 vs. 38.7 l, P < 0.005), reduced fat mass (31.6 vs. 29.8 kg, P < 0.005), reduced AGHDA score (7 vs. 4, P < 0.001) and reduced cholesterol (6.3 vs. 5.8 mmol/l, P < 0.001), LDL (4 vs. 3.33 mmol/l, P < 0.001) and cholesterol/HDL ratio (5.57 vs. 4.67, P < 0.001). IGF-1 concentrations were significantly increased following treatment (12 vs. 32.4 nmol/l). Six subjects decided to discontinue GH therapy, 2 before the end of the study due to potential drug-related side-effects and 4 subjects derived no benefit from treatment. Despite the demonstrable benefits of treatment for the remaining 33 GHD adults, 6 GPs refused to continue to prescribe GH therapy for reasons of lack of familiarity with the drug or advice from their health authority. CONCLUSION: Patients who wanted GH therapy were usually younger and more severely GHD than counterparts who elect not to be treated. However, a therapeutic trial of GH therapy is required to distinguish those subjects who derive benefit from treatment. We have shown that three months of low dose GH therapy is a sufficient period to elicit significant beneficial responses in quality of life, body composition parameters and lipids for the majority of patients and appears to be a sufficient period for patients to decide whether they want longer term therapy. The initial therapeutic trial also provides the objective evidence for the general practitioners to decide upon the continued prescription of therapy. Despite the positive evidence provided by this study, a small minority of general practitioners still refuse to prescribe GH therapy.