Influences on quality of life in GH deficient adults and their effect on response to treatment.

Abstract

Studies of the effect of GH on quality of life (QOL) in growth hormone deficient (GHD) adults have reported conflicting results. Recently, however, we have demonstrated that by selecting only those patients with impaired QOL the efficacy of GH replacement on QOL can be greatly improved. The improvement in QOL was observed to correlate significantly with that recorded before commencing GH therapy. This study aims to assess if demographic variables affect QOL in untreated GHD adults or the improvement in QOL following GH therapy. An open study of GH replacement, initiating treatment with a dose of 0.8 IU/day and titrating the dose by 0.4 IU increments to normalize the IGF-I SDS between - 2.0 and + 2.0 SD of the age related normal range. 65 severely GHD patients (peak GH < 9 mU/l to provocative testing), mean age 38.7 (range 17-72) years. Inclusion criterion was that of subjectively poor quality of life on clinical interview. Blood was taken for insulin-like growth factor 1 (IGF-I). The Psychological General Well-Being Schedule (PGWB) and Adult Growth Hormone Deficiency Assessment (AGHDA) self-rating questionnaires were used to assess quality of life at baseline, three and eight months after commencing GH. The patients were subgrouped on the basis of gender, age of onset of GHD, pathology and presence of additional pituitary hormone deficits. The cohort consisted of 40 females and 25 males, 45 of adult-onset (AO) and 20 of childhood-onset (CO). GH deficiency resulted from a hypothalamo-pituitary pathology, or treatment thereof, in 36 patients and as a result of cranial irradiation for a primary brain tumour or prophylaxis in acute lymphoblastic leukaemia in 29 patients. Isolated GH deficiency (IGHD) was present in 25 patients, and 32 patients were demonstrated to have at least two additional pituitary hormone deficits (MPHD). No significant difference was detected between baseline PGWB scores of the subgroups. Multiple linear regression analysis revealed the age of onset of GHD to be a significant determinant of both the baseline PGWB (P = 0.05) and AGHDA (P = 0.025) scores, AO patients perceiving the greater distress. A significant improvement, from baseline, in both QOL scores was observed in all subgroups at three months, and in all subgroups at eight months except IGHD, where a trend towards improvement in the AGHDA score was observed but failed to reach significance. The mean improvement in the PGWB following GH therapy was not significantly different between subgroups. Multiple linear regression analysis confirmed baseline PGWB and AGHDA scores to be the most important variable in prediction of the level of improvement in respective scores following GH therapy. Age of onset was also observed to be a significant determinant of the PGWB scores following GH therapy (P = 0.02), the CO cohort experiencing the greater improvement. A similar relationship between age of onset and AGHDA scores was not observed (P = 0.22). Baseline QOL as assessed by self-rating questionnaires is influenced by the age of onset of the GH deficiency, adult onset patients expressing the greater distress. Improvements in QOL scores are influenced by both baseline score and to a lesser extent the age of onset of GHD, the greater improvement being observed in childhood onset patients. The degree of improvement was observed to be independent of gender, pathology and number of pituitary hormone deficits. In a cohort selected by subjectively impaired QOL, we have demonstrated childhood onset GHD patients perceive themselves to have less impairment of QOL pretreatment. In contrast to previous data in unselected cohorts, however, we have shown that those childhood onset GHD patients in whom QOL is significantly reduced, show a capacity for improvement that is equal to, if not greater, than that seen in adult onset-GHD patients.