GH replacement in 1034 growth hormone deficient hypopituitary adults:: demographic and clinical characteristics, dosing and safety

OBJECTIVE Long-term experience of growth hormone (GH) replacement therapy in a large population of hypopituitary adults with GH deficiency (GHD) is limited, and safety surveillance is clearly essential, KIWIS, the Pharmacia & Upjohn International Metabolic Database, is a long-term, open, outcomes research programme of hypopituitary adult patients with GHD who are treated in a conventional clinical setting, PATIENTS The present analysis encompasses data from 1034 hypopituitary adult GHD patients treated with GH for a total of 818 patient years. RESULTS Prior to GH therapy, the KIMS patient population exhibited an increased prevalence of obesity, diabetes mellitus tin females) and hyperlipidaemia, compared with normal populations described in published studies. Quality of life, assessed using a disease-specific questionnaire (QoL-AGHDA), was also reduced in KIMS patients. The maintenance dose of GH was significantly higher in patients who were receiving GH prior to enrolment into KIWIS (non-naive patients) compared with patients who commenced GH at the time of enrolment (naive patients). In addition, dose of GH correlated significantly with body weight in the former group of patients. Analysis of serum levels of IGF-I indicated that overtreatment with GH was markedly more common in non-naive than in naive patients. The frequency of adverse events in KIMS patients was no higher than that reported in patients receiving placebo in previous clinical trials. Recurrence of pituitary or CNS tumours was reported in six patients, a rate consistent with data from control series. Three deaths were reported, none of which was obviously associated with GH treatment. CONCLUSIONS Our data, drawn from a large population of hypopituitary adults treated with GH for a total of more than 800 patient years, confirm previous reports that untreated GHD in hypopituitary adults is associated with a number of important clinical problems. In addition, the results suggest that there has been a shift in recent years from determination of GH dose on the basis of body weight to dose titration of individual patients, and indicate that the latter technique has important advantages. The data provide further evidence that GH replacement therapy is well-tolerated in adults. However, it is possible that some adverse events may not become evident over the time scale covered by the present analysis, and continued surveillance therefore remains mandatory.