THE SAFETY PROFILE OF GH REPLACEMENT THERAPY IN ADULTS

OBJECTIVE The benefits of GH replacement in GH-deficient adult patient s are becoming accepted but the safety profile continues to be defined . The GH deficiency in adults may have arisen in either childhood or d uring adult life and these two groups differ with regard to history of disease. The aim of the present report was to study differences in sa fety profile between these two groups during long-term replacement the rapy with recombinant human GH (hGH). Possible factors which placed a patient at risk of experiencing an adverse event were also examined. P ATIENTS AND DESIGN GH-deficient adult patients were randomized into tw o study protocols, differing only in age of onset of the GH deficiency syndrome. There were 98 patients with adult-onset and 67 patients wit h childhood-onset GH deficiency. Each study consisted of a 6-month dou ble-blind placebo-controlled phase followed by an open-label hGH treat ment phase. Glucose tolerance, incidence of treatment-emergent adverse events and relationship to IGF status were studied throughout the 36 months of treatment. RESULTS Human growth hormone-related adverse even ts were reported less commonly in childhood-onset patients compared wi th adult-onset patients. Adult-onset patients who continued into the o pen-label therapy phase reported an increased incidence of arthralgia, myalgia and paraesthesia. There were significant increases in fasting glucose with hGH therapy but values remained within the normal range. Hypertension was reported in 7.7% of adult-onset patients at 18 month s of hGH, which was within the expected prevalence for the number of p atients, but was not reported for any childhood-onset patients. Only i n adult-onset patients were sufficient adverse events reported to enab le analysis of risk factors. Patients reporting hGH-related adverse ev ents were significantly heavier and, therefore, received more hGH. The re was a significantly greater increase in IGF-I and IGFBP-3 in the fi rst month in patients who experienced hGH-related adverse events compa red with those who did not. CONCLUSION The risks of replacement therap y with hGH in GH-deficient adults varied with pathogenesis of disease; hGH-related adverse events occurred more frequently in patients with adult-onset compared with those with childhood-onset GH deficiency. In the adult-onset patients there was an increased risk of adverse event s in heavier patients and those who had the greatest increases in IGF- I and IGFBP-3 at 1 month of therapy.