Objective: An important safety issue with GH replacement therapy (GHRT) in hypopituitary patients with a history of a pituitary adenoma is the risk for tumour recurrence or enlargement. Design: Case-control study. Subjects and methods: We studied tumour progression rate in 121 patients with hypopituitarism on the basis of non-functioning pituitary adenomas (NFPA) receiving long-term GHRT. A group of 114 NFPA patients not receiving GHRT who were matched in terms of duration of follow-up. gender. age. age at diagnosis and radiotherapy status were used as a control population. The average duration of GHRT was 10 +/- 4 years (range 2-17). Results: In patients with a known residual adenoma, 63% had no detectable enlargement of tumour during the study. In patients who had no visible residual tumour prior to GHRT. 90% did not suffer from recurrence. In total, the 10-year tumour progression-Free Survival rate in patients with NFPA receiving GHRT was 74%). In the control population not receiving GHRT. the 10-year progress ion-free Survival rate was 70%. Radiotherapy as part of the initial tumour treatment reduced the rate of tumour progression in both GHRT and non-GHRT patients to a similar extent. Conclusions: The rate of tumour progression was similar in this large group of GHRT patients and the control population not receiving GHRT. Our results provide further support that long-term use of GH replacement in hypopituitarism may be considered safe in patients with residual pituitary adenomas.