Endocrine Abstracts

Background: Dopamine agonists (DA) are included in the management algorithm of acromegaly. Studies on cabergoline monotherapy report IGF-1 normalisation in between 0% and 100% of the patients during treatment periods ranging between 2.6 and 24 months. However, in many of these studies, previous radiotherapy is a confounding factor. Furthermore, real world data applying the current disease control criteria (normal IGF-1 and GH<1 mg/l) are not available. The aim of this study was to investigate the efficacy and safety profile of cabergoline monotherapy in non-irradiated patients with uncontrolled acromegaly.

Patients and methods: In this multicenter, retrospective cohort study, non-irradiated patients offered cabergoline monotherapy for uncontrolled acromegaly were identified from the registries of four UK Pituitary centers (Birmingham, Bristol, Leicester and Oxford). Clinical, laboratory and imaging data were collected and analyzed.

Results: Sixty-nine patients were included. Median age at diagnosis of acromegaly was 50.5 years (range 28-78), 34.7% of the patients were females and 21.7% of the tumours were prolactin-co-secreting. Prior to starting cabergoline, IGF-1 levels were 2.13 (median) times the upper limit of normal (ULN) (range 1.02-8.54). Median duration of cabergoline treatment was 23 months (3-252). Normal IGF-1 was achieved in 31.8% (22/67) of the patients within a reported median interval of 12.5 months (2-84). Median weekly cabergoline dose at most recent review was 2.5 mg (0.25-4) in the responders, and 3 mg (0.25-7) in the non-responders (P=0.39). On univariate regression analysis, IGF-1 normalisation was significantly related with the presence of a prolactin co-secreting adenoma (B 1.38, P=0.030) and lower pre-cabergoline IGF-1 ULN levels (B -0.73, P=0.015). ROC analysis showed that IGF-1<1.55 ULN had sensitivity 50% and specificity 85% in predicting achievement of normal IGF-1; sensitivity and specificity for IGF-1<1.97 ULN were 75% and 67.5%, respectively (AUC 0.760). GH<1 mg/l was found in 25% (14/56) the patients, whereas 16.1% (9/56) had achieved both GH and IGF-1 criteria. Side effects were recorded in 5 patients (nausea n=2, nasal congestion n=1, dizziness/blurred vision/abdominal pain/weakness n=1, hair loss n=1).

Conclusions: In this large cohort of non-irradiated patients with acromegaly, cabergoline normalised IGF-1 in 32% of the cases and dose did not differ between responders and non-responders; efficacy of treatment was associated with the presence of prolactin co-secreting adenoma and pre-cabergoline IGF-1 ULN levels. Achievement of both optimal GH and IGF-1 levels was seen in only 16% of the patients.