Monica Gadelha, Federal University of Rio de Janeiro, Brazil

While surgery remains the first-line treatment for the most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients. Advances in molecular and immunohistochemical markers, as well as continual advances in clinical and laboratory research may further refine treatment for these patients in the next decade.

In acromegaly, pegvisomant treatment normalises IGF-1 in a high proportion of patients, but has no effect on tumour size. Somatostatin analogues therefore remain the first-choice medical therapy for acromegaly, especially in large and/or aggressive tumours.

Virtually all acromegaly tumours express both sstr5 and sstr2 (and a smaller proportion express sstr1 or sstr3). In theory, molecules that bind to both sstr5 and sstr2 may provide improved efficacy in acromegaly (existing somatostatin analogues bind most potently to sstr2).

Investigation therapies include pasireotide, which is a pituitary targeted medical therapy with multi-sstr affinity (sstr1,2, 3 and 5). It has promising Phase I and II data in acromegaly. In the Phase I studies, pasireotide was shown to suppress GH levels more effectively than octreotide in a greater proportion of patients. In the Phase II studies, pasireotide achieved complete biochemical control in 30%, 49% and 38% of patients after  1, 2 and 3 months, respectively, with 39% of patients achieving a decrease in tumour size >20%. In the 6-month extension of this trial this increased to 55%. In tumours that are resistant to octreotide or lanreotide, sstr5 activation by pasireotide may, in a minority of patients, further lower GH and IGF-1 levels. A 12 month Phase III randomised study of pasireotide LAR is currently ongoing and results are expected in the near future.

The level of activity in this area of research promises a diversity of new drugs for acromegaly by 2020.