Endocrine Abstracts

Transsphenoidal surgery is preferred as primary therapy for acromegaly, but cure or acceptable disease control with this modality is obtained in <60%, and in some cases surgery is not eligible. Second-line treatment with long-acting somatostatin analogues (SA) is successful in ~60%. This treatment offers tumor shrinkage in addition to lowering of GH and IGF-I in most patients. A potential concern is impairment of glucose tolerance due to the concomitant suppression of insulin secretion. Pegvisomant is a specific GH antagonist, which binds to and blocks the GH receptor. This compound is very effective in providing IGF-I nomalisation and symptom relief in more than 90%. The treatment results in increased serum levels of endogenous GH, which probably reflects increased secretion and reduced clearance. This could theoretically lead to increased growth of remnant GH secreting tumor tissue.

A combination of a SA analogue and pegvisomant is potentially attractive by targeting the disease at two different levels: 1) suppression of tumor activity, and 2) peripheral blockade of GH action. Indeed, a number of trials confirm that this principle is feasible, in particular it offers superior IGF-I lowering and improved glucose tolerance as compared to SA mono-therapy in patients who are partially resistant to SA. There is also evidence to suggest that combination therapy may be cost-neutral by reducing the demand of pegvisomant.

Conclusions: 1) Disease control by medical therapy is now obtainable in almost all patients with acromegaly, 2) Long term data on the effects and side effects of combination therapy are still needed and 3) Should combination therapy be first choice to all patients who do not respond adequately to SA?