How effective are current therapies for acromegaly?

Abstract

Currently available therapies for acromegaly are transsphenoidal surgery (TSS), radiotherapy (RT) and medical therapy with the dopamine agonists and somatostatin analogues. The goals of these therapies for acromegaly are to normalize excessive hormone secretion, thus normalizing serum levels of growth hormone (GH) and of insulin-like growth factors (IGF-I), to reduce the clinical signs and symptoms of acromegaly and to reduce tumor size in order to relieve any symptoms due to tumor mass effect. These goals should be accomplished while preserving pituitary function and with as few side effects as possible.TSS, the initial choice of therapy in most patients, is the most effective therapy at reducing the signs and symptoms of mass effect such as visual or neurological compromise. TSS is potentially curative, but the outcome is highly dependent on the tumor size, the degree of tumor invasion and the expertise of the surgeon. TSS can achieve biochemical control with normalization of IGF-I in 80-90% of patients with microadenomas and in 50-60% of those with macroadenomas. RT may be used as adjunctive therapy after unsuccessful surgery. RT can lower GH levels and normalize IGF-I levels, but there is a long lag time before this effect is achieved. Biochemical control is not achieved for 6-10 years after conventional fractionated RT; the time to clinical effect after gamma knife RT seems to be shorter. The most common complication after all forms of RT for acromegaly is the development of new hypopituitarism. Medical therapy has assumed the major role as adjunctive therapy of acromegaly. The dopamine agonists used for the therapy of acromegaly include bromocriptine, quinagolide and cabergoline. Cabergoline seems to be the most efficacious of the dopamine agonists for the treatment of acromegaly, with normalization of IGF-I being achieved in up to 35% of patients treated. Dopamine agonists are generally not effective at reducing the size of pure GH-secreting pituitary tumors. Somatostatin analogues are the most effective medical therapy currently available for acromegaly. The clinically available long-acting somatostatin analogues are long-acting octreotide and slow-release lanreotide. Overall, IGF-I levels normalize in about 66% of patients treated with long-acting octreotide and in 48% of patients treated with lanreotide. About 30% of GH-secreting tumors treated with somatostatin analogues as adjunctive therapy will have some shrinkage, and the amount of shrinkage usually ranges between 20 and 50% of tumor size. Signs and symptoms of the disease improve in about two-thirds of patients treated with long-acting somatostatin analogues. Gastrointestinal side effects are common when initiating somatostatin analogue therapy, but these effects do not typically limit continued use. Multi-modality therapy for acromegaly is often needed to achieve disease control. However, even combinations of currently available therapies cannot achieve all the goals of therapy in many patients with acromegaly.