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.