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Advances in Our Understanding of Acromegaly—Is There an Optimal Management Regimen?
monitoring of liver function is required as a significant rise in BIM-23A760, that has activity at both somatostatin (SSTR 2 and 5) and
transaminases can occur, generally within the first month of therapy. The dopamine receptors (DA2) is in clinical trials following encouraging in
mechanism is poorly understood and idiosyncratic, and histologically has vitro results.
41
the appearance of drug-induced hepatitis. To date, it has resolved on
stopping the drug, and in some cases even without discontinuation of the Optimal Management Regimen
medication, with no patients having experienced long-term hepatic The treatment regimen for acromegaly should be individually tailored
damage.
34,35
The nature of action of pegvisomant, in particular the based on informed patient choice and the defined biochemical and clinical
stimulation of increased GH secretion, has resulted in an understandable goals of treatment. Treatment decisions will take into consideration the
concern that long-term therapy may be associated with tumor expansion. desire to achieve biochemical control, relieve symptoms and signs,
Reassuringly, the data from several sources suggest that the natural preserve pituitary function, and control tumor size (see Figure 2). We would
history of the tumors is unaltered by pegvisomant. Some tumors that advocate that first-line treatment for the great majority of patients remains
were growing prior to pegvisomant have continued to expand, but there TSS performed by an experienced surgeon. Microadenomas should be
is no evidence of the antagonist inducing growth.
34,36
cured and debulking of macroadenomas will relieve pressure on structures
such as the optic chiasm, and will also improve the likelihood of remission
Combination Therapy with secondary medical therapy. Controversy remains in terms of the role
Pegvisomant is indicated for patients unresponsive to SSA, and in that of primary medical therapy with SSAs, particularly in centers without
scenario the choice is whether to add it to ongoing SSA or substitute adequate neurosurgical expertise. We would certainly recommend
pegvisomant in place of SSA. Van der Lely’s group have described the pre-operative medical therapy in patients with complications such as sleep
successful addition of weekly pegvisomant to monthly SSA.
37,38
This is an apnea or cardiomyopathy. There is a lack of data to show that
attractive option as a means of maintaining any tumor shrinkage that has pre-treatment of macroadenomas improves surgical complications or
occurred with an SSA. The only reported study to randomize patients remission rates, and we feel the currently available data in terms of
unresponsive to SSA to either combination therapy or pegvisomant long-term morbidity and mortality are insufficient to recommend it replace
monotherapy found similar rates of IGF-I normalization in both groups, TSS, but it should be an option for patients who are not fit for surgery or
with patients on pegvisomant monotherapy requiring on average 5mg per under special circumstances. Conventional radiotherapy should be
day more than those on combination therapy
39
—the implication being that reserved for patients with continued tumor growth despite surgical and
there is little difference in the price of the two options, which is contrary to medical therapy. However, stereotactic radiotherapy may have a specific
previous claims that combination treatment was significantly less role in those patients with a well-defined area of residual disease at least
expensive. The decision to use monotherapy or combination treatment 5mm away from the optic chiasm post-debulking surgery.
depends on individual patient circumstances; for example, good tumor
shrinkage with SSA would be a reason for combination treatment, while Despite these interventions, the majority of patients will require medical
deteriorating glucose tolerance argues for monotherapy. therapy. SSAs provide the mainstay of medical treatment, with DA being
an option in those with mild elevations of IGF-I and co-secreting
Novel Treatments prolactin. In Europe, pegvisomant is limited to patients who remain
Pasireotide (SOM230) is a novel multireceptor ligand SSA with high uncontrolled on maximum-dose SSA or who are intolerant of SSAs due
binding affinity to SSTR-1, -2, -3, and -5 and up to 40-fold greater affinity to side effects. Combination treatments of SSAs and pegvisomant are
for SST5 than octreotide. It may have a role in the treatment of various increasingly being used as there is some evidence of a synergistic effect
types of pituitary tumor, including those secreting GH. A phase II study of the two medications and benefit in those uncontrolled on either drug
has demonstrated effective IGF-I and GH suppression with a significant alone. The management of acromegaly is complex, but with improved
reduction in tumor volume, but there are concerns in terms of surgical and radiotherapy techniques and multiple medical options,
deteriorating glucose tolerance.
40
The future role of pasireotide in the biochemical control should be achievable in all patients. As new
treatment of acromegaly remains to be determined, but it will probably medications and techniques evolve, the treatment paradigm will
have a role in the treatment of octreotide-resistant tumors, particularly almost certainly change, and patients should be followed closely and
large adenomas. Another multireceptor ligand, the chimeric molecule re-evaluated on a regular basis. n
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