Much as 76% over baseline levéis, which Is pr>b-cacised by a loss of negative feedback by fewering IGEJJevcJs.96 Accordingly, IGF-I mea-sorement is the biomarker for monitoring the success of treatment. Liver-function tests should be performed monthly for the first 6 months and then every 6 months, since elevated hepatic ami-notransferase levéis have been reportad,98 MRI should be performed every6 months to detect pos-sibie continued tumor growth.
Dopamíne Receptor Agonists De^plt^Th^pooreffícacy~oT the first dopamine receptor agonists, agenta/ such as eabefgetme ap-pear to be promising. In an uncontrblled study, high doses of cabergoline offered a partial l'en-efit, especially in combination with sflmat£j§tatin_ ij^
also secreted_projactín. The addition of high doses
of cabergolineto treatment with somatostatin re
ceptor ligands may improve the responsiveness of
growth hormone in patients who otherwise have
resistance to maximal doses of somatostatin re
ceptor ligands.99, :
MONITORING AND CLINICAL GOALS
Prolonged exposure to elevated endogenous levéis of growth hormone and IGF-I results in both di-rect structural and fiínctional tissue damage ::nd thedevelopment of secondary systemic illnes;,es. Achievement of the criteria for cure during or after therapy is determinad by assessing biocheraical control, as evidenced by controlled levéis of growth hormone and normalization of IGF-I levéis, monitoring tumor size or remnant growth, assessing residual pituitary function, and monitoring co-existing illnesses58 (Fig. 3, and Table 4 of the Sup-plementaryAppendix).
Despite the imprecisión of assays for growth hormone and IGF-I, it is clear from epidemio-logic studies that tight biochemical control is required to reduce complications and restore adverse rates of death to control levéis.37 For bio-chemically and clinically inactive disease, patients should undergo annual biochemical testing and, pituitary MRI, regardless of treatment used. Per-sistentsubtle elevations of growth hormone levéis in the preserice of norrnalized IGF-I levéis may predict recurrence, despite the remission of co-edsting illnesses and norrnalized IGF-I levéis.62 For patients with biochemically active and clini- ... cal!/ inactive disease, the tumor raass should be monitored for growth by annuai MRI, and treat-ment should be initiated; if patients are already beingtreated, the method of therapy should be altered. In symptomatic patients, treatment should be initiated or changed until the symptoms are controlled. Monitoring of endogenous pituitary reserve, cardiovascular function (including echo-cardiographic evaluation), pulmonary status, blood sugar controi, and rheumatologic complications shouíd be maintained. In patients whose disease is controlled,colonoscopy, mammography, and measurement ofprostate-specifíc antigen should be performed according to guidelines for the gen-eral population.
Disease relapse is unlikely if nadir levéis of
_ growth hormone during an oral glucose-tolerance test remain under 1 ¿tg per liter and IGF-I levéis" are normal, However, in a study of the use of a ' highly sensitive growth hormone radioimmuno- • assay tomonitor treatment outcomes in 60 pa-tients, 50% of those with elevated IGF-I levéis had . nadir growth hormone levéis that were less than 1 /¿g per liter.100 Furthermore, another study dem-onstrated that high IGF-I levéis, but not nadir levéis of growth hormone, indicated relapse o; lack of control.101 Nevertheless, compíete ñor-malization of IGF-I levéis may not necessarily , be required to preventeither progression or re-
Qinicaíjnonitsring_§hould include an aware- .
• ness of the challenges that patients with aero-I megaly face, such as fertilityjssues,, th_ejlged_far i c^sai£lic_or_ftLnctJonal maxiSlofacial surgen', and
• the repercussions of an altered self-image. Patients -', who are anxious about diffículties in interpreting
• laboratory data and making...
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