visualise the pituitary tumour and its invasion intocontiguous structures. Further and more sophisti-cated investigations are often required when thereis the suspicion of an ectopic source of hormoneproduction.
1. Management of Acromegaly
Optimal therapy for patients with acromegalyaims at removing the tumour with resolution of itsmass effects, preventing biochemical or local re-currence and preserving, as much as possible, nor-mal residual pituitary function. After achievingnormal IGF-I levels and restoration of normal andstimulated GH secretion, most clinical manifesta-tions of acromegaly may disappear and a signifi-cant relief from many symptoms occurs. The mainaim of successful treatment is to prevent disablinglong term consequences, as well as to normaliserisk factors for cardiovascular complications andfor malignancies. Since an effective treatmentlinked to an improved survival rate is stronglycorrelated with the reduction in serum GH levels,standardised criteria should be established to de-fine biochemical ‘control’and ‘cure’’.
Arecentconsensus suggested that ‘cure’ is associated withGH levels <1
g/L, as a nadir after oral glucoseload.
However, taking into account the resultsfrom studies that demonstrated a normalised sur-vival in patients with GH levels less than 2.5
g/L(5/7.5 mU/L, depending on reference standard be-foreorafterJanuary1997,respectively),
aswellas the correlation between mortality in patientswith acromegaly and GH levels after therapy,
itseems best todefine values ofGH andIGF-Iwhichreflect both the achieved clinical remission and thedecreased long term morbidity and mortality.
Such ‘safe values’ represent a more realistic con-cept, and these imply serum GH levels of less than2.5
g/L, together with a IGF-I level which is nor-mal after correction for age and gender.
Treatment options for acromegaly include sur-gical removal of the adenoma, radiotherapy andpharmacological reduction of hormonal hyper-secretion by dopamine agonists and somatostatinanalogues. Among these therapeutic approaches,the best option to be considered as suitable as pri-mary therapy for acromegaly remains controver-sial.Three decades ago only surgery and radiother-apy were the only effective treatments for pituitarytumours. The scene definitively changed with theintroduction of dopaminergic compounds, whichinpatients withprolactinoma,veryeffectivelylowerprolactin (PRL) levels, which in turn restores al-tered endocrine functions and induces significanttumour shrinkage. Already with the first genera-tion of dopamine agonists (the most widely usedofwhichisbromocriptine),andmorerecentlywiththeavailabilityofsecondgenerationdopaminergicagents(suchasquinagolideandcabergoline),med-ical therapy has replaced surgery and radiotherapyas the first line of treatment in the majority of pa-tients with microadenomas and macroadenomasproducing PRL.
This success has promptedmany investigators to search for alternative simi-larly effective medical therapies for other pituitarytumours.For many years it was generally accepted thatGH-secreting pituitary adenomas should be surgi-cally removed. However, somatostatin analogues,which have been used for more than 10 years, havebeen proven to be an effective adjuvant therapyfor acromegaly.
Somatostatinanalogueswereemployed as primary treatment only in selectedcases, including presurgical treatment in patientswith large invasive macroadenomas, for relief of symptoms in patients awaiting surgery, in cases of recurrence of morbidity in elderly patients and incontraindications to neurosurgery.
In addition,medical therapy with somatostatin analogues and/ or dopamine agonists might be advisable when pre-vioussurgicalmanagementdidnotachieveclinicaland biochemical remission.
Thus, should surgery still be considered as themost effective and well tolerated primary treat-ment foracromegaly?Furthermore,as faras radio-therapy is concerned, what should be its role in thetreatment of GH-secreting pituitary adenomas, inlight of the promising data using modern stereo-tacticradiationtherapy,includinggamma-knifera-
Treatment Options in Acromegaly83
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