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Summary
Pituitary adenomas are common benign monoclonal neoplasms, accounting for approximately 10-15% of primary intracranial tumors. Although histologically benign, pituitary tumors cause significant morbidity due to their critical location, expanding size, and/ore inappropriate pituitary hormone expression. For the average general practitioner, pituitary disorders are relatively uncommon. However, post-morten and magnetic resonance imaging studies show t hat approximately 10% of the population may harbor a pituitary mass, although most are small and non-functioning Pituitary adenomas can occur in a familial setting in multiple endocrine neoplasia type I, Carney's complex, and in the context of isolated familial acromegaly or gigantism, and less frequently, in the context of a familial predisposition to the development of other pituitary tumors. Another genetic, but not inherited disorder associated with growth hormone and prolactin-producing pituitary tumors is McCune- Although most pituitary tumors are well-differentiated and histoloigcally benign neoplasms, their clinical behaviors are varied. Invasive pituitary adenomas have a poorer prognosis than noninvasive tumors because they are difficult to remove completely. However, these differences in clinical behavior cannot be discerned from their Summary
All subtypes of pituitary adenomas may present as microadenomas, defined as tumors contained within the pituitary fossa and smaller 10mm in diameter, or as macroadenomas that have extended outside the fossa to invade adjacent tissues (greater than 10mm in diameter). Tumor extension outside the pituitary fossa may involve the cavernous sinus laterally (parasellar extension), the optic chiasm superiorly (suprasellar extension), or the sphenoid sinus inferiorly (infraselar extension). Rarely, aggressive tumors may extended along the skull base, even sometimes causing multiple cranial nerve palsies. Macroadenomas commonly come to clinical attention through pressure effects, such as headache or progressive visual failure, whereas microadenomas are usually identified through investigation of a clinical endocrine syndrome, or may be discovered as an incidental finding during scanning of the brain for other Modern treatment of pituitary tumors depends on three signal advances in medicine that had occurred in the past 40 years. First, increasingly sensitive tests can now measure picomolar levels of the entire panoply of pituitary hormones, and can therefore be used to create a profile of pituitary function that indicates whether the gland is functioning properly or secreting excessively. Second, surgical techniques revived by the energy and drive of Jules Hardy, who in the late 1960s, was the first surgeon to report the successful removal of a microadenoma. Hardy also developed many of the instruments used in modern transsphenoidal surgery and repopularized this approach to a point that it is now used for 95% of pituitary tumor resections. Third, the introduction of and ongoing improvements in magnetic resonance imaging have made increasingly earlier diagnosis of such tumors Summary
possible. Microadenomas as small as 2-3mm can now be detected with Treatment of a patient with a pituitary adenoma is dependent on the type of tumor, the effect of tumor on vision, and on pituitary function. With the exception of prolactin-producing adenomas, the first line of treatment for most patients is surgical removal of the mass lesion. Despite the ability to remove and adenoma completely or to debulk the lesion significantly, many patients require adjunctive medical treatment, and in some instances, pituitary radiation to control the disease. The goals of treatment include elimination of the mass effect. The goals of treatment include elimination of the mass effect, lowering excessive hormone production to normal, restoration of normal pituitary function, prevention of recurrence, and administration of necessary hormone replacement. Medical therapy with dopamine agonists is the treatment of choice for prolactin-secreting pituitary adenomas. Cabergoline is the first-line treatment, because it is more effective and better tolerated than the other available dopamine agonists. Transsphenoidal surgery remains an option when medical therapy is ineffective, whereas radiotherapy represents the last option because of the high incidence of major side effects. A small proportion of prolactinomas that are aggressive or rarely malignant, are often associated with a poor response to all commonly used treatments. Early diagnosis and treatment of these atypical forms currently represent the two major opens issues in the management of prolactinomas. Tumors excision, usually by the transsphenoidal route, is the most rapid way of reducing growth hormone concentration in patients with somatotropinomas. Nevertheless, these levels normalize in only 40-70% of cases, depending on the size of the tumor, preoperative growth Summary
hormone concentrations, and the surgeon's experience. Endoscopic techniques are now currently used in the majority of expert centers. Although transsphenoidal excision of the adrenocorticotropic hormone (ACTH)-producing neoplasm is often the treatment of choice in patients with Cushing's disease, medical management is itself a useful preoperative temporizing measure, an option for long-term management in nonsurgical candidates, and an option for patients in whom surgery and/or radiotherapy have failed. Three pathophysiologically based medical approaches exist in the research literature: neuromodulation to limite ACTH levels, adrenal enzyme inhibition, and glucocorticoid receptor antagonism. Unfortunately, the neuormodulatory approach involving agents such as bromocriptine, cyproheptadine, octreotide, and valproate has yielded only suboptimal results. Glucocorticoid receptors antagonism remains in its infancy, but may overall be limited by side effects and a resultant increase in ACTH and cortisol levels. Adrenal enzyme inhibitors, however, offer substantial future promise in the management of Cushing's disease, but are limited by the potential needed to use them indefinitely and by dose-tolerance effects. The transsphenoidal approach is accepted for the time being as the procedure of choice for the surgical management of most pituitary lesions (together with non neoplastic intrasellar cysts and selected cases of craniopharyngiomas). This is based on the fact that it is less traumatic, lacks visible scars, provides excellent visualization of the pituitary gland and adjacent pathologies, offers less morbidity and mortality rates, and Summary
Transcranial approaches have very limited indications for the time being. They are indicated in case where as transsphenoidal approach is contraindicated, such as sphenoid sinusitis, ecstatic midline (kissing) carotid) arteries, and patients who harbor pituitary macroadenomas with significant lateral and suprasellar extension that cannot be adequately Pituitary irradiation is effective at reducing tumor growth in the long term, and is often used as a adjunct to surgery when this has failed to achieve an adequate cure. Although irradiation is proven to reduce the risk of postoperative tumor progression, this is almost invariably at the cost of eventual hypopituitarism, which then requires life-long multiple hormone replacement therapy. Thus, patients require regular screening for progressive hypopituitarism, and eventually need substitution therapy with corticosteroids, growth hormone, thyroxine, and sex steroids (or

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