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{{Infobox disease | Name = Pituitary Adenoma | Image = PituitaryAdenoma.JPG | Alt = | Caption = T1 Coronal MRI of a pituitary adenoma | DiseasesDB = | ICD10 = {{ICD10|H|35|2|d|10}} | ICD9 = {{ICD9|237.0}} | ICDO = {{ICDO|8272|0}} | OMIM = | MedlinePlus = 000704 | eMedicineSubj = neuro | eMedicineTopic = 312 | MeshID = D010911 | GeneReviewsID = | GeneReviewsName = }} '''Pituitary adenomas''' are a collection of tumors that arise from the [http://en.wikipedia.org/wiki/Pituitary_gland pituitary gland]. They are the most common cause of [[Optic chiasm compression]].<ref name="BCSC Neuro">''Neuro-Ophthalmology.'' Basic and Clinical Science Course, Section 5. American Academy of Ophthalmology; 2010:159-165. [http://en.wikipedia.org/wiki/International_Standard_Book_Number ISBN] [http://www.amazon.com/s?search-alias=stripbooks&field-isbn=9781615251339 978-1-61525-133-9].</ref><ref name="Yanoff">Yanoff M, Duker JS. ''Ophthalmology, 3rd Ed.'' Elsevier; 2009:986-994.</ref> Ophthalmologic pathology typically involves [[Visual field defects]], although less commonly patients may also have [[Ocular motility deficits]] and/or [[Diplopia]], certain forms of [[Nystagmus]], signs and symptoms of [[Increased intracranial pressure]] due to mass effect, [[Optic atrophy]], or sequelae of [[Pituitary apoplexy]].<ref name="Robbins">Kumar V, Abbas AK, Fausto N. ''Robbins and Cotran Pathologic Basis of Disease, 7th Ed.'' Elsevier; 2005:1156-1164. [http://en.wikipedia.org/wiki/International_Standard_Book_Number ISBN] [http://www.amazon.com/s?search-alias=stripbooks&field-isbn=9780808923022 978-0-8089-2302-2].</ref><ref name="Kanski">Kanski JJ, Bowling B. ''Clinical Ophthalmology: A Systematic Approach, 7th Ed.'' Elsevier; 2011:816-827.</ref><ref name="Walsh&Hoyt">Gittinger JW. "Tumors of the Pituitary Gland." In: Miller NR, Newman NJ, eds. ''Walsh and Hoyt's Clinical Neuro-Ophthalmology, 6th Ed.'' Volume Two. Philadelphia, PA: Lippincott Williams &amp; Wilkins; 2005:1531-1546. [http://en.wikipedia.org/wiki/International_Standard_Book_Number ISBN] [http://www.amazon.com/s?search-alias=stripbooks&field-isbn=9780781748124 978-0-7817-4812-4]</ref> = Disease Entity = == General == === Epidemiology === Pituitary adenomas are reported to account for 12-15% of symptomatic intracranial neoplasms.<ref name="Yanoff" /> Overall, it is estimated that in upwards of 25% of the population have pituitary adenomas, most of which are incidentally found.<ref name="Robbins" /> One review found an average incidence of 16.7% (14.4% in autopsy studies and 22.5% in radiologic studies).<ref name="pmid15274075">Ezzat S, Asa SL, Couldwell WT, Barr CE, Dodge WE, Vance ML, McCutcheon IE. The Prevalence of Pituitary Adenomas: A Systematic Review. ''Cancer.'' 2004;'''101'''(3):613-9. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1002/cncr.20412 10.1002/cncr.20412]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/15274075 15274075].</ref> Pituitary adenomas usually occur in adults; they rarely occur in childhood.<ref name="BCSC Neuro" /><ref name="Robbins" /> Various articles have reported both male and female predilections.<ref name="pmid15274075" /><ref name="pmid16968795">Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High Prevalence of Pituitary Adenomas: A Cross-Sectional Study in the Province of Liege, Belgium. ''J Clin Endocrinol Metab.'' 2006 Dec;'''91'''(12):4769-75. Epub 2006 Sep 12. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/16968795 16968795].</ref> While most pituitary adenomas occur in isolation, 3% of cases are associated with [http://en.wikipedia.org/wiki/Multiple_endocrine_neoplasia_type_1 multiple endocrine neoplasia type 1].<ref name="Robbins" /><ref name="pmid21249756">Marini F, Falchetti A, Luzi E, Tonelli F, Luisa BM. Multiple Endocrine Neoplasia Type 1 (MEN1) Syndrome. ''Cancer Syndromes [Internet]. Bethesda (MD): National Center for Biotechnology Information (US).'' Riegert-Johnson DL, Boardman LA, Hefferon T, et al., editors. NCBI Bookshelf. 9 Aug 2008. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/21249756 21249756].</ref> === Classification === Pituitary adenomas can be classified by different methods, including size, hormonal activity, and histologic staining pattern. ==== Size ==== Historically, pituitary adenomas have been described by their size. This is performed radiographically with [http://en.wikipedia.org/wiki/Computed_tomography CT] or [http://en.wikipedia.org/wiki/Magnetic_resonance_imaging MRI].<ref name="Robbins" /><ref name="pmid15274075" /> *'''Macroadenomas''': ≥10 mm *'''Microadenomas''': <10 mm ==== Hormonal Activity ==== Adenomas can also be differentiated based on their hormonal activity in vivo as determined by [http://en.wikipedia.org/wiki/Immunohistochemical_staining immunohistochemistry] and [http://en.wikipedia.org/wiki/Electron_microscope electron microscopy]. *'''Functional (secreting) tumors''' are associated with hormonal secretion. Because of the clinical effects of hormonal disturbances, these tumors are more likely to be detected while they are still small. They are divided according to the hormone(s) produced. [http://en.wikipedia.org/wiki/Prolactinoma Prolactinomas] are the most common type of functional pituitary adenoma. *'''Nonfunctional (nonsecreting) tumors''' do not produce excess hormones. They may cause hypopituitarism due to mass effect. [http://en.wikipedia.org/wiki/Gonadotrophic Gonadotrophic adenomas] are the most common type of nonfunctional pituitary adenoma.<ref name="pmid18684022">Asa SL. Practical Pituitary Pathology: what does the pathologist need to know? ''Arch. Pathol. Lab. Med.'' 2008 Aug;'''132'''(8):1231–40. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/18684022 18684022].</ref> ==== Staining Pattern ==== Pituitary adenomas can also be divided by their staining pattern on histology.<ref name="Robbins" /> This classification is no longer clinically significant due to the more specific immunohistochemistry stains that can differentiate the hormones being secreted.<ref name="Walsh&Hoyt" /> These stains do not correlate well with other features of pituitary tumors, such as the type of secreted hormone and cell type.<ref name="Yanoff" /> *'''Acidophils''' contain [http://en.wikipedia.org/wiki/Eosinophilic eosinophilic] granules in their cytoplasm that stain brightly with acid fuschin. *'''Basophils''' contain [http://en.wikipedia.org/wiki/Basophilic basophilic] granules in their cytoplasm that stain brightly with aniline blue. *'''Chromophobes''' contain agranular cytoplasm. This term is often associated with nonfunctioning adenomas, although some hormone-secreting adenomas may also have chromophobic features. == Pathology == === Pathogenesis === Many animal studies have suggested one or more genetic factors that may contribute to the formation of pituitary adenomas. For example, the pituitary tumor-transforming gene (PTTG) has been shown to be overexpressed in hormone-secreting adenomas.<ref name="pmid10022450">Zhang X, Horwitz GA, Heaney AP, Nakashima M, Prezant TR, Bronstein MD, Melmed S. Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. ''J Clin Endocrinol Metab.'' 1999 Feb;'''84'''(2):761–767. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1210/jc.84.2.761 10.1210/jc.84.2.761]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/10022450 10022450].</ref> Mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with an increased risk of aggressively invasive growth hormone-secreting pituitary adenomas.<ref name="pmid21546764">Personnier C, Cazabat L, Bertherat J, Gaillard S, Souberbielle JC, Habrand JL, Dufour C, Clauser E, SainteRose C, Polak M. Clinical features and treatment of pediatric somatotropinoma: case study of an aggressive tumor due to a new AIP mutation and extensive literature review. ''Horm Res Paediatr.'' 2011;'''75'''(6):392-402. Epub 2011 May 6. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1159/000327831 10.1159/000327831]. [http://content.karger.com/produktedb/produkte.asp?DOI=000327831&typ=pdf Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21546764 21546764].</ref> There is evidence as well that adult pituitary stem cells may contribute to the development of pituitary adenomas.<ref name="pmid22116388">Florio T. Adult Pituitary Stem Cells: From Pituitary Plasticity to Adenoma Development. ''Neuroendocrinology'' 2011;'''94''':265–277. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1159/000330857 10.1159/000330857]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/22116388 22116388].</ref> Various cell markers have also been implicated in the behaviors of various pituitary tumors, including type of hormone produced, recurrence, regression, and response to treatment.<ref name="pmid18684022" /><ref name="pmid19786791">Fideleff HL, Boquete HR, Suárez MG, Azaretzky M. Prolactinoma in children and adolescents. ''Horm Res.'' 2009;'''72'''(4):197-205. Epub 2009 Sep 29. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1159/000236081 10.1159/000236081]. [http://content.karger.com/produktedb/produkte.asp?DOI=000236081&amp;amp;amp;typ=pdf Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/19786791 19786791].</ref><ref name="pmid22446019">Righi A, Agati P, Sisto A, Frank G, Faustini-Fustini M, Agati R, Mazzatenta D, Farnedi A, Menetti F, Marucci G, Foschini MP. A classification tree approach for pituitary adenomas. ''Hum Pathol.'' 2012 Mar 23. [Epub ahead of print]. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1016/j.humpath.2011.12.003 10.1016/j.humpath.2011.12.003]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/22446019 22446019].</ref> === Morphology === Most pituitary adenomas are soft, well-circumscribed lesions that are confined to the sella turcica. As these adenomas grow, they tend to extend superiorly and may eventually compress the optic chiasm and various cranial nerves. Expansion may lead to bony erosion of the anterior clinoid processes and sella turcica, as well as extending into the cavernous and sphenoid sinuses.<ref name="Robbins" /> === Histopathology === Pituitary adenomas have a monomorphic appearance and are arranged in sheets or cords. Adenoma cells stain on immunohistochemistry based on the type of hormone they typically secrete. The cytoplasm of these cells may be acidophilic, basophilic, or chromophobic, and is generally uniform in its appearance. These tumors also have a poor reticulin network, which distinguishes the tumor from non-neoplastic tissue, which tends to have a heterogenous appearance with an extensive reticulin network.<ref name="Robbins" /> {| border="1" class="wikitable" |+ '''Table 1. Types of Pituitary Adenomas and Their Reported Incidence'''<ref>Adapted from [http://en.wikipedia.org/wiki/Pituitary_adenoma#Classification Pituitary Adenoma]. Wikipedia. Accessed 04-28-2012.</ref> |- ! scope="col" | '''Type of adenoma''' ! scope="col" | '''Secreting Hormone''' ! scope="col" | '''Staining''' ! scope="col" | '''Reported Incidence'''<ref name="pmid12890801">Ironside JW. Best Practice No 172: Pituitary Gland Pathology. ''J Clin Pathol.'' 2003 Aug;'''56'''(8):561-8. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/12890801 12890801]</ref> |- | [[Pituitary Adenoma#Lactotroph_Adenomas_.28Prolactinomas.29|''Lactotrophic'']] (''Prolactinoma'') | [http://en.wikipedia.org/wiki/Prolactin Prolactin] | Acidophilic or chromophobic | 29% |- | [[Pituitary Adenoma#Somatotroph_Adenomas_.28Growth_Hormone_Adenomas.29|''Somatotrophic'']] | [http://en.wikipedia.org/wiki/Growth_hormone Growth hormone] (GH) | Acidophilic | 14% |- | [[Pituitary Adenoma#Corticotroph_Adenomas|''Corticotrophic'']] | [http://en.wikipedia.org/wiki/Adrenocorticotropic_hormone Adrenocorticotropic hormone] (ACTH) | Basophilic | 13% |- | [[Pituitary Adenoma#Gonadotroph_Adenomas|''Gonadotrophic'']] | [http://en.wikipedia.org/wiki/Luteinizing_hormone Luteinizing hormone] (LH), [http://en.wikipedia.org/wiki/Follicle-stimulating_hormone Follicle-stimulating hormone] (FSH) and their subunits | Basophilic | 13% |- | [[Pituitary Adenoma#Thyrotroph_Adenomas|''Thyrotrophic'']] | [http://en.wikipedia.org/wiki/Thyroid-stimulating_hormone Thyroid-stimulating hormone] (TSH) | Basophilic to chromophobic | Less than 1% |- | ''Other pituitary adenomas'' | Some multiple hormones, others are nonsecreting | <br> | 30% |} === Functional Tumors === ==== Lactotroph Adenomas (Prolactinomas) ==== ''See also [http://en.wikipedia.org/wiki/Prolactinoma Prolactinoma]'' {| border="1" class="wikitable" style="float: right;" |+ '''Table 2. Serum Prolactin Levels'''<ref name="Walsh&Hoyt" /> |- ! scope="col" | '''Condition''' ! scope="col" | '''Prolactin Level (ng/mL)''' |- | Normal Male | < 20 |- | Normal Female | < 25 |- | Pregnancy | ~200 |- | Prolactinomas | > 200 (can exceed 10,000) |} Prolactinomas are the most common type of hypersecreting pituitary adenoma. The size of these lesions varies, with women often reported to have smaller tumors than men. High prolactin levels cause [http://en.wikipedia.org/wiki/Amenorrhea amenorrhea], [http://en.wikipedia.org/wiki/Galactorrhea galactorrhea], and [http://en.wikipedia.org/wiki/Infertility infertility] in women, and [http://en.wikipedia.org/wiki/Hypogonadism hypogonadism] and [http://en.wikipedia.org/wiki/Impotence impotence] in men. Galactorrhea with amenorrhea in the setting of a prolactinoma is also called [http://en.wikipedia.org/wiki/Forbes-Albright_syndrome Forbes-Albright syndrome]. [http://en.wikipedia.org/wiki/Gynecomastia Gynecomastia] can be seen in both men and women. In adolescents, elevated prolactin levels can delay puberty. Because the symptoms in males are more subtle, pituitary adenomas tend to be detected later in males than in females.<ref name="pmid6123841">Spark RF, Wills CA, O'Reilly G, Ransil BJ, Bergland R. Hyperprolactinaemia in males with and without pituitary macroadenomas. ''Lancet.'' 1982 Jul 17;'''2'''(8290):129-32. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/6123841 6123841].</ref> Prolactinomas tend to undergo dystrophic calcification, which can appear microscopically as [http://en.wikipedia.org/wiki/Psammoma_body psammoma bodies] or encompass the entire mass ("pituitary stone").<ref name="Robbins" /> Most prolactinomas are sparsely granulated; on histology these tumor cells are weakly acidophilic or chromophobic. Rarely these cells will be strongly acidophilic and are classified as <u>densely granulated prolactinomas</u>.<ref name="Robbins" /> Other conditions can cause elevated prolactin levels, including pregnancy, medications that affect dopamine metabolism (e.g., phenothiazines, metochlorpramide, risperidone, verapamil), renal failure, and primary hypothyroidism. Other pituitary tumors can also cause elevated prolactin levels by the decrease in dopaminergic inhibition as these tumors enlarge and compress the pituitary stalk. These other conditions typically do not cause serum prolactin levels as high as those seen in prolactinomas.<ref name="Walsh&Hoyt" /> ==== Somatotroph Adenomas (Growth Hormone Adenomas) ==== Growth hormone (GH)-secreting adenomas are the second most common type of hypersecreting pituitary adenomas. They tend to be large at time of clinical diagnosis due to the subtle manifestations of excess growth hormone. Somatotrophic adenomas have more obvious signs in children, who may develop physical features that may lead to earlier detection. Many of the features of GH-secreting adenomas are related to the stimulation of [http://en.wikipedia.org/wiki/Insulin-like_growth_factor_1 insulin-like growth factor I] (IGF-I or somatomedin C) by the liver in response to excess growth hormone.<ref name="pmid21546764" /> GH-secreting adenomas can be either densely-granulated or sparsely granulated and share features similar to prolactinomas on hematoxylin-eosin staining. The densely-granulated adenomas are acidophilic, whereas the sparsely granulated adenomas are weakly acidophilic or chromophobic.<ref name="Robbins" /> ===== Gigantism ===== In children who have epiphyses that have not yet closed, GH and IGF-I cause '''<u>[http://en.wikipedia.org/wiki/Gigantism gigantism]</u>'''. Gigantism presents as a generalized increase in body size with disproportionately long arms and legs.<ref name="Robbins" /> ===== Acromegaly ===== If the epiphyses have closed (i.e., late adolescence and adulthood), the result is '''<u>[http://en.wikipedia.org/wiki/Acromegaly acromegaly]</u>'''. The features of acromegaly include characteristic coarsening of facial features (thick lips, exaggerated nasolabial folds, prominent supraorbital ridges, jaw enlargement), enlarged hands and feet, [http://en.wikipedia.org/wiki/Hirsuitism hirsuitism], and joint hypertrophy.<ref name="Kanski" /><ref name="Walsh&Hoyt" /> Skin manifestations include sweating, pigmented skin tags, [http://en.wikipedia.org/wiki/Acanthosis_nigricans acanthosis nigricans] and [http://en.wikipedia.org/wiki/Cutis_verticis_gyrata cutis verticis gyrata].<ref name="pmid3308190">Nabarro JD. Acromegaly. ''Clin Endocrinol (Oxf).'' 1987 Apr;'''26'''(4):481-512. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/3308190 3308190].</ref> ===== Complications ===== There are many complications associated with excess growth hormone, including:<ref name="Robbins" /><ref name="Kanski" /><ref name="Walsh&Hoyt" /> *[http://en.wikipedia.org/wiki/Carpal_tunnel_syndrome Carpal tunnel syndrome] *Proximal myopathy *Gonadal dysfunction *Respiratory disease *[http://en.wikipedia.org/wiki/Diabetes_mellitus Diabetes mellitus], which is related to the effect of growth hormone on insulin receptors *[http://en.wikipedia.org/wiki/Muscle_weakness Generalized muscle weakness] *[http://en.wikipedia.org/wiki/Hypertension Hypertension] *[http://en.wikipedia.org/wiki/Arthritis Arthritis] *[http://en.wikipedia.org/wiki/Congestive_heart_failure Congestive heart failure] *[http://en.wikipedia.org/wiki/Cardiomyopathy Cardiomyopathy] *Increased risk of [http://en.wikipedia.org/wiki/Gastrointestinal_cancer gastrointestinal cancers] ==== Corticotroph Adenomas ==== Corticotroph adenomas secrete [http://en.wikipedia.org/wiki/Adrenocorticotropic_hormone adrenocorticotropic hormone] (ACTH), which triggers the adrenal glands to secrete [http://en.wikipedia.org/wiki/Cortisol cortisol]. The densely granulated variant is more common and is usually basophilic, and the sparsely granulated variant is chromophobic. These tumors stain positively with [http://en.wikipedia.org/wiki/Periodic_acid-Schiff_stain periodic acid-Schiff] (PAS) because of the carbohydrates present in pre-opiomelanocorticotropin (POMC), the precursor molecule to ACTH. Most ACTH-secreting pituitary adenomas are small, with detection of the tumor earlier due to the significant systemic changes. Secondary adrenal hyperplasia often occurs due to the elevated ACTH levels.<ref name="pmid10997535">Kirk LF Jr, Hash RB, Katner HP, Jones T. Cushing's Disease: Clinical Manifestations and Diagnostic Evaluation. ''Am Fam Physician.'' 2000 Sep 1;'''62'''(5):1119-27, 1133-4. [http://www.aafp.org/link_out?pmid=10997535 Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/10997535 10997535].</ref> The elevated levels of serum cortisol lead to a constellation of signs and symptoms that is known as Cushing Syndrome. ===== Cushing Syndrome (Hypercortisolism) ===== ''See also [http://en.wikipedia.org/wiki/Cushing%27s_syndrome Cushing syndrome]'' '''Cushing syndrome''' describes the assortment of physiologic changes that occurs with elevated serum cortisol levels. Cortisol and other [http://en.wikipedia.org/wiki/Glucocorticoid glucocorticoids] have many systemic effects, which include [http://en.wikipedia.org/wiki/Immunosuppression immunosuppression], [http://en.wikipedia.org/wiki/Diabetes_mellitus diabetes] due to increased [http://en.wikipedia.org/wiki/Gluconeogenesis gluconeogenesis], [http://en.wikipedia.org/wiki/Hypertension hypertension] caused by partial [http://en.wikipedia.org/wiki/Mineralocorticoid mineralocorticoid] effects, [http://en.wikipedia.org/wiki/Osteoporosis osteoporosis] from inhibition of bone formation and calcium resorption, elevated [http://en.wikipedia.org/wiki/Intraocular_pressure intraocular pressure] (IOP), among many others.<ref name="pmid22403201">Guaraldi F, Salvatori R. Cushing syndrome: maybe not so uncommon of an endocrine disease. ''J Am Board Fam Med.'' 2012 Mar;'''25'''(2):199-208. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.3122/jabfm.2012.02.110227 10.3122/jabfm.2012.02.110227]. [http://www.jabfm.org/cgi/pmidlookup?view=long&pmid=22403201 Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/22403201 22403201].</ref> Cushing syndrome can result from both exogenous and/or endogenous sources, which makes the diagnostic workup of a patient presenting with Cushing syndrome very challenging. Hypercortisolism now most commonly results as a result of iatrogenic therapeutic modalities. While a majority of patients with endogenous Cushing syndrome have thyrotrophic adenomas (called '''Cushing Disease''' - see below), other tumors should also be considered as part of the endocrinologic workup, including adrenal tumors and especially ACTH-secreting [http://en.wikipedia.org/wiki/Small-cell_carcinoma small cell carcinoma of the lung].<ref name="Walsh&Hoyt" /> ===== Cushing Disease ===== '''Cushing disease''' is a subset of Cushing syndrome that is caused by excess production of ACTH from a corticotroph adenoma. Various studies report that pituitary adenomas account for anywhere from 66% to 80% of endogenous Cushing syndrome cases.<ref name="pmid10997535" /><ref name="pmid22403201" /> ===== Nelson Syndrome ===== Nelson syndrome describes the enlargement of an ACTH-secreting pituitary adenoma following surgical removal of the adrenal glands for treating Cushing syndrome. The adenoma grows precipitously because of the removal of the feedback inhibition of adrenal corticosteroids on the pituitary tissue. Hypercortisolism is not present because of the absence of the adrenal glands. Patients will complain of symptoms consistent with the mass effects of a pituitary tumor. They may also develop hyperpigmentation, which occurs due to the stimulation of melanocytes by POMC. Nelson syndrome does not occur as often now that neuroimaging techniques are better and more easily available.<ref name="Walsh&Hoyt" /> ==== Gonadotroph Adenomas ==== Gonadotrophic adenomas secrete lutenizing hormone (LH) and follicle-stimulating hormone (FSH). They are variable in their secretion, and often do not cause clinical symptoms related to their hormone products. As such, they tend to become symptomatic when they grow large enough to cause the associated neurological symptoms of pituitary tumors. These tumors can also have decreased pituitary hormones, most commonly related to decreased LH. LH deficiency is manifested by decreased energy and libido in men due to decreased testosterone levels, and amenorrhea in premenopausal women. Most gonadotrophic adenomas contain chromophobic cells that react to common gonadotropin α-subunit and β-FSH and β-LH subunits, with FSH being the predominantly secreted hormone. ==== Thyrotroph Adenomas ==== Thyrotrophic adenomas are one of the rarest types of secreting pituitary adenomas. Thyrotropin, or thyroid-stimulating hormone (TSH) is secreted by the pituitary gland and induces the thyroid gland to produce thyroid hormone (thyroxine). Thyrotrophic adenomas will usually induce a hyperthyroid state due to the high levels of TSH. These tumors tend to be large and invade adjoining structures, which can cause visual field defects. Because this is not an autoimmune process, the hyperthyroid state induced by these adenomas is not associated with thyroid eye disease. === Nonfunctional tumors === Truly nonsecreting pituitary adenomas are also rare; however many adenomas, particularly gonadotrophic adenomas most commonly, are clinically nonfunctional.<ref name="pmid18684022" /> Other examples of such "endocrine-inactive" tumors include null cell tumors, oncocytomas, glycopeptide-secreting corticotropin-secreting tumors, and silent corticotropin-secreting tumors. Of historical note, the term "chromophobe" was previously used to describe these nonsecreting tumors due to the lack of cytoplasmic granules seen on light microscopy.<ref name="Walsh&Hoyt" /> === Incidentalomas === Pituitary "incidentalomas" are lesions of any kind found in the pituitary on imaging performed for a different purpose. Most incidentalomas are adenomas, and are not uncommon. Microincidentalomas (<1 cm) have been reported to be more common than macroincidentalomas (4-20% vs. 0.2% on CT, 10-38% vs. 0.16% on MRI, respectively).<ref name="pmid21474686">Freda PU, Beckers AM, Katznelson L, Molitch ME, Montori VM, Post KD, Vance ML. Pituitary Incidentaloma: An Endocrine Society Clinical Practice Guideline. ''J Clin Endocrinol Metab.'' 2011 Apr;'''96'''(4):894-904. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1210/jc.2010-1048 10.1210/jc.2010-1048]. [http://jcem.endojournals.org/content/96/4/894.long Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21474686 21474686].</ref> Most of these tumors tend to remain indolent and only rarely cause pituitary apoplexy, worsening visual fields, or new endocrine dysfunction.<ref name="pmid21474687">Fernández-Balsells MM, Murad MH, Barwise A, Gallegos-Orozco JF, Paul A, Lane MA, Lampropulos JF, Natividad I, Perestelo-Pérez L, Ponce de León-Lovatón PG, Erwin PJ, Carey J, Montori VM. Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis. ''J Clin Endocrinol Metab.'' 2011 Apr;'''96'''(4):905-12.[http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1210/jc.2010-1054 10.1210/jc.2010-1054]. [http://jcem.endojournals.org/content/96/4/905.long Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21474687 21474687].</ref> = Diagnosis = == History == Patients with pituitary adenomas have a variable history, dependent on the functional (secretory) status of the tumor, its size, and any mass effect. As discussed above, a significant portion of pituitary adenomas are asymptomatic or indolent, leading their discovery to be incidental. Adenomas that have subtle features, such as hypotestosteronism, may also lead to a delay in discovery. A detailed review of systems focusing on endocrinologic and constitutional symptoms may guide the diagnosis. Patients with secretory tumors may have systemic complaints that are associated with their corresponding hormonal imbalance. Most ophthalmologic complaints are secondary to mass effects caused by macroadenomas. Together many of these symptoms form the so-called '''"chiasmal syndrome"''', which applies to any compressive lesion on the chiasm.<ref name="pmid7490416">Trevino R. Chiasmal Syndrome. ''J Am Optom Assoc.'' 1995 Sep;'''66'''(9):559-75. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/7490416 7490416].</ref> === Headache === Headaches are one of the most common symptoms reported in pituitary adenomas, with a reported incidence of 45%. These headaces are often localized to the brow or periorbital region.<ref name="pmid7490416" /> === Decreased Vision === Pituitary adenomas that compress on the chiasm can often produce a slow decrease in visual function. This may present either as decreased central acuity or as a loss in peripheral visual fields.<ref name="pmid7490416" /> ==== Loss of Peripheral Vision ==== Often patients are unaware of peripheral field loss; directed questions towards functional changes such as increased rate of car accidents due to being unaware of cars approaching in the periphery, etc., may alert the clinician to a visual field deficit. ==== Loss of Depth Perception ==== Some patients with complete bitemporal hemianopsia will complain of a complete loss of depth perception. This has been termed "post-fixational blindness", and is caused by the two blind temporal hemifields overlapping during convergence. The result is a completely blind region of the patient's vision at the point of fixation. Patients will often complain that they have trouble with anteroposterior tasks such as cutting fingernails, threading needles, and working with precision tools.<ref name="pmid7490416" /> === Diplopia === Diplopia may be due to cranial nerve paresis from lateral extension of tumors into the cavernous sinus, or as a result of "hemifield slide" (described below). The diplopia is binocular (only present when both eyes are open), and can have horizontal, vertical, or torsional components depending on the affected cranial nerve(s). The diplopia may be present constantly or intermittently.<ref name="Yanoff" /><ref name="pmid7490416" /> ==== Extraocular Muscle Paresis ==== As described above, extraocular muscle paresis is a rare presentation (~5% of patients with pituitary adenoma) most often associated with a concurrent palsy of the corresponding cranial nerve. Tumor extension into the cavernous sinus can affect cranial nerves III, IV, V, or VI and produce a limited or total [[Cavernous sinus syndrome]]. Of the cranial nerves, cranial nerve III (oculomotor nerve) is most commonly affected with variable involvement of pupillomotor fibers. Extraocular muscle paresis may also suggest [[Pituitary apoplexy]], which must considered in the setting of rapidly progressive vision loss and diplopia.<ref name="pmid7490416" /> ==== Hemifield Slide ==== Diplopia may occur as the result of a loss in the physiologic linkage between the two functioning hemifields, termed "hemifield slide phenomenon" by Kirkham in 1972.<ref name="pmid5035898">Kirkham TH. The ocular symptomatology of pituitary tumours. ''Proc R Soc Med.'' 1972 Jun;'''65'''(6):517-8. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/5035898 5035898].</ref> This binocular diplopia occurs in the presence of intact ocular motility. While the exact pathophysiology is not completely understood, it is hypothesized that when the degree of overlap between one eye's temporal visual field and the contralateral eye's nasal visual field decreases to a certain point, the brain is unable to maintain fusion.<ref name="Walsh&Hoyt" /> This can occur with vertical hemifield defects such as those seen in pituitary adenomas, as well as altitudinal hemifield defects from optic nerve disease.<ref name="pmid8797166">Borchert MS, Lessell S, Hoyt WF. Hemifield slide diplopia from altitudinal visual field defects. ''J Neuroophthalmol.'' 1996 Jun;'''16'''(2):107-9. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/8797166 8797166].</ref> Patients may experience overlapping images or divergent images corresponding to esodeviation, exodeviation, or hyperdeviation.<ref name="pmid5035898" /> == Physical examination == === Findings associated with endocrine disturbance === While there may be many subtle or obvious signs of endocrine disturbance, description of these signs is beyond the scope of this discussion. For further information, please see the [http://eyewiki.aao.org/Pituitary_Adenoma#Additional_Resources additional resources section] at the end of this article. === Visual Field Deficits === Visual field defects are caused by tumor compression on the optic nerve or chiasm leading to axonal damage. Depending on the size and location of the tumor, as well as the anatomical relationship of the chiasm to the pituitary stalk, the severity and symmetry of the visual field defect may vary. Testing strategies for visual fields are discussed below. ==== Monocular Visual Field Deficits ==== Asymmetric tumors may preferentially involve one side of the chiasm or an optic nerve, and most commonly presents as a supertemporal quadrantanopsia. The incidence of pituitary adenomas presenting as monocular visual field defects was reported to be 9% (in a series of 1,000 patients). If the presenting symptom is sudden monocular visual loss, a pituitary adenoma may be acutely missed, as other more common etiologies are evaluated. Another consideration for sudden monocular visual loss is pituitary apoplexy, though visual field evaluation is often deferred due to the emergent nature of this condition. Monocular temporal hemianopias are not always indicative of a pituitary tumor. These defects, especially in the setting of no [[Relative afferent pupillary defect]] or optic atrophy, may suggest functional (nonorganic) vision loss. Functional vision loss in the setting of a monocular temporal hemianopsia can be confirmed by the persistence of the temporal hemianopia on binocular visual field testing.<ref name="Walsh&Hoyt" /> ==== Chiasmal Field Deficits ==== Characteristically lesions at the level of the optic chiasm produce a bitemporal hemianopia. Pituitary adenomas, which grow upward from the pituitary stalk, compress the chiasm from below, which preferentially involves the inferior, nasal, and macular nerve fibers. This corresponds to superior, bitemporal, and central vision loss. While these field defects typically respect the vertical midline, pituitary adenomas large enough to cause compression tend to also reduce visual acuity and cause diffuse central depression on automated and Goldmann perimetry.<ref name="Walsh&Hoyt" /> In prefixed chiasms or tumors that preferentially grow posteriorly, selective compression of macular fibers may cause a bitemporal hemianopsia involving the central visual field while sparing the peripheral field.<ref name="pmid17004853">Chiu EK, Nichols JW. Sellar lesions and visual loss: key concepts in neuro-ophthalmology. ''Expert Rev Anticancer Ther.'' 2006 Sep;'''6'''(Suppl 9):S23-8. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/17004853 17004853].</ref> ==== Junctional Field Deficits ==== The phenomenon of a central scotoma in one eye with temporal visual field loss in the other eye has been termed a junctional scotoma. The anatomical correlate to this visual field pattern has been suggested by some as compression to an anterior loop to the decussating nasal fibers within the posterior optic nerve. This explanation, called "Wilbrand's knee," is debated within the literature; regardless of the cause, multiple studies have proven that this visual field phenomenon localizes the lesion to the anterior chiasm and posterior optic nerve. While junctional field defects have been the presenting sign of pituitary adenomas, it is more commonly seen in other etiologies (meningioma, aneurysm, inflammation).<ref name="Walsh&Hoyt" /> === Optic Atrophy === Chronic tumor compression can lead to optic atrophy. Some atrophy is reported to be present in approximately 50% of pituitary lesions with visual field defects. If only the fibers nasal to the macula are damaged (due to medial compression of the chiasm or posterior optic nerve), only the nasal and temporal optic disc may be atrophic, often described a "bow-tie" or "band-shaped" pattern.<ref name="Kanski" /> === Papilledema === [[Papilledema]] is a rare finding in pituitary adenomas. The slow-growing nature of these tumors tends to cause optic atrophy before the tumor enlarges sufficiently to increase [http://en.wikipedia.org/wiki/Intracranial_pressure intracranial pressure] (ICP). Growth hormone-secreting adenomas can increase ICP in a fashion similar to those in children taking growth hormone for short stature or patients with Turner syndrome who develop [[idiopathic intracranial hypertension]]. Asymmetric tumor growth can rarely cause the [[Foster-Kennedy syndrome]]. Bilateral hypertensive papillopathy in the setting of Cushing's disease may mimic papilledema.<ref name="Walsh&Hoyt" /> === Nystagmus === Chiasmal lesions of any kind can be associated with [[seesaw nystagmus]], an extremely rare form of nystagmus in which one eye elevates and intorts while the other eye synchronously depresses and extorts, then alternates. The exact pathophysiology of this phenomenon is unknown; however, as most of these lesions involve the chiasm and/or diencephalon, many have proposed that disruption of visual and vestibular input contribute to this pathology. Several case studies have shown that children born without a chiasm and lesions that do not affect the chiasm or diencephalon can also cause see-saw nystagmus; tumor resection can sometimes result in resolution of nystagmus.<ref name="BCSC Neuro" /><ref name="Walsh&Hoyt" /><ref name="pmid16622572" /><ref name="pmid5298192">Drachman DA. See-saw nystagmus. ''J Neurol Neurosurg Psychiatry.'' 1966 Aug;'''29'''(4):356-61. [http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/5298192/ Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/5298192 5298192].</ref> == Diagnostic procedures == === Visual Field Testing === Automated static perimetry or kinetic perimetry are used to formally assess visual fields. In an undiagnosed patient with a history suspicious for pituitary disease, this often confirms the presence of a compressive chiasmal lesion. Visual fields are also commonly documented prior and following neurosurgical intervention. [[Image:BitemporalHemianopsiaVFOS.jpg|250px]][[Image:BitemporalHemianopsiaVFOD.jpg|250px]] '''Figure 1.''' Humphrey visual field 24-2 showing a bitemporal hemianopsia.<br> [[Image:BitemporalHemianopsiaVFGoldmann.gif|500px]] '''Figure 2.''' Goldmann visual field showing a bitemporal hemianopsia.<ref name="pmid16622572">Moura FC, Gonçalves AC, Monteiro ML. Seesaw nystagmus caused by giant pituitary adenoma: case report. ''Arq Neuropsiquiatr.'' 2006 Mar;'''64'''(1):139-41. Epub 2006 Apr 5. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1590/S0004-282X2006000100030 10.1590/S0004-282X2006000100030]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/16622572 16622572].</ref> === Neuroimaging === The pituitary gland is best seen on coronal sections and normally enhances with contrast. As with any radiographic study, detailed communication with the radiologist/neuroradiologist will help guide the appropriate study as well as careful examination of the images. MRIs are the study of choice for most sellar and parasellar lesions, but high-resolution CTs with fine cuts (1.5-3 mm) have also been shown to be very helpful.<ref name="Yanoff" /> ==== Computed Tomography (CT) ==== Microadenomas may present as less-enhancing lesions within the substance of the pituitary gland, whereas macroadenomas are more variable in their appearance. Bone window scans help assess erosions and extensions into the sphenoid sinus.<ref name="Dutton">Dutton, JJ. ''Radiology of the Orbit and Visual Pathways.'' Elsevier; 2010:340-341. [http://en.wikipedia.org/wiki/International_Standard_Book_Number ISBN] [http://www.amazon.com/s?search-alias=stripbooks&field-isbn=9781437711516 978-1-4377-1151-6].</ref> ==== Magnetic Resonance Imaging (MRI) ==== [[Image:PituitaryAdenoma.JPG|border|right|150x150px|T1 Coronal MRI]]Microadenomas are best seen on unenhanced T1-weighted coronal or sagittal scans. They are seen as hypointense areas within the substance of the relatively hyperintense pituitary gland. With gadolinium contrast these lesions will remain less intense compared to the normal gland and will enhance late. On T2-weighted images, the adenoma is more indistinct, as it appears isointense or only slightly hyperintense in comparison with the surrounding gland.<ref name="Dutton" /> Macroadenomas are more obviously seen, as they extend beyond the anatomical borders of the sella. The homogenicity of the images suggests the relative solidity of the tumor. Nonsolid tumors (macrocystic and macrohemorrhagic) have been suggested to be more effectively managed with transsphenoidal hypophysectomy in comparison with solid tumors.<ref name="pmid20729452">Boxerman JL, Rogg JM, Donahue JE, Machan JT, Goldman MA, Doberstein CE. Preoperative MRI evaluation of pituitary macroadenoma: imaging features predictive of successful transsphenoidal surgery. ''AJR Am J Roentgenol.'' 2010 Sep;'''195'''(3):720-8. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.2214/AJR.09.4128 10.2214/AJR.09.4128]. [http://www.ajronline.org/content/195/3/720.long Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/20729452 20729452].</ref> == Laboratory testing == An endocrine workup is important for determining the functional status of a pituitary adenoma. This is often performed with the guidance of an endocrinologist. The laboratory tests may vary depending on the clinical presentation. One of the most sensitive tests for acromegaly is the failure to suppress GH production in a response to an oral load of glucose.<ref name="Robbins" /> == Differential diagnosis == Of all conditions causing the chiasmal syndrome, pituitary adenomas are the most common (50-55%). Some other causes of the chiasmal syndrome are listed below:<ref name="pmid7490416" /> === Compressive Lesions === *[[Craniopharyngioma]] (20-25%) *[[Meningioma]] (10%) *[[Glioma]] (7%) *Dysgerminoma *Aneurysms (internal carotid artery, middle or anterior cerebral artery, or anterior communicating artery) *Mucocele *Abscess from an intracranial infection *Lymphocytic hypophysitis *Metastatic disease *Arachnoidal and epithelial cysts === Ischemic Lesions === *[[Pituitary apoplexy]] *Radionecrosis *Arteritis *Arteriosclerosis === Inflammatory Lesions === *[[Multiple sclerosis]] *[[Sarcoidosis]] *[[Tuberculosis]] === Toxic Lesions === *Pheniprazine (Catron) *Muslin gauze *Ethchlorvynol (Placidyl) = Management = Management of pituitary adenomas depends on the size of the tumor, its secretory function (as well as what type of hormone is secreted), and its impact on the patient's vision. Goals of treatment include visual recovery/preservation, reversal of hypersecretory syndromes, and control of tumor growth.<ref name="Walsh&Hoyt" /> While some forms of pituitary adenoma can be managed medically, most pituitary adenomas that have demonstrable visual field loss are treated surgically. Radiation therapy (external beam or gamma-knife) is considered a second-line treatment. == General Approach == Medical and surgical management of pituitary adenomas require a multidisciplinary team. Ophthalmology is typically consulted to evaluate the patient's visual fields. Less commonly, ophthalmologists may be the first to detect evidence of a pituitary adenoma. Standard automated perimetry is often utilized by ophthalmologists and pituitary surgeons to document indication and follow progression of visual involvement. Endocrinology is often involved to help evaluate hormonal levels and guide medical management. Surgical debulking of pituitary tumors is often performed by otorhinolaryngology (ENT) or neurosurgery.<ref name="pmid21879656">Malenković V, Gvozdenović L, Milaković B, Sabljak V, Ladjević N, Zivaljević V. Preoperative preparation of patients with pituitary gland disorders. ''Acta Chir Iugosl.'' 2011;'''58'''(2):91-6. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21879656 21879656].</ref> == Medical therapy == === Prolactinomas === Medical treatment is considered the primary treatment for prolactinomas. Dopamine agonists (e.g., bromocriptine or cabergoline) have been shown to normalize hyperprolactinemia as well as shrink tumors. Management of prolactinomas is often in conjunction with an endocrinologist in regards to medication administration and decisions regarding indication for surgical resection.<ref name="Walsh&Hoyt" /> While both medications have similar mechanisms of action, the other medication may be tried if there is a minimal response from the first drug. [http://en.wikipedia.org/wiki/Bromocriptine Bromocriptine] is the first-line agent used in treating prolactinomas and suppresses prolactin secretion by binding to D2 dopamine receptors. Because it has been used for over 25 years, it is the recommended medication for use in treatment of pituitary adenomas in pregnancy. Side effects are three times more frequent in bromocriptine compared with cabergoline, which may include gastrointestinal, cardiovascular, or neurological symptoms.<ref name="pmid16932285">Colao A, Di Sarno A, Guerra E, De Leo M, Mentone A, Lombardi G. Drug insight: Cabergoline and bromocriptine in the treatment of hyperprolactinemia in men and women. ''Nat Clin Pract Endocrinol Metab.'' 2006 Apr;'''2'''(4):200-10. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/16932285 16932285].</ref> [http://en.wikipedia.org/wiki/Cabergoline Cabergoline] is a newer medication that also binds to D2 dopamine receptors. It has a smaller incidence of side effects when compared to bromocriptine, and various studies suggest that it has a comparable effect of normalizing hyperprolactinemia and shrinking tumor size.<ref name="pmid18812485">Ono M, Miki N, Kawamata T, Makino R, Amano K, Seki T, Kubo O, Hori T, Takano K. Prospective study of high-dose cabergoline treatment of prolactinomas in 150 patients. ''J Clin Endocrinol Metab.'' 2008 Dec;'''93'''(12):4721-7. Epub 2008 Sep 23. [http://jcem.endojournals.org/cgi/pmidlookup?view=long&pmid=18812485 Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/18812485 18812485].</ref> === Acromegaly === Somatostatin analogs ([http://en.wikipedia.org/wiki/Octreotide octreotide], lanreotide), bromocriptine, and growth hormone receptor agonists (pegvisomant) have been used to treat growth hormone-secreting tumors causing acromegaly. Octreotide has the most effect on tumor shrinkage, and pegvisomant has no effect on tumor size or growth hormone secretion but may have better effect on the overall systemic effects of elevated growth hormone.<ref name="Walsh&Hoyt" /> === Thyrotrophic adenomas === Thyrotrophic tumors can be treated with octreotide due to the presence of somatostatin receptors on the tumor.<ref name="Walsh&Hoyt" /> It is successful at decreasing levels of thyroid-stimulating hormone (TSH), and normalizes hyperthyroidism in around 75%. Octreotide can shrink thyrotropin-secreting tumors in a third of reported cases.<ref name="pmid8323093">Chanson P, Weintraub BD, Harris AG. Octreotide therapy for thyroid-stimulating hormone-secreting pituitary adenomas. A follow-up of 52 patients. ''Ann Intern Med.'' 1993 Aug 1;'''119'''(3):236-40. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/8323093 8323093].</ref> == Surgery == Pituitary adenoma debulking, or partial excision, is often carried out via transfrontal, transsphenoidal, or transpterional approaches.<ref name="pmid21933555">Liu L, Liu ZX, Liu YS, Liu JF, Zeng Y, Zeng ZC, Wang M, Wang H, Zeng CM, Jiang XJ, Chen X, Yang SG. Applied anatomy for pituitary adenoma resection. ''Chin Med J (Engl).'' 2011 Aug;'''124'''(15):2269-74. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21933555 21933555].</ref> Endoscopic techniques have improved visualization of the tumor and allowed for smaller incisions and faster healing.<ref name="pmid22036116">Rosseau GL. Pituitary tumors and transsphenoidal surgery. ''Dis Mon.'' 2011 Oct;'''57'''(10):607-14. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/22036116 22036116].</ref><ref name="pmid22252670">DeKlotz TR, Chia SH, Lu W, Makambi KH, Aulisi E, Deeb Z. Meta-analysis of endoscopic versus sublabial pituitary surgery. ''Laryngoscope.'' 2012 Mar;'''122'''(3):511-8. Epub 2012 Jan 17. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.1002/lary.22479 10.1002/lary.22479]. [http://dx.doi.org/10.1002/lary.22479 Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/22252670 22252670].</ref> === Surgical Indications === The following are some of the indications for surgical debulking of a pituitary adenoma:<ref name="pmid18166812">Kreutzer J, Buslei R, Wallaschofski H, Hofmann B, Nimsky C, Fahlbusch R, Buchfelder M. Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients. ''Eur J Endocrinol.'' 2008 Jan;'''158'''(1):11-8. [http://eje-online.org/cgi/pmidlookup?view=long&pmid=18166812 Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/18166812 18166812].</ref><ref name="pmid21839965">Müslüman AM, Cansever T, Yılmaz A, Kanat A, Oba E, Çavuşoğlu H, Sirinoğlu D, Aydın Y. Surgical results of large and giant pituitary adenomas with special consideration of ophthalmologic outcomes. ''World Neurosurg.'' 2011 Jul-Aug;'''76'''(1-2):141-8; discussion 63-6. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21839965 21839965].</ref><ref name="pmid21845568">Ceylan S, Anik I, Koc K. A new endoscopic surgical classification and invasion criteria for pituitary adenomas involving the cavernous sinus. ''Turk Neurosurg.'' 2011;'''21'''(3):330-9. [http://en.wikipedia.org/wiki/Digital_object_identifier doi]:[http://dx.doi.org/10.5137/1019-5149.JTN.4149-11.0 10.5137/1019-5149.JTN.4149-11.0]. [http://www.turkishneurosurgery.org.tr/pubmed.php3?year=2011&volume=21&issue=3&page=330 Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21845568 21845568].</ref> *Patients with prolactinomas who cannot tolerate the side effects from dopaminergic agonist therapy *Patients with prolactinomas who had no tumor shrinkage with dopaminergic agonist therapy *Patients with prolactinomas who decided on primary surgical excision *Patients with prolactinomas who had cystic features on MRI (80% of tumor volume on T2 sequences) that were unlikely to shrink sufficiently with medical management alone *Patients with cavernous sinus involvement *Patients with pituitary apoplexy === Surgical Outcomes === Surgical debulking in a timely fashion (within 6 months of onset of visual symptoms) has been shown to normalize or improve visual acuity as well as improve visual field with rare worsening or severe surgical complication.<ref name="pmid21839965" /> The outcome is affected by the severity of symptoms - for example, sudden ophthalmoplegia due to pituitary apoplexy would have a different result than a slow-growing prolactinoma.<ref name="pmid21920756">Chuang CC, Chen E, Huang YC, Tu PH, Chen YL, Pai PC. Surgical outcome of oculomotor nerve palsy in pituitary adenoma. ''J Clin Neurosci.'' 2011 Nov;'''18'''(11):1463-8. Epub 2011 Sep 14. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21920756 21920756].</ref> == Follow up == === No Ophthalmologic Involvement/No Surgery/Medical Therapy === Patients with pituitary adenomas will follow with ophthalmology up to several times a year with repeated visual fields to evaluate for presence/progression of visual field defects to guide medical and surgical treatment. Indications for surgical intervention are discussed above. === Postoperative Follow Up === Because pituitary adenomas are incompletely excised, recurrence is an important consideration and reason for continued screening following surgical treatment. The first sign of recurrence may be visual loss; therefore, baseline visual fields and visual acuity testing are recommended 2-3 months after treatment and at intervals of 6-12 months afterwards.<ref name="BCSC Neuro" /> Periodic neuroimaging is also essential, as recurrence may occur even as late as 10 years post-surgery.<ref name="pmid21900406">Reddy R, Cudlip S, Byrne JV, Karavitaki N, Wass JA. Can we ever stop imaging in surgically treated and radiotherapy-naive patients with non-functioning pituitary adenoma? ''Eur J Endocrinol.'' 2011 Nov;'''165'''(5):739-44. Epub 2011 Sep 7. [http://eje-online.org/cgi/pmidlookup?view=long&pmid=21900406 Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [http://www.ncbi.nlm.nih.gov/pubmed/21900406 21900406].</ref> == Complications == === Pituitary Apoplexy === ''See also [http://en.wikipedia.org/wiki/Pituitary_apoplexy pituitary apoplexy] on wikipedia'' Pituitary apoplexy is a life-threatening complication of pituitary adenoma caused by a sudden hemorrhage or infarction of the tumor. It is characterized by the presentation of severe headache, nausea, and altered consciousness. Sudden expansion of the pituitary mass into the cavernous sinus can cause sudden ophthalmoplegia and facial hypoesthesia due to compression of cranial nerves III, IV, V, and VI, with cranial nerve III being affected most commonly. Superior extension of the pituitary mass can cause sudden vision loss or visual field loss. Patients can have decreased consciousness or strokes from extravasation of blood into the subarachnoid space. The life-threatening emergency associated with pituitary apoplexy is adrenal crisis, as well as other acute endocrine abnormalities. The diagnosis is confirmed by MRI. Because this condition is a true emergency, corticosteroids have to be started immediately and severe cases have to be taken to the operating room for emergent surgical decompression of the sella.<ref name="BCSC Neuro" /> === Tumor Recurrence === Pituitary adenomas often recur following resection. Nonfunctioning adenomas are less likely to enter remission following surgical treatment than functioning adenomas. Recurrence of tumor is most likely to occur between 1-5 years following surgery, with prolactinomas having the highest incidence of recurrence. Having a high basal hormonal level postoperatively was predictive of recurrence in functional adenomas, but there are no known predictive factors for recurrence in nonfunctioning adenomas.<ref name="pmid21918830">Roelfsema F, Biermasz NR, Pereira AM. Clinical factors involved in the recurrence of pituitary adenomas after surgical remission: a structured review and meta-analysis. ''Pituitary.'' 2012 Mar;'''15'''(1):71-83. [http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21918830/ Available online]. [http://en.wikipedia.org/wiki/PubMed_Identifier PMID] [https://www.ncbi.nlm.nih.gov/pubmed/21918830 21918830].</ref> It was found that recurrence rates can be decreased with a combination treatment of surgery and radiotherapy (from 7-35% to 7-13%).<ref name="Walsh&Hoyt" /> === Secondary Empty Sella === Following surgical excision of a pituitary adenoma, the sella can remain radiographically "empty." The chiasm can herniate into this space, causing visual loss. Treatments are often geared towards decreasing the traction on the chiasm surgically or by decreasing medical therapy and allowing the tumor to regrow.<ref name="Walsh&Hoyt" /> === Other Complications === Other complications associated with pituitary adenomas include delayed radionecrosis if radiotherapy was performed, chiasmal traction from adhesions, and chiasmal compression from expansion of fat.<ref name="BCSC Neuro" /> == Prognosis == Visual recovery following treatment of pituitary adenomas is largely dependent on pre-treatment visual acuity/visual fields/etc., age of patient, duration of symptoms, severity of visual defects, presence of optic atrophy, and size of the tumor. The timeframe of recovery ranges from early (within 24 hours after surgery, between 24-72 hours after starting medical therapy) to late (6 months to 3 years). Most improvement takes place between 1-4 months. Most patients show improvement of visual acuity, visual fields, or both following surgical treatment. Patients undergoing radiation therapy tend to have a slower recovery and time to improvement.<ref name="Walsh&Hoyt" /> = Additional Resources = #''Neuro-Ophthalmology.'' Basic and Clinical Science Course, Section 5. American Academy of Ophthalmology; 2010:159-165. #Gittinger JW. "Tumors of the Pituitary Gland." In: Miller NR, Newman NJ, eds. ''Walsh and Hoyt's Clinical Neuro-Ophthalmology, 6th Ed.'' Volume Two. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:1531-1546. #Yanoff M, Duker JS. ''Ophthalmology, 3rd Ed.'' Elsevier; 2009:986-994. #Kanski JJ, Bowling B. ''Clinical Ophthalmology: A Systematic Approach, 7th Ed.'' Elsevier; 2011:816-827. #[http://en.wikipedia.org/wiki/Pituitary_adenoma Pituitary adenoma] article on [http://en.wikipedia.org Wikipedia] = References = <references /> Please note that all contributions to EyeWiki may be edited, altered, or removed by other contributors. If you do not want your writing to be edited mercilessly, then do not submit it. 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