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Pituitary Incidentaloma:An Endocrine Society Clinical Practice Guideline

T h e E n d o c r i n e S o c i e t y s

CLINICAL GUIDELINES


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Authors: Pamela U. Freda, Albert M. Beckers, Laurence Katznelson, Mark E. Molitch, Victor M. Montori, KalmonD. Post, and Mary Lee Vance

Co-Sponsoring Associations: European Society of Endocrinology.

Afliations: Columbia College of Physicians & Surgeons (P.U.F.) New York, New York; CHU de Lige,Universityof Lige Domaine Universitaire du Sart-Tilman (A.M.B.) Lige, Belgium; Stanford University (L.K.) Stanford,California; Northwestern University Feinberg School of Medicine (M.E.M.) Chicago, Illinois; Mayo ClinicRochester (V.M.M.), Rochester, Minnesota; Mount Sinai Medical Center (K.D.P.) New York, New York; andUniversity of Virginia Health Science Center (M.L.V.) Charlottesville, Virginia

Disclaimer: Clinical Practice Guidelines are developed to be of assistance to endocrinologists and otherhealth care professionals by providing guidance and recommendations for particular areas of practice. The Guide-

lines should not be considered inclusive of all proper approaches or methods, or exclusive of others. The Guidelinescannot guarantee any specic outcome, nor do they establish a standard of care. The Guidelines are not intendedto dictate the treatment of a particular patient. Treatment decisions must be made based on the independentjudgment of health care providers and each patients individual circumstances.

The Endocrine Society makes no warranty, express or implied, regarding the Guidelines and specicallyexcludes any warranties of merchantability and tness for a particular use or purpose. The Society shall not beliable for direct, indirect, special, incidental, or consequential damages related to the use of the informationcontained herein.

First published in Journal of Clinical Endocrinology & Metabolism, 96(4):894904, 2011.

The Endocrine Society, 2011


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Pituitary Incidentaloma:An Endocrine Society Clinical Practice Guideline

T h e E n d o c r i n e S o c i e t y s

CLINICAL GUIDELINES


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Table of Contents

Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Summary of Recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4

Method of Development of Evidence-Based Clinical Practice Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5

Denition, Etiology, and Epidemiology of Pituitary Incidentalomas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6

Initial Evaluation of a Patient with a Pituitary Incidentaloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Follow-Up Testing of the Pituitary Incidentaloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10

Indications for Surgical Therapy of the Pituitary Incidentaloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Order Form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19

Reprint Information, Questions & Correspondences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Inside Back Cover


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AbstractObjective: The aim was to formulate practice guide-lines for endocrine evaluation and treatment ofpituitary incidentalomas.

Participants: The Task Force consisted of a chair,selected by the the Clinical Guidelines Subcommitteeof The Endocrine Society, ve additional experts, a

methodologist, and a medical writer. The Task Forcereceived no corporate funding or renumeration.

Evidence: This evidence-based guideline was devel-oped using the Grading of Recommendations, Assess-ment, Development, and Evaluation (GRADE) systemto describe both the strength of recommendations andthe quality of evidence.

Consensus Process:Consensus was guided by system-atic reviews of evidence and discussions through aseries of conference calls and e-mails and one in-personmeeting.

Conclusions:We recommend that patients with apituitary incidentaloma undergo a complete historyand physical examination, laboratory evaluationsscreening for hormone hypersecretion and for hypo-pituitarism, and a visual eld examination if the lesionabuts the optic nerves or chiasm. We recommend thatpatients with incidentalomas not meeting criteriafor surgical removal be followed with clinical assess-ments, neuroimaging (magnetic resonance imagingat 6 months for macroincidentalomas, 1 yr for a micro-incidentaloma, and thereafter progressively lessfrequently if unchanged in size), visual eld examina-tions for incidentalomas that abut or compress theoptic nerve and chiasm (6 months and yearly), andendocrine testing for macroincidentalomas (6 andyearly) after the initial evaluations. We recommendthat patients with a pituitary incidentaloma be

referred for surgery if they have a visual eld decit;signs of compression by the tumor leading to othervisual abnormalities, such as ophthalmoplegia, orneurological compromise due to compression by thelesion; a lesion abutting the optic nerves or chiasm;pituitary apoplexy with visual disturbance; or if theincidentaloma is a hypersecreting tumor other than aprolactinoma.

J Clin Endocrinol Metab 96(4):894904, 2011

Abbreviations: CT, Computed tomography; GHD, GH deciency; MRI, magnetic resonance imaging; VF, visual eld.


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SUMMARY OFRECOMMENDATIONS

1.0. Initial evaluation of a patient with apituitary incidentaloma

1.1. We recommend that patients presenting with apituitary incidentaloma undergo a complete historyand physical examination that includes evaluationsfor evidence of hypopituitarism and a hormone hyper-secretion syndrome. Patients with evidence of eitherof these conditions should undergo an appropriatelydirected biochemical evaluation:

1.1.1. We recommend that all patients witha pituitary incidentaloma, including those withoutsymptoms, undergo clinical and laboratory evalua-tions for hormone hypersecretion (1| ).

1.1.2. We recommend that patients with apituitary incidentaloma with or without symptomsalso undergo clinical and laboratory evaluations forhypopituitarism (1| ).

1.1.3. We recommend that all patientspresenting with a pituitary incidentaloma abuttingthe optic nerves or chiasm on magnetic resonanceimaging (MRI) undergo a formal visual eld (VF)examination (1| ).

1.1.4. We recommend that all patients havea MRI scan, if possible, to evaluate the pituitaryincidentaloma [if the incidentaloma was initiallyonly diagnosed by computed tomography (CT) scan]to better delineate the nature and extent of the

incidentaloma (1| ).

2.0. Follow-up testing of the pituitaryincidentaloma

2.1. Patients with incidentalomas who do not meetcriteria for surgical removal of the tumor shouldreceive nonsurgical follow-up (2| ) withclinical assessments and the following tests:

2.1.1. MRI scan of the pituitary 6 months afterthe initial scan if the incidentaloma is amacroinci-dentaloma and 1 yr after the initial scan if it is amicro-incidentaloma (1| ). In patients whoseincidentaloma does not change in size, we suggestrepeating the MRI every year for macroinciden-talomas and every 12 yr in microincidentalomas forthe following 3 yr, and gradually less frequently there-after (2| ).

2.1.2. VF testing in patients with a pituitaryincidentaloma that enlarges to abut or compress theoptic nerves or chiasm on a follow-up imaging study(1| ). We suggest that clinicians do not needto test VF in patients whose incidentalomas are notclose to the chiasm and who have no new symptoms

and are being followed closely by MRI (2| ).

2.1.3. Clinical and biochemical evaluationsfor hypopituitarism 6 months after the initial testingand yearly thereafter in patients with a pituitarymacro-incidentaloma, although typically hypopituita-rism develops with the nding of an increase in size ofthe incidentaloma (1| ). We suggest thatclinicians do not need to test for hypopituitarism inpatients with pituitary microincidentalomas whoseclinical picture, history, and MRI do not change overtime (2| ).

2.2. Patients who develop any signs or symptomspotentially related to the incidentaloma or who showan increase in size of the incidentaloma on MRIshould undergo more frequent or detailed evaluationsas indicated clinically (1| ).

3.0. Indications for surgical therapy of thepituitary incidentaloma

3.1. We recommend that patients with a pituitaryincidentaloma be referred for surgery if they have thefollowing (1| ):

A VF decit due to the lesion.

Other visual abnormalities, such as ophthal-moplegia or neurological compromise due tocompression by the lesion.

Lesion abutting or compressing the opticnerves or chiasm on MRI.


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Pituitary apoplexy with visual disturbance.

Hypersecreting tumors other than prolacti-nomas as recommended by other guidelinesof The Endocrine Society and The PituitarySociety.

3.2. We suggest that surgery be considered for patientswith a pituitary incidentaloma if they have thefollowing (2| ):

Clinically signicant growth of the pituitaryincidentaloma.

Loss of endocrinological function.

A lesion close to the optic chiasm and aplan to become pregnant.

Unremitting headache.

METHOD OF DEVELOPMENTOF EVIDENCE-BASED CLINICALPRACTICE GUIDELINES

The Clinical Guidelines Subcommittee of The Endo-crine Society deemed the subject of pituitary inciden-talomas a priority area in need of practice guidelinesand appointed a Task Force to formulate evidence-based recommendations. Consensus was guided bysystematic reviews of evidence and discussionsthrough a series of conference calls and e-mails andone in-person meeting. An initial draft guideline wasprepared by the Task Force, with the help of a medicalwriter, and reviewed and commented on by membersof The Endocrine Society and the European Societyof Endocrinology. A second draft was reviewed and

approved by The Endocrine Society Council. At eachstage of review, the Task Force received writtencomments and incorporated substantive changes.The evidence was developed using the Grading ofRecommendations, Assessment, Development, andEvaluation (GRADE) system to describe the strengthof recommendations and the quality of evidence,which was low or very low. The GRADE group is aninternational group with expertise in developmentand implementation of evidence-based guidelines

(1). A detailed description of the grading scheme hasbeen published elsewhere (2). The Task Force usedthe best available research evidence identied andone commissioned systematic review to develop someof the recommendations (3). The Task Force also usedconsistent language and graphical descriptions ofboth the strength of a recommendation and thequality of evidence. In terms of the strength of therecommendation, strong recommendations use thephrase we recommend and the number 1, and weakrecommendations use the phrase we suggest and thenumber 2. Cross-filled circlesindicate the quality ofthe evidence, such that denotes very lowquality evidence; , low quality; ,moderate quality; and , high quality. The nalcategory may include circumstances in which there

is a consistent observation of uniformly poor seriousoutcomes that will not reverse spontaneously, butwhen treated, often through surgical means, maydramatically improve or be cured. The Task Force hascondence that persons who receive care accordingto the strong recommendations will derive, onaverage, more good than harm. Weak recommenda-tions require more careful consideration of the personscircumstances, values, and preferences to determinethe best course of action. Linked to each recommen-

dation is a description of the evidence and the valuesthat panelists considered in making the recommenda-tion; in some instances, there are remarks, a section inwhich panelists offer technical suggestions for testingconditions, dosing, and monitoring. These technicalcomments reect the best available evidence appliedto a typical person being treated. Often this evidencecomes from the unsystematic observations of thepanelists and their values and preferences; therefore,these remarks should be considered suggestions.


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10% (6, 7, 9). In another series of 139 mass lesionswithout overt symptoms, 73 had a cystic appearanceon imaging study (5). Cystic lesions are most likely tobe Rathkes cleft cysts, which often present inciden-tally, or craniopharyngiomas (11, 12). Of thenon-cystic-appearing incidentalomas, nearly all arelikely to be pituitary adenomas, and most clinicallynonfunctioning pituitary adenomas are of gonado-trope origin as determined by immunocytochemicalstudies (1315). However, the differential diagnosis ofsellar incidentalomas is broad and should includeother possibilities (10).

Epidemiology of pituitary incidentalomas

The prevalence of pituitary incidentalomas has beenestimated from data on pituitary adenomas found atautopsy and from imaging in patients who underwenta CT or MRI of the head for reasons other thanpituitary disease. Because most pituitary inciden-talomas are adenomas, autopsy data on adenomas mayprovide information relevant to incidentalomadetected during life. In combined autopsy data, theaverage frequency of a pituitary adenoma was 10.6%(16). The tumors were distributed equally acrossgenders and the adult age range, and nearly all of

these incidentalomas were microadenomas (16). Inadults who underwent cranial imaging studies forreasons other than pituitary disease, microinciden-talomas were seen on CT in 420% (1719) or onMRI in 1038% (20) of patients. Macroinciden-talomas were found in 0.2% of patients who under-went CT scans for central nervous system symptoms(21) and by MRI in 0.16% of a population studycohort (22). In pooled data from 10 series of pituitaryincidentalomas, 160 of 353 (45%) were macroinci-dentalomas (4 9, 2326), a larger percentage thanhas been found on autopsy studies and the otherscreening studies. This suggests that these patientsmay in fact have had some symptom that was notreadily apparent or reported but that led to theimaging study or that microincidentalomas were notreferred to these centers for evaluation.

Data are not available on pituitary incidentalomas inthe pediatric population; these guidelines are limitedto adults.

DEFINITION, ETIOLOGY, ANDEPIDEMIOLOGY OF PITUITARYINCIDENTALOMAS

Denition of pituitary incidentaloma

A pituitary incidentaloma is a previously unsuspectedpituitary lesion that is discovered on an imaging studyperformed for an unrelated reason. By denition, theimaging study is not done for a symptom specicallyrelated to the lesion, such as visual loss, or a clinicalmanifestation of hypopituitarism or hormone excess,but rather for the evaluation of symptoms such asheadache, or other head or neck neurological orcentral nervous system complaints or head trauma(49). Studies reviewed for these guidelines vary,however, in their denition of a pituitary inciden-taloma. For example, some studies exclude cysticlesions and include only those that fulll radiographiccriteria for a pituitary adenoma (4, 5), whereas othersinclude all lesions (69). The guidelines presentedhere are relevant to all pituitary incidentalomas, thosethat have the appearance typical of a pituitary

adenoma as well as cystic lesions. By convention,microincidentalomas are less than 1 cm and macroin-cidentalomas are at least 1 cm in size.

Etiology of pituitary incidentalomas

Because incidentalomas infrequently come to surgery,the true pathological diagnoses of most are unknown.In a series of sellar masses that required surgery, 91%were pituitary adenomas and about 9% were nonpitu-

itary in origin, of which most were craniopharyngi-omas and Rathkes cleft cysts (10). It is unknownwhether the etiologies of incidentalomas are similarto this surgical cohort, but in one series of 29 inciden-talomas that did come to surgery, 23 were found to bepituitary adenomas, four were Rathkes cleft cysts, andtwo were craniopharyngiomas (6, 7, 9). Immunohisto-chemical analysis of 20 of these adenomas wasreported as negative in 50%, plurihormonal in 20%,gonadotroph positive in 15%, and GH positive in


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The evaluation for hypersecretion should include anassessment for prolactin, GH, and ACTH hypersecre-tion. Evidence is strongest for the need to measure aserum prolactin level in all patients presenting withan incidentaloma. Ideally, for patients with largemacroincidentalomas, the laboratory should measureprolactin levels in diluted serum to ensure that levelsare not falsely lowered by a hook effect in the assay.Hyperprolactinemia was found in ve of 42 patientswith microincidentalomas at initial evaluation (4),but in other studies none of 22 developed a prolactinelevation on prospective follow-up (8, 9). In otherstudies, prolactinomas were detected in seven of 46patients with incidentalomas (micro and macrocombined) (7). In macroincidentalomas, prolactinlevels were elevated in two of 16 (9). In a large autopsy

study, 39.5% of the adenomas detected (most micro-adenomas) were found to stain positive for prolactin(30). These data might suggest that prolactinomas arevery common among pituitary incidentalomas, whichis contrary to the literature. Autopsy data shouldcautiously be considered representative of inciden-talomas presenting in life because the autopsy studieslack clinical data, and prolactin staining may nothave been associated with clinically relevant circu-lating hyperprolactinemia. Patients with hyperprolac-

tinemia could receive a trial of dopamine agonisttherapy so long as it is recognized that mild/moderateelevations may be due to stalk compression from alesion other than a prolactinoma. In these patients,tumor shrinkage is unlikely, and growth of the inci-dentaloma is still possible, so continued follow-upwith repeat imaging is warranted. The treatment ofhyperprolactinemia has been recently reviewed (31).

Although silent somatotroph-secreting tumors arerare, evaluation for the possibility is recommended. In

a prospective study, one of 11 macroincidentalomaswere found to have an elevated IGF-I consistent withsubclinical GH excess (8), and in another study, twoof 13 incidentalomas that were surgically removedwere positive on immunohistochemistry for GH (7).One series of 3048 autopsies reported 334 pituitaryadenomas, of which 1.8% stained positive for GH(30). Because the initial treatment for a GH-secretingtumor is surgery and GH secreting microadenomascan be cured surgically in almost all cases, screening

1.0. INITIAL EVALUATIONOF A PATIENT WITH A PITUITARYINCIDENTALOMA

Recommendations

1.1. We recommend that patients presenting with apituitary incidentaloma undergo a complete historyand physical examination that includes evaluationsfor evidence of hypopituitarism and a hormone hyper-secretion syndrome. Patients with evidence of eitherof these conditions should undergo an appropriatelydirected biochemical evaluation.

1.1.1. We recommend that all patients witha pituitary incidentaloma, including those withoutsymptoms, undergo clinical and laboratory evalua-tions for hormone hypersecretion (1| ).

1.1.1.1.1. Evidence

The goals of the endocrine evaluation of pituitaryincidentalomas are to identify hormone hypersecre-tion and hypopituitarism. The recommendations for

evaluation of pituitary function considered the likeli-hood of an abnormality in a given patient. However,valid estimates of the pretest probability of anabnormal test of pituitary function could not be den-itively determined because literature on this topic issparse. Therefore, recommendations for the evalua-tion relied heavily on clinical experience.

Data on the prevalence of hormone hypersecretion inpatients with an incidentaloma are available fromsmall observational studies (most retrospective) andestimated from autopsy data. Screening for hypersecre-tion is important to perform because the prevalence ofclinically evident pituitary adenomas has recentlybeen appreciated to be as high as 1/1000 in a Belgianpopulation (27), and 0.776/1000 (of which 0.542/1000were hormone secreting) in a region of the UnitedKingdom (28), or as low as 0.04/1000 in Finland (29).The incidence of incidentally discovered pituitaryadenomas was recently reported as 0.016/1000 in aretrospective review from Finland (29).


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Screening for certain hormone hypersecretionsyndromes was considered important, even if thepatient was asymptomatic or if the abnormality wasunlikely in the patient population. Screening forhyperprolactinemia was considered essential becauseof the potential for successful treatment with an oraldopamine agonist. Screening for GH excess with aserum IGF-I level was recommended because earlydetection of a GH-secreting tumor, which wouldlikely be asymptomatic, could reduce long-termmorbidity and increase the likelihood of surgical cure.Some consider screening also for glucocorticoid excessin all patients, but others may limit screening topatients for whom there is a clinical suspicion, due tothe high false positive rate and low rate of true-posi-tive testing in the former group of patients.

1.1.1.1.1. Remarks

The pros and cons of detailed vs. limited screening forhypersecretion syndromes (other than for prolacti-noma) were debated, and the Task Force was split onthis point. The quality of evidence for or against oneparticular testing strategy was weak.

Recommendation

1.1.2. We recommend that patients with a pituitaryincidentaloma with or without symptoms alsoundergo clinical and laboratory evaluations for hypo-pituitarism (1| ).

1.1.2. Evidence

Evidence to support screening for hypopituitarism inpatients with an incidentaloma also comes from smallobservational studies. In combined data in micro- andmacroincidentalomas, hypopituitarism was present inseven of 66 (5) and 19 of 46 patients (7). Decits ofgonadotropins (not associated with hyperprolac-tinemia) were detected in up to 30% of patients (4, 7,8), of the ACTH/cortisol axis in up to 18% (7, 8),thyroid axis in up to 28% (7, 8), and GH axis in upto 8% (4).

Different approaches can be taken to the initialevaluation of the patient for hypopituitarism. SomeTask Force members recommend a minimal screening

for a GH-secreting tumor by measurement of an IGF-Ilevel is warranted. If this is elevated, further evalua-tion for GH excess is suggested.

Screening for glucocorticoid excess due to a possiblecorticotroph tumor may also be considered when thisis suspected clinically. In the series of 3048 autopsies,13.8% of 334 pituitary adenomas stained positive forACTH (30). No systematic screening of inciden-talomas for subclinical glucocorticoid excess has beenreported (8, 9). However, patients with adrenal inci-dentalomas may have Cushings syndrome-associatedmorbidities such as diabetes mellitus, hypertension,obesity, and osteoporosis (32), so in a patient with apituitary incidentaloma subclinical Cushings diseasecould also be associated with these morbidities (16).

In patients with a clinical suspicion for glucocorticoidexcess, laboratory screening is therefore suggested.Detection of subclinical hypercortisolism should befollowed by evaluation for possible Cushings disease.The screening and evaluation of Cushings diseasehas been reviewed in the Diagnosis of CushingsSyndrome: an Endocrine Society Clinical PracticeGuideline (33).

The Task Force does not recommend the routinemeasurement of plasma ACTH levels in patientswith incidentalomas. However, some of the TaskForce members often measure ACTH because asmall percentage of incidentalomas may be silentcorticotroph tumors (34), and occasionally plasmaACTH levels are elevated in patients harboring thesetumors despite the lack of clinical manifestations ofcortisol excess (34).

In patients whose personal or family history suggeststhe possibility of a multiple endocrine neoplasiasyndrome, additional screening and follow-up asappropriate to the suspected syndrome should beundertaken.

1.1.1.1.1. Values and preferences

The recommendations for screening for hypersecre-tion needed to balance the potential benets of earlydetection with the relatively low likelihood of ndingcertain abnormalities in a given patient and the costsand burden of potentially unnecessary testing.


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of hypopituitarism and other anatomic characteristicsof the incidentaloma need to be considered. Theevidence was downgraded because only observationaldata from relatively small studies are available, andsome decisions had to be made based on the clinicalexperiences of the Task Force members rather thanrigorous studies.

1.1.2. Remarks

Our recommendations include routine screening forGH deciency (GHD) with an IGF-I level in allpatients, but the Task Force recognized that this aloneis insufcient evidence for or against GHD in adults.In patients with a clinical suspicion of GHD, inparticular if the IGF-I is low, further testing should be

undertaken as recommended in the Evaluation andTreatment of Adult Growth Hormone Deciency: anEndocrine Society Clinical Practice Guideline (36).The authors of this guideline also recognized that theapproach taken to the testing for and treatment ofGHD varies among endocrinologists and that somewould only consider performing the testing if theclinical setting suggested the potential for a benet ofGH therapy.

Recommendation

1.1.3. We recommend that all patients presentingwith a pituitary incidentaloma abutting or compressingthe optic nerves or chiasm on MRI undergo a formalVF examination (1| ).

1.1.3. Evidence

Baseline VF testing is recommended for all patientswith an incidentaloma abutting the optic nerves orchiasm, even without visual symptoms (Fig. 1). In oneprospective study of 11 macroincidentalomas, onepatient had VF abnormalities, and two had compres-sion of the optic chiasm (8). In other studies, 15%(32) and 5% (4) of patients had unrecognized VFabnormalities at presentation.

Recommendation

1.1.4. We recommend that all patients have a MRIscan, if possible, to evaluate the pituitary incidentaloma

with the measurement of free T 4, morning cortisol,and testosterone levels, whereas others recommendthat the initial evaluation should also include themeasurement of TSH, LH, and FSH and IGF-I. Abroad initial approach to this testing is favored bysome to avoid the repeated blood sampling that wouldbe needed to conrm a central origin of target organdeciencies should they be detected. Low gonado-tropin levels in postmenopausal women provideevidence of hypopituitarism and in men excludeprimary hypogonadism when testosterone levels arelow. Similarly, normal or low TSH levels help distin-guish a pituitary etiology of hypothyroidism when thefree T4 is low. Gonadal function can be assessed inpremenopausal women by history and examination. Ifbaseline testing suggests hypopituitarism, further

stimulation tests of the pituitary-adrenal or GHIGF-Iaxis should be performed.

1.1.2. Values and preferences

The size of the incidentaloma may also be relevant tothe risk of hypopituitarism, so the Task Force debatedwhether the size should factor into the decision toscreen or not to screen for hypopituitarism. TheTask Force more strongly favored routine testing forhypopituitarism in macroincidentalomas and largermicroincidentalomas, for example 69 mm, and notnecessarily in smaller microincidentalomas becauseasymptomatic pituitary hormone decits can bedetected and larger lesions seem more likely to beassociated with hypopituitarism. Although there areno specic data on the prevalence of hypopituitarismin larger vs. smaller microincidentalomas, in the TaskForces experience some larger microincidentalomasmay behave more like macroincidentalomas, whichleads some endocrinologists to routinely evaluate

larger microincidentalomas for hypopituitarism.Routine screening for hypopituitarism among smallermicroincidentalomas may not be necessary becausethe rate of hypopituitarism among them appears to bevery low, although the number of patients reported isvery small (4, 8, 9). However, recent data do showthat hypopituitarism can occur in microadenomas(35). The Task Force recognized that there is acontinuum of size of pituitary incidentalomas, so a1-cm size cutoff may be arbitrary in evaluating the risk


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rism develops with the nding of an increase in sizeof the incidentaloma (1| ). We suggest thatclinicians do not need to test for hypopituitarism inpatients with pituitary microincidentalomas whoseclinical picture, history, and MRI do not change overtime (2| ).

2.1. Evidence

The options for treatment of patients with asymptom-atic, clinically nonfunctioning pituitary inciden-talomas are conservative follow-up without surgery(Fig. 1) or immediate surgery despite the lack of indi-cations for this. Conservative follow-up was recom-mended with the recognition that the properalgorithm for this and its appropriateness and safety

have not been tested prospectively. Few data areavailable for or against a nonsurgical approach tomanagement of asymptomatic pituitary inciden-talomas. Therefore, evidence in support of theseguidelines also relied on the clinical experiences ofthe Task Force members.

The proper algorithm for endocrine testing duringthis follow-up has not been tested as prospectivelyconducted endocrine testing of patients with pituitaryincidentalomas who were followed without surgeryhas only been reported in 49 patients (8, 9). Follow-up endocrine testing is recommended for patientswith macroincidentalomas because they are at risk ofdeveloping hypopituitarism. Of the macroinciden-talomas followed prospectively, worsening hypopitu-itarism developed in one of seven (8) and three of 28(25) patients, all of whom had enlargement of theirtumors. Hypopituitarism also developed in four of 37(5) and one of 248 (6) patients who developedapoplexy on follow-up. Follow-up endocrine testing

was recommended despite the paucity of data becauseof the potential high risk to the patient of untreatedhypopituitarism. In a meta-analysis of incidentalomastudies, new endocrine dysfunction developed overallin 2.4% of patients per year (3). It is unclear howoften new hypopituitarism develops in the absence oftumor growth. Rapid growth may increase the risk ofnew hypopituitarism. Routine follow-up endocrinetesting is not required for microincidentalomas whoseclinical picture does not change because the risk of

(if the incidentaloma was initially only diagnosed byCT scan) to better delineate the nature and extent ofthe incidentaloma (1| ).

1.1.4. Remarks

For the MRI, a specic pituitary protocol should bedone that includes ne cuts thorough the sella withand without the administration of the contrast agentgadolinium. Guidelines for the evaluation of renalfunction before administration of gadolinium shouldbe followed.

2.0. FOLLOW-UP TESTING OFTHE PITUITARY INCIDENTALOMA

Recommendations

2.1. Patients with incidentalomas who do not meetcriteria for surgical removal of the tumor shouldreceive nonsurgical follow-up (2| ), withclinical assessments and the following tests:

2.1.1. MRI scan of the pituitary 6 monthsafter the initial scan if the incidentaloma is a macro-incidentaloma and 1 yr after the initial scan if it is amicro-incidentaloma (1| ). In patients whoseincidentaloma does not change in size, we suggestrepeating the MRI every year for macroinciden-talomas and every 12 yr in microincidentalomas forthe following 3 yr and gradually less frequently there-after (2| ).

2.1.2. VF testing in patients with a pituitary

incidentaloma that enlarges to abut or compress theoptic nerves or chiasm on a follow-up imaging study(1| ). We suggest that clinicians do not needto test VF in patients whose incidentalomas are notclose to the chiasm and who have no new symptomsand are being followed closely by MRI (2| ).

2.1.3. Clinical and biochemical evaluationsfor hypopituitarism 6 months after the initial testingand yearly thereafter in patients with a pituitarymacro-incidentaloma, although typically hypopituita-


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FIG. 1. Flow diagram for the evaluation and treatment of pituitary incidentalomas. a, Baseline evaluation in all patients shouldinclude:a history and physical exam evaluating for signs and symptoms of hyperfunction and hypopituitarism and a laboratory evaluation

for hypersecretion.b This group may also include large microlesions (see Section 2.1 Evidence).c The recommendation for surgery includes the presence of abnormalities of VF or vision and signs of tumor compression

(Section 3.1); surgery is also suggested for other ndings (see Section 3.2).d VF testing is recommended for patients with lesions abutting or compressing the optic nerves or chiasm at the initial evaluation

and during follow-up.e Evaluation for hypopituitarism is recommended for the baseline evaluation and during follow-up evaluations. This is most strongly

recommended for macrolesions and larger microlesions (see Section 1.3).f Repeat MRI in 1 yr, yearly for 3 yr, and then less frequently thereafter if no change in lesion size.g Repeat the MRI in 6 months, yearly for 3 yr, and then less frequently if no change in lesion size.

[Modied from Molitch ME: J Clin Endocrinol Metab80:36, 1995 (49).]

Evaluation & Treatment of Pituitary Incidentalomas

Evaluation of Pituitary Function a

Hyperfunctioning Clinically Nonfunctioning

Prolactinoma Micro-Incidentaloma

Other Macro-Incidentalomab

DopamineAgonist

Surgery/MedicalTherapy

VF testingd Hypopituitarism

Evaluatione

Surgery

Repeat MRIf Repeat MRIgPituitary Functione,

VFd

Tumor Growth, VF Abnormality

Surgery

abnormalc

normal


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so long as the lesion continues not to threaten thepatients health. Some Task Force members wouldcontinue imaging every 5 yr. Uncertainty as to theoptimal interval and duration of long-term follow-upimaging can be shared with the patient, and thescheme followed can be individualized to balance thephysicians assessment of the risk that the lesion posesto the patients health with the burden to the patientof surveillance testing.

2.1. Values and preferences

The decision to proceed with conservative nonsur-gical management of pituitary incidentalomas notmeeting criteria for surgery (see Section 3.0) puts a rela-tively high value on avoiding surgical intervention

and its associated morbidity and cost, and a relativelylow value in avoiding apoplexy. The evidence thatmost incidentalomas do not progress over time tocause visual or other disturbances supports this valuejudgment. On the other hand, apoplexy developed inseven of 248 patients with incidentalomas (46, 8, 9,26). Large-scale prospective studies of conservativenonsurgical management of pituitary incidentalomasare needed to further inform this judgment.

2.1. Remarks

The Task Force recognized that a continuum of size ofincidentalomas exists, and some large microinciden-talomas (69 mm) may behave more like macroinci-dentalomas. Therefore, some Task Force memberswould also perform follow-up MRIs and hypopituita-rism evaluations in larger microincidentalomas as theywould for macroincidentalomas. Some also consideredthat follow-up evaluations for hypopituitarism wereneeded only for patients with enlarging incidentalomas

because new hypopituitarism would be very unlikely todevelop without tumor growth. However, no data areavailable to support one particular size threshold forthe increase in size that should trigger this evaluation.The Task Force was split on these points.

Recommendation

2.2. Patients who develop any signs or symptomspotentially related to the incidentaloma or who showan increase in size of the incidentaloma on MRI

developing new hypopituitarism is extremely low. Inprevious studies, none of the pituitary microinciden-talomas followed prospectively was reported to beassociated with changes in pituitary function (49).

The proposed algorithms for the MRI follow-up ofpituitary incidentalomas took into account thoseadopted in prior studies. However, those algorithmsvaried considerably from study to study (49), andnone was validated. As a result, the imaging follow-up proposed in this guideline incorporated theexperiences of the Task Forces members. Follow-upMRI scans were recommended for macroinciden-talomas because it has been demonstrated thatalthough generally these lesions grow slowly, some doenlarge and become symptomatic. In data combined

from a number of studies, macroincidentalomasenlarged in 85 of 353 (24%) patients (49, 2326).VF abnormalities developed in 28 (8%) patients overtime, which demonstrated that the enlargementadversely affected the patients health. Pituitaryapoplexy developed in seven of 353 (2%) patients, ofwhom most developed permanent hypopituitarismand one had permanent vision impairment (5). In ameta-analysis of these studies, 8.2% of incidentalomasenlarged per year with a follow-up of 472 person-years(3). Less frequent surveillance of microincidentalomaswas recommended because their rate of enlargementwas low, being reported in 17 of 160 patients (10.6%)followed from 2.3 to 7 yr (59, 2325). In the meta-analysis, 1.7% of microincidentalomas enlarged peryear (3). Importantly, none of the patients with thesemicroincidentalomas developed new VF abnormali-ties that would have necessitated surgery.

Overall, the Task Force considered that repeat scan-ning within the rst year was warranted for all patients

because, although most incidentalomas grow slowly,some do enlarge, and the true proliferative nature ofthe incidentaloma is unknown (Fig. 1). If no grow thisdetected, then the interval between MRI scans can beincreased. Evidence does not support one particularalgorithm for the frequency of follow-up imaging, butwe recommend repeating the MRI every year inmacroincidentalomas, every 12 yr in microinciden-talomas for the next 3 yr, and then every other year forthe next 6 yr and gradually less frequently indenitely


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or for those within certain proximity of the chiasm butwhere no VF abnormalities are present have not beenquantied, in the Task Forces experience signicantrisk of future vision disturbance in these patients existsto warrant surgery. The age of the patient is also animportant consideration. Surgery may be favored inyounger vs. older patients given the higher lifetimeprobability of tumor enlargement in the former and thegreater risks of surgical intervention in the latter groupof patients. Some may elect to follow elderly patientswith signicant risks to surgery conservatively andclosely for any deterioration in vision. The decision torecommend surgery should also consider whetherfuture fertility is of concern to the patient. Difcultcases could also be discussed at a pituitary multidisci-plinary team meeting when this is available.

Surgery is indicated in patients with apoplexy andvisual disturbance. In a retrospective review of 30subjects with pituitary apoplexy, the 20 who werefollowed conservatively had a similar long-term risk ofhypopituitarism as those treated surgically (37).Therefore, patients with apoplexy and without visualcompromise may be followed conservatively withserial imaging and hormonal assessments.

3.1. Values and Preferences

Our recommendations for surgery for incidentalomasput a high value on alleviating or preventing visual orneurological compromise. Although the benets ofsurgery in preventing future visual abnormalities arenot known, a relatively higher value was put on theprevention of VF abnormalities than on avoiding themorbidity ( e.g. diabetes insipidus, hypopituitarism)and the cost of surgery. New hypopituitarism as aresult of transsphenoidal surgery is rare in the Task

Forces experience, but the risk should be consideredin the clinical context of the particular patient.

3.1. Remarks

The recommendations for surgical therapy of a pitu-itary incidentaloma were based on the Task Forcesexpectations for outcome and improvements in visionand endocrine function. These expectations werebased on known literature and Task Force membersclinical experience with surgery performed by a

should undergo more frequent or detailed evaluationsas indicated clinically (1| ).

3.0. INDICATIONS FORSURGICAL THERAPY OF THEPITUITARY INCIDENTALOMA

Recommendation

3.1. We recommend that patients with a pituitaryincidentaloma be referred for surgery if they have thefollowing (1| ):

A VF decit due to the lesion.

Other visual abnormalities, such as ophthal-moplegia or neurological compromise dueto compression by the lesion.

Lesion abutting or compressing the opticnerves or chiasm on MRI.

Pituitary apoplexy with visual disturbance.

Hypersecreting tumors other than prolacti-nomas as recommended by other guidelines

of The Endocrine Society and The PituitarySociety (31, 33).

3.1. Evidence

The decision to recommend surgery as initial therapyfor a patient with a pituitary incidentaloma needs to beindividualized (Fig. 1). Few data are available thatspecically examine the outcome of surgery for inci-dentalomas. Some of the evidence considered in devel-oping the recommended criteria for surgery was from

transsphenoidal surgical series of symptomatic andoften large pituitary lesions. From these data and basedon the clinical experiences of the Task Force members,it is clear that substantial evidence supports the needfor surgery for pituitary incidentalomas causing visualor neurological compromise. The presence of visual orneurological abnormalities due to compression of theoptic nerves or chiasm by the incidentaloma is thestrongest indication for surgery. Although the risks ofnot performing surgery on tumors that abut the chiasm


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threaten vision in the near future) should be consid-ered for surgery before the incidentaloma progressesto abut the chiasm or produce visual decits. Aconsideration of the clinical characteristics of thepatient including their age and other risks for surgeryneeds to be incorporated into the decision to proceedto surgery.

The evidence for or against a recommendation forsurgery because of the presence of hypopituitarism isalso limited. Although some surgical series of symp-tomatic incidentalomas show that hypopituitarismcan improve with surgery (40, 41), these data may notbe applicable to the incidentaloma, and as a resulthypopituitarism was considered only a relative indica-tion for surgery. Adequate replacement therapy should

be instituted whether or not surgery is recommended.Some patients planning pregnancy may benet fromsurgery if their tumor is close to the optic chiasmbecause there is a small risk that lactotroph hyper-plasia in the normal gland may lead to tumor compres-sion of the optic nerve or chiasm, and closer follow-upin such patients should be undertaken. Headache mayor may not improve with transsphenoidal removal ofthe tumor, so it can only be suggested as an indicationfor surgery, and the quality of evidence is low.

Medical therapy of the pituitary incidentaloma

In patients with incidentalomas and hyperprolac-tinemia that may be due to tumoral compression ofthe hypothalamic-pituitary stalk, symptomatic hyper-prolactinemia may be treated with a dopamineagonist. However, incidentalomas other than a prolac-tinoma will rarely shrink, and dopamine agonistscannot be relied upon for this purpose. Therefore,continued monitoring of lesion size is necessary,

regardless of changes in prolactin levels.

Medical therapy of pituitary incidentalomas hasnot been systematically studied. Some parallels to theeffects of medical therapy on pathologically conrmednonfunctioning pituitary tumors are possible, butthis connection needs to be made cautiously. Thereported efcacy of dopamine agonist therapy ofnonfunctioning pituitary adenomas varies widely.With cabergoline or bromocriptine treatment forpatients with residual tumor after surgery, some

surgeon experienced in transsphenoidal pituitarysurgery. The success of surgery for hormone-secretingtumors is highly dependent on the expertise, skill, andcase volume of a pituitary surgeon supported by anexperienced team (38, 39). This is likely to also betrue for pituitary surgery of other types of lesions. Theavailability of such a pituitary surgeon needs to beconsidered when following these guidelines.

Recommendation

3.2. We suggest that surgery be considered for patientswith a pituitary incidentaloma if they have thefollowing (2| ):

Clinically signicant growth of the pituitaryincidentaloma.

Loss of endocrinological function.

A lesion close to the optic chiasm and aplan to become pregnant.

Unremitting headache.

3.2. Evidence

The evidence for or against a recommendation forsurgery because of growth of a pituitary incidentalomais limited. Surgery was suggested for incidentalomasthat demonstrate clinically signicant growth onfollow-up imaging studies, which is growth that couldpose a health risk to the patient such as to their vision.Such growing incidentalomas typically continue togrow, and surgery is most effective for smaller lesions.A specic size cutoff for the incidentaloma was notconsidered a requirement for surgery because somelarge incidentalomas are predominantly intra- andinfrasellar. Although there are no established changesin size or growth rate that would automatically trigger

the need for surgery, the pattern of growth of theincidentaloma was considered more important. Forexample, a 1-mm enlargement within the sella of a5-mm intrasellar microadenoma would not be clini-cally signicant, but a 1-mm enlargement toward thechiasm in a lesion only 3 mm from the chiasm wouldbe signicant. Therefore, incidentalomas exhibitingsignicant growth (which includes growth that israpid, occurring over a 1- to 2-yr period, and/or thatis toward the optic chiasm and if continued could


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degree of tumor shrinkage was detected in 845%(4244), and the amount of shrinkage varied from1062%(43, 44) or 314 mm(42). Somatostatinanalogs have also been tried. With no more than 1 yrof octreotide therapy, shrinkage was reported inapproximately 525%, increase in 12%, and stabiliza-tion in 83% of tumors (4548). Insufcient data areavailable to suggest the routine use of medical therapyof pituitary incidentalomas.


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1. Atkins D, Best D, Briss PA, Eccles M, Falck-Ytter Y, Flottorp S, Guyatt GH, Harbour RT, Haugh MC, HenryD, Hill S, Jaeschke R, Leng G, Liberati A, Magrini N,Mason J, Middleton P, Mrukowicz J, OConnell D, Oxman

AD, Phillips B, Schnemann HJ, Edejer TT, Varonen H,Vist GE, Williams Jr JW, Zaza S 2004 Grading quality ofevidence and strength of recommendations. BMJ 328:1490

2. Swiglo BA, Murad MH, Schnemann HJ, Kunz R,Vigersky RA, Guyatt GH, Montori VM 2008 A case forclarity, consistency, and helpfulness: state-of-the-art clinicalpractice guidelines in endocrinology using the grading ofrecommendations, assessment, development, and evaluationsystem. J Clin Endocrinol Metab 93:666673

3. Fernandez-Balsells M MM, Barwise A, Gallegos-Orozco J,Paul A, Lane M, Carpio I, Perestelo-Perez LI, Ponce deLeon Lovaton P, Erwin, P, Carey J, Montori VM 2010 Thenatural history of pituitary incidentalomas: a systematicreview and meta-analysis. J Clin Endocrinol Metab (In press)

4. Feldkamp J, Santen R, Harms E, Aulich A, Mdder U,Scherbaum WA 1999 Incidentally discovered pituitarylesions: high frequency of macroadenomas and hormone-secreting adenomasresults of a prospective study. ClinEndocrinol (Oxf) 51:109113

5. Arita K, Tominaga A, Sugiyama K, Eguchi K, Iida K,Sumida M, Migita K, Kurisu K 2006 Natural course ofincidentally found nonfunctioning pituitary adenoma, withspecial reference to pituitary apoplexy during follow-upexamination. J Neurosurg 104:884891

6. Sanno N, Oyama K, Tahara S, Teramoto A, Kato Y 2003 Asurvey of pituitary incidentaloma in Japan. Eur J Endocrinol149:123127

7. Fainstein Day P, Guitelman M, Artese R, Fiszledjer L,Chervin A, Vitale NM, Stalldecker G, De Miguel V,Cornal D, Aleri A, Susana M, Gil M 2004 Retrospectivemulticentric study of pituitary incidentalomas. Pituitary7:145148

8. Reincke M, Allolio B, Saeger W, Menzel J, Winkelmann W1990 The incidentaloma of the pituitary gland. Is neuro-surgery required? JAMA 263:27722776

9. Donovan LE, Corenblum B 1995 The natural history of thepituitary incidentaloma. Arch Intern Med 155:181183

10. Freda PU, Post KD 1999 Differential diagnosis of sellarmasses. Endocrinol Metab Clin North Am 28:81117, vi

11. Zada G, Lin N, Ojerholm E, Ramkissoon S, Laws ERCraniopharyngioma and other cystic epithelial lesions of thesellar region: a review of clinical, imaging, and histopatho-logical relationships. Neurosurg Focus 28:E4

12. Kanter AS, Sansur CA, Jane Jr JA, Laws Jr ER 2006Rathkes cleft cysts. Front Horm Res 34:127157

References13. Black PM, Hsu DW, Klibanski A, Kliman B, Jameson JL,

Ridgway EC, Hedley-Whyte ET, Zervas NT 1987 Hormoneproduction in clinically nonfunctioning pituitary adenomas.

J Neurosurg 66:244250

14. Esiri MM, Adams CB, Burke C, Underdown R 1983Pituitary adenomas: immunohistology and ultrastructuralanalysis of 118 tumors. Acta Neuropathol 62:114

15. Al-Shraim M, Asa SL 2006 The 2004 World Health Organi-zation classication of pituitary tumors: what is new? Acta

Neuropathol 111:17

16. Molitch ME 2008 Nonfunctioning pituitary tumors andpituitary incidentalomas. Endocrinol Metab Clin North Am37:151171, xi

17. Wolpert SM, Molitch ME, Goldman JA, Wood JB 1984Size, shape, and appearance of the normal female pituitary

gland. AJR Am J Roentgenol 143:37738118. Chambers EF, Turski PA, LaMasters D, Newton TH

1982 Regions of low density in the contrast-enhancedpituitary gland: normal and pathologic processes. Radiology144:109113

19. Peyster RG, Adler LP, Viscarello RR, Hoover ED,Skarzynski J 1986 CT of the normal pituitary gland. Neuro-radiology 28:161165

20. Hall WA, Luciano MG, Doppman JL, Patronas NJ,Oldeld EH 1994 Pituitary magnetic resonance imaging innormal human volunteers: occult adenomas in the generalpopulation. Ann Intern Med 120:817820

21. Nammour GM, Ybarra J, Naheedy MH, Romeo JH, AronDC 1997 Incidental pituitary macroadenoma: a population-based study.AmJ Med Sci 314:287291

22. Yue NC, Longstreth Jr WT, Elster AD, Jungreis CA,OLeary DH, Poirier VC 1997 Clinically serious abnormali-ties found incidentally at MR imaging of the brain: data fromthe Cardiovascular Health Study. Radiology 202:4146

23. Igarashi T, Saeki N, Yamaura A 1999 Long-term magneticresonance imaging follow-up of asymptomatic sellar tumorstheir natural history and surgical indications. Neurol MedChir (Tokyo) 39:592598; discussion 598599

24. Karavitaki N, Collison K, Halliday J, Byrne JV, Price P,Cudlip S, Wass JA 2007 What is the natural history ofnonoperated nonfunctioning pituitary adenomas? ClinEndocrinol (Oxf) 67:938943

25. Dekkers OM, Hammer S, de Keizer RJ, Roelfsema F,Schutte PJ, Smit JW, Romijn JA, Pereira AM 2007 Thenatural course of nonfunctioning pituitary macroadenomas.Eur J Endocrinol 156:217224

26. Nishizawa S, Ohta S, Yokoyama T, Uemura K 1998Therapeutic strategy for incidentally found pituitary tumors(pituitary incidentalomas). Neurosurgery 43:13441348;discussion 13481350


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27. Daly AF, Rixhon M, Adam C, Dempegioti A, TichomirowaMA, Beckers A 2006 High prevalence of pituitary adenomas:a crosssectional study in the province of Liege, Belgium. JClin Endocrinol Metab 91:47694775

28. Fernandez A, Karavitaki N, Wass JA Prevalence ofpituitary adenomas: a community-based, cross-sectionalstudy in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf)72:377382

29. Raappana A, Koivukangas J, Ebeling T, Piril T 2010Incidence of pituitary adenomas in Northern Finland in19922007. J Clin Endocrinol Metab 95:42684275

30. Buurman H, Saeger W 2006 Subclinical adenomas inpostmortem pituitaries: classication and correlations to clin-ical data. Eur J Endocrinol 154:753758

31. Casanueva FF, Molitch ME, Schlechte JA, Abs R, BonertV, Bronstein MD, Brue T, Cappabianca P, Colao A, Fahl-busch R, Fideleff H, Hadani M, Kelly P, Kleinberg D, LawsE, Marek J, Scanlon M, Sobrinho LG, Wass JA, Giustina A

2006 Guidelines of the Pituitary Society for the diagnosisand management of prolactinomas. Clin Endocrinol (Oxf)65:265273

32. Angeli A, Terzolo M 2002 Adrenal incidentalomaamodern disease with old complications. J Clin EndocrinolMetab 87:48694871

33. Nieman LK, Biller BM, Findling JW, Newell-Price J,Savage MO, Stewart PM, Montori VM 2008 The diagnosisof Cushings syndrome: an Endocrine Society ClinicalPractice Guideline. J Clin Endocrinol Metab 93:15261540

34. Karavitaki N, Ansorge O, Wass JA 2007 Silent cortico-troph adenomas. Arq Bras Endocrinol Metabol 51:13141318

35. Yuen KC, Cook DM, Sahasranam P, Patel P, Ghods DE,Shahinian HK, Friedman TC 2008 Prevalence of GH andother anterior pituitary hormone deciencies in adults withnonsecreting pituitary microadenomas and normal serumIGF-1 levels. Clin Endocrinol (Oxf) 69:292298

36. Molitch ME, Clemmons DR, Malozowski S, Merriam GR,Shalet SM, Vance ML, Stephens PA 2006 Evaluation andtreatment of adult growth hormone deciency: an EndocrineSociety Clinical Practice Guideline. J Clin Endocrinol Metab91:16211634

37. Gruber A, Clayton J, Kumar S, Robertson I, Howlett TA,Mansell P 2006 Pituitary apoplexy: retrospective review

of 30 patientsis surgical intervention always necessary?Br J Neurosurg 20:379385

38. Barker 2nd FG, Klibanski A, Swearingen B 2003 Transs-phenoidal surgery for pituitary tumors in the United States,19962000: mortality, morbidity, and the effects of hospitaland surgeon volume. J Clin Endocrinol Metab 88:47094719

39. Gittoes NJ, Sheppard MC, Johnson AP, Stewart PM 1999Outcome of surgery for acromegalythe experience of adedicated pituitary surgeon. QJM 92:741745

40. Arafah BM, Kailani SH, Nekl KE, Gold RS, Selman WR1994 Immediate recovery of pituitary function after transs-phenoidal resection of pituitary macroadenomas. J ClinEndocrinol Metab 79:348354

41. Arafah BM 1986 Reversible hypopituitarism in patients withlarge nonfunctioning pituitary adenomas. J Clin EndocrinolMetab 62: 11731179

42. Greenman Y, Tordjman K, Osher E, Veshchev I, Shen-kerman G, Reider-Groswasser II, Segev Y, Ouaknine G,Stern N 2005 Postoperative treatment of clinically nonfunc-tioning pituitary adenomas with dopamine agonists decreasestumour remnant growth. Clin Endocrinol (Oxf) 63:3944

43. Lohmann T, Trantakis C, Biesold M, Prothmann S,Guenzel S, Schober R, Paschke R 2001 Minor tumourshrinkage in nonfunctioning pituitary adenomas by long-term treatment with the dopamine agonist cabergoline.Pituitary 4:173178

44. Pivonello R, Matrone C, Filippella M, Cavallo LM, Di

Somma C, Cappabianca P, Colao A, Annunziato L,Lombardi G 2004 Dopamine receptor expression and func-tion in clinically nonfunctioning pituitary tumors: compar-ison with the effectiveness of cabergoline treatment. J ClinEndocrinol Metab 89:16741683

45. Shomali ME, Katznelson L 2002 Medical therapy of gonad-otropin-producing and nonfunctioning pituitary adenomas.Pituitary 5:8998

46. Merola B, Colao A, Ferone D, Selleri A, Di Sarno A,Marzullo P, Biondi B, Spaziante R, Rossi E, Lombardi G1993 Effects of a chronic treatment with octreotide in patientswith functionless pituitary adenomas. Horm Res 40:149155

47. de Bruin TW, Kwekkeboom DJ, Vant Verlaat JW, Reubi JC, Krenning EP, Lamberts SW, Croughs RJ 1992 Clini-cally nonfunctioning pituitary adenoma and octreotideresponse to long term high dose treatment, and studies invitro. J Clin Endocrinol Metab 75:13101317

48. Colao A, DiSomma C, Pivonello R, Faggiano A, LombardiG, Savastano S 2008 Medical therapy for clinically non-functioning pituitary adenomas. Endocr Relat Cancer15:905915

49. Molitch ME 1995 Clinical review 65. Evaluation and treat-ment of the patient with a pituitary incidentaloma. J ClinEndocrinol Metab 80:36


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AcknowledgmentsThe members of the Task Force thank The Endocrine Societys Clinical Guidelines Subcommittee, Clinical AffairsCore Committee, and Council for their careful, critical review of earlier versions of this manuscript and theirhelpful comments and suggestions. We also thank the leadership of the European Society of Endocrinology for their

review and comments. In addition, we thank the many members of The Endocrine Society who reviewed the draftversion of this manuscript when it was posted on the Societys web site and who sent a great number of additionalcomments and suggestions, most of which were incorporated into the nal version of the manuscript. Finally, wethank the staff at the Society ofce for their helpful support during the development of this guideline.

Financial Disclosure of Task ForcePamela U. Freda, M.D.* Financial or Business/Organizational Interests: Novartis, Ipsen, and Pzer; SignicantFinancial Interest or Leadership Position: none declared. Albert M. Beckers, M.D., D.Sc., Ph.D. Financial orBusiness/Organizational Interests: Novartis, Ipsen, and Pzer; Signicant Financial Interest or Leadership Position:none declared. Laurence Katznelson, M.D. Financial or Business/Organizational Interests: Novartis, Ipsen, and

Novo Nordisk; Signicant Financial Interest or Leadership Position: none declared. Mark E. Molitch, M.D. Financial or Business/Organizational Interests: Tercica/Ipsen, Novartis; Signicant Financial Interest or LeadershipPosition: none declared. Victor M. Montori, M.D.* Financial or Business/Organizational Interests: KER Unit(Mayo Clinic); Signicant Financial Interest or Leadership Position: none declared. Kalmon D. Post, M.D. Financial or Business/Organizational Interests: none declared; Signicant Financial Interest or Leadership Posi-tion: none declared. Mary Lee Vance, M.D. Financial or Business/Organizational Interests: Novartis; SignicantFinancial Interest or Leadership Position: none declared.

*Evidence-based reviews for this guideline were prepared under contract with The Endocrine Society.


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Developed independently by a team of experts, evidence-based, and vetted through a rigorous, multi-step peer reviewprocess, the Pituitary Incidentaloma Guideline addresses:

Initial evaluation of a patient with a pituitaryincidentaloma

Follow-up testing of the pituitary incidentaloma Indications for surgical therapy of the pituitary

incidentaloma

2011 The Endocrine Society

NEW


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Commercial Reprint InformationFor information on reprint requests of 101 and more and commercial reprints contact:

Karen BurkhardtWalchli Tauber Group Inc

Phone: 443.512.8899, ext. 111Email: [email protected]

Single Reprint InformationFor information on reprints of 100 and fewer, complete the guideline order form and return using one of thefollowing methods:

Mail: The Endocrine SocietyPO Box 17020

Baltimore, MD 21297-1020

Fax: 301.941.0257Email: [email protected]

Questions & CorrespondencesThe Endocrine SocietyAttn: Government & Public. Affairs Department8401 Connecticut Avenue, Suite 900

Chevy Chase, MD 20815

Phone: 301.941.0200Email: [email protected]: www.endo-society.org

For more information on The Endocrine Societys Clinical Practice Guidelines,visit: http://www.endo-society.org/guidelines/index.cfm

To view patient guides (companion pieces to the clinical practice guidelines) visit The Hormone Foundationswebsite at: http://www.hormone.org/Resources/patientguides.cfm.

Visit http://www.guidelinecentral.com to purchase pocket cards developed from select Endocrine Society guidelines.


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The Endocrine Society8401 Connecticut Avenue, Suite 900

Chevy Chase, MD 20815

301.941.0200www.endo-society.org

Documents

032811 PituitaryIncident FinalA-2