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V Vasilev, L Rostomyan and Pituitary incidentaloma 175:4 R171–R184 Review others

Management of endocrine disease Pituitary ‘incidentaloma’: neuroradiological assessment and differential diagnosis

Vladimir Vasilev1,2,*, Liliya Rostomyan1,*, Adrian F Daly1, Iulia Potorac1, Sabina Zacharieva2, Jean-François Bonneville1 and Albert Beckers1 Correspondence should be addressed 1Department of , Centre Hospitalier Universitaire de Liège, University of Liège, to A Beckers Belgium and 2Clinical Centre of Endocrinology and Gerontology, Medical University, Sofia, Bulgaria Email *(V Vasilev and L Rostomyan contributed equally to this work) [email protected]

Abstract

Pituitary incidentalomas are a by-product of modern imaging technology. The term ‘incidentaloma’ is neither a distinct diagnosis nor a pathological entity. Rather, it is a collective designation for different entities that are discovered fortuitously, requiring a working diagnosis based on the input of the radiologist, endocrinologist and often a neurosurgeon. In addition to pathological conditions affecting the , a thorough knowledge of the radiological characteristics of normal variants and technical artifacts is required to arrive at an accurate differential diagnosis. After careful radiological and hormonal evaluation, the vast majority of pituitary incidentalomas turn out to be non-functioning pituitary microadenomas and Rathke’s cleft cysts (RCCs). Based on the low growth potential of non-functioning pituitary microadenomas and RCCs, periodic MRI surveillance is currently considered the optimal management strategy. Stricter follow-up is required for macroadenomas, as increases in size occur more frequently. European Journal of Endocrinology (2016) 175, R171–R184 European Journal European of Endocrinology

Introduction

New diagnostic and therapeutic methods influence scan. Hence, it is a challenge to know what to do when in many positive ways. However, besides faced with such ‘diseases of modern technology’ that are the obvious benefits they also have some unintended often termed incidentalomas. consequences. Modern radiological investigations are The term ‘incidentaloma’ can be applied to a random no exception. High-resolution imaging provides the discovery in any organ. In everyday clinical practice, opportunity to visualize anatomical structures more incidentalomas are most frequently found in kidneys, clearly. On the other hand, it increases the number of gland, liver, adrenal glands and pituitary gland. findings that are unrelated to the reason for the original However, incidentalomas of endocrine glands present

Invited Author’s profile Dr Albert Beckers, MD PhD is the Chief of the Department of Endocrinology at the University Hospital Centre, Liège and Full Professor at the University of Liège, Belgium. He oversees a department with multiple clinical and research areas of interest, including pituitary tumors, , genetic causes of endocrine cancers and rare inherited syndromes. Dr Beckers has authored a highly regarded series of digital projects on pituitary disease and has published more than 250 original articles in prestigious peer-reviewed journals. His research for which he received the 2016 Geoffrey Harris Prize, includes the original characterization and description of the syndrome, familial isolated pituitary adenomas (FIPA), and a newly described pediatric syndrome X-linked acrogigantism (X-LAG).

www.eje-online.org © 2016 European Society of Endocrinology Published by Bioscientifica Ltd. DOI: 10.1530/EJE-15-1272 PrintedinGreat Britain

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10.1530/EJE-15-1272 Review V Vasilev, L Rostomyan and Pituitary incidentaloma 175:4 R172 others

additional challenges not only for their high prevalence, The aim of this review is to discuss the differential but also for the risk of autonomous hormonal activity or diagnosis of pituitary incidentalomas from the radiologist’s for impairing normal glandular function. As frank clinical and endocrinologist’s perspectives. manifestations are characteristically absent, resolving the true hormonal status of incidentalomas may be challenging. Recent progress in neuroimaging has resulted How frequent are pituitary incidentalomas? in increased recognition of sellar and parasellar lesions. In order to be termed as a pituitary incidentaloma, the Data on the prevalence of pituitary incidentalomas imaging investigation should be performed in patients is generally derived from retrospective autopsy and without overt signs and symptoms of pituitary disease. imaging studies. The estimated figures vary widely from Pituitary adenomas and Rathke’s cleft cysts (RCCs) are 1.5 to 38% depending on the era of the study and the the most frequently encountered incidentally discovered study population. This variability reflects differences in entities in the pituitary region. However, the differential definitions of pituitary incidentaloma used by the authors diagnosis of an incidentally discovered sellar mass is much (asymptomatic, non-functioning or broader and includes a large number of other entities incidentally noted lesion); the type of the study (autopsy (Table 1) (1). or radiological) and the imaging technique (CT, 1.5 T or 3.0 T MRI) (2, 3). Table 1 Differential diagnosis of pituitary incidentalomas. In the largest meta-analysis of autopsy studies comprising 18 902 examined pituitaries from 32 series, Anterior pituitary tumors the mean prevalence of pituitary incidentaloma was Pituitary adenoma Pituitary 10.7% (range 1.5–31%) (2). Lesions were uniformly Pituitary carcinoma distributed between sexes and among adult age groups. Posterior pituitary tumors Importantly, the prevalence of macroadenomas in autopsy series is <1% (2). Some studies report slightly increased Granular cell tumors Benign parasellar tumors prevalence in the elderly population (4, 5). Kastelan and Meningioma Korsic suggested that an age-related decline in peripheral Craniopharyngioma hormonal secretion could lead to compensatory feedback Neurinoma stimulation of gonadotropic cells, thereby stimulating the Lipoma Malignant tumors early stages of pituitary tumor development (4). European Journal European of Endocrinology Glioma The radiological prevalence of incidentalomas in Germ cell tumor the sellar and parasellar regions has increased with Primary lymphoma Chordoma technological advances (6, 7, 8, 9, 10). Earlier studies were Chondrosarcoma performed using CT, which is considered less sensitive Chondroma than MRI for detecting lesions of the pituitary. Pituitary Ependymoblastoma incidentalomas detected during PET have also been Plasmocytoma Pituitary metastases reported in clinical case studies and in retrospective series Malformative lesions of patients with cancer (11, 12, 13, 14, 15). MRI studies Rathke’s cleft cyst in unselected populations report micro-incidentaloma Dermoid cyst Epidermoid cyst rates of 10–38% (16, 17). Similar to autopsy series the Arachnoid cyst percentage of macroadenomas is quite low: 0.2% in CT Hamartoma series (18) and 0.16–0.3% in MRI studies (19, 20). These Inflammatory and granulomatous lesions data derived from normal populations or apparently Lymphocytic hypophysitis Granulomatous hypophysitis asymptomatic patients are in contrast with the prevalence Langerhans cell histiocytosis of clinically relevant pituitary adenomas, which is closer Tuberculosis to 1 case per 1064–1200 (21, 22). It is clear that few of Sarcoidosis the incidentally discovered microadenomas in pathology Pituitary abscess Vascular lesions and radiology series progress to macroadenomas (2, 3). Aneurysms The proportion of macroadenomas, however, is higher Cavernous angiomas in some neuroradiological series, where imaging was Cavernous sinus thrombosis performed in patients with non-specific symptoms/signs

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Downloaded from Bioscientifica.com at 09/30/2021 02:05:41PM via free access European Journal of Endocrinology narrow sellainanadolescentgirl (C). enhancement showsmarkedupward bulgingofthenormalpituitaryglandwithextensive sphenoid sinuspneumatizationanda normal pituitarygland;and(B) smallsellaandthickdorsumsellae(arrow).CoronalT1-weightedimageaftercontrast Small sella.agittalT1-weightedimagesshow( A) smallorflatsella,extensive pneumatization ofsphenoidsinus,andabulging Figure 1 of gadoliniumcontrastagents(30).Properlyperformed andcarefuluse (to fullyevaluatetheposteriorpituitary), T2-weighted images,sagittalandaxialT1-weightedimages coronal spin-echoT1-weightedandfast items shouldbeobtained:useofhighmatrixsize(512), amount ofclinicallyusefulinformation,thefollowing are alsooftenacquired.Inordertogainthemaximum T1-weighted spin-echo gadolinium-enhanced images sagittal sectionswiththinslices.Coronaland/or T1-weighted andT2-weightedspin-echocoronal MRIstudiesusuallyincludepre-contrast pituitary fromcentertocenter,While individualpracticesvary Pitfalls inpituitaryimaging challenges wheninterpretingacquiredimages. inherent tohigh-resolutionscanningmayposeadditional anditsadjacentstructures.Noiseartifacts the pituitary field MRI allows for multiplanar high contrast images of sella andcalcifications(29).Theincreasinguseofhigh- in theevaluationofchangesbonestructure rolemainlyforitsadvantages CT hasasupplementary lesions,while assessment ofthemajoritypituitary disorders, visualloss,andsyncope(23,25,27,28). spine or transientischemicattacks,sinusitis,cervical indications included trauma, cerebrovascular accidents most oftenforinvestigationofheadache(40%).Other lesions,imagingwasperformed discovered pituitary ( 23, 24,25,26).Inthelargestseriesofincidentally Review Currently MRIisthemodalityofchoicefordetailed others V Vasilev, LRostomyanand pituitary. some incidentalfindingsmaybevariantsofthenormal partial volume,chemicalshiftorpulsatility. Occasionally recognizing artifactssuchasmagneticsusceptibility, by using pulse sequences adapted for the sella and by of certainsellarlesions. Diagnostic pitfallscan be avoided of significantadditionaluseinthedifferentialdiagnosis chance. Whilenotusedroutinely, axialsequencescanbe the routinesettingwhenasellarlesionisdiscoveredby lesion progression,buttheseareoftennotperformedin volumetric assessmentscanbehelpfulforfollow-upof adolescent femalesthepresenceofasmallornarrowsella fossadiameter.anteroposterior pituitary Furthermore,in or consistingoffatandbone,candecreasethe sellar aperture.Athickdorsumsellae,eitherpneumatized glandmayprojectbeyondthe In suchcasesthepituitary fossa. of thesinusmaylimitdepthpituitary associated withasmallsellasincethepneumatization hyperpneumatization ofthesphenoidsinusmaybe hyperplasia’.Inadults, adenomaor‘pituitary pituitary mass such as isointenseincorrect diagnosis of a pituitary fossaandcanleadtoan of thecontentpituitary anatomical variantcanbemistakenforanenlargement visualized inarelativelysmallsella(31,32).Thisnormal is onimageswhereanormal-sizedpituitary pituitary turcica sometimesproduces apseudoenlargementofthe The inter-individualvariabilityofthesizesella The smallsella Pituitary incidentaloma Downloaded fromBioscientifica.com at09/30/202102:05:41PM 175:4 www.eje-online.org R173 via freeaccess Review V Vasilev, L Rostomyan and Pituitary incidentaloma 175:4 R174 others

Figure 2 Enlarged pituitary content of multiple origins in a female with intracranial hypotension after failed lumbar puncture. Sagittal (A) and coronal (B) T1-weighted, coronal T1-weighted contrast-enhanced (C) and coronal T2-weighted (D) images reveal a large T1-isointense RCC with an intracystic T2-hypointense nodule (curved arrow) associated with an enlarged inferior coronary sinus (thin arrows).

can increase the physiological convexity of the pituitary pituitary hyperplasia due to hypersecretion of releasing (Fig. 1). Therefore, in cases of an enlarged pituitary gland hormones (corticotropin-releasing hormone and growth with normal T1 and T2 signals and normal enhancement hormone-releasing hormone) should also be ruled out after gadolinium injection, a small sella should be when such diffuse pituitary abnormalities are revealed on considered in the differential diagnosis. The degree of MRI (Fig. 4) (40, 41, 42, 43). Recent reports suggest that a the pneumatization of the sphenoid sinus, the shape lack of sex hormone feedback might induce development of the dorsum sellae and the width of the sella should of pituitary hyperplasia in (44). also be taken in account. Other possible conditions that may be associated with upward convexity of the pituitary gland include isointense holosellar pituitary Technical artifacts adenoma and an isointense Rathke’s cleft cyst which A number of artifacts may complicate the correct European Journal European of Endocrinology are infrequent (Fig. 2). Although rare, the volume of a interpretation of sellar and parasellar MRI (30). They can normal-sized sella can also be reduced by an unusually easily mimic intrasellar lesions, in particular pituitary large inferior coronary sinus, a sellar spine or a medial microadenomas. Partial volume artifacts occur when a deviation of the internal carotid arteries (‘kissing’ carotid 3 mm thick cut includes parts of different anatomical arteries) or trigeminal arteries (Fig. 3). structures, such as anterior pituitary gland and sphenoid sinus anteriorly, dorsum sellae posteriorly, or intracavernous internal carotid arteries laterally. In such Physiological and secondary pituitary enlargement cases the average intensity of the different components Another incidental finding on neuroimaging is an of the cut section calculated by the computer can increase in pituitary size following physiological simulate an intrasellar tumor. Partial volume effects can hypertrophy of pituitary cells (33). A number of imaging be eliminated by coupling orthogonal projections or by studies of healthy volunteers reported sex-dependent using 1 mm thick cuts. Magnetic susceptibility artifacts and age-dependent variations in size and contour of are responsible for geometrical distortion and localized normal pituitary. In up to half of young women the signal intensity changes at the interface between superior pituitary contour is convex, although the size of anatomical structures with different signal intensities, the pituitary rarely (0.5%) exceeds 9 mm (34, 35, 36, 37). predominantly in the case of a curved interface. Magnetic The increase in height of the normal pituitary, generally susceptibility artifacts are often present at the level of the observed in younger women, could be due to age-related sellar floor and are more pronounced on 3.0 T MRI, but changes of the hypothalamic–pituitary–gonadal axis (38, these can be accounted for with technical adjustments. 39). Lactotroph hyperplasia during pregnancy, thyrotroph Chemical shift artifacts and ghosting are related to the hyperplasia due to severe primary or high signal of fat. They can compromise the visualization

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Downloaded from Bioscientifica.com at 09/30/2021 02:05:41PM via free access European Journal of Endocrinology sagittal T2-weightedimage(B). image (A).T internal carotidarteries(arrows)oncoronalT1-weighted Vascular anomaliesnarrowing thesellarcontent.‘Kissing’ Figure 3 posterior lobeitself,which isbeyondthemidlinein 5 ). Thetopographyofthe T2-weighted images(Fig. adenomaoncoronal for aposteriorlylocatedpituitary and itsfossulahypophyseos sometimescanbemistaken can be useful insuch cases. A prominent posteriorlobe fatty, particularlyon3.0TMRI.Fatsaturation techniques axial T1-weightedsectionswhenthedorsumsellae is of thestoragevasopressininposteriorlobeon Review rigeminal arterypiercingthedorsumsellaon others V Vasilev, LRostomyanand mistakes indiagnosis. the natureofincidentallesions inordertoavoidpossible of theseartifactsshouldbe consideredwhenclarifying fossaorthesubarachnoidspaces.All pollute thepituitary fluid. Theyaremoresevereon3.0TMRIandcanblur or to pulsatinginternalcarotidarteriesandcerebrospinal axial T1-weightedimages.Fluxartifactsarisemainlydue about halfofcases,isreadilyvisualizedonnon-enhanced pituitary isshownwitharrow). and coronal(B)T1-weightedimages(upwardconvexityofthe enlargement ofahomogeneouspituitaryglandonsagittal(A ) Primary hypothyroidismina9-year-old girl.Regular Figure 4 Pituitary incidentaloma Downloaded fromBioscientifica.com at09/30/202102:05:41PM 175:4 www.eje-online.org R175 via freeaccess Review V Vasilev, L Rostomyan and Pituitary incidentaloma 175:4 R176 others

Subclinical Cushing’s disease occurred in about 4% of histologically confirmed incidentaloma cases. Systematic screening for hypercortisolism and silent adrenocorticotropic hormone (ACTH)-secreting tumors should be considered at the time of identification of a pituitary incidentaloma (50). Distinguishing pituitary adenomas from other non- adenomatous lesions may be quite challenging. However, there are some radiological characteristics that may provide clues to the diagnosis. Figure 5 Posterior lobe mimicking a pituitary lesion on coronal Solid lesions T2-weighted image (arrow) (A). Deep fossula hypophyseos on axial CT (B). The differential diagnosis of a solid mass in the sellar regions should start with a pituitary adenoma. There may Determining the nature of pituitary be areas of necrosis and hemorrhage with different signals incidentalomas on T1-weighted and T2-weighted sequences (51). In cases Pituitary adenomas and Rathke’s Cleft cysts (RCCs) are of cavernous sinus invasion, the internal carotid artery is the most common entities in patients with pituitary usually unaffected (51). Intrasellar microadenomas (<10 incidentalomas and account for up to 90% of all lesions mm) have some specific characteristics: lateralization (6, 27, 28, 45). Other etiologies are less frequent – other inside the adenohypophysis, possible deformation tumors, mostly craniopharyngiomas in 4.2–5.6% and of the sellar diaphragm and displacement of the cystic malformations in 2.9–5.2% (46, 47, 48). It should pituitary stalk. Classically, microprolactinomas appear be noted that these figures come generally from surgical hypointense on T1-weighted images and hyperintense on series since definitive diagnosis is only possible after T2-weighted sequences (Fig. 6), while many GH-secreting histopathological examination. The proportions of the microadenomas can be isointense or hypointense on two most common entities – pituitary adenomas and T2-weighted sequences (46). The enhancement after RCCs – also depend on the localization of the lesions. In contrast injection is often minimal. About 5–10% of cases of suprasellar lesions adenomas predominate, while microadenomas are discovered exclusively on post- European Journal European of Endocrinology RCCs are more common among intrasellar lesions. contrast images (30, 51, 52). Dynamic imaging with The majority of incidental pituitary adenomas are contrast is not always useful and may cause false-positive small clinically non-functioning tumors. Secreting results. In 50% of normal glands, the posterior pituitary is adenomas usually present with clinical symptoms of off the midline (JF Bonneville, Personal Communication). hypersecretion that facilitate their diagnosis, although If only the early phase of dynamic imaging is considered subtle hormonal changes may not be clinically evident. (when only the posterior pituitary but not the In a recent study, 77% of incidentally discovered adenohypophysis is enhanced), this can falsely mimic a pituitary adenomas were found to be non-functioning, pituitary adenoma (Fig. 7). 18% were and 3% were growth hormone secreting; the prevalences of different secretion patterns may be biased by the study population and the reason for pituitary imaging (28). Many large series of pituitary incidentalomas exclude hyperfunctioning adenomas and the overall prevalence of different secretory types is, therefore, not well established. Moreover, some patients with hypersecreting pituitary tumors discovered incidentally have clinical manifestations that were unrecognized at the initial examination (25). Such incidentally found functioning adenomas are usually Figure 6 prolactinomas. Unsuspected can be revealed Microprolactinoma. The adenoma (arrows) is T1-hypointense in some cases of pituitary incidentalomas (28, 49). (A) and T2-hyperintense (B) on coronal images.

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Downloaded from Bioscientifica.com at 09/30/2021 02:05:41PM via free access European Journal of Endocrinology that about5–10%ofgermcell tumorsarefoundbothin rarely causediabetesinsipidus. Taking intoaccount the posteriorlobeor infundibulum, thesetumors adenohypohysis anteriorly. Althoughoriginatingfrom gray matterinT1andsometimes displacethenormal These lesions are usually isointense compared with considered whenassessingintrasellarmasses(48,53 ). pituicytoma andgranularcelltumorsmustalsobe is, however, arareevent(56). carotid lumen resulting in cerebrovascular insufficiency the cavernoussinus(55).Substantialnarrowingof is often compressed when the meningioma invades artery 8)(47).Theinternalcarotid called the‘duraltail’(Fig. and homogeneouswithalinearthickeningofthedura T2-weighted imagesandtumorenhancementisintense are isointenseinT1-weightedimagesandhyperintense tissue canbevisualizedunderthetumor. Meningiomas do notenlargethesizeofsellaandnormalpituitary be distinguished from other sellar lesions (54). They usually Their imagingcharacteristics,however, oftencanthemto headache, visualdisturbancesandhypopituitarism(53). adenomaswith picture ofnon-functioningpituitary arachnoid cellsoftheduraandcanoftenmimicclinical region. They arise from the tumors in the pituitary (arrow) onanaxialT1-weightedimage. shows normaloff-midline locationoftheposteriorlobe pituitary simulatingaadenoma(arrow).Panel(D) magnification ofnormaldelayedenhancementtheanterior Normal dynamicimaging(A,BandC).Panel)shows Figure 7 Review Tumors arisingfromthe neurohypophysislike Meningiomas arethesecondmostcommonsolid others V Vasilev, LRostomyanand sellar diaphragm(46,48).PEThasalsobeensuggested stalk,boneerosions,andinvasionofthe of thepituitary include lossofposteriorlobe brightspotandthickening distinguishing featuresofmetastasis, albeitnon-specific, adenomasinappearance.Some are similartopituitary serious clinicaldifficultiesbecausemetastaticlesions are morelikelytobedetected.Suchcasescanpresent cancer,primary lesions othernon-metastaticpituitary However, while searching forbrain disseminationofa metastatic lesionsarenotconsideredincidentalfindings. tumor,In patients with a known primary likely the posteriorlobeandpresentswithdiabetesinsipidus. region.Metastasis usuallyaffects rarely tothepituitary and lungcarcinomas, havebeenreportedtometastasize fortuitous. Somesolidmalignanttumors,especiallybreast detection asanincidentalfindingwouldbeextremely symptoms, hypopituitarismanddiabetesinsipidus.Their silent forlongandusuallypresentwithcompression region (58).Malignanttumors,however, seldomremain lymphomas havealsobeendescribedintheparasellar CNS the optictract/hypothalamus(46,48,57)Primary braintumorslikegliomasoriginatingfrom primary suprasellar regionissometimestheoriginofmalignant bifocal lesionscanaidinthedifferentialdiagnosis.The the suprasellarandpinealregions,findingofsuch with asterisk). has strongerenhancementthanthepituitarygland(marked a meningiomainsertedontheplanumsphenoidale(arrow).It T1-weighted sagittal(C)andcoronal(D)imagesdemonstrate T2-weighted (B)sequencesandcontrast-enhanced Presellar meningioma.SagittalT1-weighted(A)and Figure 8 Pituitary incidentaloma Downloaded fromBioscientifica.com at09/30/202102:05:41PM 175:4 www.eje-online.org R177 via freeaccess Review V Vasilev, L Rostomyan and Pituitary incidentaloma 175:4 R178 others

Figure 10 Mucoid T1-hyperintense RCC on axial T1-weighted image (A), located in the midline between the anterior and posterior lobes. A coronal T1-weighted image (B) shows an RCC on the upper surface of the pituitary, as an ‘egg in an egg cup’.

Cystic lesions Figure 9 Incidentally found cystic lesions in the sellar and Lymphocytic hypophysitis. Coronal T1-weighted (A) and parasellar region need to be distinguished from a T2-weighted (B) sequences and contrast-enhanced necrotic pituitary adenoma and non-pituitary entities T1-weighted coronal (C) and sagittal (D) images show such as RCCs, dermoid and epidermoid cysts, and cystic enlarged sellar content abutting the optic chiasm (curved craniopharyngiomas. Necrotic macroadenomas usually arrow). The lesion is T1-isointense, T2-hyperintense, and lead to sellar enlargement and the walls of the tumor becomes markedly enhanced after gadolinium injection. The show distinct contrast uptake (51). A fluid level may be dural tail is shown with arrows. present in some cases. as being useful to differentiate malignant from benign RCCs are malformations that originate from the lesions. Positive PET findings can be consistent with remnant of the squamous epithelium of Rathke’s pouch and malignant lesions rather than benign ones (59). There is consist of a single layer of cuboidal or columnar epithelial a significant overlap, however, between the appearances cells filled with cystic components (64, 65). RCCs occur European Journal European of Endocrinology of metastatic lesions, meningiomas and adenomas mostly in adults and usually are small and asymptomatic on PET images, hence caution should be used in their and as such they are the most common cystic pituitary interpretation (13, 14, 60). incidentaloma and can be found in up to 22% at autopsy Chordomas and chondromas are rare bone- (46). Most of these lesions are intrasellar, but they can destroying tumors that arise from the primary notochord also lie on the sellar diaphragm, as ‘an egg in an egg cup’ and cartilaginous remnants respectively (48). They (Fig. 10). They can expand above the sellar region and can mimic invasive macroadenomas with inferior may become symptomatic causing compression of the expansion (51). Occasionally the normal pituitary optic tract or pituitary dysfunction. The basal MRI signal tissue can be distinguished above the tumor, which of RCC is highly variable and depends on the content of can help in its differentiation from invasive pituitary the cyst, which can be serous or mucinous (66). They are adenomas (61). Lymphocytic hypophysitis is another more frequently hyperintense on T1-weighted images. entity to be considered in the differential diagnosis of Characteristic of RCC are T2-hypointense intracystic symmetric homogeneous enlargement of the pituitary. nodules formed by cholesterol and are observed in 70% This autoimmune disorder usually affects women in of T1-hyperintense RCC. Usually the cyst wall does not the peripartum period and is characterized by frequent enhance after contrast administration, except in cases of suprasellar extension, thickening of the stalk and complications such as infection, hemorrhage or rupture intensive contrast accumulation (Fig. 9) (62, 63). Again, (Fig. 11) (64). Intrasellar RCCs cause no or limited mass most of these conditions are associated with clinical effects, whereas pituitary adenomas may imprint the symptomatology and would be exceptional findings if bony contours of the sella, compress the posterior lobe discovered fortuitously. and displace the pituitary stalk.

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Downloaded from Bioscientifica.com at 09/30/2021 02:05:41PM via free access European Journal of Endocrinology lesions maybedifficult. Dermoid cysts usuallycontainfat are non-specificandtheirdifferentiation fromothercystic cutaneous ectoderm(48).Theirimagingcharacteristics incomplete separationofthe neuroectodermfromthe region. Theyincludeepithelialelementsresultingfrom often ariseinthemidlinesellarandparasellar definitive diagnosis. both MRIandCTshouldbeperformedtoestablish a lesionandasuspicionofcraniopharyngioma, pituitary 74, 75). In all patients with an incidentally discovered (46,72,73, characteristicofacraniopharyngioma very rim (71). Although calcifications are not specific, they are T1-weighted sequences with a thincontrast-enhancing T2-weighted sequences.Thecysticpartishyperintenseon or hypointense on T1-weighted and hyperintense on usually appears isointense portion of craniopharyngiomas calcification, andthecontentsofcyst(70).Thesolid and cysticcomponents,thepresenceorabsenceof on MRIvariesdependingtheproportionofsolid and diagnosiscanbedelayed(67).Theappearance however, thesesymptomsmaynotberecognizedinitially anddiabetesinsipidus.Inchildren, commonly presentwithheadache,visualdisorders, (69). Hence,theyrarelyremainasymptomaticandmost have anaggressivebehaviorandatendencytoinfiltrate arebenigntumors,theyusually craniopharyngiomas cases andinalmostallchildren(68).Although in nature.Calcificationsarepresenttwo-thirdsofall predominantly cystic, predominantly solid or mixed cells oftheremnantsRathke’s pouchandcanbe occurrence intheelderly(67).Theyarisefromsquamous and adolescents,butthereisalsoanotherpeakof complicated RCC. enhanced. Panel(B)showscystwallenhancementofa Panel (A)showstheusualpattern:cystwallisnot RCC oncoronalT1-weightedimageaftergadoliniuminjection. Figure 11 Review Dermoid andepidermoidcystsareotherlesionsthat occurinchildren About 50%ofcraniopharyngiomas others V Vasilev, LRostomyanand enhanced bygadolinium(74). on T1-weightedandT2-weightedsequencesarenot defined lesionsthatareisointensetocerebrospinalfluid intrasellar orsuprasellar(76).OnMRItheyappearaswell- diverticulum throughthesellardiaphragmandcanbe Arachnoid cystsarerareherniationsofthearachnoid cerebrospinal fluidwithnocontrastenhancement(65). contain keratinandarealmostidenticalinappearanceto hyperintense onT2images(46,65,76).Epidermoidcysts components andareheterogeneousonT1images are severe or progressive – in such cases surgery may are severeorprogressive– insuchcasessurgery largely managed conservatively, except when symptoms like lymphocyticandgranulomatous hypophysitisare compression symptoms.Infiltrative lesions,however, frequent tumors as well as large cysts when these cause and otherless meningiomas, craniopharyngiomas other lesionsinthesellarandparasellarregionslike Usually surgicalreferralisalsoindicatedinmany of which mayprovideimportantclinicalimprovements. the case of prolactinomas and acromegaly respectively, somatostatin analogscanproducetumorshrinkage in deciding thetreatmentstrategy. are importantissuesthatneedtobeconsideredwhen The age of the patients and their general health status metastases(77). lesions,particularlypituitary pituitary a commonclinicalmanifestationassociatedwithother adenomas,whereasitis occurs infrequentlyinpituitary and signsoftumormasseffect.Diabetesinsipidus visual abnormalitiesduetocompressionofopticchiasm lesionscausing secreting andnon-secretingpituitary remains the treatment of choice for many Neurosurgery surgicalinterventions. can helptoavoidunnecessary and physiologicalvariationstechnicalartifacts by hormonal evaluation. Close attention to normal hyposecretion thatmayhavebeenoverlooked,followed performed for signs and symptoms of hypersecretion or secretion). Thoroughclinicalexaminationshouldbe hormonal status (hyposecretion/hypersecretion/normal symptomatology (visualandneurologicaldisorders), etc.),itssizeandclinical RCC, craniopharyngioma, adenoma, suspected natureofthetumor(pituitary of incidentallyfoundsellarlesionsdependsonthe with adecisionabout what todo.Themanagement and adifferentialdiagnosismade,theclinicianisfaced incidentalomahasbeendiscovered Once apituitary To treat ornottotreat? Pituitary incidentaloma Medical therapywithdopamineagonistsand Downloaded fromBioscientifica.com at09/30/202102:05:41PM 175:4 www.eje-online.org R179 via freeaccess Review V Vasilev, L Rostomyan and Pituitary incidentaloma 175:4 R180 others

be performed or corticosteroids may be used. (63, 78, having greater growth potential. In a systematic review 79, 80) Primary lymphomas in the region are managed and meta-analysis, Fernandez-Balsells and coworkers. with chemotherapy and radiotherapy and rarely surgically, reviewed the natural history of incidentalomas and although stereotactic biopsy may be needed for accurate non-functioning pituitary adenomas (85). In a group diagnosis (61). of 11 studies (patient number ranged from 50 to 289 As the vast majority of pituitary incidentalomas are per study), the authors reported a higher incidence of non-functioning pituitary adenomas and most of these tumor growth in macroadenomas and solid lesions as are microadenomas, the decision about their management compared with microadenomas and cystic lesions (85). is determined by their growth potential. The behavior of Macroadenomas and microadenomas had incidences of incidentally found pituitary adenomas has been studied tumor growth of 12.53 and 3.32 per 100 patient-years by a number of separate groups worldwide (25, 49, 81, respectively. Although data quality was poor (due to 82, 83, 84). Based on the current data regarding the small numbers of studies with heterogeneous designs), natural history of small incidentally discovered non- macroadenomas had a significantly higher incidence functioning adenomas, watchful waiting is considered of new endocrine dysfunction (11.9 per 100 patient- the most appropriate strategy (1). The growth potential years) and visual field worsening (0.5 per 100 patient- of non-functioning pituitary adenomas is heavily years), as compared with microadenomas (85). In other dependent on their size at diagnosis, with larger tumors detailed reviews, tumor enlargement occurred in 10% European Journal European of Endocrinology

Figure 12 Flowchart for decision making in the management of pituitary incidentaloma.

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Downloaded from Bioscientifica.com at 09/30/2021 02:05:41PM via free access European Journal of Endocrinology ). per patient(notincluding follow-up assessments)(91). suggests theinitialevaluation costs>6000USdollars widely availablefordifferent countries,theUSexperience costs ofevaluationcanbesignificant. Whiledataarenot patients withincidentally found microadenomas,the yardstick toassessanychangeovertime.Inasymptomatic endocrine change is present at diagnosis, and to provide a warranted, bothtoestablishwhetheranyclinicallyrelevant expand aggressively(51).Baselinehormonalevaluationis although thisapproachcouldmisstherarelesionsthat for non-functioningmicroadenomas<5 needsto beimplemented suggested thatnosurveillance ifnogrowthoccurs. Othershaveeven frequently afterward, 1–2 yearsformicroadenomasthenext3 years andless should be repeatedannuallyfor macroadenomas andevery MRI microadenomas. Whennotumorgrowthisobserved, for for macroadenomasandafter1yearthediscovery MRI 6monthsaftertheinitialincidentaldiscovery consensus guidelinesrecommendperformingafollow-up follow-up alsodependsontumornatureandsize.Current and radiologicalevaluation(1,90). might besafelyfollowedupwithcarefullaboratory other cystic lesions may stay stable without growth and decrease insizearecystic(25).Thus,manyRCCsand in size.Furthermore, more than 50% oftumorsthat months, whileonly5.3% of 94probableRCCsincreased functioning adenomasenlargedoverthecourseof10–173 solid tumors(85).Duringfollow-up,20%of115non- itselfmayoccur.hypopituitarism duetosurgery can improvehypopituitarism,furtherworseningof must bestronglyconsidered(1 field defectsandvisionabnormalities,surgicaltreatment development of compression symptoms such as visual adenomasduringfollow-uporthe growth ofpituitary (0–41% ofmacroadenomas)(1,2).Incasessignificant or panhypopituitarismvariesgreatlyinpublishedseries incidentalomas(28).Thepresenceofpartial pituitary the usualcauseofhypopituitarisminpatientswith in mostcases(83,88,89).Macroadenomasarealso 10, 85,86,87),althoughvisuallossmaybereversible size andmostfrequentlyoccuringrowingtumors(2, occurrence ofapoplexydirectlydependontumor suchasvisualdisturbancesandthe symptoms cases (2,73). growth in macroadenomascan occur in up to 24% of (2 during 2.5–8yearsofobservation of microadenomas,withtumorreductionseenin6% Review The duration and periodicity of radiological The durationandperiodicityofradiological Cystic lesionsincreaseinsizelessfrequentlythan The developmentandworseningofclinical others V Vasilev, LRostomyanand ). Although surgery ). Althoughsurgery ). Incontrast,tumor mm in size, mm insize,

treatment teams. require activeandregularfollow-upbymultidisciplinary lesions associatedwithhormonalorlocalsymptoms, Largeorgrowinglesions,pituitary surveillance. by periodical MRI monitoring allied with simple clinical inmostcases that theycanbemanagedconservatively adenomasorRCCsandcurrentdatasuggest pituitary lesionsturnouttobenon-functioning found pituitary isrequired.Themajorityofincidentally neurosurgery among specialistsinradiology, endocrinologyand clues forthedifferentialdiagnosis,closecollaboration 12.Sinceimagingcharacteristicsprovidevaluable Fig. variants. Asuggesteddiagnosticpathwayisoutlinedin pathological conditionsfromnormalorphysiological the initialworkupshouldbefocusedondistinguishing of afortuitouslydiscoveredsellarorparasellarlesion, endocrinepractice.Inthecase common ineveryday lesions,andtheirevaluationisbecomingmore pituitary techniques has led to a rise in the detection of incidental Increased availability of high-quality neuroimaging Conclusions precise andeasiercomparisonwithpreviousimages. clinical center, usingthesameimagingprotocolsformore the follow-up analysis should be performed at the same the questionofMRIreproducibilityissignificant.Ideally, incidentalomas, particularlynon-functioningadenomas, particularly ofchronicallystablesmalllesions(1 expensesinlong-termfollow-up, avoid unnecessary adherence toexistingguidelines/recommendations incidentalomasand of thegrowthpotentialpituitary Cost containmentwillrequireimprovedunderstanding References Liège, Belgium. de RechercheScientifiques(FIR)oftheCentreHospitalierUniversitaire This researchwassupportedbyagrantfromtheFondsd’Investissement Funding perceived asprejudicingtheimpartialityofresearchreported. The authorsdeclarethatthereisnoconflictofinterestcould be Declaration ofinterest Pituitary incidentaloma 1 Metabolism 201196894–904.(doi:10.1210/jc.2010-1048) ofClinicalEndocrinologyand clinical practiceguideline.Journal Post KD &Vance ML. incidentaloma: anendocrinesociety Pituitary Freda PU, Beckers AM,Katznelson L, Molitch ME,Montori VM, For accurate follow-up evaluation of pituitary For accuratefollow-up evaluation ofpituitary Downloaded fromBioscientifica.com at09/30/202102:05:41PM 175:4 www.eje-online.org ). R181 via freeaccess Review V Vasilev, L Rostomyan and Pituitary incidentaloma 175:4 R182 others

2 Molitch ME. Pituitary tumours: pituitary incidentalomas. Best Practice MR imaging of the brain: data from the Cardiovascular Health Study. & Research: Clinical Endocrinology & Metabolism 2009 23 667–675. Radiology 1997 202 41–46. (doi:10.1148/radiology.202.1.8988190) (doi:10.1016/j.beem.2009.05.001) 20 Vernooij MW, Ikram MA, Tanghe HL, Vincent AJ, Hofman A, 3 Lania A & Beck-Peccoz P. Pituitary incidentalomas. Best Practice Krestin GP, Niessen WJ, Breteler MM & van der Lugt A. Incidental & Research: Clinical Endocrinology & Metabolism 2012 26 395–403. findings on brain MRI in the general population.New England Journal (doi:10.1016/j.beem.2011.10.009) of Medicine 2007 357 1821–1828. (doi:10.1056/NEJMoa070972) 4 Kastelan D & Korsic M. High prevalence rate of pituitary 21 Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA incidentaloma: is it associated with the age-related decline of the sex & Beckers A. High prevalence of pituitary adenomas: a cross- hormones levels? Medical Hypotheses 2007 69 307–309. (doi:10.1016/ sectional study in the province of Liege, Belgium. Journal of Clinical j.mehy.2006.11.044) Endocrinology and Metabolism 2006 91 4769–4775. (doi:10.1210/ 5 Char G & Persaud V. Asymptomatic microadenomas of the pituitary jc.2006-1668) gland in an unselected autopsy series. West Indian Medical Journal 22 Fernandez A, Karavitaki N & Wass JA. Prevalence of pituitary 1986 35 275–279. adenomas: a community-based, cross-sectional study in Banbury 6 Molitch ME. Nonfunctioning pituitary tumors and pituitary (Oxfordshire, UK). Clinical Endocrinology 2010 72 377–382. incidentalomas. Endocrinology and Metabolism Clinics of North America (doi:10.1111/cen.2010.72.issue-3) 2008 37 151–171. (doi:10.1016/j.ecl.2007.10.011) 23 Feldkamp J, Santen R, Harms E, Aulich A, Modder U & 7 Buurman H & Saeger W. Subclinical adenomas in postmortem Scherbaum WA. Incidentally discovered pituitary lesions: high pituitaries: classification and correlations to clinical data.European frequency of macroadenomas and hormone-secreting adenomas – Journal of Endocrinology 2006 154 753–758. (doi:10.1530/eje.1.02107) results of a prospective study. Clinical Endocrinology 1999 51 109–113. 8 Kim JH, Seo JS, Lee BW, Lee SY, Jeon SH & Lee KB. The characteristics (doi:10.1046/j.1365-2265.1999.00748.x) of incidental pituitary microadenomas in 120 Korean forensic 24 Arita K, Tominaga A, Sugiyama K, Eguchi K, Iida K, Sumida M, autopsy cases. Journal of Korean Medical Science 2007 22 (Supplement) Migita K & Kurisu K. Natural course of incidentally found S61–S65. (doi:10.3346/jkms.2007.22.S.S61) nonfunctioning pituitary adenoma, with special reference to pituitary 9 Auer RN, Alakija P & Sutherland GR. Asymptomatic large during follow-up examination. Journal of Neurosurgery 2006 adenomas discovered at autopsy. Surgical Neurology 1996 46 28–31. 104 884–891. (doi:10.3171/jns.2006.104.6.884) (doi:10.1016/0090-3019(96)00085-7) 25 Sanno N, Oyama K, Tahara S, Teramoto A & Kato Y. A survey of 10 Bancos I, Natt N, Murad MH & Montori VM. Evidence-based pituitary incidentaloma in Japan. European Journal of Endocrinology endocrinology: illustrating its principles in the management of 2003 149 123–127. (doi:10.1530/eje.0.1490123) patients with pituitary incidentalomas. Best Practice & Research: 26 Fainstein Day P, Guitelman M, Artese R, Fiszledjer L, Chervin A, Clinical Endocrinology & Metabolism 2012 26 9–19. (doi:10.1016/j. Vitale NM, Stalldecker G, De Miguel V, Cornalo D, Alfieri Aet al . beem.2011.06.003) Retrospective multicentric study of pituitary incidentalomas. 11 Hodolic M, Huchet V, Balogova S, Michaud L, Kerrou K, Nataf V, Pituitary 2004 7 145–148. (doi:10.1007/s11102-005-1757-1) Cimitan M, Fettich J & Talbot JN. Incidental uptake of (18) 27 Famini P, Maya MM & Melmed S. Pituitary magnetic resonance F-fluorocholine (FCH) in the head or in the neck of patients imaging for sellar and parasellar masses: ten-year experience in 2598 with prostate cancer. Radiology and Oncology 2014 48 228–234. patients. Journal of Clinical Endocrinology and Metabolism 2011 96 (doi:10.2478/raon-2013-0075) 1633–1641. (doi:10.1210/jc.2011-0168) 12 Weng JH, Lee JK, Wu MF, Shen CY & Kao PF. Pituitary FDG uptake 28 Anagnostis P, Adamidou F, Polyzos SA, Efstathiadou Z, Panagiotou A in a patient of lung cancer with bilateral adrenal metastases causing & Kita M. Pituitary incidentalomas: a single-centre experience. adrenal cortical insufficiency.Clinical Nuclear Medicine 2011 36 International Journal of Clinical Practice 2011 65 172–177. European Journal European of Endocrinology 731–732. (doi:10.1097/RLU.0b013e31821a26bf) (doi:10.1111/ijcp.2011.65.issue-2) 13 Jeong SY, Lee SW, Lee HJ, Kang S, Seo JH, Chun KA, Cho IH, Won KS, 29 Orija IB, Weil RJ & Hamrahian AH. Pituitary incidentaloma. Zeon SK, Ahn BC et al. Incidental pituitary uptake on whole-body Best Practice & Research: Clinical Endocrinology & Metabolism 2012 26 18F-FDG PET/CT: a multicentre study. European Journal of Nuclear 47–68. (doi:10.1016/j.beem.2011.07.003) Medicine and Molecular Imaging 2010 37 2334–2343. (doi:10.1007/ 30 Bonneville JF, Bonneville F & Cattin F. Magnetic resonance imaging s00259-010-1571-5) of pituitary adenomas. European Radiology 2005 15 543–548. 14 Hyun SH, Choi JY, Lee KH, Choe YS & Kim BT. Incidental focal (doi:10.1007/s00330-004-2531-x) 18F-FDG uptake in the pituitary gland: clinical significance and 31 Bonneville JF, Cattin F & Dietemann JL. Hypothalamic-pituitary differential diagnostic criteria. Journal of Nuclear Medicine 2011 52 region: computed tomography imaging. Baillière’s Clinical 547–550. (doi:10.2967/jnumed.110.083733) Endocrinology and Metabolism 1989 3 35–71. (doi:10.1016/ 15 Currie GM, Trifunovic M, Kiat H, Saunders C, Chung D, Ong YY, S0950-351X(89)80022-9) Wilkinson M, Witte K & Magnussen J. Pituitary incidentaloma found 32 Cattin F & Bonneville JF. [MRI study of the hypophysis]. on O-(2-18F-fluoroethyl)-l-tyrosine PET.Journal of Nuclear Medicine Journal of Neuroradiology 1996 23 133–138. Technology 2014 42 218–222. (doi:10.2967/jnmt.113.136291) 33 Chanson P, Daujat F, Young J, Bellucci A, Kujas M, Doyon D & 16 Hall WA, Luciano MG, Doppman JL, Patronas NJ & Oldfield EH. Schaison G. Normal pituitary hypertrophy as a frequent cause Pituitary magnetic resonance imaging in normal human volunteers: of pituitary incidentaloma: a follow-up study. Journal of Clinical occult adenomas in the general population. Annals of Internal Medicine Endocrinology and Metabolism 2001 86 3009–3015. (doi:10.1210/ 1994 120 817–820. (doi:10.7326/0003-4819-120-10-199405150-00001) jcem.86.7.7649) 17 Chong BW, Kucharczyk W, Singer W & George S. Pituitary gland 34 Tsunoda A, Okuda O & Sato K. MR height of the pituitary gland as MR: a comparative study of healthy volunteers and patients with a function of age and sex: especially physiological hypertrophy in microadenomas. AJNR. American Journal of Neuroradiology 1994 15 adolescence and in climacterium. American Journal of Neuroradiology 675–679. 1997 18 551–554. 18 Nammour GM, Ybarra J, Naheedy MH, Romeo JH & Aron DC. 35 Suzuki M, Takashima T, Kadoya M, Konishi H, Kameyama T, Incidental pituitary macroadenoma: a population-based study. Yoshikawa J, Gabata T, Arai K, Tamura S, Yamamoto T et al. Height of American Journal of the Medical Sciences 1997 314 287–291. normal pituitary gland on MR imaging: age and sex differentiation. 19 Yue NC, Longstreth WT Jr, Elster AD, Jungreis CA, O’Leary DH & Journal of Computer Assisted Tomography 1990 14 36–39. Poirier VC. Clinically serious abnormalities found incidentally at (doi:10.1097/00004728-199001000-00006)

www.eje-online.org

Downloaded from Bioscientifica.com at 09/30/2021 02:05:41PM via free access European Journal of Endocrinology 53 52 51 50 49 48 47 46 45 44 43 42 41 40 39 38 37 36 Review 289–299. (doi:10.1097/01.rmr.0000224685.83629.18) and sellaturcica. Topics inMagneticResonanceImaging200516 Huang BY &Castillo M.Nonadenomatous tumorsofthepituitary 2005 16277–288.(doi:10.1097/01.rmr.0000224684.76006.cf) adenomas.TopicsRumboldt Z. Pituitary inMagneticResonanceImaging d’Endocrinologie 201576191–200.(doi:10.1016/j.ando.2015.04.004) incidentaloma. Annales Management ofnonfunctioningpituitary Bonneville JF, Jouanneau E,Vidal-Trecan G &Chanson P. Galland F, Vantyghem MC, Cazabat L,Boulin A,Cotton F, (doi:10.1530/EJE-14-0599) ofEndocrinology 2015172363–369. incidentaloma. European Journal dependent hypercortisolism inpatientsaffectedwithpituitary Chiodini I, Beck-Peccoz P, Arosio M et al.ScreeningforACTH- Toini A, Dolci A,Ferrante E, Verrua E, Malchiodi E,Sala E,Lania AG, jama.1990.03440200076026) required? JAMA19902632772–2776.(doi:10.1001/ gland.Isneurosurgery The ‘incidentaloma’ofthepituitary Reincke M, Allolio B,Saeger W, Menzel J&Winkelmann W. Related Cancer200815885–903.(doi:10.1677/ERC-08-0170) and managementofparasellartumoursthepituitary. Endocrine- Kaltsas GA, Evanson J,Chrisoulidou A&Grossman AB.Thediagnosis Radiology 20066042–45.(doi:10.1016/j.ejrad.2006.04.003) of patients withdifferentintracranialpathologies.European Journal Rokni-Yazdi H &Sotoudeh H.Prevalenceof“duraltailsign”in (doi:10.1016/S0889-8529(05)70058-X) America19992881–117. Endocrinology andMetabolismClinicsofNorth Freda PU &Post KD.Differentialdiagnosisofsellarmasses. (doi:10.1136/pgmj.72.847.258) 199672258–262. disease.PostgraduateMedicalJournal pituitary Soule SG &Jacobs HS.Theevaluationandmanagementofsubclinical 2005 16133–138.(doi:10.1385/EP:16:2) Lloyd RV. inklinefelter syndrome.EndocrinePathology Thepituitary Scheithauer BW, Moschopulos M,Kovacs K,Jhaveri BS,Percek T & jcem.78.3.8126126) Endocrinology andMetabolism199478555–560.(doi:10.1210/ releasing hormone-producingbronchialcarcinoid. ofClinical Journal adenoma associatedwithalongstandinggrowthhormone- Kovacs K &Frohman LA.Somatotrophhyperplasiawithoutpituitary Ezzat S, Asa SL,Stefaneanu L,Whittom R,Smyth HS,Horvath E, edrv-9-3-357) manifestations. EndocrineReviews19889357–373.(doi:10.1210/ producing tumors:clinical,biochemical,andmorphological Sano T, Asa SL&Kovacs K.Growthhormone-releasinghormone- Reviews 199213164–191.(doi:10.1210/edrv-13-2-164) Orth DN. Corticotropin-releasinghormoneinhumans.Endocrine beem.2009.05.006) Endocrinology &Metabolism200923597–606.(doi:10.1016/j. tumours: TSH-secretingadenomas.BestPractice&Research: Clinical Beck-Peccoz P, Persani L,Mannavola D&Campi I.Pituitary Metabolism 2004896039–6047.(doi:10.1210/jc.2004-0735) population: theTromso Study. ofClinicalEndocrinologyand Journal relation toage,sex,lifestylefactors,andchronicdiseasesinageneral Oian P&Berntsen GK.Endogenoussexhormonesin Acharya G, Bjornerem A, Straume B, Midtby M, Fonnebo V, Sundsfjord J, Svartberg J, Metabolism 199071963–969.(doi:10.1210/jcem-71-4-963) ofClinicalEndocrinologyand men: itsrelationtoimpotence.Journal Silver AJ, Viosca SP hypogonadisminolder &Garza D.Secondary Korenman SG,Morley JE,Mooradian AD,Davis SS,Kaiser FE, 1992 131295–1299. ofNeuroradiology age- andgender-relateddifferences.AmericanJournal glandmorphologyinhealthyvolunteers: MR assessmentofpituitary Na C,EscalonaPR,McDonaldWM,FigielGS,Ellinwood EHJr Doraiswamy PM,PottsJM,AxelsonDA,HusainMM,LurieSN, 174 681–685.(doi:10.1148/radiology.174.3.2305049) imaging ofphysiologichypertrophyinadolescence.Radiology1990 Elster AD, Chen MY, Williams DW gland:MR 3rd&KeyLL.Pituitary others V Vasilev, LRostomyanand et al. 73 72 71 70 69 68 67 66 65 64 63 62 61 60 59 58 57 56 55 54 Pituitary incidentaloma Afshar F, Trainer PJ, Monson JP, Besser GM&Grossman AB. Clinical, Mukherjee JJ, Islam N,Kaltsas G,Lowe DG, Charlesworth M, 1986 6522–27.(doi:10.3171/jns.1986.65.1.0022) ofNeurosurgery Areviewof74cases.Journal craniopharyngiomas. Baskin DS &Wilson CB. Surgicalmanagementof 77–87. ofNeuroradiology 199718 AmericanJournal craniopharyngiomas. MR differentiationofadamantinousandsquamous-papillary Sartoretti-Schefer S, Wichmann W, Aguzzi A&Valavanis A. (doi:10.1210/er.2013-1115) EndocrineReviews2014 35 513–543. Muller HL.Craniopharyngioma. Endocrine Reviews200627371–397.(doi:10.1210/er.2006-0002) Karavitaki N, Cudlip S,Adams CB&Wass JA. Craniopharyngiomas. 36 80–84.(doi:10.1159/000048357) 2002 clinicomorphological studyof189cases.PediatricNeurosurgery Zhang YQ, Wang CC &Ma ZY. Pediatriccraniopharyngiomas: 2265.2005.02231.x) Clinical Endocrinology200562397–409.(doi:10.1111/j.1365- adults: systematicanalysisof121caseswithlong-termfollow-up. Shine B, Turner HE &Wass JA. inchildrenand Craniopharyngiomas Karavitaki N, Brufani C,Warner JT, Adams CB,Richards P, Ansorge O, (doi:10.2463/mrms.2.1) cyst inMRimaging.MagneticResonanceMedicalSciences200321–8. Tominaga JY, Higano S&Takahashi S. CharacteristicsofRathke’s cleft 16 269–276.(doi:10.1097/01.rmr.0000224683.98876.51) gland andparasellarregion.Topics inMagneticResonanceImaging2005 Spampinato MV &Castillo M.Congenitalpathologyofthepituitary Neuroradiology 200021485–488. of cleft cysts:significanceofintracysticnodules.AmericanJournal Byun WM, Kim OL&Kim D.MRimagingfindingsofRathke’s (doi:10.1530/eje.1.02183) ofEndocrinology2006155101–107. correlations. European Journal hypophysitis:clinical-pathological & Buchfelder M.Primary Gutenberg A, Hans V, Puchner MJ,Kreutzer J,Bruck W, Caturegli P 315–321. ofPediatricEndocrinologyandMetabolism199710 Journal Heinze HJ &Bercu BB. Acquired hypophysitisinadolescence. 195–211. (doi:10.1016/j.ecl.2007.10.003) America200837 Endocrinology andMetabolismClinicsofNorth Glezer A, Paraiba DB&Bronstein MD.Raresellarlesions. (doi:10.2478/v10019-010-0050-8) with prostatecarcinoma. RadiologyandOncology20114517–21. Hodolic M. Roleof(18)F-cholinePET/CTinevaluationpatients Medicine 200849730–737.(doi:10.2967/jnumed.107.050005) ofNuclear MRI insmallnonspecificincidentalbrainlesions.Journal Langen KJ. Prognosticvalueof18F-fluoroethyl-L-tyrosinePETand Floeth FW, Sabel M,Stoffels G,Pauleit D,Hamacher K,Steiger HJ& s12022-009-9062-6) literature review. EndocrinePathology20092046–49.(doi:10.1007/ a histological,immunohistochemical,andultrastructuralstudywith lymphoma: pituitary Patterson BJ, Kamel-Reid S&Kovacs K.Primary Moshkin O, Muller P, Scheithauer BW, Juco J, Horvath E, Oncologist 20005312–320. Packer RJ, Cohen BH&Cooney K.Intracranialgermcelltumors. 27 1532–1534. ofNeuroradiology 2006 endovascular stentplacement.AmericanJournal irresectable medialsphenoidwingmeningioma:treatmentby duetoan of thecavernousportioninternalcarotidartery Heye S, Maleux G,Van Loon J&Wilms G. Symptomaticstenosis ofNeuroradiology 1988935–38. American Journal parasellar masses:comparisonwithangiographyandCT. Zimmerman RA &Bilaniuk LT. MRofvascularencasementin Young SC, Grossman RI,Goldberg HI,Spagnoli MV, Hackney DB, (doi:10.1097/01.rmr.0000224687.29371.9a) Topics inMagneticResonanceImaging200516307–315. Smith JK. Parasellartumors:suprasellarandcavernoussinuses. Downloaded fromBioscientifica.com at09/30/202102:05:41PM 175:4 www.eje-online.org R183 via freeaccess Review V Vasilev, L Rostomyan and Pituitary incidentaloma 175:4 R184 others

radiological and pathological features of patients with Rathke’s cleft in human pituitary incidentalomas. Endocrine Pathology 2006 17 cysts: tumors that may recur. Journal of Clinical Endocrinology and 263–275. (doi:10.1385/EP:17:3) Metabolism 1997 82 2357–2362. (doi:10.1210/jcem.82.7.4043) 83 Karavitaki N, Collison K, Halliday J, Byrne JV, Price P, Cudlip S & 74 Shin JL, Asa SL, Woodhouse LJ, Smyth HS & Ezzat S. Cystic lesions Wass JA. What is the natural history of nonoperated nonfunctioning of the pituitary: clinicopathological features distinguishing pituitary adenomas? Clinical Endocrinology 2007 67 938–943. craniopharyngioma, Rathke’s cleft cyst, and arachnoid cyst. Journal (doi:10.1111/cen.2007.67.issue-6) of Clinical Endocrinology and Metabolism 1999 84 3972–3982. 84 Lenders N, Ikeuchi S, Russell AW, Ho KK, Prins JB & Inder WJ. (doi:10.1210/jcem.84.11.6114) Longitudinal evaluation of the natural history of conservatively 75 Tsuchiya K, Makita K, Furui S & Nitta K. MRI appearances of calcified managed nonfunctioning pituitary adenomas. Clinical Endocrinology regions within intracranial tumours. Neuroradiology 1993 35 341–344. 2016 84 222–228. (doi:10.1111/cen.2016.84.issue-2) (doi:10.1007/BF00588364) 85 Fernandez-Balsells MM, Murad MH, Barwise A, Gallegos-Orozco JF, 76 Rennert J & Doerfler A. Imaging of sellar and parasellar lesions. Paul A, Lane MA, Lampropulos JF, Natividad I, Perestelo-Perez L, Clinical Neurology and Neurosurgery 2007 109 111–124. (doi:10.1016/ Ponce de Leon-Lovaton PG et al. Natural history of nonfunctioning j.clineuro.2006.11.001) pituitary adenomas and incidentalomas: a systematic review and 77 Komninos J, Vlassopoulou V, Protopapa D, Korfias S, Kontogeorgos G, metaanalysis. Journal of Clinical Endocrinology and Metabolism 2011 Sakas DE & Thalassinos NC. Tumors metastatic to the pituitary gland: 96 905–912. (doi:10.1210/jc.2010-1054) case report and literature review. Journal of Clinical Endocrinology and 86 Igarashi T, Saeki N & Yamaura A. Long-term magnetic resonance Metabolism 2004 89 574–580. (doi:10.1210/jc.2003-030395) imaging follow-up of asymptomatic sellar tumors. – their natural 78 Honegger J, Schlaffer S, Menzel C, Droste M, Werner S, Elbelt U, history and surgical indications. Neurologia medico-chirurgica 1999 Strasburger C, Stormann S, Kuppers A, Streetz-van der Werf C et al. 39 592–598. (doi:10.2176/nmc.39.592) Diagnosis of Primary Hypophysitis in Germany. Journal of Clinical 87 Oyama K, Sanno N, Tahara S & Teramoto A. Management of Endocrinology and Metabolism 2015 100 3841–3849. (doi:10.1210/ pituitary incidentalomas: according to a survey of pituitary jc.2015-2152) incidentalomas in Japan. Seminars in Ultrasound, CT and MRI 2005 79 Honegger J, Buchfelder M, Schlaffer S, Droste M, Werner S, 26 47–50. Strasburger C, Stormann S, Schopohl J, Kacheva S, Deutschbein T 88 Dekkers OM, Hammer S, de Keizer RJ, Roelfsema F, Schutte PJ, et al. Treatment of Primary Hypophysitis in Germany. Smit JW, Romijn JA & Pereira AM. The natural course of non- Journal of Clinical Endocrinology and Metabolism 2015 100 functioning pituitary macroadenomas. European Journal of 3460–3469. (doi:10.1210/jc.2015-2146) Endocrinology 2007 156 217–224. (doi:10.1530/eje.1.02334) 80 Caturegli P, Newschaffer C, Olivi A, Pomper MG, Burger PC & 89 Nishizawa S, Ohta S, Yokoyama T & Uemura K. Therapeutic strategy Rose NR. Autoimmune hypophysitis. Endocrine Reviews 2005 26 for incidentally found pituitary tumors (“pituitary incidentalomas”). 599–614. (doi:10.1210/er.2004-0011) Neurosurgery 1998 43 1344–1348. 81 Donovan LE & Corenblum B. The natural history of the pituitary 90 Scangas GA & Laws ER Jr. Pituitary incidentalomas. Pituitary 2014 incidentaloma. Archives of Internal Medicine 1995 155 181–183. 17 486–491. (doi:10.1007/s11102-013-0517-x) (doi:10.1001/archinte.1995.00430020067008) 91 Randall BR, Kraus KL, Simard MF & Couldwell WT. Cost of evaluation 82 Suzuki M, Minematsu T, Oyama K, Tahara S, Miyai S, Sanno N, of patients with pituitary incidentaloma. Pituitary 2010 13 383–384. Osamura RY & Teramoto A. Expression of proliferation markers (doi:10.1007/s11102-010-0241-8)

Received 30 December 2015 European Journal European of Endocrinology Revised version received 23 March 2016 Accepted 31 March 2016

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