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Page 1: The 'incidentaloma' of the pituitary gland. Is ... · ditorial Assistants: Mary Cannon, Kemberly Evans, Anne recka, Helen M. Giese, Shirley Goines, Sharon Iverson, Patricia ... Controlling

JAMA The Journal of the American Medical Association

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JAMA he Journal of the American Medical Association

06 Years of Continuous Publication dttor: George D. Lundberg, MD

eputy Editor: Richard M. Glass, MO eputy Editor (West): Drummond Rennie, MD enior Editors: Helene Μ. Cole, MD, Don Riesenberg, MD

enior Contributing Editors: Bruce B. Dan, MD, M. Therese outhgate. MD ontr lbut ing Editors: Charles B. dayman, MD, David S. ooper, MD, Harriet S. Meyer, MD, Carin M. Olson, MD, Jody W. /Ike, MD onsul t ing Editor: Roger C. Bone, MD tatistical Editor: Naomi Vaisrub, PhD lorris Fishbein Fellow: Jeanette Μ. Smith, MD ssistant to the Editor: Annette Flanagin

iternational Fellow in Medical Journal ism: Zhihong Li, MD ledicai N e w s - E d i t o r : Phil Gunby; Associate Editors: Paul ötton, Marsha F. Goldsmith, Charles Marwick (Washington, DC), 9ri Randall, Andrew Skolnick esociate Editors: Chariene Breedlove, Roxanne K. Young pecial Assignments Editor: Dennis L. Breo ditorial Services Manager: Elaine Williams reduction Manager: Marlene Μ. Hinsch ssistant Production Managers: John R. Sayban, Mary C. teermann lectronic Manager: Nawin Gupta ditorial Processing Manager: Cheryl Iverson

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jlMA, The Journal of the American Medical Associat ion J3SN 0098-7484), is published four issues per month by the nerican Medical Association, 535 Ν Dearborn St, Chicago, IL »610. Phone (312) 645-5000. Cable address "Medic" Chicago. JBSCRIFTION RATES—The subscription rate per year for embers of the ΑΜΑ is $2 included in the annual membership les. The subscription rate per year for nonmembers is $69 for /ear, $123 for 2 years in the United States and US possessions;

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May 23/30,1990, Vol 263, No. 20 To promote the science and art of medicine and the betterment of the public health.

Original Contributions Value of the Ventilation/Perfusion Scan in Acute Pulmonary Embolism 2753 The PIOPED Investigators, Bethesda, Md

Methods Used to Quit Smoking in the United States .. .2760 M. C. Fiore, Madison, Wis; T. E. Novotny, J. P. Pierce, G. A. Giovino, Rockville, Md; E. J. Hatziandreu, Washington, DC; P. A. Newcomb, TS. Surawicz, Madison, Wis; R. M. Davis, Rockville, Md

Exercise Training Combined With Antihypertensive Drug Therapy .................... ...2766 Μ. H. Kelemen, Columbia, Md; Μ. B. Effron, Baltimore, Md; S. A. Valenti, Columbia, Md; K. J. Stewart, Baltimore, Md

The 'Incidentaloma' of the Pituitary Gland 2772 M. Reincke, B. Allolio, Cologne, West Germany; W. Saeger, Hamburg, West Germany; J. Menzel, W. Winkelmann, Cologne, West Germany

Special Communications The Cystic Fibrosis Gene: Medical and Social Implications for Heterozygote Detection ......2777 B. S. Wilfond, N. Fost, Madison, Wis

Who Profits From Tobacco Sales to Children? .2784 J. R. DiFranza, Rtchburg, Mass; J. B. Tye, Springfield, Mass

Brief Report Revaluation of Serum-Plasma Differences in Total Cholesterol Concentration 2788 T.CIoey, P. S.Bachorik, D. Becker, C. Finney, D. Lowry, W.Sigmund, Baltimore, Md

Council Report Conflicts of Interest in Medical Center/Industry Research Relationships .2790 Council on Scientific Affairs and Council on Ethical and Judicial Affairs, Chicago, III

Editorials Ventilation/Perfusion Scan in Pulmonary Embolism 2794 R. C. Bone, Chicago, III

Methods of Smoking Cessation—Finally, Some Answers 2795 Τ J. Glynn, Bethesda, Md

Resident Forum 2712

The Cover Horace Pippin, Barracks 2713 Μ. T. Southgate, Chicago. Ill

Medical News & Perspectives 2717 Medium Isn't Accurate Ice Age* Message... Long Struggle Continues to Find New Weapons Against an Old Foe—the Malaria Parasite . . . Miscellanea Medica

From the Alcohol, Drug Abuse, and Mental Health Administrat ion ...........2725

From the Centers for Disease Control 2729 Recommendations for the Prevention of Malaria Among Travelers

2709

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ΑΜΑ Insights 2744

Poetry and Medicine 2745

Letters 2746 A Trial of Clonidine to Stop Smoking L. M. Lucas, D. H. Mark, S. A. Ornish

Vitamins During Pregnancy and Neural Tube Defects J. L Mills, G. G. Rhoads, J. L. Simpson, G. C. Cunningham, S. Shapiro, A. A. Mitchell, Μ. M. Werler, A. Milunsky, H. Jick, S. S. Jick. K. J. Rothman. W. Willett, M. J. Seller, N. C. Nevin

Controlling the Hemorrhage of Routine Coagulation Tests G. N. Fox. S. B. Erban

Miffed by Medical Musings J. Pesti

Fluphenazine and Postherpetic Neuralgia Η. I. Hurt ig, τ. Μ. Murphy

Correction 2750 Should Hyperbaric Oxygen Be Used to Treat the Pregnant Patient for Acute Carbon Monoxide Poisoning? A Case Report and Literature Review Κ. B. Van Hoesen, E. M. Camporesi , R. E. Moon, M. L. Hage, C. A. Piantadosi

A Piece of My Mind 2798

Portraits

Specialty Abstracts 2800

JAMA 100 Years Ago 2804 Wood as a Source of Human Food.

At Large With Dennis L. Breo 28Ο6 The doctor in the House diagnoses flux and frustration

Questions and Answers 2βιβ STDs and Used Condoms K G . Castro

Treatment of Dermatofibrosarcoma Protuberans G. S. Rogers, R. M. Beazley

BOOkS 2826 Cancer of the Head and Neck (Myers, Suen. eds) Reviewed by G. Matz

The American General Hospital (Long, Golden) Reviewed by N. L. Cannon

The Medical Cost-Containment Crisis (McCue, ed) Reviewed by B. Stuart

Clinical Urography (Pollock, ed) Reviewed by R. D. Harris

Consultation in Internal Medicine (Harrington) Reviewed by S. Wessler

Gastrointestinal Disorders (Greenberger) Reviewed by P. M. Berman

Literature and Medicine (Rabuzzi. Daly, eds) Reviewed by J. S. Alpert, H. Mathiasen

Books Received

Obituary Listing 2837

Classified Advertising 2839

CME Comer 2851

Index to Advertisers 2352

JAMA Journal Club Reading Assignments 2852

Instructions for Authors See April 11,1990, ρ 1897.

Reference Directories US Meetings, May 2; Organizations of Medical Interest, January 12; State Associations and Examinations and Licensure, January 19, Meetings Outside the United States, January 26; ΑΜΑ Officials, April 4

JAMA The Journal of the American Medical Association EDITORIAL BOARD

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2710 JAMA, May 23/30,1990-Vol 263, No. 20

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Martin Reincke, MD; Bruno Allolio, MD; Wolfgang Saeger, MD; Jürgen Menzel, MD; Werner Winkelmann, MD

The 'Incidentaloma' of the Pituitary Gland Is Neurosurgery Required?

We describe a series of 18 patients with an intrasellar mass incidentally discov­ered by computed tomography or magnetic resonance imaging. The average size of the mass was 13 mm, with a range from 5 to 25 mm. Initial ophthalmologic examination revealed bitemporal hemianopia in 2 patients. Results of routine endocrine testing showed partial hypopituitarism in 5 patients and growth hor­mone hypersecretion without signs and symptoms of acromegaly in 1 patient. Four patients underwent neurosurgery. Histologically, one chondroid chordoma and three pituitary adenomas were found. In the remaining 14 patients treated conservatively, repeated computed tomography and magnetic resonance imag­ing revealed no significant change in tumor size at the time of follow-up (median, 22 months). Our results suggest that the "incidentaloma" of the pituitary gland is a benign condition that does not necessarily require neurosurgical intervention.

{JAMA. 1990;263:2772-2776)

I N 1936, Costello1 reported in his inves­tigation entitled "Subclinical Adenomas of the Pituitary Gland" that in a series of 1000 pituitary glands obtained from un-selected autopsies pituitary adenomas occurred with the remarkable frequen­cy of 22.5%. The tumors were unassoci-ated with clinical signs or obvious hor­monal abnormalities and remained undiagnosed during the subjects' life­time.

Costello's investigation has been cited in numerous publications. The

From the Department of Medicine II, University of Cologne, Krankenhaus Merheim, West Germany (Drs Reincke and Allolio and Prof Dr Winkelmann); Depart­ment of Pathology, Marienkrankenhaus Hamburg, West Germany (Prof Dr Saeger); Department of Neuro­surgery, Krankenhaus Merheim, Cologne, West Ger­many (Prof Dr Menzel).

Reprint requests to Department of Medicine II, Kran­kenhaus Merheim, Ostmerheimer Str 200, 5000 Köln 91, West Germany (Dr Reincke).

prevalence of subclinical pituitary ade­nomas has been reexamined by many subsequent investigators and was found to vary from 4.8% to 27% in unselected autopsy subjects.2 In most cases, these adenomas were small and could only be detected by microscopy. Adenomas vis­ible at the time of gross examination are detected less frequently. In the series of McComb et al,2 4 of 100 pituitary adeno­mas incidentally discovered at the time of autopsy were detected already by gross examination.

During the last two decades, the in­troduction of radioimmunoassays, new radiological procedures, and microsur­gical techniques have allowed early di­agnosis and removal of small pituitary adenomas. However, even today, pitu­itary adenomas are a common incidental finding at the time of autopsy.3,4 With wider application of computed tomogra­

phy (CT) and magnetic resonance imag­ing (MRI), pituitary masses will be de­tected incidentally during patients' lifetimes in increasing frequency. The diagnostic and therapeutic approach to patients with "incidentalomas" of the pituitary gland has not yet been estab­lished. We, therefore, present herein the findings of 18 patients with a sub­clinical pituitary mass incidentally dis­covered by CT or MRI.

PATIENTS AND METHODS Since 1980, we studied 27 patients (21

female and 6 male) with an intrasellar mass incidentally discovered by CT or MRI (incidentaloma), which was de­fined as follows: (1) the patient under­went CT scanning (or MRI) for evalua­tion of an unrelated disease, and (2) the patient did not complain of symptoms associated with a sellar mass (visual dis­turbance, symptoms of hypopituita­rism, or anterior pituitary hormone ex­cess). Headache as an isolated symptom was considered to be nonspecific i f the life profile of it was chronic, recurrent, and unassociated with other important signs. Patients with headache of in­creasing frequency and intensity were excluded. Patients with a primary para-sellar or suprasellar mass or with the empty-sella syndrome were not in­cluded in the study.

Of the 27 patients with an incidenta­loma of the pituitary gland, 9 cases were excluded from this study for the follow­ing reasons: 6 patients were unavailable for follow-up, 1 patient had suspected

2772 JAMA, May 23/30,1990-Vol 263, No. 20 'Incidentaloma'—Reincke et al

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Table 1.—Clinical, Radiological, and Biochemical Characteristics of Four Patients With an 'Incidentaloma* of the Pituitary Gland That Required Neurosurgery*

Maximum Patient/ Age, y/

Sex Complaint

(Reason for CT)

Tumor Diameter,

mm

Endocrine Function Visual Acuity Patient/ Age, y/

Sex Complaint

(Reason for CT)

Tumor Diameter,

mm Surgery Preoperative Postoperative Preoperative Postoperative Histology Immunostaining 1/55/F Concussion 25 Transfrontal Hypopituitarism

(LH, FSH) Hypopituitarism

(C, TSH, LH, FSH) Bitemporal

hemianopia Bitemporal

hemianopia Chondroid

chordoma 2/64/M Cerebrovascular

disease 25 Transfrontal Hypopituitarism

(LH, FSH) Hypopituitarism

(C, TSH, LH, FSH) Bitemporal

hemianopia Bitemporal

hemianopia Chromophobic

pituitary adenoma

LHf, FSHt

3/66/M Epilepsy 20 Transfrontal Normal Normal Normal Left hemianopia

Oncocytic pituitary adenoma

FSH}:, TSHt a-subunit§

4/35/M Cervical myelopathy

17 Transsphenoidal GH hypersecretion Normal Normal Normal Acidophilic pituitary adenoma

GHt, PRLt.TSHt

*CT indicates computed tomography; LH (luteinizing hormone), FSH (follicle-stimulating hormone), C (corticotropin), and TSH (thyrotropin [thyroid-stimulating hormone]), hormone deficiencies in patients with hypopituitarism; GH, growth hormone; and PRL, prolactin.

tLess than 10% of tumor cells stained. ^Greater than 50% of tumor cells stained. §Ten percent to 50% of tumor cells stained.

Table 2.—Clinical, Radiological, and Biochemical Data of 14 Patients With an 'Incidentaloma' of the Pituitary Gland Treated Conservatively*

Patient/ Age, y/

Sex Complaint

(Reason for CT)

Maximum Tumor Diameter, mm

First CT Last CT Endocrine Function Follow-up,

mo 5/65/F Concussion 22 25 Hypopituitarism (LH, FSH) 19 b/bö/M cerebrovascular disease 20 20 Normal 20 7/61/F Headache 16 15 Hypopituitarism (LH, FSH) 42 8/59/M Cluster headache 14 20 Normal 20 9/56/M Vertigo 14 14 Hypopituitarism (LH, FSH) 48

10/32/F Psychiatric disorder 12 12 Normal 48 11/27/F Headache 11 11 Normal 17 12/15/F Epilepsy 9 9 Normal 29 13/19/F Concussion 8 8 Normal 12 14/22/F Syncope 8 4 Normal 14 15/24/F Headache 8 8 Normal 17 16/43/F Vertigo 8 8 Normal 24 17/37/F Psychiatric disorder 5 5 Normal 20 18/44/F Headache 5 9 Normal 96

*CT indicates computed tomography; and LH (luteinizing hormone) and FSH (follicle-stimulating hormone), hormone deficiencies in patients with hypopituitarism.

pituitary hyperplasia caused by prima­ry hypothyroidism, and 2 patients had normal CT scans at the time of follow-up, suggestive of artifacts that imitated a pituitary tumor in the initial scans.

In the remaining 18 patients, com­plete medical histories were recorded and physical examinations given initial­ly and during follow-up. In addition, ophthalmologic examinations, including Goldman and computed perimetry, and routine pituitary function testing5 were performed. Assessment of the hormon­al status included determination of baseline (and stimulated) hormone con­centrations of plasma corticoptropin and serum Cortisol (corticoptropin-stim-ulation test, overnight metyrapone test, and since 1986 corticotropin-re-leasing hormone stimulation test), thyrotropin (thyroid-stimulating hor­mone), triiodothyronine and thyroxine

(thyrotropin-releasing hormone stimu­lation test until 1988), prolactin (thyro­tropin-releasing hormone stimulation test), luteinizing hormone and follicle-stimulating hormone (gonadotropin-releasing hormone stimulation test), testosterone, growth hormone (GH), somatomedin C. α-Subunit was not measured. Follow-up studies were done every 12 months and earlier in pa­tients with large tumors.

Plasma corticotropin levels were de­termined by radioimmunoassay after extraction with microfine precipitated silica granules as described previously.6

Cortisol, prolactin, thyrotropin, triio­dothyronine and thyroxine, luteinizing hormone, follicle-stimulating hormone, GH, and somatomedin C levels were measured by radioimmunoassay or im-munoradiometric assay with commer­cially available reagents.

Sections of tumor tissue were exam­ined by light microscopy using conven­tional and immunocytochemical tech­niques described previously.7 Using the peroxidase-antiperoxidase method on paraffin-embedded sections, the follow­ing commercial primary antibodies were tested: anticorticotropin, anti-GH, antiprolactin, antithyrotropin, an­ti-follicle-stimulating hormone, anti-luteinizing hormone, anti-ct-subunit.

High-resolution CT of the pituitary fossa in 2-mm sections was performed after intravenous administration of con­trast material with second- and third-generation scanning machines (Siemens Somatotom DR1 and DR2, Munich, Germany). Reformatting of multiple ax­ial images was obtained in all patients; thin-section coronal scans were ob­tained in 10 patients.

Since 1987, in addition to CT, magnet­ic resonance images in the coronal and sagittal views were obtained in eight patients at 1.0 Τ (Siemens Magentom LOT, Munich, Germany). Both T r and T2-weighted spin-echo pulse sequences were acquired before and after the ad­ministration of gadolinium-diethylene-triaminepentaacetic acid.

RESULTS Clinical data of the patients are sum­

marized in Tables 1 and 2. In 17 pa­tients, the pituitary mass was discov­ered by CT and in patient 4 by MRI. Patients' ages ranged from 15 to 68 years at the time of admission. The rea­sons for CT scanning (or MRI) were headache of chronic pattern (n = 3), cluster headache (n=l ) , cerebrovascu­lar disease (n = 2), psychiatric disorders (n = 2X vertigo (n=2), epilepsy (n=2), concussion (n = 2), and other causes (n = 4). Al l female patients except for the postmenopausal women had regular menses. None of the male patients com-

JAMA, May 23/30,1990-Vol 263, No. 20 'Incidentaloma'—Reincke et al 2773

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Fig 1.—Initial coronal computed tomographic (CT) scan of patient 5 showing a large pituitary mass (maximum diameter, 22 mm) with suprasellar extension. The lesion was incidentally discovered by CT after head trauma and was completely asymptomatic.

plained of loss of libido. On coronal CT scans, an intrasellar

soft-tissue mass greater than 10 mm in maximum diameter was identified in 11 patients (range, 11 to 25 mm) (Fig 1). Enhancement characteristics were var­iable, with uniformly isodense lesions (5 patients), uniformly hypodense le­sions (1 patient), and mixed-density le­sions (5 patients) encountered relative to the adjacent cavernous sinus. Seven tumors extended into the suprasellar region. Magnetic resonance imaging was available in 6 of these patients. In 2 patients (patients 1 and 2) with bitem­poral visual field defects, the chiasm could not be discerned from the tumor by MRI. Displacement of the optic nerve was noted in patient 3, who had normal visual acuity.

In seven patients, pituitary gland CT scans showed a small lesion (diameter, <10 mm) within the sella turcica. In five of these patients, the sella cavity was almost completely filled by homoge­neously enhancing soft tissue, with a convex upper contour of the gland. The two other patients had a small, hypo-dense lesion within the pituitary gland that was clearly distinguished from the normal enhancing parenchyma. Neither suprasellar nor parasellar extension nor sellar floor erosion was seen.

Goldman or computed perimetry re­vealed normal visual fields in 16 pa­tients. Two patients showed a bitem­poral visual field defect in the superior quadrant. The results of pituitary func­tion testing was normal in 13 patients. Patients 1, 2, 5, and 7 had partial hypo­pituitarism (secondary hypogonadism). Patient 3 showed elevated baseline lev­els of GH and elevated somatomedin C concentrations without signs and symp­toms of acromegaly. The GH concentra­tions were not suppressed to less than 2 μg/L during oral glucose tolerance testing and rose paradoxically after pro-tirelin administration.

In 4 patients, (Table 1) neurosurgery was performed for the following rea­sons: visual field defects in patients 1 and 2, displacement of the chiasm by the tumor demonstrated by MRI in patient 3, and biochemical evidence of acromeg­aly in patient 4. In all cases, complete removal of the tumor was achieved by the transfrontal (η = 3) and transsphe­noidal (n = 1) route, respectively. Histo­logically, a chondroid chordoma and three pituitary adenomas were found. Immunohistochemical studies showed strong GH immunoreactivity in patient 4, follicle-stimulating hormone and thy­rotropin immunoreactivity in patient 3, and luteinizing hormone and follicle-stimulating hormone immunoreactivity in a few scattered cells in patient 2.

Postoperatively, complete hypopituita­rism that required replacement therapy developed in patients 1 and 2. Patient 4 had normal baseline GH levels that were suppressible to less than 2 μg/L during the oral glucose tolerance test. Patient 3 had evidence of a left temporal visual field defect; visual field defects were unchanged in patient 2 and worse in patient 1. Follow-up studies were un­eventful in all patients 12 to 24 months after surgery.

During the follow-up period of the 14 patients who were treated conserva­tively (median, 22 months; range, 11 to 96 months), no change in tumor size oc­curred in 10 patients. Three patients had evidence of tumor growth (patients 5, 8, and 18). Patient 14 showed tumor regression. Visual acuity remained in­tact in all patients. The results of endo­crine follow-up studies were unchanged in 13 patients. Patient 5 had a further decrease of serum gonadotropin levels, but thyrotropin and corticotropin secre­tion remained intact. In 4 additional pa­tients (patients 5, 8, 9, and 18), trans­sphenoidal surgery was considered be­cause of tumor growth or hypopituita­rism. However, 3 patients refused to

undergo neurosurgical intervention. The fourth patient was ineligible for surgery because of severe pulmonary disease.

COMMENT In our report, we describe 18 patients

with an incidentally discovered sellar mass. In 11 patients, the lesion was greater than 10 mm in diameter. How­ever, only 2 of the patients had visual field defects, and only 5 patients (28%) had partial hypopituitarism. In 4 pa­tients (22%), neurosurgery was per­formed. Follow-up studies in the re­maining 14 patients showed tumor growth in 3, whereas in the majority the lesions remained unchanged. To our knowledge, this is the first report of patients with an incidentaloma of the sellar region that provides complete clinical, biochemical, and follow-up data.

We included patients who complained of chronic headache in our series of inci­dentalomas of the pituitary gland. This symptom was considered to be nonspe­cific and not to be caused by the tumor because patients with symptomatic pi­tuitary lesions typically complain of

2774 JAMA, May 23/30,1990-Vol 263, No. 20 'Incidentaloma'—Reincke et al

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Incidentally Discovered Pituitary Mass

Ophthalmologic Examination Pituitary Function Testing

Abnormal Visual Fields and/or Hypopituitarism

and/or Pituitary Hormone Excess

I

I Prolactinoma

ι

Treatment With Dopamine Agonist

Normal Visual Fields Normal Pituitary Function

Review Magnetic Resonance Imaging

No Prolactinoma

I Consider

Neurosurgery

Mass <1 cm

I Repeat Magnetic Resonance

Imaging, Ophthalmologic Examination and Pituitary Function Testing

After 1 y

No Change

I

No Further Studies Necessary

Mass >1 cm

I Repeat Magnetic Resonance

Imaging, Ophthalmologic Examination and Pituitary Function Test

After 72, 1, and 2 y

^ Tumor Growth Abnormal Visual Fields

Hypopituitarism

Consider Neurosurgery

Fig 2.—Approach to the incidentally discovered noncystic mass.

headache of recent onset or increasing frequency and intensity. In addition, Cohen et al8 reported in their large se­ries of 100 patients with nonfunctioning pituitary adenomas that headache—the second most frequent symptom—was never observed as an isolated com­plaint; it was always accompanied by visual symptoms.

The pituitary region can now be easily evaluated by means of high-resolution CT9 and MRI. 1 0 By CT, it is best demon­strated either directly on coronal scans or indirectly from data obtained in the axial plane and reformatted into coronal and sagittal images. The use of high-resolution CT scans for the diagnosis of pituitary tumors is well established. In the case of tumors greater than 10 mm in diameter, the mass will be easily dem­onstrated radiologically. However, in patients with suspected pituitary ade­nomas smaller than 10 mm, CT has been found to be of less value in localizing the lesion.1112

Magnetic resonance imaging has been shown to be superior to CT in the evalu­ation of large pituitary tumors.1 0 1 3 I t is able to yield excellent anatomic presen­tations of the tumor and its immediate surroundings. The suprasellar exten­

sion of the tumor and the impinging of the optic apparatus and the third ventri­cle is more easily identified from MRI reconstructions than from CT images. In addition, MRI before and after ad­ministration of gadolinium-diethylene-triaminepentaacetic acid has been dem­onstrated to be more effective in the detection of microadenomas of the pitu­itary gland.14 Therefore, since 1987, MRI frequently has been used by us to confirm the presence of a pituitary tu­mor and to define the relationship of the lesion to the surrounding anatomic structures.

Asymptomatic pituitary adenomas are a common incidental finding at the time of autopsy.1"4 Most reported series showed an incidence of approximately 20%.2 We believe that most of the inci-dentalomas in our patients represent slowly growing pituitary microadeno­mas and macroadenomas. No change in tumor size was noted in the majority of cases. This may be explained by the slow growth characteristics of pituitary adenoma cells,

Patients with incidentalomas of the pituitary gland should be carefully mon­itored for anterior pituitary hormone excess, although the majority of pa­

tients have nonfunctional pituitary tu­mors. In the present study, only one patient with a GH-secreting adenoma had biochemical evidence of anterior pi­tuitary hormone excess. No prolactin-secreting pituitary tumor was detected. Immunohistochemistry revealed a gon­adotroph cell adenoma in one patient whereas gonadotropin levels were nor­mal or low in all patients. However, gonadotroph cell adenomas cannot real­ly be excluded on this basis since serum α-subunit was not measured in our patients.

Nevertheless, subclinical masses may be caused by abnormalities other than microadenomas or macroadeno­mas. The differential diagnosis includes aneurysm, meningioma, and cranio­pharyngioma,15 pituitary hyperpla­sia,1 6 1 7 lymphoid adenohypophysitis,18,19

pars intermedia cysts,3 metastasis to the pituitary gland,3 , 2 0 , 2 2 infarcts of the pituitary gland,23 and abscesses.3

Aneurysm, parasellar meningioma, and craniopharyngioma sometimes mimic the CT characteristics of pitu­itary tumors, especially the large pitu­itary adenomas with suprasellar exten­sion. However, generally they present a characteristic constellation of findings

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on CT scans and MRI, which allows the differential diagnosis.15

I t is well known that in patients with suspected microadenomas, artifacts may mimic low-density lesions on CT.3

Earnest et al2 1 stated that a significant percentage of intrasellar low-density areas, visualized on reformatted images especially, represented artifacts associ­ated with the bones of the skull base. We excluded two patients with normal CT scans at the time of follow-up from this study in whom probable artifacts initially imitated the findings of a true pituitary tumor.

The therapeutic approach to patients with an incidentally discovered pitu­itary mass has not yet been established. We believe that it is rational to observe

References

1. Costello RT. Subclinical adenoma of the pitu­itary gland. Am J Pathol 1986;12:205-216. 2. McComb DJ, Ryan N, Horvath E , Kovacs K. Subclinical adenomas of the human pituitary: new light on old problems. Arch Patlvol Lab Med. 1983;107:488-491. 3. Chambers E F , Turski PA, LaMasters D, New­ton TH. Regions of low density in the contrast-enhanced pituitary gland: normal and pathologic processes. Radiology. 1982;144:109-113. 4. Parent AD, Bebin J, Smith RR. Incidental pitu­itary adenomas. J Neurosurg. 1981;54:228-231. 5. Wilson JD, Foster DW, ed. Williams Textbook of Endocrinology. Philadelphia, Pa: WB Saunders Co; 1985. 6. Allolio B, Winkelmann W, Hipp FX. Effect of meclastine, an Hj-antihistamine, on plasma ACTH, in adrenal insufficiency. Acta Endocrinol (Co-penh). 1981;97:98-102. 7. Saeger W, Schmidt W. Classification and im-munohistology of clinically silent adenomas in post­mortem pituitaries. In: Levy E , ed. Advances in Pathology. Elmsford, NY: Pergamon Press Inc; 1982;2:343-355. 8. Cohen AR, Cooper PR, Kupersmith MJ, Flamm E S , Ransohoff J. Visual recovery after transsphe­noidal removal of pituitary adenomas. Neurosur­gery. 1985;17:446-452.

the clinical course carefully in patients with normal visual acuity and normal pituitary function. Serial CT scans or MRI, pituitary function testing, and ophthalmologic examination should be performed depending on the size of the lesion (Fig 2). Magnetic resonance im­aging may be useful to confirm the pres­ence of the mass (especially in the case of small lesions), to define the bound­aries of the tumor, and to characterize its relationship to normal gland and vas­cular, neural, and bony structures. I f the lesion shows no increase in size and endocrine and visual function remain in­tact, we recommend a conservative ap­proach. However, in patients with tu­mor growth, loss of vision, or dis­placement of the optic apparatus shown

9. Roppolo HMN, Latchaw R E , Meyer JD, Curtin HD. Normal pituitary gland, I: macroscopic anato­m y - C T correlation. AJNR. 1983;4:927-935. 10. Kaufmann Β, Kaufman ΒΑ, Arafah BM, Roessmann U, Selman WR. Large pituitary gland adenomas evaluated with MRI. Neurosurgery, 1987;21:540-546. 11. Davis PC, Hoffman JC, Tindall GT, Braun IF. CT-surgical correlation in pituitary adenomas: evaluation in 113 patients. AJNR. 1985;6:711-716. 12. Saris SC, Patronas NJ, Doppmann J L , et al. Cushing's syndrome: pituitary CT scanning. Radi­ology. 1987;162:775-777. 13. Snow RB, Lavyne MH, Lee BCP, Morgello S, Patterson RH. Craniotomy versus transsphenoidal excision of large pituitary tumors: the usefulness of MRI in guiding the operative approach. Neurosur­gery. 1986;19:59-64. 14. Dwyer AJ, Frank FA, Doppmann J L , et al. Pituitary adenomas in patients with Cushing's dis­ease: initial experience with Gd-DTPA-enhanced MR imaging. Radiology. 1987;163:421-426. 15. Clark WC, Acker JD, Robertson J H , Eggers F, Muhlbauer MS. Reformatted sagittal images in the differential diagnosis of meningeomas and pitu­itary adenomas with suprasellar extension. Neuro­surgery. 1986;18:555-558. 16. Floyd J L , Dorwart RH, Nelson MJ, Mueller

on MRI or hypopituitarism or anterior pituitary hormone excess initially or at the time of follow-up, immediate neuro­surgery is the treatment of choice.

In conclusion, we describe a series of 18 patients with an incidentally de­tected sellar mass. These lesions seem to be heterogenous in origin, however, at least some of them represent slowly growing nonfunctional pituitary adeno­mas. Our preliminary results suggest that in most cases the incidentaloma of the pituitary gland is a benign condition that does not necessarily require neuro­surgical intervention.

Dedicated to Professor Doctor of Medicine Wer­ner Kaufmann on the occasion of his 65th birthday.

GL, DeVroede M. Pituitary hyperplasia secondary to thyroid failure: CT appearance. AJNR. 1984;5:469-471. 17. Mösli Ρ, Hedinger C. Noduläre Hyperplasie und Adenome des Hypophysenvorderlappens bei Hypothyreose. Acta Endocrinol (Copenh). 1968; 58:507-520. 18. Hungerford GD, Biggs PJ, Levine JH, Shelley E , Perot PL, Chambers JK. Lymphoid adenohypo-physitis with radiologic and clinical findings resem­bling a pituitary tumor. AJNR. 1982;3:444-446. 19. Ikeda H, Okudaira Y. Spontaneous regression of pituitary mass in temporal association with preg­nancy. Neuroradiology. 1987;29:488-492. 20. Kovacs K. Metastatic cancer of the pituitary gland. Oncology. 1973;27:533-542. 21. Earnest FIV, McCullough E C , Frank DA. Fact or artifact: an analysis of artifacts in high-resolution computed tomographic scanning of the sella. Radiology. 1981;140:109-113. 22. Gurling KJ, Scott GBD, Baron DN. Metastases in pituitary tissue removed at hypophysectomy in women with mammary carcinoma. Br J Cancer. 1957;11:519-522. 23. Kovacs K. Adenohypophysial necrosis in rou­tine autopsies. Endokrinologie. 1972;60:309-316.

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