endocrine-related cancer a meta-iodobenzylguanidine

A meta-iodobenzylguanidine scintigraphicscoring system increases accuracy in thediagnostic management ofpheochromocytoma

D Cecchin, F Lumachi1, M C Marzola, G Opocher 2 , C Scaroni 2 , P Zucchetta,F Mantero2 and F Bui

Nuclear Medicine Service, Department of Diagnostic Medical Sciences, School of Medicine, University of Padua, Via Ospedale 105, 35128 Padua, Italy1Endocrine Surgery Unit, Department of Surgical and Gastroenterological Sciences, School of Medicine, University of Padua, Padua, Italy2Division of Endocrinology, Department of Medical and Surgical Sciences, School of Medicine, University of Padua, Padua, Italy

(Requests for offprints should be addressed to D Cecchin; Email: [email protected])

Abstract

As observed by other authors, normal adrenal medullary tissue frequently gives an apparentlypositive meta-iodobenzylguanidine (MIBG) scan in cases studied using 123I-MIBG and lessfrequently 131I-MIBG. The aim of this study was to assess the usefulness of a scoring system,based on different uptakes of the radiopharmaceutical, to improve the accuracy of 123I-MIBGscintigraphy in patients with either adrenal or extra-adrenal pheochromocytomas. Charts from 67consecutive patients (29 males and 38 females, median age 48 years, range 14–80 years) withsuspected pheochromocytoma (either sporadic or familial: multiple endocrine neoplasia (MEN)2a, MEN2b, Von Hippel–Lindau, neurofibromatosis type 1) who underwent 123I-MIBGscintigraphy (scans acquired 4–24 h after injection) from 1991 to 2004, were independentlyreviewed by two experienced nuclear medicine physicians using liver uptake as a reference(scores: 1, uptake absent or less than the liver; 2, equal to the liver; 3, moderately more intensethan the liver; 4, markedly more intense than the liver). Interfering medications were discontinuedfor the appropriate time before MIBG injection. Histological data were obtained for all patientswho underwent adrenalectomy. Scintigraphies were classified as positive using the followingcriteria: extra-adrenal focal uptake, adrenal enlargement together with non-homogeneous uptakeand adrenal uptake more intense than the liver (score 3–4). After surgical resection, asconfirmed by histological findings and long-term follow-up (range 1–14 years, average 9.25years), 43 patients were considered true positives using the proposed scoring system, 20 weretrue negatives, four were false negatives and none was false positive. In conclusion, theproposed scoring system demonstrated high specificity (100%), sensitivity (91.5%) and accuracy(94%) in the management of pheochromocytoma. Positive predictive value and negativepredictive value were 100% and 83.3% respectively. Normal adrenal tissue uptake was correctlydiscriminated from pheochromocytomas in 18 out of 20 patients, with adrenal uptake equal to theliver (grade 2), using the proposed cut-off level.

Endocrine-Related Cancer (2006) 13 525–533

Introduction

At present, the high spatial resolution of morpho-logic modalities (computed tomography (CT) ormagnetic resonance imaging (MRI)) leads to anincreasing number of incidentally discoveredadrenal masses. Nearly 25% of pheochromocytomas

are discovered incidentally (Lenders et al. 2005). Thefunctional meaning of these masses often remainsuncertain, especially if the mass is small with lowlevels of catecholamine secretion (Taı̈eb et al. 2004)and where plasma-free metanephrine measurementis not available (Eisenhofer et al. 1999). In the caseof an epinephrine-secreting pheochromocytoma,

Endocrine-Related Cancer (2006) 13 525–533 DOI:10.1677/erc.1.010661351-0088/06/013–525 # 2006 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology-journals.org


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MIBG adds little to the pre-operative evaluation ofthe sporadic adrenal mass identified by CT or MRIassociated with a positive biochemical test. On theother hand, MIBG is crucial in revealing extra-adrenal uptake and metastatic localization ofpheochromocytomas. It is also useful in revealingbilateral uptake. Furthermore, it has been suggestedthat, in a rare group of patients, 123I-MIBG, accu-mulating in intracellular vesicles via the monoaminetransporter, may confirm the presence of a tumoreven when biochemical tests are negative ordoubtful (Hanson et al. 1991). The finding of highlevels of plasma free normetanephrines and normalplasma levels of catecholamines could be associatedwith a pheochromocytoma in the case of an episodicrelease of catecholamines and a continuous leakageof normetanephrine (Goldstein et al. 2004). In thisgroup of patients, it is worth noticing how functionaldata may be useful in distinguishing between anormal adrenal and a pheochomocytoma. Manystudies have compared the accuracy of CT, MRIand 131I-MIBG scintigraphy in the diagnosis ofsuspected pheochromocytomas (Maurea et al. 1993,1996, Van Gils et al. 1994, Elgazzar et al. 1995,Freitas 1995). Others have reported results with123I-MIBG, which enjoys the advantages of havingan energy more suitable for the g camera, a shorterhalf-life than 131I and the absence of b emission(Maurea et al. 1995). High sensitivity and specificity(100%) values have been reported for 123I-MIBG(Furuta et al. 1999). However, the problem ofnormal adrenal medullary tissue, which frequently

gives an apparently positive 123I-MIBG scan(Maurea et al. 1995), has not, to our knowledge,been fully clarified in the literature.

The aim of this study was to assess the usefulnessof a scoring system, based on different uptakes of theradiopharmaceutical, in improving the accuracy ofMIBG scintigraphy in patients with either adrenalor extra-adrenal pheochromocytomas. In particular,the purpose was to identify a score that could beuseful in distiguishing pheochromocytoma fromthe physiological uptake of the adrenals.

Materials and methods

Charts from 67 consecutive patients who underwent123I-MIBG scintigraphy from 1991 to 2004 werereviewed: 29 (43.3%) were males and 38 (56.7%)were females with a median age of 48 years (range14–80 years). 123I-MIBG might be preferred to131I-MIBG because of its superior dosimetriccharacteristics, its shorter physical half-life (13 h vs8 days) and lack of b emission (Hanson et al. 1991,Maurea et al. 1993, 1996). Furthermore, theadsorbed dose from a given activity of 123I is 1=80to 1=100 compared with that from 131I-MIBG(Berman et al. 1975).

Three major clinical indications for performing123I-MIBG scintigraphy have been identified (Table1). (1) Severe arterial hypertension or paroxysm(n ¼ 49) and adrenal or extra-adrenal mass at CT orMRI associated with an increased level of urinarycatecholamines (UC) and/or fractionated urine

Table 1 Patients grouped according to reasons for performing MIBG scintigraphy

No. of patients Clinical indications Other characteristics of the patients

49 Severe arterial hypertension or paroxysms Adrenal/extra-adrenal mass at CT scan or MRI and UC and/or UM

elevation (n ¼ 47); adrenal mass (n ¼ 2) at CT scan, without UC

elevation

14 Familial syndromes MEN2A (n ¼ 6) all submitted to total thyroidectomy for MTC, with

slight UC elevation, hypertension (3/6) and adrenal mass (5/6) or

enlargement(1/6)

NF1 (n ¼ 2) with hypertensive crisis, monolateral adrenal mass and

elevated UC and UM

VHL (n ¼ 4) with hypertensive crisis, elevated UC and UM, bilateral

(2/4) or monolateral (2/4) adrenal mass. 1/4 cases were identified

after genetic study of the family and revealed a somatic mosaicism

(Murgia et al. 2000)

Isolated MTC (n ¼ 2) and adrenal enlargement

4 Incidentally discovered adrenal masses Slight (n ¼ 3) or marked (n ¼ 1) increase of UC, CT scan (n ¼ 3) or

MRI (n ¼ 1) suggesting a pheochromocytoma

UC¼ urinary catecholamines, UM¼ urinary metanephrines, MEN¼multiple endocrine neoplasia, MTC¼medullary carcinoma of the thyroidgland, VHL¼ von Hippel–Lindau syndrome, NF1¼neurofibromatosis type 1.

D Cecchin et al.: An MIBG scintigraphic scoring system

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metanephrines (FUM). In two cases out of 49, an123I-MIBG scan was performed without elevationof urinary catecholamines (metanephrines were notmeasured) because of an adrenal mass and persistentsevere hypertension. (2) Patients with familial syn-dromes (n ¼ 14) presenting adrenal masses andincreased UC and/or FUM. (3) Patients with inci-dentally discovered adrenal masses (n ¼ 4) andslight or marked increase of UC and/or FUM.

Twenty four-hour FUM or urinary catechol-amine measurements were obtained in all patientssince 2000, while urinary catecholamines were deter-mined in the remaining patients. Abdominal CTscan was performed in all patients and, moreover,20 (29.8%) patients underwent MRI between 10 to24 days (median 14 days) beforeMIBG scintigraphy.Premenopausal women who were pregnant wereexcluded. Informed consent was obtained fromeach patient.

Medications that could interfere with MIBGuptake (i.e. calcium antagonist, labetalol, reserpine,tricyclic antidepressant) were discontinued for theappropriate time (opioids and sympathicomimeticsfor 7–14 days, tricyclic antidepressant for 7–21days, antihypertensive/cardiovascular agents for14–21 days and antipsychotics for 21–28 days).

Patients (n ¼ 65 out of 67) received orally tendrops of Lugol’s solution (potassium iodide 10%and iodine 5%), three times a day for a total of 6days starting on the day before injection of the radio-pharmaceutical or potassium perchlorate (200mgorally at least 30min before administration ofMIBG, n ¼ 2 out of 67 patients) to prevent thyroiduptake of unbound iodine.

123I-MIBG (300–370MBq; GE Healthcare Bio-sciences, Saluggia (VC), Italy) was administered byslow intravenous injection (at least 5min) in apheripheral vein, flushed with saline.

In two patients (one female of 15 years and onemale of 14 years; median age 14.5 years), theactivity administered was calculated on the basis ofa reference dose for an adult, scaled to bodyweight according to the schedule proposed by theEuropean Association of Nuclear Medicine Pedia-tric Task group (Piepsz et al. 1990). All patientswere encouraged to drink fluids following theMIBG injection and to void frequently. Anteriorand posterior total body scans were acquired 4 and24 h after 123I-MIBG injection. Spot images (about350–400 kcounts) of the suspicious areas wereobtained occasionally. Images of kidneys (using99mTc-diethylenetriaminepentacetic acid (DTPA))or liver (using 99mTc-Albures) were frequently

obtained for a better localization of the tumor. Asingle-headed, large field-of-view g camera (SophaMedical DSX; GE Healthcare Technologies–Waukesha, WI, USA) equipped with a low-energy,high-resolution collimator was used.

Two experienced nuclear medicine physiciansreviewed the images independently. The intensityof adrenal MIBG uptake compared with hepaticuptake was evaluated at 24 h.

The results were scored from 1 to 4 as follows:score 1, uptake absent or uptake less intense thanin the liver, score 2, uptake equal to the liver,score 3, uptake moderately more intense than inthe liver and score 4, uptake markedly moreintense than in the liver. Scintigraphies wereclassified as positive in the case of an extra-adrenalfocal uptake, an adrenal enlargement together withnon-homogeneous uptake or an adrenal uptakemore intense than in the liver (score 3–4). Theremaining scans were classified as negative (score1) or doubtful (score 2).

True positive (TP), true negative (TN), falsepositive (FP) and false negative (FN) results wereestablished according to clinical, biochemical andhistological data and on the basis of a long-termfollow-up.

Sensitivity was defined as (TP)/(TPþFN), specifi-city as (TN)/(TNþFP), positive predictive value(PPV) as (TP)/(TPþFP), negative predictive value(NPV) as (TN)/(TNþFN), and accuracy as(TNþTP) over all patients.

Results

Forty-eight (71.6%) patients thought to be affectedby pheochromocytoma/paraganglioma underwentsurgery followed by histological examination of theremoved tumor (Table 2) and long-term follow-up.The largest mass was 12 cm and the smallest 1 cmin diameter (median 4.53 cm). Initially, one of thepatients (one out of 48) from the incidentalomagroup was considered as having a pheochromo-cytoma because of a 2.5 cm (CT) adrenal enlarge-ment and a slight increase in urinarycatecholamines. 123I-MIBG showed an uptake lessintense than in the liver (score 1), thus this wasconsidered to be a true negative in the presentstudy. Histological examination of the removedtumor revealed a cortical adenoma.

The percentage of extra-adrenal uptake of 123I-MIBG (five out of 67; 10.63%) was very close to pre-viously published data (Werbel & Ober 1995). Oneout of five was an extra-adrenal pheochromocytoma


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occurring at the bladder, three out of five were in thepara-adrenal area and the last (one out of five) waslocalized near to the inferior mesenteric artery. Thelargest extra-adrenal pheochromocytoma was 8 cmand the smallest 2.5 cm in diameter (median4.3 cm). None of the paragangliomas have provedto be malignant to date.

The remaining 19 (28.4%) patients, not referredto surgery, underwent long-term (range 1–14 years,median 9.25 years) follow-up. Imaging (CT orMRI) performed in this group of patients, clinicalexaminations and biochemical investigations haveshown no sign of malignancy to date. In two cases,a slight increase of urine catecholamines wasobserved 3 years after a negative 123I-MIBG scan.No increase in adrenal mass diameter was observedby MRI in either case and no symptoms werepresent. Repeated metanephrine levels were normal-ized and, at present, both patients are consideredtrue negatives. A case of an asymptomatic adrenalmass revealed by CT in 1998 (1.6 cm) with anuptake of 123I-MIBG scoring 1 is still stable(1.5 cm at CT in 2004) and symptom free.

Findings of MIBG scintigraphy according to thescoring system for each group are reported inTable 3. For each patient the higher uptake of the

two adrenals was considered. In all monolateralcases considered positive (score 3–4), the contralat-eral uptake was negative (scoring 1 or 2). Two outof three patients with bilateral masses (indicated inTable 3 by an asterisk) had an adrenal uptake ofgrade 3 or 4 and a contralateral uptake of grade 3or 4. In the remaining case (one out of three) therewas an adrenal mass scoring 4 and a contralateralmass that revealed an adrenal enlargement togetherwith non-homogeneous uptake of 123I-MIBG.

Overall there were 13 patients who scored 1, 12patients who scored 2, 10 patients who scored 3, 27patients who scored 4 and five extra-adrenaluptakes.

Forty-three patients (27 scoring 4þ 10 scoring3þ five extra-adrenal uptakesþ one significantadrenal enlargement together with non-homoge-neous uptake of 123I-MIBG) were considered truepositives, 20 (13 scoring 1þ 12 scoring 2� fourfalse negative� one significant adrenal enlargementtogether with non-homogeneous uptake of 123I-MIBG considered true positives) were consideredtrue negatives, four patients (three from thehypertensive groupþ one from the incidentalomagroup) with a score of 1–2 but with a surgicallyand histologically proved pheochromocytoma were

Table 2 Outcome of procedures

Group Referred to surgery Monolateral PH Bilateral PH Others

Severe paroxysm or hypertension (n ¼ 49) 36/49 29/36 2/36 5/36 PG

Familial syndromes (n ¼ 14) 9/14 8/9

3/9 MEN2A

2/9 NF1

3/9 VHL

1/9

1 MEN2A

0/9

Incidentally discovered masses (n ¼ 4) 3/4 2/3 0/3 1/3 CA

Total (n ¼ 67) 48/67 (71.6%) 39/48 3/48 6/48

Not referred to surgery 19/67 (28.4%)

PH¼ pheochromocytoma, PG¼paraganglioma, CA¼ cortical adenoma.

Table 3 Number of patients scored for each group

Group Score 1 Score 2 Score 3 Score 4

Extra-adrenal

uptake Total

Severe paroxysm or hypertension 7 (þ1*) 10 7 20 (þ1*) 5 49

Familial syndromes

MEN2A

VHL

NF1

MTC

3

0

1

0

2

2

2

0

0

0

3

1 (+1*)

2

0

0

6

3

1

2

0

0

0

0

0

0

14

6

4

2

2

Incidentaloma 3 0 0 1 0 4

Total 13 12 10 27 5 67

MTC¼ isolated medullary carcinoma of the thyroid gland and adrenal enlargement, �bilateral pheochromocytoma.



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considered false negatives. No false positives wereobserved (Table 4).

The sensitivity of the proposed method was91.5%. The specificity and PPV were 100%, theNPV value 83.3% and the accuracy 94%. Cohen’sk score between two experienced nuclear medicinephysicians was 81% (P < 0:001). An agreementwas reached in every discordant case. The ninediscordant cases had a final score of 1 (n ¼ 1), 2(n ¼ 6) and 4 (n ¼ 2). In all but one case out of sixscoring 2, the two physicians independentlyassigned a score of 1 or 2. In only one out of sixcases scoring 2 did one physician score the mass 2while the other scored it 3.

Discussion

CT or MRI represent the first diagnostic step in thelocalization of phaeochromocytoma (Van Gils et al.1994), but frequently the nature of the identifiedadrenal mass remains to be clarified (Berglund et al.2001). Furthermore, the functional meaning ofsuspected paragangliomas or metastatic malignantmasses can be difficult to obtain with CT or MRIand it has been demonstrated that when post-operative changes are present (Pacak et al. 2001)the sensitivity of both MRI and CT decreases.

On the other hand, when dealing with sporadicphaeochromocytomas, especially when plasma and

urinary metanephrines are elevated, MIBG scinti-graphy contributes little additional information tothat obtained by a clearly positive and unilateralCT or MRI (Taı̈eb et al. 2004). Furthermore, whenmanaging the familial forms, MIBG scintigraphyseems to lack specificity, as demonstrated in astudy concerning MEN2A (De Graaf et al. 2000).

High sensitivity and specificity values have beenreported in the literature for MIBG scintigraphy(Table 5). However, as observed by other authors(Maurea et al. 1995), normal adrenal medullarytissue frequently gives an apparently positive scanwith 123I-MIBG. Indeed, normaI adrenals are visua-lized in 2% of cases at 24 h and in 16% of cases at48 h for 131I-MIBG (Lindbery et al. 1988, Nakajoet al. 1983) and even more frequently using 123I-MIBG (Shapiro et al. 2001). Possible explanationsfor the variable uptake of normal adrenals may bean increased number of storage granules (Bomanjiet al. 1987) and/or the increased size of the gland.Nowadays the rapid improvement and diffusion ofmorphological imaging techniques (echography,CT or MRI) leads to detection of a greater numberof slightly ‘enlarged’ adrenals. When dealing withfunctional imaging a decision has to be made as towhether the uptake of 123I-MIBG, revealed inthose adrenals, relates to a physiological uptake, ahyperplasia or a pheochromocytoma. Althoughdiffuse adrenal medullary hyperplasia is a rare

Table 4 Score results

TP TN FP FN Total

Score 1

Score 2

Score 3

Score 4

Extra-adrenal uptake

Non-homogeneous enlargement

–

–

10

27

5

1

10 (13� 2A ¼ 10)

10 (12� 2A � 1B ¼ 10)

–

–

–

–

–

–

–

–

–

–

2

2

–

–

–

–

12

12

10

27

5

1

Total 43 20 0 4 67

A ¼ false negatives, B ¼ adrenal enlargements together with non-homogeneous uptake of I-MIBG.

Table 5 Sensitivity and specificity values of MIBG scintigraphy (various authors)

Sensitivity (%) Specificity (%) 131I or 123I-MIBG Cases Reference

87.4

88.5

88

85

85.7

90

99

–

89

>95

100

100

Overall

A=66.1%, B=33.9%

Overall

Overall

A

B

400

174

64

R

29

16

Shapiro et al. 1985

Mannelli et al. 1999

Berglund et al. 2001

Shapiro et al. 1995

Furuta et al. 1999

Furuta et al. 1999

Overall¼ 131I-MIBG and 123I-MIBG, A ¼ 131I-MIBG, B ¼ 123I-MIBG, R¼ review.



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condition (Babington et al. 2000), frequently relatedto multiple neoplasia type II, it is a possible source offalse positive uptake using MIBG.

It is therefore of some interest to discuss sepa-rately the patients presenting a doubtful uptakescore 2 (equal to the liver) because, in our opinion,this is probably where the score could be potentiallyuseful.

All adrenals scoring 2 (n ¼ 20) are shown in Table6 including patients with a contralateral uptakescoring 3 (n ¼ 1) or 4 (n ¼ 4) considered truepositives, patients with an extra adrenal uptaketogether with an adrenal uptake scoring 2 (n ¼ 3)and two false negative results.

All but one patient (considered false negative after1 year) scoring 2 were followed-up for a long period(9.2 years). Among true positive scintigraphies, CTor MRI, clinical examinations and biochemicalinvestigations have shown no sign of malignancy inthe contralateral gland scoring 2 to date. In thisgroup of patients, the proposed score has correctlycharacterized a true positive uptake (scoring 3 or4) and a negative contralateral uptake (scoring 2).Patient number 18 (Table 6) showed an uptakescoring 2 in the left adrenal but it was consideredtrue positive because of an adrenal enlargementtogether with non-homogeneous uptake. Thesurgically removed tumor was 5.3 cm in diameterand presented central necrosis. Another three

patients (nos 15, 16 and 17 in Table 6) showed anextra-adrenal uptake and a monolateral (n ¼ 2) orbilateral (n ¼ 1) uptake scoring 2. The extra-adrenal masses removed measured respectively3 cm (bladder), 8 cm (inferior mesenteric artery)and 4 cm (para-adrenal) in diameter. A longfollow-up (median 10 years) in this group ofpatients has shown no adrenal masses to date.

Among the other true positive studies (with amonolateral uptake scoring 3 or 4 and a contra-lateral uptake scoring 1), uptake 3 or 4 preciselycharacterized the adrenal mass as a pheochromo-cytoma as confirmed in all cases by surgery. Themedian diameter of the removed mass was 4.9 cmin this group of patients.

Two patients (nos 2 and 7) listed in Table 6 as truenegatives, scoring 2, had adrenal lesions measuringmore than 2 cm in diameter. Nevertheless, atpresent (after 13 and 8 years of follow-up respec-tively), no increase in metanephrines has beenfound in either patient and arterial hypertension isunder control. Both, at present, are considered truenegatives. Of the remaining patients scoring 2 andconsidered true negatives (nos 1, 3, 4, 5, 6, 8 and 9in Table 6), one case (no. 8 in Table 6 with a bilateraluptake scoring 2 thus considered true negative) hasrecently shown a slight increase in urinary catechol-amines. In this patient, MRI has not revealedadrenal masses and FUM are normal at present.

Table 6 Details of patients scoring 2

Case no. Sex Age (years) LAU RAU Results Symptoms FU

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

F

F

F

M

M

M

F

F

F

M

F

M

F

F

F

M

M

M

F

F

44

55

47

59

47

68

56

45

18

65

47

48

53

29

31

43

14

41

44

70

1

1

1

1

2

2

2

2

2

4

3

4

4

4

1

2

1

2

2

2

2

2

2

2

1

1

2

2

1

2

2

2

2

2

2

2

2

1

1

2

TN

TN

TN

TN

TN

TN

TN

TN

TN

TP

TP

TP

TP

TP

TP (EXTRA)

TP (EXTRA)

TP (EXTRA)

TP – BIG

FN

FN – horseshoe

AH,H

AH

AH

AH

AH

AH,S

AH

AH

AH

AH,P

AH

AH,P

AH

AH,H

AH

AH,P

AH,P

AH,P

AH

AH

8

13

9

5

13

8

9

14

13

12

10

8

7

10

8

13

10

5

1

8

LAU¼ uptake of left adrenal, RAU¼ uptake of right adrenal, EXTRA¼extra adrenal uptake, BIG¼ enlarged adrenal and non-homogeneousuptake, AH¼ arterial hypertension, P¼ paroxysm, S¼ sweating, H¼ headache, FU¼ follow-up (years).



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Among false negative results (n ¼ 4), two patientsshowed a monolateral (n ¼ 1) or bilateral (n ¼ 2)uptake scoring 2. In one case (no. 20 in Table 6),echography revealed a horseshoe kidney while inthe other (no. 19), thought to have hyperplasia ofone adrenal, severe paroxysm and elevated urinemetanephrines suggested a pheochromocytoma.The surgically removed left adrenal showed a 3 cmpheochromocytoma. In the other two patients withfalse negative scintigraphy (both scoring 1), anintra-adrenal pheochromocytoma was histologicallyconfirmed; the extensive colliquative necrosis withinthe mass (4 cm in diameter) justified the falsenegative result in one case, while the low uptakeremains unexplained in the other patient.

Special attention should be given to the fact that amild (score 2) uptake, even if highly suggestive of anormal pattern or mild hyperplasia, could beassociated with unilateral pheochromocytoma as

shown by false negative results. On the other hand,among doubtful scintigraphies (scoring 2), theproposed method correctly discriminated pheochro-mocytoma from normal adrenal (or hyperplasia) in18 out of 20 patients. Nevertheless, despite thegood k scores of agreement between two experiencednuclear medicine physicians (81%), it is to be takeninto account that a nuclear medicine physician whois not used to 123I-MIBG could experience somedifficulties in assigning a score of 2 (as demonstratedby the six discordant opinions on six patients scoring2). Finally, we must point out that 15 adrenalsscoring 2 were located on the right side while onlynine were on the left adrenal. This may be due to ahigh uptake by the liver which increases the counton the right side. On the other hand, the livershadow could also obscure the right adrenal insome cases (as shown in Fig. 1). Thus, especially inthe case of a high uptake of the radiopharmaceutical

Figure 1 Example images of the proposed scoring system, extra-adrenal uptake and adrenal enlargements together with non-

homogeneous uptake.



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by the liver, special attention should be paid whendealing with a mild uptake (score 2) or an absentuptake in the right adrenal.

Acknowledgements

Early results of this work were presented at the 6thCongress of the Italian Association of NuclearMedicine 15–19 November 2002, Genoa, Italy andat the 6th European Congress of Endocrinology26–30 April 2003, Lyon, France. There is noconflict of interest prejudicing the impartiality ofthis study.

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