ual cortical activity. Split renal function was perfectly symmetrical response to captopril mimicking false-positive results, rare (Fig. 1). In contrast, baseline scintigraphy was near normal (Fig. 2). conditions, such as the one described here, should be consid ered. DISCUSSION In the differential diagnosis of hypertension, captopril renal scintigraphy plays an important role in the detection of second REFERENCES 1. Rudin A. Bartter's syndrome. A review of 28 patients followed for 10 yr. Ada Med ary forms sustained by renin secretion and angiotensin II Scand 1988;224:165-171. production (renovascular hypertension). Increased plasma renin 2. Nivet H. Rolland JC, Lebranchu Y, et al. Bartter's syndrome in seven children of the activity and angiotensin II levels are also present in Bartter's same family. Nouv Presse Med 1980;9:1287-1290. 3. de la Blanchardiere A. Duron F. Bartter's syndrome. Rev Med Intern 1993:14:101- syndrome which usually presents bilateral hyperplasia of the 106. iuxta-glomerular apparatus. 4. Rosenblum MG, Simpson DP, Evenson M. Factitious Bartter's syndrome. Arch Inlern In this report, we present captopril-induced renography ab Med 1977:9:305-315. 5. Colussi G, Rombolà G, DeFerrari ME. Distal nephron function in familiar hypokal- normalities that were exactly as expected on the basis of emiahypomagnesemia (Gitelman's syndrome). Nephron 1994:66:122-123. underlying pathophysiology. This finding confirms that scinti- 6. Kono T. Oseko F. Shimbo S, Nanno M, Ikeda F, Endo J. Blood pressure fall by angiotensin II antagonist in patients with Bartter's syndrome. J Clin Endocrinol Metab graphic modifications induced by captopril administration on 1976:43:692-695. renal scintigraphy are expressions of renin-angiotensin system 7. Goodman AD, Vagnucci AH, Hartroft PM. Pathogenesis of Bartter's syndrome. activation whether it is determined by RAS or other rare causes N EngU Med 1969:281:1435-1439. such as Bartter's syndrome. The use of captopril renography 8. Gill JR, Bartter FC. Evidence for a prostaglandin independent defect in chloride re-absorption in the loop of Henle as a proximal cause of Bartter's syndrome. Am J may be useful to help diagnose Bartter's syndrome, especially Med 1978:65:766-772. when it has to be differentiated from other causes of hypoka- 9. Gordon RD, Tunny TJ, Klemm SA. Indomethacin and atrial natriuretic peptide in Bartter's syndrome. N EnglJ Med 1986:315:459. lemia such as diuretic intoxication and laxative abuse. 10. Garrick R, Ziyadeh FN, Jorkasky D, Goldfarb S. Bartter's syndrome: a unifying Finally, in recent years, several studies have confirmed the hypothesis. Am J Nephrol 1985:5:379-384. 11. Maldonado MM. Pathophysiology of renovascular hypertension. Hypertension 1991; accuracy of captopril renal scintigraphy in renovascular hyper 17:707-719. tension (14). Some authors, however, have reported a high 12. Nally JV, Chen C, Fine E, et al. Diagnostic criteria of renovascular hypertension with incidence of false-positive results when a symmetrical, bilateral captopril renography. Am J Hypertens 1991;4:749s-752s. 13. Dondi M. Monelli N, Fanti S, et al. Use of "™Tc-MAG3 for rénalscintigraphy after response is observed, as in the case reported here (15,16). It is angiotensin converting enzyme inhibition. J NucíMed 1991:32:424-428. still to be determined if such false-positive results may be 14. Fine EJ. Nuclear medicine evaluation of hypertension. Urol Radiology 1992; 14:85-95. related to the activation of renin-angiotensin system or to 15. Dubovsky EV, Russell CD, Japanwalla M, Mangipudy M. Bilateral response to captopril is nonspecific [Abstract]. J NucíMed 1991;32(suppl):575. different mechanisms. It may be suggested that in the presence 16. Pelsang RE, Rezai K. Abnormal captopril renogram in a patient without renovascular of patent renal arteries and bilateral symmetrical scintigraphic hypertension. Clin NucíMed 1992:17:303-305.

False-Positive Iodine-131 Whole-Body Scans Due to Cholecystitis and Sebaceous Cyst

Françoise Brucker-Davis, James C. Reynolds, Monica C. Skarulis, Douglas L. Fraker, H. Richard Alexander, Bruce D. Weintraub and Jacob Robbins Molecular and Cellular Endocrinology Branch and Genetics Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health (NIH); Nuclear Medicine Department, Warren Grant Magnuson, NIH; and Surgical Metabolic Section, Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland

Key Words: whole-body scan; iodine-131; sebaceous cyst; chole False-positive whole-body 131I scans are not frequent but have cystitis; thyroid cancer serious consequences in the management of patients with thyroid J NucíMed 1996; 37:1690-1693 cancer. They can be classified in four main groups: elimination of iodine in body fluids, infection or inflammation, cysts or transudates and nonthyroid tumors. We report on two patients with false- Whole-body I311scanning (1,2), along with serum thyroglob- positive post-therapy 131Iscans. The first patient had uptake pro ulin measurement (3,4), is the reference method for detecting jected in the right pelvic area which was later proven to be a large residual or metastatic well-differentiated thyroid carcinoma. gluteal sebaceous cyst. The second patient had uptake in the gallbladder area that did not disappear after 131Itreatment; she The presence of uptake outside the areas of physiologic elimi underwent exploratory laparotomy which revealed extensive nation (nasopharynx, salivary glands, bladder, gastrointestinal chronic cholecystitis. These cases illustrate two new causes of tract) is suggestive of functional metastasis. Abnormal tracer false-positive 131Iwhole-body scans (sebaceous cyst and cholecys localization usually triggers treatment with I31I, and a post- titis), which highlights two mechanisms (elimination in body fluid and therapy scan may detect additional métastasesnot visible on the inflammation). diagnostic scan (5). However, the whole-body scan is not a perfect tool and can Received Jul., 27, 1995; revision accepted Nov. 1,1995. result in both false-negative and false-positive findings. An For correspondence contact: FrançoiseBrucker-Davis, MD, NIH, Bldg. 10. Rm. optimal quality scan requires proper preparation of the patient 8014,10 Central Dr., MSC 1758, Bethesda, MD 20892-1758. (including a low-iodine diet, TSH > 25 mU/liter after thyroid For reprints contact: Monica Skarulis, MD, NIH, Bldg. 10, Rm. 83235,10 Central Dr., MSC 1770, Bethesda, MD 20892-1770. hormone withdrawal or more recently after injection of recom-

1690 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 10 •October 1996 Transvaria

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RGURE 1. Patient 1. Post-therapy 131Iwhole-body scan. (Left) Posterior image: arrow shows the uptake in the right pelvic area; physiologic uptake in FIGURE Z Patient 1. SPECT with simultaneously acquired ""Tc and 131I the bladder. (Right) Anterior image: physiologic uptake in the nose and ¡mages.(Left) Technetium-99m-MDP bone scan depicts transverse, sagittal mouth; activity in the thyroid remnant and minimal uptake in the liver. and coronal ¡magesof the pelvis. Uptake in the bone scan is normal. (Right) lodine-131 post-therapy scan. Corresponding images (transverse, sagittal and coronal) and coordinate lines show the focus of 131Iactivity to be to the binant human TSH (6), and the use of a laxative before scanning) and appropriate technique (dose of 13II, sensitive right of and posterior to the bony pelvis. imaging equipment). False-negative findings are suspected when serum thyroglobulin is elevated, and, in these patients, a positive uptake was suspected because of low serum thyroglobulin post-therapy scan is particularly useful (7). False-positive re (3 ng/ml, normal 3-480 ng/ml), absence of pelvic pain and the sults are important to identify in order to avoid unnecessary 131I discovery of a 6-cm subcutaneous mass easily palpated in the right buttock area. The next day, a bone scan (99nTc-MDP) combined treatment. Experience and improvements in technique (tomog with '3ll tomography revealed normal bony structures and local raphy, repeat scan after cleansing, use of other agents such as ized the focus of I3ll to soft tissue posterior to the bony pelvis (Fig. thallium or sestamibi) usually can rule out a mistaken diagnosis of metastasis. 2). Surgical removal of the gluteal mass revealed a large sebaceous Whole-body imaging was performed on a dual-head camera cyst filled with thick material. Six months later, after T4 with drawal and a low-iodine diet, a repeat scan, using 4 mCi ml, was using high-energy collimators. SPECT images were processed using a Hamming filter. We report here two new causes of negative and no further treatment was administered. false-positive whole-body 131Iscans. Patient 2 A 57-yr-old woman with a right thyroid nodule underwent CASE REPORT incomplete surgical resection of a highly invasive papillary carci Patient 1 noma. Four months later, completion of the thyroidectomy and A 58-yr-old man underwent total thyroidectomy for a 4-cm debulking of a 4 X 5-cm tumor invading muscles and soft tissues follicular carcinoma in the right lobe with two foci of occult was performed at our institution. Two months later, a 2-mCi papillary carcinoma in the left lobe. Three months later, a 2-mCi whole-body I3II scan showed uptake in the thyroid bed and whole-body 131Iscan showed two foci of uptake in the thyroid bed adjacent neck. The thyroglobulin was elevated (36 ng/ml) and she for which he received an ablative I31l dose of 144 mCi. The received 152 mCi 13II.The post-therapy scan confirmed uptake in post-therapy scan 1 wk later showed four foci in the thyroid bed, the neck but revealed a prominent focus in the gallbladder region one prominent focus in the right pelvic region compatible with (Fig. 3A). Ultrasound, CT and MRI of the abdomen failed to detect bone metastasis and diffuse hepatic uptake indicating thyroid a tumor but showed a small gallbladder with adjacent liver hormone biosynthesis with hepatic metabolism (Fig. 1). A false- calcification. Nine months later, a 5-mCi diagnostic I3'l scan was

FALSE-POSITIVEIooiNE-131 WHOLE-BODYSCANS•Brucker-Davis et al. 1691 Nine months later, there were no cervical masses and no hepatomegaly, but a complaint of atypical positional pain in the ' , •...•> right flank. Another I31I (5 mCi) diagnostic scan was again »ttk-'"~- negative but she was treated with 297 mCi 131Ion the basis of f'Ä1ftt"'^. " persistent elevated thyroglobulin (56 ng/ml). Again, the post- **2?vV-.»'-•••'.- therapy scan showed uptake only in the gallbladder area. A

*• :.'"'' "*,'-,' 99mTc-sestamibi scan showed a questionable small focus in the r V' ,.•fd ••'W-. . Cr ''f"^-,:^- • right neck, but neither the sestamibi or thallium scan visualized the 3 o •, >,'• gallbladder. At laparotomy, chronic cholecystitis and cholelithiasis with extensive peritoneal adhesions and choleduodenal fistula were found. A hard, partially intrahepatic gallbladder, was removed. Pathology examination revealed a partially calcified gallbladder .* .V »r^ . with chronic cholecystitis and a 2.5-cm gallstone but no thyroid ;-^ : i- cancer. •'.„•*•v .. .. - DISCUSSION We report a large sebaceous cyst and chronic cholecystitis as two new causes of false-positive, post-therapy whole-body 13II scans. Table 1 lists previously reported causes of false-positive scans (9-11) classified in four main groups according to mechanism: (a) elimination of iodine in body fluids (12-22), including a septated gallbladder (22); (b) inflammation or infection (25-25); (c) transudates or cysts (9,26); (d) nonthyroid neoplasms (27-38). However, other rare causes are possible (39-41). Some false-positives are easy to rule out (skin contamination by saliva, sputum, sweating, "handkerchief sign") and should be avoided with adequate technique. Accu mulation of iodine in the esophagus or gastrointestinal tract can usually be proven by repeat scanning after the patient drinks or the GI tract is cleansed. The major diagnostic problems are FIGURE 3. Patient 2. (A) lodine-131 post-therapy scan, anterior view of the false-positives projecting in areas where thyroid cancer may upper abdomen, lodine-131 activity accumulates in the gallbladder area. Diffuse 131Iuptake in the liver suggests residual functioning thyroid tissue metastasize (lungs, bones and liver): one should be suspicious in the case of discordant serum thyroglobulin or clinical history. with subsequent hepatic catabolism. (B) Composite of simultaneously ac quired ""Tc-sulfur colloid and 131Iliver and spleen images. Corresponding Additional views (obliques) or imaging studies (other isotopes, coronal sections from SPECT image are shown. Intense 131Iactivity (arrow) CT scan) are recommended to avoid unwarranted treatment. was located in the gallbladder fossa and not in the liver parenchyma. In Patient 1, the uptake in the right pelvis suggested the possibility of bone metastasis, but serum thyroglobulin was negative, but the thyroglobulin level remained high (43 ng/ml), and low, the bone scan was negative and combined 131I/"mTc she was treated with 147 mCi 13II.The post-therapy scan showed tomography permitted localization of the activity to superficial a single focus of uptake in the gallbladder area. A hepatobiliary soft tissue. Analysis of the cyst showed no evidence of scan (99nTc-IDA) failed to visualize the gallbladder, even after inflammation or infection, and we speculate that the uptake was administration of 0.04 mg/kg morphine (8). She then underwent due to the elimination of iodine in the sebum. sulfur colloid liver imaging. Dual-energy planar and tomographic The second case was more difficult to solve because of images (ml and 99mTc-sulfur colloid) showed that the ml activity persistent high thyroglobulin levels and uptake in the gallblad was located in the gallbladder fossa (Fig. 3B). A liver biopsy under der area, suggesting either an unusual gallbladder metastasis or ultrasound guidance revealed only normal hepatic cells in the false-positive gallbladder uptake with residual tumor elsewhere region of calcification. that did not take up iodine. One case of false-positive uptake in

TABLE 1 Classification of False-Positive Whole-Body lodine-131 Scans

FluidsSweatingBody infectionInflammatory cystsRenal tumorsGastric

hairSputumin diseaseLung lung cystHydroceleParotid cancerOvarian (tracheostomy)SalivaBreast fungusSkin (cystadenoma,teratoma,tumors excavatumEctasia bumPsoriasisCholecystitisTransudatescystPericardial ovarii)Lung struma of carotid milkColon effusionNonthyroidcancerPapillary esophagusEsophagealgraft replacement of meningiomaNeurilemomaWarthin's strictureHiatal herniaMeckel's tumorOthersThymusPectus diverticulumSeptated gallbladderSebaceous cystInflammation

The two conditions in bold are the new cases reported here.

1692 THEJOURNALOFNUCLEARMEDICINE•Vol. 37 •No. 10 •October 1996 the gallbladder on a post-therapy scan has been reported (22). In 14. Ceccarelli C. Pacini F, Lippi F, Finchera A. An unusual case of a false-positive whole-body scan in a patient with papillary thyroid cancer. Clin NucíMed I988;13: that patient, two discrete foci were seen, and a septated 192-193. gallbladder was detected by ultrasound. In addition, abdominal 15. Kirk GA, Schultz EE. Post-laryngectomy localization of ml of tracheostomy site on CT showed a grossly abnormal gallbladder with a calcified a total-body scan. Clin NucíMed 1984;9:409-411. 16. Park HM, Tarver RD, Schauwecker DS, Burl R. Spurious thyroid cancer metastasis: stone. The authors concluded that the persistent gallbladder saliva contamination artifact in high dose iodine-131 métastasessurvey. J NucíMed radioactivity was explained by gallbladder morphology and 1986;27:634-636. abnormal functional dynamics. In our patient, none of the 17. Bakheet S. Hammami MM. False-positive thyroid cancer metastasis on whole-body radioiodine scanning due to retained radioactivity in the esophagus. Eur J NucíMed imaging studies was diagnostic; only surgical exploration es 1993:20:415-419. tablished the diagnosis. We therefore believe that the 13II 18. Willis LL, Cowan RJ. Mediastinal uptake of ml in a hiatal hemia mimicking uptake resulted from chronic inflammation of the gallbladder. recurrence of papillary thyroid carcinoma. Clin NucíMed 1993;18:%l-963. 19. Boulahdour H, Meignan M, Melliere D, Braga F. Galle P. False-positive ml scan Leukocytes, mainly neutrophilic polymorphonuclear cells, are induced by Zenker's diverticulum. Clin NucíMed 1992; 17:243-244. rich in myeloperoxidase (42) and exert part of their bactericidal 20. Kistler AM, Yudt WM, Bakalar RS, Turton DB, Silverman ED. Retained esophageal effect by iodination of bacteria (43-45). Organification of activity on iodine-131 survey in patient with benign esophageal stricture. Clin Nucí iodine in leukocytes may explain the retention of 131I. Our Med 1993;18:908-909. 21. Caplan RH, Gundersen GA, Abellara RM, Kiskcn WA. Uptake of iodine-131 by a patient received three I treatments totaling 600 mCi, with Meckel's diverticulum mimicking metastatic thyroid cancer. Clin NucíMed 1987; 12: estimated radiation doses of 17.1, 17.1 and 34.2 rads to the 760-762. gallbladder wall. We believe that these doses are too small to be 22. Achong DM, Gates E, Lee SL, Doherty FJ. Gallbladder visualization during post- therapy iodine-131 imaging of thyroid carcinoma. J NucíMed l991;32:2275-2277. responsible for the extensive lesions with adhesions and fistula 23. Geatti O, Shapiro B. Orsolon PG, Mirólo R, Di Donna A. An unusual false-positive formation. scan in a patient with pericardial effusion. Clin NucíMed 1994; 19:678-682. Interestingly, these two false-positive findings were not 24. Hoschl R, Choy DHL, Gandevia B. Iodine-131 uptake in inflammatory lung disease: detected on the diagnostic scans (2-5 mCi) but only after 131I a potential pitfall in treatment of thyroid carcinoma. J NucíMed 1988;29:701-703. 25. Maslack MM, Wilson CA. Iodine-131 accumulation in a pericardial effusion. J Nucí therapy. This corroborates the observation that the incidence of Med 1987:28:133. false-positive scans increases with the dose used for diagnostic 26. Brachman MB, Rothman BJ, Ramanna L, Tanasescu DE, Adelberg H, Waxman AD. False-positive iodine-131 whole-body scan caused by a large renal cyst. Clin NucíMed scanning (46). Therefore, the increase in sensitivity (fewer 1988;13:416-418. false-negative scans) obtained with higher doses (up to 10 mCi) 27. Acosta J, Chitkara R, Khan F, Azuela V, Silver L. Radioactive iodine uptake by a has to be balanced with the decrease in specificity (more large-cell undifferentiated bronchogenic carcinoma. Clin NucíMed 1982:7:368-369. false-positives). 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FALSE-POSITIVEIooiNE-131 WHOLE-BODYSCANS•Brucker-Davis et al. 1693