Cholescintigraphy in the Diagnosis of Rotor Syndrome

Andrew M. Fretzayas, Anastasia I. Garoufi, Christopher X. Moutsouris and Themistocles E. Karpathios

Second Department ofPediatrics, University ofAthens, First Depamnent ofPediatric Surgery, A.P. Ky,iakou Children's Hospiu4 Athens, Greece

pigmented cells. Ultrasound examination revealed normal Inthreepatientswithchronicconjugatedhyperbilirubinemlawho andgallbladder. earned the diagnoaisof Rotorsyndrome, @9c-HIDAcholescin Cholescintigraphywasperformedusing @Tc-HIDA.Thepa tigraphywas performed.In thesepatients,the liverwaseither tientwas given 5 mCi(185MBq)andserialimageswere obtained. not Visualizedor it was seen very faintiy with slow liver uptake, The liver,gallbladderandbiliarytreewere not visualizedeven persistent visualization of the cardiac blood pool and prominent after 2 hr and no radioactivitywas excreted into the intestine. kidneyexcretion.The presentobservationemphasizesthe con Persistent visualization of the cardiac blood pool and prominent tilbution of cholescintigraphyinthe diagnosisof Rotorsyndrome. kidneyexcretionwas noticed(Fig.1). Key Words: Rotor syndrome; technetium-99m-HIDA cholescin PedantTwo tigraphy;hyperbilirubinemia;Dubs@-Johnsonsyndrome A 6-yr-oldmalewas hospitalizedbecauseof jaundicenoticed the fifthdayof life. He was the onlychildof healthyunrelated J NucIMed1994;35:1048-1050 parents. Family history was not contributory forjaundice or liver disease. There was no history of hepatitis or blood transfusion. Physical examination was unremarkable except for obvious ictericsclerae.Totalbilirubinwas71.82 @mole/literwitha conju hronic nonhemolytic conjugated hyperbiirubinemia gated component of 59.85 pmole/liter. The hemoglobin electro characterizes both Rotor and Dubin-Johnson syndromes phoreticpatternshowed elevationof HbA2(5.9%)and HbF (6.4%).Otherbloodchemistrieswerenormal.Liver biopsywas (1 ). Differentiation between these two hereditary disorders denied by the family. Ultrasound examination of liver and gall is based mainly on histologic findingsseen in liver biopsy bladderwas normal. specimens (2). Plasma clearance of Bromosulfophthalein A hepatobiliaiyscanwas performedusing @Tc-HIDA.The (BSP) and other anionic dyes alongwith urinarycopropor patient was injected with 5 mCi (185 MBq) and serial images were phyrin isomer excretion have long been considered as di obtainedfor 24hr The liverwas not visualizedduringthe entire agnostic procedures (3). examination. The radiotracer was retained for a long period of In this report we present our experience with @“Tctime in the circulation and persistent visualization of the kidneys HIDA cholescintigraphy in three patients with chronic was noticed (Fig. 2). conjugatedhyperbiirubinemiawho carriedthe diagnosisof PatientThree Rotor syndrome. A 2-yr-oldmalewasadmittedwithpersistentjaundicethatfirst appearedon thethirddayoflife. His6-mo-oldsisterwas healthy CASE REPORTS withoutjaundice.Familyhistorywasnotcontributory.Thephys Patient One icalexaminationwas benign.Admissiontotal biiburin valuewas Thispatientwas a 14-yr-oldmalewhohadjaundicesincebirth. 42.75 @mole/literwith a conjugated component of 39.33 @mole/ Thepatientwas the onlychildin the family.Therewas neither liter. Hemoglobinelectrophoresisshowed that he was a carrierof parentalconsanguinitynor familyhistoryof jaundiceor liver f3-thalassemiatrait.ThepatienthadalsoG6PDdeficiency.Liver function tests were normal. Liver biopsy was denied by the fam disease. No past history of hepatitis or blood transfusion could be elicited. There were no significantfindingson physical examina ily. Ultrasoundexaminationof liverand gallbladderwas normal. tion except for icteric sclerae and soft, painless hepatomegaly 2 A hepatobiiaryscan was performedusing @“Tc-HIDA.A cm below the right costal margin.On investigation,total serum dose of 5 mCi(185MBq)was injectedandserialimageswere obtained.A very fainthepaticaccumulationof radiotracerwas concentration was 83.79 prnole/liter, with a conjugated fractionof 80.37 @mole/liter.Otherliverfunctiontestsandblood noticedafter3hrwithpersistentvisualizationof thecardiacblood chemistries were normal except for glucose-6-phosphate dehydro pool (Fig. 3). genase (O6PD) deficiency. The liver biopsy was normal without DISCUSSION Conjugated hyperbilirubinemia may be attributed to a ReceivedJuly20,1993;revisionaceeptedFeb.24,1994. number of infections, metabolic disorders, anatomic de For correspondence or rep@ntscontact: Andrew M. Fretzayas, MD, 2nd De pertinentofPediatñcs,UnWera!tyofAthens,A.P.KyriakouChi@ren'sHospftal, fects, chemical liver injury from a wide variety of drugs Athens,11527,Greece. (i.e., androgenic and estrogenic steroids, erythromycins,

1048 The Journal of Nudear Medicine•Vol.35 •No.6 •June 1994 :; T 1:@C1 13 —.@TE=@1= 4K. FR 1 - c@;= @7; ROT 180Z1.Ø TC= RATE= 3< T'FR= ii: ANT 3H

ANT FiGURE3. Technetium-99m-HIDAcholesantigram.A veryfaint a HPSPOSTIN@. hepaticaccumulationofradiotracerisnoticedafter3 hr.Thehepa tobiliatysystemis notVisualized. FIGURE1. Technelium-99m-HIDAcholescintigram.Theliveris not visualizedand no radioactivityis excretedin the intestineafter 2 hr. fered to the patient. The latteris no longeradvised because of reportsof fatalanaphylactoidreactionswith BSP (6). As phenothiazines) or may be inherited (4). There are two far as urinary coproporphyrinis concerned, it is known distinct familial pathophysiologic entities, namely the that measurement of isomer I and III can safely differen Dubin-Johnson and Rotor syndromes, characterized by tiate these two syndromes (5). These determinationswere chronic, benign, nonhemolyticjaundice due to raised, pre not done in our patients due to the unavailabilityof rele dominantlydirectbiirubin (1). Differentiationbetween the vant analyticalprocedures in our hospital. two is made on the basis of liver biopsy, plasma clearance Previous reportshave stressed the patternsof somewhat patterns of BSP and determination of coproporphyrin in variable cholescintigraphic findings by using radioactive urine (3,5). The former is not an easily accepted procedure dyes such as ‘31I-Rosebengal, ‘311-BSP,@‘@‘Tc-mebrofenin especially in cases where no therapeutic gain can be of as well as @Tc-IDAderivatives in diagnosing Rotor syn

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Diagnosisof RotorSyndrome•Fretzayaset aJ. 1049 drome and differentiating this disorder from Dubin-John uted to advanced hepatocellular damage in as much as the son syndrome and hepatocellular disease (7—11).In pa same pattern can be seen in a benign entity as the Rotor tients with Dubin-Johnson syndrome, a combination of syndrome. prolonged and intense visualization of the liver with de In conclusion, cholescintigraphy is a simple and infor layed visualization of can be seen. By contrast, mative procedure for the diagnosis of Rotor syndrome and in Rotor syndrome scintigraphic findings are markedly dii has a place in pediatric . ferent with absent or very faint uptake and prolonged vi sualizationof thecardiacbloodpool. REFERENCES In the first patient, normal histology and isotopic find 1. AriasIM. Studiesof familialnon-hemolyticjaundicewithconjugatedbil ings identicalto thatreportedby other investigators,can be irubinintheserumwithandwithoutanidentifiedpigmentinthelivercells. regarded as compatible with the diagnosis of Rotor syn AmJMed 1961;31:510—518. drome. In this syndrome, abnormal transfer of BSP into 2. Case records ofthe Massachusetts general hospital. Case 36-1975. NEng1J Med 1978;299:592—598. the liver associated with abnormalitiesin storage and con 3. Wolpert E, Pascasio FM, WolkoffAW, Arias IM. Abnormal sulfobromoph jugation of the dye have been found (3). Thus, the absent thalein metabolism in Rotor's syndrome andobligate heterozygotes. N Engi or very poor uptake of @Tc-HIDAseems to be antici JMed 1977;296:1099—11O1. 4. King PD, Blitzer BL. Drug-induced cholestasis: pathogenesis and clinical pated. features. Semin LiverDis 1990;1O:316—321. Although a liver biopsy was not done in the remaining 5. ShünizuY, NarutoH, Ida5, KohakuraM.Urinarycopropurphyrinisomers two patients,the cholescintigraphicfindingswere identical in Rotor's syndrome:a studyin eightfamilies.Hepatologj@1981;1:173—178. 6. Wierum C. Sulfobromphthaleintest increasingly unnecessary.JAMA 1969; to the first and the tentative diagnosis of Rotor syndrome 210:1102. was made. This is supportedby the similarclinical presen 7. Bar-Meir S, Baron J, Seigson U, Gottesfeld F, Levi R, Gilat T. Techne tation and laboratory findings of the three patients while tium.99m-HlDAcholescintigraphyinDubin-JohnsonandRotorsyndromes. RadiOlogy 1982;142:743—746. the isotopic pattern is totally different from that seen in 8. GaIIi0, Focacci C, Maini CL, Ct al. The hepatic excretion of ‘311-Rose patients with Dubin-Johnson syndrome. bengaland @“Tc-IDAderivativesin Rotor'ssyndrome.EurJ Nucl Med In our patients, the @‘@Tc-HIDAcholescintigraphicpat 1982;7:311—317. 9. Pinos T, Constansa JM, Palacin A, Figueras C. A new diagnostic approach tern resembles that seen in patients with hepatoceilular to the Dubin-Johnson syndrome. Am I Gastroenterol 1990;85:91—93. disease andmarkedlyelevated serumbiirubin. Thus, from 10. I.e Bouthiier 0, Morais J, PicardM, ChartrandR, Pomier 0. Scintigraphic the practical point of view, in patients with conjugated aspect of Rotor's diseasewith Technetium-99m-Mebrofenin.I Nucl Med 1992;33:1550—1551. hyperbiirubinemiaof unknown origin, nonvisualizationof 11. SarkarSD. Hepatic clearance ofTechnetium-99m-lminodiacetic acid deny the liver with @‘@Tc-HIDAmay not necessarily be attrib atives in hypenbilinubinemicstates. J Nuci Med 1992;33:1551—1552.

1050 The Journal of Nuclear Medicine•Vol. 35 •No. 6 •June 1994