and elevated serum TSH levels may stimulate enlargement of any metastases.

Studies are being conducted in an attempt to reducethe number of 1311scans and consequent hypothyroidism.An alternativeapproachto WBSis the localizationof thyroid tumor tissue by the use of labeled anti-Tgmonoclonal antibodies (6, 7) or cell tropic tracers such

as thallium-20i (8) together with determination ofserum Tg levels during suppressive therapy (9,10).

In this study, we have compared the results of @IWBS with serum Tg levels measured both during replacement therapy and after suspension of therapy in61 patients who underwent thyroidectomy for DTC.

MATERIALS AND METhODS

PatientsSixty-one patients with histologically confirmed differen

tiated carcinoma (38 papillary, 14 follicular, and 9 mixed)were followed in our outpatient clinic. Patients with mixedcarcinomas were included with those with papillary carcinomas for clinicaland prognosticpurposes.Duration of followup in these patients varied from a few weeks to 30 yr.

Each patient was under treatment with L-thyroxine (2.5—3.5 pg/kg body weight) according to serum FF3 and Ff4levels. Suppression ofTSH levels was confirmed by TRH test.

Patients were divided into three groups based on diagnosticcriteria: 1) absence of clinical, hormonal or scintigraphicevidence of thyroid activity; 2) presence of residual thyroidtissue and no metastases; and 3) suspected or confirmed localrecurrence of tumor and/or presence of metastases. Patientswith circulating anti-thyroglobulin antibodies were excludedfrom the study.

ThyroglobulinDeterminationSerum Tg was determined during replacement therapy and

after complete suspension of therapy on the same day ofdiagnostic WBS, as specified in the next paragraph. A noncompetitive immunoradiometric assay (IRMA), (Sorin Biomedica, Saluggia,Italy)was used for serum Tg determination.Levelshigherthan 1000ng/ml werein somecasesdifficultto

This study compared serum thyroglobulinmeasurementand whole-bodyscans in the post-surgicalfollow-upofpatientswith differentiatedthyroidcarcinoma.Thyroglobulin levels were measured in 61 patients receiving Lthyroxine therapy after thyroidectomy,and again aftersuspension of therapy, before performing a whole-bodyscan with iodine-i 31. The sensitivity, specificity, and accuracyof thyroglobulinlevels,measuredduringL-thyroxme therapy, for diagnosis of tumor residue or metastaseswerethencalculatedandcomparedwithresultsobtainedby diagnostic whole-body scanning. Our data show thatneither thyroglobulin levels nor whole-body scans alonecan discriminatebetweenpatientswith or withoutmetastases. Sensitivityreached 95.7%, specifIcityi 00%, andaccuracy 96.7% if results of both procedures were alsotaken intoconsideration.We concludethat inthe management and follow-upof patientswith differentiatedthyroidcarcinomabothparametersneedto be evaluated.

J NucI Med 1990; 31:1766—1771

fter thyroidectomy and, in most cases, iodine-i 31(@‘I)ablation of residual thyroid tissue, follow-up ofdifferentiated thyroid carcinoma (DTC) is currentlybased on periodic whole-body scan (WBS) and serumthyroglobulin (Tg) determination, both performed afteran adequate period without replacement therapy (1—5).

This protocol presumes that withdrawal of thyroxinetherapy will result in an increase ofendogenous thyroidstimulating hormone (TSH) and increased functionalactivity of any residual thyroid tissue (Tg synthesis, @Iuptake), information which is important for treatment.However, withdrawing thyroxine induces hypothyroidism, which may not be well tolerated by the patient,

ReceivedNov. 22, 1989; revision accepted Mar. 26, 1990.Forreprintscontact: Dr.G. Ronga,Clin@caMedICaII,PoliclinicoUmberto

I, 00161Roma,Italy.

1766 The Journalof NuclearMedicine•Vol. 3i •No. i 1 •November1990

Can Iodine- 13 1 Whole-Body Scan Be Replacedby Thyroglobulin Measurement in the PostSurgical Follow-up of Differentiated ThyroidCarcinoma?Giuseppe Ronga, Artemisia Fiorentino, Enrico Paserio, Alberto Signore, Valeno Todino,Maria A. Tummarello, Mauro Filesi, and Ivo Ba.schieri

Clinica Medica I!, Service ofNuclear Medicine, University ofRome “LaSapienza, “and Department of NuclearMedicine, University ofL ‘Aquila,Italy

TABLE2ClinicalandScintigraphicDataofPatientsinGroup21311No.Pt.SexHistologyTglTg2dWBS(mCi)tWBS

MIX= mixedcarcinoma;PAP= papillarycarcinoma;FOLL=follicular carcinoma; Tgi = serum Tg level during replacementtherapy(ng/ml);Tg2 = serumTg levelaftersuspensionof therapy(ng/mI); dWBS = diagnostic whole-body scan; RES = presenceof residualthyroidtissue;tWBS = WBS performedafter therapeuticdoseof 1311.

TABLE1ClinicalandScintigraphicData ofPatientsin Group11311No.Pt.SexHistology

TglTg2dWBS(mCi)tWBS

determine precisely and, therefore, are reported as >1000.Serum Tg levels @5ng/ml were consideredas normal bothduring and after suspension of suppressive therapy.

Whole-BodyScanThis was always performed after suspension of therapy. In

our protocol, L-thyroxine is suspended 40 days before theWBSand is substitutedfor the first 22 days with triiodothyronine (80 ag/day). The diagnostic WBS was performed 24 hrafter the administration of 74-148 MBq (2-4 mCi) of ‘@‘I,using a double-head rectilinear scanner (ITAL-ELETTRONICA).The detectionpowerofour scanner is 0.12 @Ci/cm2,asdescribed elsewhere (11), with some modifications. In patientswith functioning metastases or significant residual thyroidactivity, therapeutic doses of ‘@‘i,varying from 1480 to 5550MBq (40-150 mCi) were administered according to theamount and extent ofpathologic iodine uptake and the age ofthe patient. In these cases, a second WBS was performed 48-72 hr after the therapeutic dose of @‘ito locate any metastasesmissed by WBS performed with diagnostic doses of 1311

StatisticsThe Mann Whitney U-test was used to compare Tg levels

from the different groups of patients and the Fisher exactprobability test was used for calculating the significance ofcorrelation coefficients. Mac-Nemar's test was used to cornpare the diagnostic value of Tg measurement with diagnosticWBS.Specificity,sensitivity,and accuracyofTg measurementand WBS were also calculated.

1GAFPAP570RES52RES255FPAP3.189RES72RES3VAFPAP1

.745.2RES30.7RES4VAFPAP331RES54.7RES5CMFPAP14240RES105RES6ElFFOLL16385RES40RES7TAMPAP6.832RES42.3RES8COMPAP1158RES104RES9OAFMIX1440RES97RES10MLFPAP68.7RES75RES11DGFPAP1028.7RES60RES12CGMPAP3037.6RES93RES13SOFMIX24120RES——14LVMPAP640RES——15CMFMIX916RES——16SMFFOLL5.828RES——17MLFPAP825.2RES——

therapy, 20 patients had either clinically, radiologically,or scintigraphically confirmed metastases. These wereobserved in the lungs (n = 11), lymph nodes (n = 6),bones (n = 4), or mediastinum (n = 3); four patientshad multifocal neoplastic lesions. Six patients had localrecurrences and 18 had residual thyroid tissue.

The means of serum Tg levels during and after suspension of therapy are reported in Figure 1. The trendof mean values is to increase in the three groups bothduring and after suspension of therapy but no statistically significant difference was observed within andbetween groups (Mann Whitney U-test). In Group 3,we found a significant correlation (r = 0.685, p <0.0001)betweenlevelsof Tg during replacementtherapy and after suspension of therapy (Fig. 2). This correlation was not observed for Tg levels of patients inGroups 1 and 2.

Tg values of patients from all groups are reported inFigure 3 and show that there are no patients fromGroup 1 with Tg levels during therapy higher than 5ng/ml and there are no patients from Group 2 withlevels higher than 12 ng/ml. However, out of23 patientswho had normal Tg levels (@5 ng/mi) during suppressive therapy, 19 (82.6%) reached pathologic levels aftersuspension of therapy. Of these, four had residual thyroid tissue and five had metastases. Overall, results ofWBS after a diagnostic dose of 31Jcorrelated withserum Tg during therapy in only 36 out of 6 1 cases(59%).

1SMFMIX228NEG2PAFPAP32.5NEG3MDMPAP4.25.1NEG4TAFPAP536NEG5CSMPAP547NEG6DRFPAP33NEG7CPFPAP33NEG8TMMFOLL2.68.9NEG9PAFPAP4.617.5NEG10SEFPAP329NEG11BEFPAP539.3NEG12LPFPAP3.432NEG13DLFFOLL2.725NEG14SMMPAP2.937.5NEG

131 NEG

MIX= mixedcarcinoma;PAP= papillarycarcinoma;FOLL=follicularcarcinoma;Tgl = serumTg levelduringreplacementtherapy(ng/mI);Tg2= serumTglevelaftersuspensionof therapy(ng/ml);dWBS = diagnosticwhole-bodyscan;NEG = NegativeWBS; tWBS = WBS performedafter therapeuticdose of 1311.Patient 11 received 131 mCi of 1311due to suspicion of lymphnodemetastases.

1767Serum Thyroglobulin Measurement •Ronga et al

RESULTS

Clinical and scintigraphic data of the patients arereported in Tables 1, 2, and 3.

After thyroidectomy and, when necessary 31Jablative

MIX = mixedcarcinoma;PAP= papillarycarcinoma;FOLL= follicularcarcinoma;Tgl = serumTg levelduringreplacementtherapy(ng/ml); Tg2 = serum Tg level after suspension of therapy (ng/mI); dWBS = diagnostic whole-body scan; NEG = negative WBS; LOC.

REC. = presenceof localrecurrence;RES = presenceof residualthyroidtissue;MET. LYM. = Regionallymphnode metastases;MET. Lung= lungmetastases;MET. MED. = mediastinalmetastases;MET. Bone= bonemetastases;tWBS = WBS performedaftertherapeuticdoseof 1311

TABLE3Clinical and Scintigraphic Data of Patients in Group 3

No. Pt. Sex Histology Tgl Tg2 dWBS

LOC. REC.MET. LYM.MET. LungMET.LYM.LOC. REC. and MET.

LungLOC. REC.LOC. REC.MET.MED.MET. BoneMET. BoneMET. BoneMET.MED.+ MET.

LungMET. MED.MET. LYM.MET. LYM.LOC. REC.

1311 (mCi) tWBS

98 LOC.REC.120 MET. LYM.133 MET. Lung107 MET. LYM.143 LOC. REC. and MET.

Lung141 LOC. REC.125 LOC.REC.132 MET. MED.100 MET. Bone176 MET. Bone157 MET. Bone47.3 MET. MED. and

MET. Lung128 MET. MED.101 MET. LYM.140 MET. LYM.124 LOC. REC. and MET.

Bone130 RES and MET. Lung123 MET.Lung116 MET. Lung160 MET.Lung100 MET. Lung112 MET. Lung53 MET. Lung

175 MET. Lung94 MET. LYM.

101 MET. LYM.107 LOC.REC.125 NEG87 NEG

117 NEG

1BSMFOLL100042702TIFPAP9547443CEFFOLL70210004ARFPAP852505SEFFOLL>1000>1000

6 VF M PAP7 MF M PAP8 GA F FOLL9 GL F PAP

10 RF F FOLL11 MR F FOLL12 VC F FOLL

187 990256 1400

69 11382 150

214 740400 839161 490

225 52142 6645 30624 78

13 CA14 ZM15 MO16 CL

17 MG18 SF19 AF20 PA21 BI22 CN23 BL24 CV25 CC26 DF27 PK28 MS29 SV30 GM

F FOLLF MIXF PAPM MIX

F PAPF FOLLM MIXM PAPM MIXF FOLLF PAPF PAPM PAPM PAPF PAPM PAPM PAPF MIX

95162

830178.8434.853

13240293

721400

80160251

24.64072

4734180

1000>1000

800

RESNEGNEGNEGNEGNEGNEGNEGMET. LYM.MET. LYM.LOC. REC.NEGNEGNEG

Figure 4 shows the sensitivity, specificity, and accuracy of Tg measurement and diagnostic WBS. Sensitivity of Tg measurement during therapy was 83.3%,whereas sensitivity ofdiagnostic WBS was only 76.6%.When both Tg levels and diagnostic WBS are considered specificity reaches 100% and sensitivity 95.7%.

Eleven patients (18%) had a negative diagnostic WBSdespite the presence of metastases: eight had positivepost-therapy WBS, whereas in the other three posttherapy WBS was still negative and the presence ofmetastases was suspected because of the high Tg levelseither during or after suspension ofL-thyroxine therapy.Only one of these three patients showed the presenceof metastases in the latero-cervical region 5 mo afterthe last WBS was performed. Five patients with metastases (8.2%) had low levels ofTg during therapy, whichincreased to above normal after suspension of therapy.

Comparison of cases selected for 1311treatment by

the two methods (Tg during therapy and diagnosticWBS) showed a statisticallysignificant difference (MacNemar's test, p < 0.001), thus, indicating that the twoparameters are not ofthe same diagnostic value and arenot interchangeable (Table 4).

DISCUSSION

This study demonstrates the importance of both Tgdetermination and WBS in the post-surgical follow-upof differentiated thyroid carcinoma. The aim of ourwork was to establish ifmeasurement ofserum Tg levelsalone, during replacement therapy, was adequate in thefollow-up ofpatients with DTC, thus avoiding the needof interrupting therapy to perform a WBS. Results ofthis study clearly demonstrate that this is not the caseand that both parameters must be evaluated (Table 4).Moreover, after suspension of therapy, a second Tg

1768 The Journalof NuclearMedicine•Vol. 31 •No. 11 •November1990

TABLE4Identificationof Patients to Be Treated with 131IBasedonthe

Tg Value During Hormone Therapy and/or ontheDiagnosticWBSTg@5

Tg>5 Total

Total 23 38 61

Tg = serumTg levelduringreplacementtherapy(ng/mI);dWBS= diagnostic whole-body scan; NEG = negative WBS; RES =

presence of residual thyroid tissue; P05 = positive WBS forpresenceof metastases Mac Nemar'stest p< 0.001.

0

E

C

C0SC

aSS

S=S

000@ 000@ 0

00

I

•0@ 0

0 oI 0

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@j?:1 I... 0 Groupl

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C

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1000

100

10

EC

.S

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1 10 100 1000 10000

Tg durIng th.rapy (ng/mI)

FIGURE3Distribution of Tg levels (during and after suspension of therapy) in all groups of patients. It can be seen that it is notpossible to clearly separate patients belonging to the threegroupson the basis of Tg levels.

I 2 3

Patlsnt group

FIGURE1Serum thyroglobulin levels during replacement therapy andafter suspensionof therapy in the three groups of patients.Differences between the groups are not statisticallysignificant. Dataare mean±s.e.m.

I 10 100 1000

Tg durIng thsrapy (ng/mI)

FIGURE2Correlation between Tg levels during replacement therapyand after suspensionof therapy in patientsof Group3.

In patients with residual thyroid tissue (shown inTable 2), the specificity of Tg determination is, ofcourse, very low (23.5%) and affects the calculation ofspecificity when all patients are considered. Therefore,it is also important to perform a diagnostic WBS soonafter surgery to determine the presence of residual thyroid tissue.

A particular comment must be made concerning fivepatients (Patients 19, 22, 23, 24, and 28 of Table 3) inwhich we found a negative diagnostic WBS and Tglevels within the normal or borderline (@13 ng/ml)range. On the basis of Tg levels and diagnostic WBS,these patients would have been considered free of anylocal recurrence or metastases but Tg levels after suspension of therapy were high in all cases and led us toadminister a therapeutic dose of ‘@‘Ito elicit possiblemetastases. Four out of these five had metastases. Theexplanation may be that partial loss of iodine uptakecapacity by metastatic cells means that visualization isonly possible with high doses of 1311.

determination should be performed which may be ofadditional importance for a therapeutic decision.

The sensitivity of Tg determination during replacement therapy is higher than the sensitivity ofa diagnostic WBS(83%and 76.6%,respectively)but by combining the two parameters the sensitivity reaches 95.7%.The sensitivity of Tg determination after suspension oftherapy (data not shown) is 100%, but the specificityis as low as 12.9% and, therefore, this measurementmust be considered only together with the other twoparameters.

EDC

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1769SerumThyroglobulinMeasurement@ Rongaet al

I@1 gWg@ Tgl+dWBS that serum TSH levels >30 @U/ml are needed to induce

uptake activity of differentiated tumor cells. A smallpercentage of patients, particularly those followed for a

____________ long period of time for DTC, do not show elevatedTSH levels after withdrawal of therapy in spite of apparently total thyroid ablation. This could be due eitherto self-administration of thyroxine or to a true lack ofresponse of the hypothalamic-pituitary axis (15,16).These patients do not benefit from a prolonged periodof withdrawal of L-thyroxine therapy. As previouslyreported by us and other authors, 18 days of completehormone withdrawal is sufficient to obtain a good TSHresponse in patients with normal hypothalamic-pituitary function (17,18). The increase in TSH is usuallygreater in patients under 45 yr of age, but even in olderpatients TSH levels rise above 30 @tU/mlafter an adequate period of suspension of therapy (1 7). We havealso observed that patients with low TSH levels andnegative WBS do not benefit from exogenous TSHadministration before performing a new WBS (unpublished observation). Thus, we do not routinely measureTSH levels before performing a diagnostic WBS.

CONCLUSIONS

In the follow-up of DTC, thyroglobulin determination has good sensitivity but low specificity and therefore cannot replace the WBS. The two methods identifydifferent cases to be treated with ‘@‘I.

In light ofthese results, it appears that optimal followup for these patients should be based on a combinationof the two methods since neither alone is sufficientlysensitive or specific.

ACKNOWLEDGMENTS

The authors wish to thank Mrs. Marion Smith for hervaluable help in writing the manuscript and Mr. AntonioCancellaro for his technical assistance in the scintigraphicstudies.

REFERENCES

1. Torregiani G, Doniach F, Roitt IM. Serum thyroglobulinlevels in healthy subjects and in patients with thyroid disease.J C/inEndocrino/Metab 1969;29:305—314.

2. Van Herle AJ, Uller RP. Elevated serum thyroglobulin: amarker of metastases in differentiated thyroid carcinomas. JC/in Invest 1975; 56:272—277.

3. HüfnerM, Stumpf HP, Grussendorf M, Hermann HJ, Kimming B. A comparison ofthe effectiveness of 1311whole-bodyscans and plasma Tg determinations in the diagnosis ofmetastatic differentiated carcinoma of the thyroid: a retrospective study. Ada Endocrino/ 1983; 104:327—332.

4. Blahd WH, Drickman MV, PorterCV, Hill VA, BaumgartnerWA.Serum thyroglobulin,a monitor ofdifferentiated thyroidcarcinoma in patients receiving thyroid hormone suppressiontherapy: concise communication. J Nuc/ Med 1984;25:673—676.

5. Panza N, Lombardi 0, Minozzi M et al. Iodine-l3l total

M+ M- Tot

Tg>5 25 13 38Tg5 5 18 23

Tot 30 31 61

M+ N- Tot

T+ 36 0 36T- 11 14 25

Tot 47 14 61

M+ M- Tot

T+45 0 45T- 2 14 16

Tot47 14 61

Ig.1 @.w.as Tgl+dWBS

Sensitivity: 83.3 76.6 95.7SpecifIcity: 58.1 100 100Accuracy: 70.5 82.0 96.7

FIGURE 4The calculationof sensitivity,specificityand accuracy of diagnosis of metastases on the basis of Tg levels during replacement therapy(Tgl), on the basisof the diagnosticwhole-bodyscan(dWBS),or takingboth parametersinto consideration(Tgl +dWBS). When only Tg determinationwas considered,M+ indicates patients with metastases. When WBS wasconsidered,M+ indicatespatientswith metastasesor residualthyroid tissue. T+M+ indicates the number of true-positivesin which the WBS correctly identified either metastases orresidual thyroid tissue. Tot=total of cases in rows and columns.

Three patients (28, 29, and 30 of Table 3) hadpersistently negative diagnostic WBS despite a marked

increase in Tg levels after suspension of therapy. Inthese cases, a therapeutic WBS should be performed todetect metastases.These patients were over 45 yr oldwith papillary (n = 2) or mixed (n = 1) carcinoma; allreceived at least two therapeutic doses of 1311within afew months. The probable reasons for the discrepancybetween the WBS and Tg levels were the decreasediodine uptake activity of papillary carcinoma and thereduced TSH secretion in older subjects (12). If metastases should appear, these patients would be treated, inall probability, with conventional chemotherapy and/or surgery. Therefore, these patients were closely followed and, to date, only one has shown clinical andradiologic signs of metastatic recurrence in the laterocervical region and has been referred to surgery.

A certain degree of functional autonomy of neoplastic tissuewasobservedin severalpatients (Table 3). Tglevels were high both during and after suspension oftherapy, with little variation between the two measurements.

It is known that synthesis and secretion of Tg bytumor cells is a process independent of the iodineuptake capacity of these cells (13). In our study, wefound patients in whom Tg production was abolishedbut ‘@‘Iuptake was not. On the other hand, we foundeight patients in whom Tg secretion by tumor cells wasstill present but â€@̃‘Iuptake was abolished after suspension ofreplacement therapy. This may also be explainedas functional autonomy of neoplastic tissue and, insome cases, as lack of TSH dependency. TSH levelsattained during suspension of hormone therapy areimportant from both the diagnostic and therapeuticpoints ofview. Edmonds et al. (14) have demonstrated

1770 The Journalof NuclearMedicine@ Vol. 31@ No. 11@ November1990

body scan and serum thyroglobulin assay in the follow-upofsurgically treated patients affected by differentiated thyroidcarcinoma.J Nuc/MedAilSci 1984;28:9—11.

6. Shepherd PS,LazarusCR, MistryRD. MaiseyMN. Detectionof thyroidal tumour using a monoclonal 1231anti-humanthyroglobulin antibody. Eur J NuclMed 1985; 10:291—295.

7. Fairweather DS, Bradwell AR, Watson-Jones SF, et al. Detection ofthyroid tumours usingradiolabeledanti-thyroglobulin.C/inEndocrino/1983;18:563—570.

8. Brendel AJ, Guyot M, Jeandot R, Lefort G, Manciet 0.Thalliurn-201 imaging in the follow-upof differentiated thyroid carcinoma. iNuc/Med 1988;29:1515—1520.

9. Girelli ME, BusnardoB,Amerio R, et al. Serum thyroglobulinlevels in patients with well-differentiated thyroid cancer during suppression therapy: study on 429 patients. Eur J NudMed 1985; 10:252—254.

10. Pacini F, Lan R, Mazzeo S, Grasso L, Taddei D, Pinchera A.Diagnosticvalueof a singlethyroglobulindeterminationonand off thyroid suppressive therapy in the follow-up of patients with differentiated thyroid cancer. Clin Endocrino/1985;23:405—411.

11. BaschieriI, Pavoni P, SemprebeneL, BenedettiGA. Improvementsin tumourdetectionby scanning.In: SchattauerFK,ed. Radionuk/ide in der klinischen und experimenteilenonko/ogie. Stuttgart, Verlag; 1965:181—193.

12. Baschieri I, Sardano 0, Ronga 0, Lirna 0. Length of discon

tinuation of substitutive therapy in the follow-upof patientswith differentiated thyroid neoplasm. J Nuci Med Ail Sci1979; 23:181.

13. Edmonds CJ, Kermode JC. Thyrotropin receptors, tumourradioiodineconcentration,andthyroglobulinsecretionin differentiated thyroid cancer. J Cancer 1985;52:537—541.

14. Edmonds 0, Hayes S. Kermode JC, Thompson BD. Measurement of serum TSH and thyroid hormones in the management oftreatment ofthyroid carcinoma with radioiodine.BrfRadio/1977;50:799—803.

15. Stahl TJ, Shapiro B. Use of human thyrotropin radioimmunoassayin the managementof patientswith thyroidcarcinoma.JNuc/Med 1973; 14:900—904.

16. Galligan JP, Winship J, Van Doom T, Markmer R. A comparison ofserum thyroglobulin measurement and whole-body1311 scanning in the management of treated differentiated

thyroid carcinoma. Aust NZ J Med 1982; 12:248—254.17. Baschieri I, Di Caprio P, Ronga 0. Age, histological type, and

radioiodine uptake in metastases of differentiated thyroidcarcinomas.In: JaffiolC, Milhaud0, eds. Thyroidcancer.New York: ElsevierSciencePublishers B.V.; 1985:351—352.

18. SchlumbergerM, Charbord P, Fragu P. Lumbroso J, Parmentier C, Tubiana M. Circulating thyroglobulin and thyroidhormones in patients with metastases ofdifferentiated thyroidcarcinoma: relationship to serum thyrotropin levels. J C/inEndocrino/Metab1980;51:513—519.

A lthough the majority of thyroid adenocarcinomas canberemovedsurgically,there

is often uncertainty as to the completeness of the resection and thepresence of local or distant histologic metastases despite the absenceof clinically detectable abnormalities. Radioiodine ‘@Ihas been usedas adjunctive therapy in the management of thyroid adenocarcinoma for more than 40 yr. There ismounting evidence indicating an increased rate of survival and a decreased tumor recurrence rate in patients who have received radioiodine therapy. Ablation withradioiodine of any residual thyroidtissue that has not been removedsurgically appears to be well accepted management since completeablation of normal thyroid tissue

ReceivedJuly 23, 1990;acceptedJuly 23,1990.

For reprIntscontact: WilliamH. Blahd, MD,WadsworthDlv. (691-w115),VA MedicalCtr.,WlIst*e & Sawtelle Blvds., Los Angeles, CA90073.

usually assures radioiodine uptakein remaining tumor deposits andtumor metastases (1).

The efficacy of radioiodine therapy with rare exception is relateddirectly to tumor uptake and retention. Efficient uptake and responseto therapy is observed in tumorsthat are of differentiated cell typessuch as papillary or follicular,whereas undifferentiated tumorsand HUrthle cell and medullary carcinomas rarely concentrate radioactive iodine. Effective tumor uptake is -@-0.5%ofthe dose per gramwith a biologic half-life of -‘-‘4days(2). From the administration of5.55 GBq ‘@‘I,a tumor will receive‘@.-25,O00cOy or five times the absorbed dose that can be delivered bya course of external radiation therapy. Ablation of small thyroid remnants afterneartotal thyroidectomymay be accomplished with the administration of 2.78 to 3.70 GBq

@@‘iRepeat doses are given at intervals of 4—6mo until no imagingevidence ofresidual thyroid or func

tioning tumor tissue is demonstrable.

The recurrence of tumor following radioiodine ablation of all functioning tumor tissue has been foundin more than 50% of patients whohad tumor metastases at the time oftherapy and in 25% ofpatients whodid not have metastases (3). Recurrences have been observed after 5 to10 yr of negative diagnostic studies(3,4). In view of the possibility oflate recurrence, all patients in whomtotal radioiodine ablation has beenobtained should be followed for atleast 10yr to assure that they remainfree ofrecurrent functioning tumor.

Although whole-body imagingwith radioiodine is considered to bethe most sensitive means of detecting recurrent disease, it is a formidable procedure requiring withdrawal of thyroid hormone andperiods of symptomatic hypothyroidism. In recent years therehave been numerous reports suggesting that the determination ofserum thyroglobulin (Tg) may be as

SerumThyroglobulininThyroidCancerManagement@ Blahd 1771

EditorialSerum Thyroglobulin in the Management of Thyroid Cancer