THYROIDVolume 11, Number 11, 2001Mary Ann Liebert, Inc.

Techniques in Thyroidology

Iodine-131 Treatment of Thyroid Papillary Carcinoma inPatients Undergoing Dialysis for Chronic Renal Failure:

A Dosimetric Method

Rosario García Jiménez,1 Alfonso Soto Moreno,2 Elena Navarro Gonzalez,2 F. Javier Luis Simón,3

Jose Ramón Rodriguez Rodriguez,1 Juan Castilla Jimenez,4 Miguel Herrador Córdoba,3

Ricardo Vazquez Albertino,1 and Ricardo Astorga Jimenez2

Until recently, the therapeutic protocol widely accepted for ablation of the thyroid remnant and for metastasesof thyroid papillary carcinoma was the administration of 131I after surgery. However, at present, some dataquestion the usefulness of such treatment in patients considered low risk. The treatment with radioiodine inpatients suffering from end-stage renal disease (ESRD) undergoing hemodialysis requires controlled dosagesand individualized administration guidelines. The need to include these patients on the waiting list for a renaltransplantation, once they have overcome the disease, and the higher prevalence of thyroid carcinoma in ESRDpatients makes this an increasingly significant problem. The cases reported in the literature are few and thetherapeutic models followed are very difficult. In this paper we propose a therapeutic model that provides thehighest thyroid ablative dosage, minimizing radiation exposure to the rest of the organs. The main differencebetween our protocol and that already described is the performance of daily hemodialysis during the first 5days of treatment, as well as the administration of a dose of 131I equivalent to that administered to patientswho show normal renal function.

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Introduction

UNTIL RECENTLY, the therapeutic protocol widely acceptedin case of ablation of the thyroid remnant and for metas-

tases of thyroid papillary carcinoma was the administrationof 131I (1) after surgery. However, at present, some data ques-tion the usefulness of such treatment in patients consideredas low risk (2). Both the therapeutic guidelines and dosime-try have been exhaustively studied in patients with normalrenal function (3,4). However, because iodide removal fromthe body occurs by renal extraction, the treatment with ra-dioiodine in patients suffering from end-stage renal disease(ESRD) undergoing hemodialysis requires controlleddosages and individualized administration guidelines. Theneed to include these patients on the waiting list for renaltransplantation, once they have overcome the disease, andthe higher prevalence of thyroid carcinoma in ESRD patients(5) makes this an increasingly significant problem. Moreover,we must also consider other questions such as the safety ofthe therapeutic procedure in order to minimize radiation ex-posure to the patient, family, and personnel. The cases re-ported in the literature are few and the therapeutic modelsfollowed are very different (6–9). In this paper we propose

a therapeutic model that provides the highest thyroid abla-tive dosage minimizing radiation exposure to the rest of theorgans.

Patients and Methods

Patients

Three ESRD patients undergoing hemodialysis were stud-ied and diagnosed with thyroid papillary carcinoma.

Patient 1. A 42-year-old male suffering from ESRD hadbeen undergoing hemodialysis for 20 years. He had under-gone two unsuccessful renal transplantations, and as a re-sult he had to continue dialysis. The patient had a previoushistory of hepatitis B, and showed tertiary hyperparathy-roidism that prompted surgery. The surgical procedure re-vealed a thyroid nodule that was removed; the anato-mopathologic analysis confirmed a papillary carcinoma.Total thyroidectomy was then performed revealing in theanatomopathological study a multicentric papillary carci-noma that did not show local or remote metastases either inthe surgical procedure or in the presurgical imaging tests.

Departments of 1Nuclear Medicine, 2Endocrinology, 3Science, and 4Nephrology, Virgen del Rocio Universitary Hospital, Seville, Spain.

Patient 2. A 51-year-old man had been suffering fromESRD for 8 years. He had never undergone surgery and hadserious hypertension and tertiary hyperparathyroidism. Hewas diagnosed with thyroid papillary carcinoma by meansof PAAF and underwent total thyroidectomy. The anato-mopathologic analysis revealed a cystic thyroid papillarycarcinoma of 1.5 3 1 cm in diameter that showed no local orremote metastases in the morphologic analysis.

Patient 3. A 34-year-old male had been suffering fromESRD for 2 years. The patient showed tertiary hyper-parathyroidism that prompted surgery to remove anadenopathy that later was found to be metastasis of a pap-illary carcinoma. Total thyroidectomy was performed andthe ganglia were completely drained. The anatomopatho-logic analysis revealed a thyroid papillary carcinoma of 1.5cm in diameter located in the inferior one third of the rightthyroid lobe. The removed adenopathies showed no otherlymphatic metastases. A computed axial tomography (CAT)of the affected area revealed no further adenopathies.

We emphasize the favorable prognosis of these three tu-mors in accordance with the MACIS scale.

Methods

Diagnostic scintiscans. To evaluate the extent of the dis-ease and to collect data for radiation dosimetry, whole-body131I scans and snapshots were obtained (Elscint APEX SPX6-HR) using 74 MBq (2 mCi) of 131I. All data were collected ona dedicated computer. The radioiodine was administered im-mediately after the patient had undergone dialysis. The firstscan was performed 48 hours later, before the next sched-uled dialysis, a second scan was obtained on the same dayafter dialysis. Geometric means (anterior counts 3 posteriorcounts)1/2 were calculated from each study. Regions of in-terest were drawn on computer images around the thyroid,the thyroid remnant, metastases, and background to calcu-late iodine uptake in functioning tissue. The dialyses wereconducted in a private room of the metabolic unit. Uptakemeasurement was performed with a 2-inch sodium iodidecrystal centered at 10-cm distance from the trachea. Mea-suring time was 60 seconds. After each dialysis the room andequipment used were monitored using a contaminatio mon-itor (Berthold LB122). The total effluent dialysate waste wascollected in the 40001 tank of this unit. Samples were col-lected to calculate the proportion of radioactivity removedby dialysis. Patient blood samples were collected to measurewhole-blood radioactivity. Arterialized blood radioactivitywas measured at hourly intervals during the 3 hours of each

session. All sessions were performed with HEMOPHAN di-alyzers (1.8 m2).

Radioiodine treatments. Patients were admitted for treat-ment to a metabolic unit room that was prepared accordingto the institution’s procedures. The protocol used for thetreatment was almost the same as that used for diagnosticscintigraphy. The patients received a therapeutic dose im-mediately after dialysis. Dialysis was performed 24 hours af-ter the dosage and again 48 h, 72 h, 96 h, and 144 h later. Ra-diation emitted from patients was monitored daily using aBabyline (Nardeux) survey meter at a distance of 10 cm, 50cm, 1, and 2 meters. The drain hose from the dialysis unitwas connected to the 40001 tank to collect the effluentdialysate waste. All personnel including the dialysis opera-tor and nurses wore PB aprons, film badges, and surveydosimeters (Thospe PSD-6000) to monitor radiation expo-sure. After the patient was released the portable dialysisequipment and room were monitored for contamination.

Dosimetry calculations. The purpose of the dosimetricstudy prior to therapy is to obtain potentially helpful infor-mation to decide how much activity should be administered.Masón et al. (3) found that a dose of 8,000 rad to metastasessignificantly improved the outcome and that there was littleor no response when the dose administered was below 3,500rads. We used repeated uptake measurements to determinethe effective half-life.

The absorbed dose was calculated according to Kereiakesand Rosenstein (10) based on Medical Internal RadiationDose Committee of the Society of Nuclear Medicine (MIRD)dosimetry.

Dose 5 1.44 (f) (A) (Teff) (S)

The values for f (organ fraction), A (activity), Teff (effec-tive half life) and S (mean dose per unit cumulated activity)are given for all treatments in Table 1.

Results

Patient 1

Scanning with 2 mCi of 131I after 1 month without levothy-roxine (LT4) showed an uptake area in the front part of theneck suggesting normal thyroid tissue remnant. Thyrotropin(TSH) and thyroglobulin (Tg) levels were 52.5 mU/mL and48.9 ng/mL, respectively. The patient was admitted to themetabolic therapy unit of our hospital immediately after un-dergoing hemodialysis and 75 mCi of 131I was administered.

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TABLE 1. DOSIMETRY FOR 131I TREATMENTS

A Teff S Dose DosePatients Comments f (mCi) (h) (cGy/mCi 3 h) (cGy) (Gy)

1 Thyroid 0.033 75.1 3 103 192 2.2 3 1022 15,074 150Whole-body 1 75.1 3 103 45 1 3 1025 48.6 0.48

2 Thyroid 0.03 87 3 103 71.5 2.2 3 1022 5,911.9 59.11Whole-body 1 87 3 103 52.9 1 3 1025 66.27 0.66

3 Thyroid 0.02 120 3 103 119.5 2.2 3 1022 9,085.8 90.85Whole-body 1 120 3 103 38 1 3 1025 65.66 0.65

f, organ fraction; A, activity; Teff, effective half-life; S, mean dose per unit cumulated activity.

Dialysis and gammagraphic scannings were performed ac-cording to the protocol already described. Neither of the twoscannings performed 48 and 168 hours after 131I administra-tion showed any other uptake area. The patient was re-scanned 1 year later and showed a TSH level of 57.67 mU/mLand Tg of 11.02 ng/mL. No uptake area was observed, there-fore, 131I was not administered and the patient was asked toreturn for a new scan in 6 months. Therefore, this patientwill not be considered cured until a new scanning is per-formed.

Patient 2

Scanning with 2 mCi of 131I after 1 month without LT4 re-vealed a TSH level of 47.1 mU/mL and Tg of 0.68 ng/mL.Uptake areas were observed in the front part of the neck sug-gesting thyroid remnant, but the scans did not reveal lym-phatic metastases. Following the same protocol as that usedwith the first patient, 87 mCi of 131I were administered. Thegammagraphic scannings performed immediately after 131Iadministration did not show any other uptake areas. The pa-tient was rescanned 1 year later, no uptake area was ob-served, and the levels of TSH and Tg were 52.3 mU/mL and1.19 ng/mL, respectively. 131I was not administered and weexpect a new negative scan to include the patient in the pro-tocol of renal transplantation.

Patient 3

Scanning with 2 mCi of 131I after 1 month without LT4showed TSH levels greater than 40 mU/mL and Tg at 4.3

ng/mL. An uptake area was observed corresponding to nor-mal thyroid tissue remnant. The patient received a 120 mCidose of 131I according to the protocol already described. Thescan performed immediately after 131I administration re-vealed uptake areas corresponding to lymphatic metastasesnot observed in the previous scan. Another CAT scan wasperformed revealing no new adenopathy. Two more scanshave been performed 12 and 18 months afterwards that havenot shown uptake areas. Moreover, the Tg levels have beennormal, with TSH 40 mU/mL. At present, the patient is con-sidered cured of the disease; he follows a substitutive ther-apy with LT4 and is included on the list for renal transplan-tation.

Figure 1 shows levels of 131I in the patients after succes-sive hemodialyses. After 15 hours of hemodialysis (Table 2),the first two patients removed 89% of the dose administeredand the third patient, 98%. Table 1 presents the dosimetricdata. In all cases the total dose in the first 168 hours was be-low 1 Gy, always reaching effective thyroid doses. However,contamination of dialysis equipment was not detected andthe environmental dosimetry was below 64 mSv.

Discussion

The number of patients with differentiated thyroid carci-noma suffering from ESRD undergoing hemodialysis is in-creasingly higher because of several factors such as thestricter control of ESRD patients by means of parathyroidechography, the higher prevalence of thyroid papillary car-cinoma in this group of patients, which according to some

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TABLE 2. 131I THERAPY IN DIALYSIS

Patient 1 Patient 2 Patient 3

% Dose % Dose % DoseDialysis % Reduction eliminatedb % Reduction eliminatedb % Reduction eliminatedb

1aHD 38 43 55 58 38 572aHD 55 76 35 75 38 683aHD 24 84 22 82 47 844aHD 13 87 12 86 44 925aHD 1 89 6 89 63 98

aValues are percentage reductions in whole-body radioactivity.bValues are elimination percentage of the initial dose.

FIG. 1. Whole-body radioactivity after treatment dose.

authors is related to the rise of parathyroid hormone levels(11,12), the higher survival rate of ESRD patients undergo-ing hemodialysis, etc. However, it is extremely important tocure these patients because they could then be included inthe protocol of renal transplantation, which is not possibleif the thyroid remnant is not destroyed with 131I.

There are several studies in the literature reporting expe-riences with this type of patients (6–9) and others about thepreoccupation this situation creates (13), but there is noagreement on the treatment and the dosages that should beadministered. The main problem is the bioavailability of 131Iin the blood of ESRD patients undergoing hemodialysis ascompared to that of patients with normal renal function.Gadner et al. (14) observed elevated blood iodine in patientsundergoing dialysis, which remained the same in spite ofstopping povidone-iodine use. 131I clearance rates in ESRDpatients depends on the type, duration, and frequency ofdialysis therapy and also on the interval between dialysisprocedures (5). Howar et al. (6) calculated that 131I half-lifein patients on hemodialysis was 4 1/2 times higher than thatof patients with normal renal function, and therefore decidedto administer a smaller dose of 131I to their patients.Daumerie et al. (9) acted similarly, but not Donald et al. (7)or Mello et al. (8) who used equal or even higher dosagesthan in the case of patients with normal renal function, be-cause they observed faster clearance rates of 131I in these pa-tients which made them obtain smaller doses of 131I in thethyroid.

In order to obtain an effective thyroid dosage while avoid-ing a dangerous dosage of total body radiation (4), we care-fully measured the amount of 131I present both in the thy-roid and in the body at every stage of the treatment. Themain difference between our protocol and that already de-scribed is the performance of daily hemodialysis during thefirst 5 days of treatment, as well as the administration of adose of 131I equivalent to that administered to patients whoshow normal renal function. It should also be mentioned thatall hemodialysis procedures were performed in the meta-bolic therapy unit, where the nephrology personnel at-tempted to avoid radiation exposure to the rest of patients.Table 1 shows how effective dosages of 131I in the thyroidwere obtained without reaching dangerous levels of bodyradiation. Figure 1 indicates iodine removal in each dialysisprocedure, showing a clearance rate of about 57% of the to-tal amount in the first dialysis. After 15 hours of dialysis (5dialysis procedures of 3 hours each), the clearance rate in thefirst two patients was 89%, and 98% in the third patient(Table 2). All measurements performed for the personnel re-vealed that no dangerous levels of radiation were reached;in the same way, no environmental contamination was de-tected. The protocol here described has proved useful to curethese patients and allow them to be included in the waitinglist for renal transplantation.

In conclusion, the number of ESRD patients undergoinghemodialysis who show a thyroid carcinoma may continueto grow. These patients must undergo total thyroidectomyand subsequent ablative treatment with 131I in order to curethem, and, if possible, include them in the protocol for renaltransplantation. We present a therapeutic protocol that pro-vides effective 131I thyroid dosages while avoiding body ra-diation beyond allowed limits, and that therefore seems use-ful for attaining the goal previously established.

References

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2. Hay ID, Bergstralh EJ, Goellner J, Ebersold JR, Grant CS 1993Predicting outcome in papillary carcinoma: Development ofa reliable prognostic scoring system in a cohort of 1779 pa-tients treated surgically at one institution during 1940–1989.Surgery 114:1050–1058.

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9. Daumerie CH, Vynckier S, Caussin J, Jadoul M, Squifflet JP,de Patoul N, Wambersie A 1996 Radioiodine treatment ofthyroid carcinoma in patients on maintenance hemodialy-sis. Thyroid 6:301–304.

10. Kereiakes JG, Rosenstein M 1980 Handbook of RadiationDoses in Nuclear Medicine and Diagnostic X-Ray. CRC,New York.

11. Miki H, Oshimo K, Inoue H, Kawano M, Morimoto T, Mon-den Y, Yamamoto Y, Seyzo K 1992 Thyroid carcinoma in pa-tients with secondary hyperparathyroidism. J Surg Oncol49:168–171.

12. Prinz RA, Barbato AL, Braithwaite SS, Brooks MH, En-manuele MA, Gordone DL, Lawrence AM, Paloyan E 1982Simultaneous primary hyperparathyroidism and nodularthyroid disease. Surgery 92:454–458.

13. Victoria Novic A, Renato Gonzalez E, Marcela Díaz C, JorgeVega S 1998 Necesidad de administrar 131I en una pacienteen hemodiálisis crónica con carcinoma papilar tiroideo. RevMed Chile 126:874–875.

14. Gadner DF, Mars DR, Thomas RG, Burungsup C, Misbin RI1986 Iodine retention and thyroid dysfunction in patients onhemodialysis and continual ambulatory peritoneal dialysis.Kidney Dis 7:471–476.

Address reprint requests to:Rosario Garcia Jimenez

Department of Nuclear MedicineVirgen del Rocio University Hospital

Urubamba 1Seville 41012

Spain

E-mail: charingarciaj@hotmail.com

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