Treatment of Radiation-Induced Nodular Goiters
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TREATMENT OF RADIATION-INDUCED NODULAR GOITERS ZsoltG. de Papp,RalphA. Pincusand LouisH. Hempelmann University of Rochester School of Medicine and Dentistry, Rochester, New York Retrospective and prospective epidemiological all patients presented to palpation as solitary or mul studies have shown that prior radiation exposure is tiple nodulesrangingin size from somethat were an important factor in the development of thyroid barely palpable to one massive nodular goiter meas cancer and multinodular goiter in adolescents and uring 6 X 8 X 2 cm. Prior to start of therapy, all young adults (1 ) . In retrospective studies of young patients were examined at least twice by the two persons with thyroid cancer, a history of antecedent senior authors to check on the accuracy and re radiation therapy to the neck or upper chest can producibility of the clinical findings. In each patient usually be elicited by specific questioning (2) . In with a palpably abnormal gland, the serum PB! and prospectivesurveysof selectedpopulationsof young 24-hr 131Juptake were determined, and a “scintiscan― adults with known radiation exposure, the incidence of the gland was carried out. In all but one patient, of neoplasticthyroid diseasecan be remarkably there was no evidence of hypothyroidism. high (1 ) . For example, in the 19 young Marshall In seven patients with nonfunctioning, fixed, stony, Islanders whose thyroid glands were heavily irradi hard or rapidly enlarging nodules, surgery was per ated during childhood by radioactive fission products formed. This was followed by suppressive therapy from a nuclear explosion in 1954, 15 or 78% de with L-thyroxin (0.2 mg daily) for 10 days; then, veloped nodular thyroid disease by 1967 (3) . Simi the daily dose was increased to 0.3 mg if the patient larly, in a subgroup of persons in Rochester, New had no toxic symptoms. Nineteen additional patients York, treated with x-rays in infancy for alleged with suppressive therapy were treated. without sur thymic enlargement,almost 5% have developed gery. The remaining three patients who refused thyroid cancer and 28% , nodular thyroid disease treatment were examined repeatedly several times a (4,5). year. In studying the Rochester subgroup with a high After 3 months of treatment with 0.3 mg L-thy risk of developing nodular thyroid disease, the cmi roxin daily, the patients were reexamined to deter cal managementof patientswith radiation-induced mine changes in the size of the gland and nodules nodular lesions became an important consideration. and to check for clinical evidence of toxicity. The The question that arose was whether all such lesions dose of 0.3 mg was well tolerated by all but one should be removed surgically or whether careful patient whose daily dose had to be reduced to 0.2 followup alone or combined with suppressive thyroid mg. If the thyroid lesions did not respond after 6 therapy would be sufficient. The present report deals months of therapy, the PB! and 1311uptake were with the authors' experience with the clinical care rechecked to determine the degree of suppression of of 29 patients in the Rochester series with radiation thyroid function. induced nodular thyroid disease. RESULTS METHODS Surgery followed by suppressive therapy with thy Of the 105 young adults in the high-risk, thymus roxin (Table 1). Seven patients were treated surgi irradiated subgroup (5), 35 are known to have or cally (Case 1603F in Table 3 was not included in to have had nodular goiters.All patientshad re this group because of the long period of suppressive ported no thyroid problems on a mail questionnaire therapy preceding surgery) . On the initial examina in 1963. Twenty-nine of these patients are consid tion, the findingsin five patientswereconsistentwith ered in this article; the other six have been lost to followup or have not been followed long enough Received July 23, 1969; revision accepted Feb. 5, 1970. to merit inclusion in this study. Except for one gland For reprints contact: Louis H. Hempelmann, The Uni versity of Rochester School of Medicine and Dentistry, 260 that was diffusely enlarged, the thyroid lesions in Crittenden Blvd., Rochester, N.Y. 14620. 496 JOURNAL OF NUCLEAR MEDICINE TABLE 1. SURGICALLYEXCISED NODULES* CaseAgeMonthsNo/Sex(yr) Initial physical findings HistologyCurrent status postoperative 0347M 26 50-gm nodular gland, very Macrofollicular New 4-cm cysticlesion 3 yr after thy 50 mo. firm, It. lower lobe nodule adenoma roidectomy while on continuous sup pression with Proloid 2 gr and L-thyroxin 0.2 mg; shrank to 3 cm on most recent exam 1789F 17 Hard 0.8-cm nodule in rt. Focal adenomatous Not on thyroid for first 24 months post 60 mo. lobe hyperplasia operative; now on L-thyroxin 0.3 mg; no new nodules 3024F 34 3-cm firm nodule in It. lobe. Colloid nodule and Private physician says no new nodules; 10 mo. Nonfunctional on scan follicular adenoma 1 gr thyroid 164SF 26 3-cm firm nodule in rt lobe. Adenoma On 0.3 mg L.thyroxin, no palpable 27 mo. Nonfunctional on scan thyroid tissue 0368M 26 1.5-cm stony, hard nodule Follicular adenoma No thyroid treatment for first 40 months 58 mo. in It. lobe with ossification postoperative;on re-examination re sidual rt. lobe is enlarged; after L-thyroxin therapy (0.3 mg daily) gland shrank 1735M 24 Massive goiter > 125 gm Adenomatous goiter On 2 gr thyroid; only remnant of gland 39 mo. post-traumatic palpable 0385M 31 Granular gland. Four years Papillary and follicu On 0.3 mg L-thyroxin; no palpable 20 mo. later, 2 cm stony, hard br carcinoma rt. residual tissue; no metastases cvi nodules in rt. lobe; soft lobe dent 3.5-cm nodule on left; both were nonfunctional on scan. * Nodules were functional on scintiscan unless otherwise indicated. thoseof malignantdiseaseand, in the sixthpatient, 1% of the 13lJ administered at this time was taken an enormous goiter was present. The weight of the up by the gland indicating that thyroid function was excised thyroid tissue of the last patient exceeded completely suppressed. The patient refused a second 125 gm. The lesions of all six patients proved to be operation. benign on histologic examination. In the seventh Suppressive therapy without surgery. Nine patients patient (0385M), the initial examination revealed with solitary nodules, nine with multinodular glands a normal sized gland with multiple small lobulated and one with a diffusely enlarged gland were treated areas. Since no definite nodules or changes in con with levothyroxin. sistency could be found, it was decided to follow Patients with solitary nodules (Table 2). The nod him without therapy. The patient did not return for ules of all patients were “warm―on scintiscan. All examination by the authors for 4 years by which but the one patient mentioned above were able to time two stony, hard, nonfunctioning nodules were tolerate 0.3 mg of L-thyroxin daily. Even though the present. A total thyroidectomy was performed and daily dose was reduced to 0.2 mg, the thyroid nod a papillar-follicular carcinoma was removed; there ules of this patient (Case 1722M) regressed almost was no evidence of metastasis. All patients were completely. In one patient ( 1728F) there was a given levothyroxin to suppress function of the re complete spontaneous regression of a sizable nodule maining thyroid tissue. during a 3-year observation period prior to treat Repeated examination of five of the patients over ment. When the lesions recurred 1 year later, treat periods up to 60 months disclosed no recurrence of ment with thyroxin was begun. the nodular lesions. One female patient (Case 3024) The lesions in all but one patient responded to did not return to us but her private physician re therapy by shrinking to less than half of the initial ported that there was no recurrence of nodularity 10 size. In two patients under treatment, the lesions months after thyroidectomy. Three years after sur disappeared completely and in three others, almost gery, one patient (0374M) on suppressive therapy completely. In three patients, the nodules were re (Proloid 2 grains and thyroxin 0.2 mg), developed a duced in size to about half that observed at the onset cystic lesion in the remnant of the thyroid gland. of treatment and, in one patient, the size of the The cystic lesion transilluminated readily. Less than nodulewas unchangedafter 10 monthsof therapy. Volume 11, Number 8 497 DE PAPP, PINCUS AND HEMPELMANN The last patient was pregnant, and it is possible that disappeared and then reappeared. At the last exami this might have had something to do with the failure nation, only the smooth residual left lobe could be to respond. In one patient ( 161 SM) the size of the palpated. initial lesion decreased to about half during 20 Complete remission was not achieved in any pa months of treatment but a small new nodule ap tient, but partial response occurred in all but two peared. cases. In three patients, the response to treatment Patients with multinodular goiters (Table 3). The was good with almost complete disappearance of nodulesof most patientswere diagnosedas func the lesions;in four, the lesionsbecamesomewhat tional on scan, but hypofunctional nodules were dis smaller and, in two, there was little, if any, response. covered in two patients. In four patients, the thyroid In one patient showing a partial response,the dose gland was normal on the initial examination but of thyroxinwas increasedto 0.4 mg and in another becamemultinodularduring pretreatmentfollowup a presumptive diagnosis of Hashimoto's disease was periodsof 1—3½years.In one patient with a dif made on the basis of the antithyroid antibody titer, fusely enlargednodular goiter, there was complete a normal PB!, an elevated 24-hr 131! uptake and spontaneous remission with recurrence of the lesion lack of TSH dependence.in one patient whosele 1 year later.