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ABSTRACT. Radionuclide thyroid scanning of pa-tients with Hashimoto’s thyroiditis (HT) may mim-ic other thyroid disorders including cold nodules,multinodular goiter and rarely hot nodules. Theassociation of single hot nodules in such patientsin the face of primary hypothyroidism has notbeen previously reported. We describe 6 femalepatients with HT who presented either with symp-toms of overt thyroid failure or a sensation oflump in the neck (and later found to have mild thy-roid failure) who had single firm thyroid nodules.

These nodules were hot by both 99mTc pertech-netate and radioiodine thyroid scans. In three of 4patients followed up for longer than 6 months onadequate thyroid replacement therapy the nod-ules regressed by up to 60%. Given “Best prac-tice” recommendations patients with thyroid fail-ure and single thyroid nodules would not be sub-mitted to radionuclide scanning and this presen-tation of HT would have gone undetected.(J. Endocrinol. Invest. 25: 643-645, 2002)©2002, Editrice Kurtis

INTRODUCTION

Hashimoto’s thyroiditis (HT) is a common diseasewhose pathogenesis is influenced by genetic andenvironmental factors. Variations in the latter mayaccount for fluctuations in disease prevalence overtime and by geographic location (1-3). HT presentsas a goiter that not infrequently is asymmetric. Mostpatients with the disorder do not progress to thy-roid failure. A diffuse firm goiter associated withhigh titres of thyroid autoantibodies allow for thediagnosis of HT, although a nodular feeling goitermay also be commonly encountered (1). Hypoecho-genecity on ultrasound (US) and diffuse patchy ap-pearances on radionuclide thyroid scans are con-firmatory (4, 5) but are only indicated if doubts ex-ist as to the diagnosis or the existence of coinci-dental lesions.In a past era when radionuclide thyroid scans were

performed in a high proportion of patients with HT,scan appearances were reported to mimic manyother thyroid disorders. Rarely, HT has been asso-ciated with the presence of “hot” nodules (5, 6).The description of this feature in the context of thy-roid failure has not been previously documented.Having encountered a patient with a single hotnodule and hypothyroidism, we undertook a pro-spective survey of all patients with goitrous thy-roiditis and hypothyroidism referred to the GhaemMedical Center.

PATIENTS AND METHODS During 2 yr from March 1997-February 1999, all patients referredwith goiter and hypothyroidism were evaluated. Aside from care-ful physical examination, all patients were tested for thyroid func-tion, thyroid autoantibodies and submitted to thyroid radionu-clide scan using 99mTc pertechnetate. Thyroid scan was performed with 2 mCi of 99mTc pertechnetateusing a rectilinear scanner (Picker). The thyroid nodules werepalpated and marked during scintigraphy. When a hot nodulewas detected, the nodule was shielded and scanning repeatedto exclude contralateral lobe hemiagenesis (4). Thyroid scan wasrepeated with 131I in all patients with hot nodules. Radio-iodine uptake at 2 and 24 h (normal range 4-14% and 6-28% respectively) were measured in 2 patients.Total thyroxine RIA (normal range 4.5-12.5 μg/dl). T3 RU (nor-mal 24-36%), TSH IRMA (normal range 0.3-4.0 mIU/l) antiper-

1Presented in part at the 83rd Annual Meeting of the Endocrine Society,Denver, CO, June 20-23, 2001.

Key words: Hashimoto’s thyroiditis, hypothyroidism, radionuclide scan,hot nodules.

Correspondence: Prof. Nadir R. Farid, Osancor Biotech Inc, 31 WoodlandDrive, Herts, WD17 3BY, UK.

E-mail: farid@osancor96.fsnet.co.UK

Accepted April 5, 2002.

CASE REPORT

Hashimoto’s thyroiditis presenting as single hot nodule andhypothyroidism1

Z. Mousavi*, S.R. Zakavi**, and N.R. Farid****Departments of Endocrinology, **Nuclear Medicine, Ghaem Medical Center, Mashad University ofMedical Sciences, Mashad, Iran, and ***Osancor Biotech. Inc, Watford, Herts, UK

Thyroiditis, hypothyroidism and hot nodule

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oxidase (normal range <100 IU/ml) and antithyroglobulin (TGAb)(normal range: <150 IU/ml) antibodies by ELISA were measured.Fine needle biopsy of the nodules was performed in 3 patientsafter informed consent. Patients were treated with L-T4 to nor-malize serum TSH and were followed up for a minimum of 6months.

RESULTS

Including the index patient, 6 female patients withsingle hot nodule and hypothyroidism were un-covered in our study. Excluding the index, 5.2%of 96 patients with goiter and hypothyroidismwere found to have a single hot nodule, suggest-ing that this is not an insignificant clinical mani-festation of autoimmune thyroiditis. The mean ageof the patients was 35.3 yr (range 20-56 yr).Thyroid nodules were firm on palpation andranged in diameter from 2 x2 to 4x5 cm. Three pa-tients (patient 1, 3 and 5) were referred with symp-toms of hypothyroidism and 3 with a sensationlump in the neck. Hypothyroidism was mild (sub-clinical) in patient 5 and in all the remaining pa-tients except for patient 1.

Serum TSH levels ranged from 4.5 to >100 IU/ml,anti-TPO antibody from 234 to>5000 IU/ml andTGAb titers from 257 to >5000 IU/ml.FNA biopsy of the nodules showed lymphocytic in-filtration compatible with HT in 2 patients (in addi-tion to normal follicular cells or cells with Hurtle cellmorphology) and normal thyroid cells in the third(Table 1).All 6 patients had single hot thyroid nodules onscintigraphy using 99mTc pertechnetate. We alsoperformed radioiodine scans in all these patientsto exclude discordant nodules (1, 4). Both tech-niques were concordant in that they revealed hotnodules (Fig. 1).Radioiodine uptake performed in 2 patients (pa-tient 2 and 6) were 6.5 % and 18% and 6% and 15%at 2 h at 24 h respectively, suggesting an organifi-cation defect in the thyroid, typical of HT (1, 4).Four patients were followed up for at least 6months on adequate thyroid hormone replace-ment. The thyroid nodules diminished in size to be-tween 1-3 cm diameter in 3 (up to 60% reduction incalculated volume) but showed no change in thefourth.

Table 1 - Summary of the clinical presentation and results of the investigations of the 6 patients with single hot thyroid nodules andhypothyroidism.

Case Age Presenting symptoms Thyrod T4 μg/dl Free thyroxine TSH TGAb Anti-TPO FNA noduleno. (yr) nodule (4.5-12) index mIU/l IU/ml IU/ml

(cm) (1.08-4.5) (0.3-4.0) (�150) (�100)

1 56 Choking sensation** 4X5 R 4.2 1.00 4.5 - >5000 Normal follicular cells

2 24* Hypothyroidism** 2X2.5 L <1 0.23 >100 400 700 Lymphocytic infiltration

3 40 Lump in neck 2X2 R 4.5 - 15 >5000 >5000 ND

4 45 Hypothyroidism 2X2.5 L 1.5 0.37 115 257 235 ND

5 20 Lump in neck** 2X2 L 12 3.48 5.7 >5000 1600 Lymphocytic infiltration

6 27* Hypothyroidism** 3.5X2.5 L 2.5 0.6 60 800 1100 NDAll the patients were female. Free thyroxine index was calculated for T3 RU values and Total T4. *Radioiodine thyroidal uptakes were performed onthese 2 patients at 2 and 24 hr and were respectively: 15 and 6.5% in patient 2 and 18 and 6% in patient 6. The single thyroid nodules identified were“hot” by both Tc-99m pertechnetate and radioiodine scintigraphy. **Patients treated with enough L-T4 to bring TSH to within the normal range and whowere available for follow-up �6 months later. Estimated nodule size was 3X2.5 cm in patient 1, 1.6X2.2 cm in patient 2, 1X0.8 cm in patient 5 and 2.4X1.3 in patient 6. The greatest reduction in nodule volume was noted in the last patient.

Fig. 1 - Thyroid scans of patient 2 using99mTc pertechnetate before (A) and af-ter shielding of the nodule (B) showed ahot nodule in the left lobe. Repeat scanwith 131I (C) showed the same pattern.(SSN: suprasternal notch.)A B C

SSN SSN SSN

Shield

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DISCUSSION

“Best Practice” recommendations streamline en-docrine investigations to exclude those not ger-mane to establishing a diagnosis. Some such testsmay uncover unusual or previously unrecognizedpresentation of disease. Radioisotopic investiga-tions of single thyroid nodules in the face of nor-mal or elevated serum TSH are an example in point(1). We have taken advantage of this continuedpractice in many medical centers worldwide tobring to attention an unusual presentation of au-toimmune thyroiditis.HT commonly presents as euthyroid goiter, with hy-pothyroidism less commonly and rarely as Hashito-xicosis. Radionuclide thyroid scan may show diffusegoiter with patchy uptake, diffuse goiter with asym-metric uptake, hyperfunctioning or hypofunction-ing nodules or a pattern consistent with multin-odular goiter (4-6). The common cause of hot nod-ules in thyroid scan is autonomous thyroid adeno-mas, but hyper-functioning normal tissue in a glandwith previous injury such as surgery or thyroiditismay uncommonly show the same pattern. Most ofthe patients with hot nodules are euthyroid with hy-perthyroidism more common in patients with largenodules (>3 cm in diameter) (1, 4).Although HT has been called a great mimic from aradionuclide-scanning viewpoint (5), and there havebeen reports of HT presenting as hot nodule (6-10),there is no report of patients with hypothyroidismand single hot nodules in the literature. That serumTSH was elevated in all patients, but particularly inpatients 2, 4 and 6 almost certainly contributed toboth nodular growth and to the increased ability ofnodular tissue to concentrate isotopes. Moreover,the significant regression of most nodules in the pa-tients available for follow-up is in keeping with thatnotion. An issue may be raised about the appro-priateness of classing these nodules, particularlythose that showed regression with T4 treatment as“hot”.The relative regional scintigraphic appearancemakes no assumption of the underlying nature (andthus histology) of the nodule and thus classing thenodules we describe as “hot” is not inappropriate. We must emphasize that we do not advocate as a

result of our findings that the current paradigm inthe investigation of thyroid nodules in the face ofnormal or elevated TSH be modified.After the completion of this study, Hoogenberg etal. (11) reported a similar patient. The Authors didnot emphasize the patient’s thyroid failure. The“functional adenoma” regressed with thyroxine re-placement.

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