Toxic Multinodular Goiter with Low Radioactive Iodine Uptake

□ CASE REPORT □

Toshio Kahara 1, Akiko Shimizu 1, Akio Uchiyama 2, Shintaro Terahata 2, Junichi Tajiri 3, Eijun Nishihara 4, Akira Miyauchi 4, Hitoshi Abo 5, Hisashi Sumiya 5, Kazuhide Ishikura 1, Rika Usuda 1 and Hirofumi Noto 6

Abstract

A 74-year-old woman was referred to our hospital for goiter and persistent thyrotoxicosis. She had no signs of ophthalmopathy. She was not taking thyroid hormone. Thyroid CT revealed multiple nodules. The thyroid gland was not detected on 99mTc scintigraphy, 123I uptake rate was 4.5% at 24 hours without hot nodules, and aberrant goiter was negative. After partial thyroidectomy, she was treated with levothyroxine. TRAb was undetectable during the disease course, and focal destructive change or chronic lymphocytic thyroiditis on the pathological specimens was not evident. We report a rare case of toxic multinodular goiter with low radioactive iodine uptake.

Key words: hyperthyroidism, toxic multinodular goiter, radioactive iodine uptake, SPECT, thyrotoxicosis, 99mtechnetium

(Intern Med 50: 1709-1714, 2011) (DOI: 10.2169/internalmedicine.50.5256)

uptake (RAIU) without clear hot nodules. Introduction Case Report Toxic multinodular goiter is found more frequently in the iodine deficient regions and accounts for 37% of thyrotoxi- The patient was diagnosed with goiter and thyrotoxicosis cosis cases in Sweden (1). On the other hand, the frequency on medical examination at a neighboring hospital at the age of toxic multinodular goiter is relatively low in countries of 44, and she was treated with thiamazole. However, she with excess iodine intake, and accounts for only 6.2% of had drug eruption and stopped the treatment on her own thyrotoxicosis cases in Iceland (2) and 0.3% in Japan (3). judgment. She did not have subjective symptoms afterwards. Thyroid scintigraphy using 99mTc or 123I is useful for the di- A large goiter was detected when she visited a neighboring agnosis of toxic multinodular goiter, and shows diffuse inho- clinic at the age of 74 and was referred to our hospital in mogeneous tracer uptake reflecting areas of hyperfunction September 2007. She took carbazochrome because of central and hypofunction within the thyroid gland. Radioactive io- retinal vein occlusion, but did not take any other medicines. dine treatment using 131I is well accepted for toxic multi- Physical findings were as follows: height, 156.8 cm; weight, nodular goiter, because it is mainly the hyperactive tissue 51.7 kg; body mass index, 21.02 kg/m2; blood pressure, 130/ that traps the radioactive iodine and not the suppressed tis- 73 mmHg; and pulse rate, 83/minute. She had a non-tender sue (4). However, a higher 131I dose is necessary when the diffuse goiter (with a markedly enlarged right lobe). iodine uptake rate is not high. We report a specific case of Exophthalmos was not evident, and she did not have pretib- toxic multinodular goiter with low thyroid radioactive iodine ial edema. Laboratory data are shown in Table 1, and her

１Department of Internal Medicine, Toyama Prefectural Central Hospital, Japan, ２Department of Clinical Pathology, Toyama Prefectural Central Hospital, Japan, ３Tajiri Thyroid Clinic, Japan, ４Center for Excellence in Thyroid Care, Kuma Hospital, Japan, ５Department of Radiology, Toyama Prefectural Central Hospital, Japan and ６Department of Thoracic Surgery, Toyama Prefectural Central Hospital, Japan Received for publication February 2, 2011; Accepted for publication April 22, 2011 Correspondence to Dr. Toshio Kahara, [email protected] and [email protected]

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Table 1. Laboratory Data on September 2007

Figure 2. The thyroid gland was not detected on 99mTc scintigraphy in September 2007.

scintigraphy in September 2007 (Fig. 2). Destructive thyroiditis was diagnosed, but thyrotoxicosis continued (Fig. 3). Figure 1. Thyroid ultrasonography showed right lobe swell- Transition of thyroid function tests showed thyrotropin ing and multiple low echoic areas. (TSH) <0.01 μIU/L, free triiodothyronine (T3) 4.6-5.5 pg/ mL, free thyroxine (T4) 2.0-2.3 ng/dL, TSH receptor antibody (TRAb) <1.0 IU/L, anti-thyroglobulin antibody (TgAb) thyroid function tests showed mild thyrotoxicosis with nega- <0.3 IU/L, anti-thyroid peroxidase antibody (TPOAb) <0.3 tive thyroid autoantibodies. Thyroid ultrasonography showed IU/L, and serum thyroglobulin (Tg) 141-155 ng/mL. 123I up- right lobe swelling and multiple low echoic areas in the thy- take rate was 1.1% at 3 hours, 4.5% at 24 hours (normal roid (Fig. 1). The thyroid gland was not detected on 99mTc range; 10-40%), and no hot nodules were observed in June

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Figure 3. Clinical course and transition of thyroid function.

2009 (Fig. 4, top). On whole body 123I scintigraphy, aberrant sent. Lymphocytic infiltration, suggesting the presence of goiter was negative. Single photon emission computed to- chronic thyroiditis, was not evident. There were no findings mography (SPECT) using 123I revealed uneven irregular up- of malignancy. Histopathologic studies demonstrated striking take and an uptake rate of 10.1% at 24 hours in January immunoreactive thyroglobulin showed diffuse colloid im- 2010 (Fig. 4, bottom). As shown in Fig. 5, the thyroid had munostaining, supporting the hypothesis of an overproduc- swelled from the right lobe to isthmus, excluding the trachea tion of hormone rather than a destructive release. to the left on cervical computed tomography (CT) in August The transition of thyroid function tests are shown in 2009. Contrast-enhanced CT showed multiple low density Fig. 3; she had hypothyroidism after partial thyroidectomy, areas in the thyroid gland, while the other areas were en- and hypercholesterolemia. She was treated with levothyrox- hanced normally. Thyroid biopsy was performed in October ine (L-T4) 50 μg/day, and her Tg level was decreased. Ac- 2009, and histological findings showed no destruction of cording to a previous report, in gene analysis for functional follicles and no lymphocytic infiltration. Adenomatous goiter thyroid tumor performed by surgical specimens, neither the was suspected based on the findings of ultrasonography, CT mutation around 9,10 exon of the TSH receptor gene nor and thyroid biopsy, and she was diagnosed with toxic multi- the 7-10 exon of Gs alpha protein gene was present (5). nodular goiter. Urinary iodine was 1.91 mg/day, which is the average level in Japan. Although she was treated with 50 Discussion mg/day of potassium iodide (KI) before operation, her thyroid function did not change. The common cause of thyrotoxicosis with low thyroid We performed partial thyroidectomy of the right lobe in RAIU is the release of stored thyroid hormone (6). Thyro- June 2010. The surgical specimen was 90×78×35 mm, and toxicosis due to silent thyroiditis associated with destructive multiple nodules were seen, some were partially encapsu- changes in the thyroid is caused by an increased release of lated (Fig. 6). The nodal border was clear, and the nodule stored hormone and not by increased thyroid hormone syn- contained various sizes but predominantly large colloid folli- thesis. It is almost always associated with positive anti- cles (Fig. 7, top). Many thyroid follicles were lined by hy- thyroid autoantibodies, and is almost always transient thyro- perplastic columnar epithelium with marginal vacuolization, toxicosis, followed by transient or permanent hypothyroid- but these findings were not diffuse (Fig. 7, bottom). Exten- ism due to depleted thyroid hormone stores. Painful, sub- sive destruction of follicle and interstitial fibrosis were ab- acute thyroiditis is probably of viral etiology and presents

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Figure 4. 123I uptake rate was 1.1% at 3 hours, 4.5% at 24 hours (normal range; 10-40%), and there was no hot nodule in June 2009 (top). Single photon emission computed tomography (SPECT) using 123I revealed uneven irregular uptake and uptake rate of 10.1% at 24 hours in January 2010 (bottom). with the signs and symptoms of thyrotoxicosis with a ten- decreased after partial thyroidectomy. der, enlarged thyroid frequently associated with fever. The Iodine-induced thyrotoxicosis is the only cause of thyro- thyrotoxic phase is almost always followed by transient hy- toxicosis with low thyroid RAIU that is true hyperthyroid- pothyroidism, and complete recovery is common. The pre- ism with increased synthesis and release of excess thyroid sent case did not demonstrate drifting of thyroid hormone hormone from the thyroid. It is most often seen in patients levels such as destructive thyroiditis. Previously reports on with underlying nontoxic nodular goiter (especially the eld- persistent thyrotoxicosis with low thyroid RAIU have focal erly) who are given medications such as amiodarone or destructive change or chronic lymphocytic thyroiditis on iodine-containing expectorants or who have radiological and pathological specimens (7-9); however, this case did not cardiac studies done with iodine-rich contrast agents. The have these findings on the surgical specimens. etiology of iodine-induced hyperthyroidism is unclear but Thyrotoxicosis factitia could show low thyroid RAIU. may be the result of supplying excess iodine to the patients The patients with this disorder purposely or inadvertently in- having thyroid autonomy. The thyrotoxicosis will usually gest excess amounts of thyroid hormone, leading to thyro- persist as long as the excess iodine remains in the circula- toxicosis in the absence of a goiter. On the thyrotoxicosis tion, and it has been reported that 24-hour urinary iodine factitia, the serum Tg level is not increased and is usually levels of patients with iodine-induced thyrotoxicosis were low (10). However, our patient’s thyroid was enlarged, and 0.297 to 1.66 mg/day (11, 12). Many Japanese eat seaweed the serum Tg levels were high during the disease course and and make soup stock from kelp on a daily basis. In reports

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Figure 7. The nodal border was clear, and the nodule contained various sizes but predominantly large colloid follicles (top, Hematoxylin and Eosin staining ×10). Many thyroid follicles were lined by hyperplastic columnar epithelium with Figure 5. The thyroid swelled from the right lobe to isth- marginal vacuolization (bottom, Hematoxylin and Eosin stain- mus, excluding the trachea on the left on cervical CT (top). ing ×200). Contrast-enhanced CT showed low density areas in the thyroid gland; the other areas were enhanced normally (bottom). Although the thyroid gland in the present case was not detected on thyroid 99mTc scintigraphy, 123I uptake was not completely suppressed and only SPECT using 123I showed diffuse inhomogeneous tracer uptake, suggesting the presence of chronic thyroiditis or adenomatous goiter. However, TgAb, TPOAb and TRAb were undetectable during the disease course, and focal destructive change or chronic lymphocytic thyroiditis on the pathological specimens was not evident. The findings from ultrasonography, CT and the pathological specimen revealed adenomatous goiter, and she was diagnosed with toxic multinodular goiter with low thyroid RAIU. It has been shown that patients with large toxic multinodular goiter have lower thyroid RAIU than those with Figure 6. The surgical specimen was 90×78×35 mm. Multi- Graves’ disease, and 63% of patients with large toxic multiple nodules were seen, some were partially encapsulated. nodular goiter (estimated weight larger than 100 g) have thyroid RAIU of less than 30% (15). The present case had 149.9 g of estimated goiter weight, and her thyroid RAIU on urinary iodine in Japanese, Suzuki et al have shown that was relatively low. It seems that the thyroid nodules in the the mean daily iodine excretion was 1.565 ± 1.482 mg for surgical specimen correlated with SPECT image, but not two patients in Sapporo maintained on regular hospital di- with the low echoic area of thyroid ultrasonography and low ets (13), and Nagataki et al have reported 3.286 mg for out- density area of CT. When large toxic multinodular goiter patients on habitual diets (14). The urinary iodine level in shows lower thyroid RAIU and a diagnosis via 99mTc or 123I the present patient was 1.91 mg/day, which is the average planar thyroid imaging is difficult, SPECT imaging may be level in Japan. useful for the diagnosis for large toxic multinodular goiter.

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