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Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1163
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The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 11 4497-4500
Copyright © 2006 by The Endocrine Society

BRIEF REPORT

Radioactive Iodine Therapy for Goitrous Hashimoto’s Thyroiditis

Junichi Tajiri

Tajiri Thyroid Clinic, Kumamoto 862-0950, Japan

Address all correspondence and requests for reprints to: Junichi Tajiri, M.D., Tajiri Thyroid Clinic, 2-6-20 Suizenji, Kumamoto 862-0950, Japan. E-mail: rabbit{at}j-tajiri.or.jp.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: Hashimoto’s thyroiditis is an autoimmune disease that can produce marked clinical symptoms when patients have large diffuse goiters.

Design: This retrospective cohort study was designed to evaluate whether radioactive iodine (RAI) is effective for Hashimoto’s thyroiditis with a large goiter. Starting in November 1999, 13 Hashimoto’s patients with large goiters, whose thyroiditis was refractory to TSH suppression therapy with thyroid hormone administration [two men and 11 women with a mean age of 61.2 ± 8.9 yr (50–79 yr)], were recruited for the present study. The duration of symptomatic goiter before undergoing RAI was 12.0 ± 7.9 yr (4–33 yr). Thirteen millicuries of 131I was administered two to six times, at an interval of 1–6 months on an outpatient basis. Thyroid weight was measured ultrasonographically, or by computed tomography if ultrasound was not possible due to the large size of the goiter.

Results: RAI was administered an average of 4.7 ± 1.4 times (two to six times), with a total dose of 59.8 ± 17.3 mCi (25.0–78.0 mCi). The observation period was 47.9 ± 13.4 months (26–66 months) after the first RAI. The average weight of the thyroid gland was 125.3 ± 57.7 g (42.9–269.4 g) before the first RAI, decreasing significantly to 49.7 ± 25.8 g (18.3–93.3 g) after the last RAI (P < 0.001, paired Student’s t test). The percent reduction from baseline was 58.7 ± 14.2% (35.7–84.0%). None of the patients showed an increase in goiter size or complained of a pressure sensation after any of the RAI treatments.

Conclusion: RAI is effective in Hashimoto’s thyroiditis with a large goiter.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
HASHIMOTO’S THYROIDITIS IS an autoimmune disease. Particular problems arise when goiters become markedly enlarged. Microscopic examination suggests that a goiter is attributed to infiltrates of lymphocytes, plasma cells, and macrophages (1, 2). In 50–90% of patients, the goiter size decreases by an average of 30% after treatment with levothyroxine for 6 months, irrespective of the initial serum TSH concentration (3, 4). This finding suggests that TSH is associated with goiter. Ultrasonography shows a goiter with a diffusely hypoechogenic pattern in 18–77% of patients, but the findings are not specific (5, 6). A color Doppler shows that the increased vascularity observed in patients with hypothyroid Hashimoto’s thyroiditis suggests that thyroid stimulation by TSH is responsible for the increased thyroid blood flow (7).

There is also a risk of respiratory distress from pressure on the trachea due to an enlarged goiter. Furthermore, patients suffer an additional psychological burden caused by their altered appearance. Under these circumstances, surgery is normally recommended; however, patients are generally reluctant to undergo surgery. Unfortunately, in current clinical practice, thyroid hormone therapy is administered even without the possibility of effectiveness, or the patient’s clinical course is followed without treatment.

Radioactive iodine (RAI) is the standard treatment for Graves’ disease with a toxic nodule or toxic multinodular goiter (8). It has recently been reported that RAI is also effective against nontoxic multinodular goiter (9, 10); however, no report has focused on whether RAI is effective in Hashimoto’s thyroiditis patients with large goiters.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Since November 1999, RAI has been administered to 16 Hashimoto’s thyroiditis patients with a large goiter, refractory to TSH suppression therapy with T4. These 16 patients had compressive symptoms or requested a goiter size reduction for the purpose of improving cosmetic deformity. Two patients did not come to the clinic after the first RAI and, therefore, were considered to have dropped out of this study. One patient who was still receiving therapy was excluded; the remaining 13 patients were assessed in the present study. The subjects were two men and 11 women, with a mean age of 61.2 ± 8.9 yr (50–79 yr). The goiter had been present for 12.0 ± 7.9 yr (4–33 yr) before RAI. One patient (case 7) had previously undergone surgical resection of the left lobe of the thyroid gland for nodular goiter (Tables 1Go and 2Go).


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  		TABLE 1. Profile of 13 patients with Hashimoto’s thyroiditis before receiving RAI

 

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  		TABLE 2. Profile of 13 patients with Hashimoto’s thyroiditis after receiving last dose of RAI

 
Hashimoto’s thyroiditis was diagnosed by palpation, thyroid hormone level, TSH level, ultrasonographic findings, and the presence of thyroid autoantibodies [antimicrosomal antibody (tanned red cell hemagglutination; microsomal hemagglutination antibody, MCHA) and antithyroglobulin antibody (tanned red cell hemagglutination; thyroglobulin hemagglutination antibody, TGHA)], as well as antithyroglobulin antibody and thyroperoxidase antibody (RIA) in some cases. Low-echo areas were observed by ultrasound and, thereby, the absence of malignant lymphoma was confirmed by echo-guided aspiration biopsy. None of our patients had a goiter that had suddenly enlarged. Accordingly, malignant lymphoma of the thyroid was ruled out. No nodular lesions were observed in any of our cases.

Thyroid weight was estimated by ultrasound (SSA-350A; Toshiba Inc. Ltd., Tokyo, Japan) according to the method of Yokozawa (11) using a rectangular strip, as briefly described below. When the long diameter of the thyroid gland exceeded 4 cm, the length of the long diameter could not be measured with a probe in real time. Therefore, applying a short strip of paper (3 x 15 or 5 x 15 cm) at the center of the thyroid gland, we measured the lengths (centimeters) extending above (A) and below (B) the strip. The width of the strip (3 or 5 cm) added to A and B was taken as the long diameter of the thyroid. The weight of the thyroid gland was obtained by the formula: (long diameter) x (short diameter) x (thickness) x 0.7 (g). Computed tomography was performed when ultrasound was not possible due to the large size of the goiter.

At 24 h after administration of 100 µCi (3.7 MBq) 131I, RAI uptake (RAIU) was measured using a thyroid uptake system (AZ-800; Anzai Medical Co. Ltd., Tokyo, Japan). RAIU was measured 24 h after each RAI session.

The dose was calculated from RAIU and thyroid weight, using the formula: RAI dose (mCi) = thyroid weight (g) x 120 µCi/24-h RAIU (%) x 10.

For nontoxic diffuse goiter, 100 µCi/g (3.7 MBq) total thyroid weight was administered according to the European protocol (12, 13). Considering that RAIU is relatively low because of high iodine intake in Japan, 120 µCi/g (4.4 MBq) total thyroid weight was administered. RAI was performed on an outpatient basis for all of our patients.

In all cases, the calculated dose exceeded the maximum dose (13.5 mCi; 500 MBq) allowed in the outpatient setting in Japan. Therefore, 13.0 mCi (481 MBq) was administered. Iodine intake restriction and suspension of levothyroxine were mandated for 1 month before and 1 wk after RAI. The absorbed radioisotope dose was calculated by Quimby’s formula, with an effective half-life of 5.9 d. RAI was administered two to six times at an interval of 1–6 months. After the last RAI, the patients were followed up every 6 months.

Statistical analyses were performed using Student’s t test and Pearson’s correlation coefficient test. Values are shown as means ± SD.

Written informed consent was obtained from all participants before enrollment, after explaining the treatment. The present study was approved by the Institutional Review Board of our clinic.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The average thyroid weight was 125.3 ± 57.7 g (42.9–269.4 g) before the first RAI, and decreased significantly to 49.7 ± 25.8 g (18.3–93.3 g) after the last RAI (P < 0.001, paired Student’s t test) (Tables 1Go and 2Go). The percent reduction from baseline was 58.7 ± 14.2% (35.7–84.0%). RAI was administered an average of 4.7 ± 1.4 times (two to six times), with a total dose of 59.8 ± 17.3 mCi (25.0–78.0 mCi). The observation period was 47.9 ± 13.4 months (26–66 months) after the first RAI (Tables 1Go and 2Go).

Significant correlations were demonstrated between the percent reduction from baseline and total radiation doses (r = 0.613, P < 0.05), antibody titers (MCHA; r = 0.767, P < 0.01, TGHA; r = 0.581, P < 0.05), and 24 h RAIU (r = 0.631, P < 0.05), but not free T4 (FT4) (not significant, Pearson’s correlation coefficient test).

The decrease in antibody levels after RAI was not statistically significant (Table 2Go). In six cases (case 2, 4, 7, 9, 10, and 12), MCHA and/or TGHA titers decreased after the last RAI, whereas MCHA and TGHA titers were unchanged or increased after the last RAI in seven cases (case 1, 3, 5, 6, 8, 11, and 13).

Nine of 10 patients who received a total radiation dose exceeding 100 Gy showed a more than 50% reduction in goiter size, whereas all three patients who received a total radiation dose less than 100 Gy did not (Table 2Go).

Table 3Go shows RAIU (24 h) and absorbed doses for all cases at each RAI session. The RAIU value changed so greatly among patients and even in the same patient under different treatment. There was no correlation between RAIU and values of TSH, FT4, and goiter weight.


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  		TABLE 3. RAI uptake (24 h) and absorbed dose in all cases at each RAI

 
FT4 and TSH levels after discontinuation of levothyroxine for 1 month before the first RAI were 0.92 ± 0.30 (0.32–1.45) ng/dl [11.9 ± 3.9 (4.1–18.7) pmol/liter] and 6.36 ± 8.09 (0.15–30.32) mU/liter, and after discontinuation of levothyroxine for 1 month before the last RAI were 0.80 ± 0.22 (0.51–1.24) ng/dl [10.3 ± 2.8 (6.6–19.8) pmol/liter] and TSH 29.46 ± 46.86 (1.53–146.7) mU/liter, respectively. There were no significant differences in FT4 and TSH levels after discontinuation of levothyroxine for 1 month between the first and the last RAI sessions (NS). Severe hypothyroidism with TSH values higher than 100 mU/liter and low FT4 levels developed after the last RAI in two of the 13 cases (146.7 and 115.7 mU/liter). In eight of the remaining 11 cases, mild hypothyroidism, associated with a small increase in the TSH value from that before therapy, was observed, whereas TSH increased moderately to 44.5 mU/liter in one case.

None of the patients showed an increase in goiter size or complained of a pressure sensation after any of the RAI treatments.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Recently, the Society of Nuclear Medicine published guidelines for RAI (8), including nontoxic diffuse goiter as a target disease. However, the guidelines did not recommend RAI for large goiters due to Hashimoto’s thyroiditis.

No reports have described long-term follow-up to assess the risk of malignant tumors including thyroid cancer for patients who had received RAI for nontoxic goiters, benign thyroid disorders, or Hashimoto’s thyroiditis. In patients 65 yr of age or older treated with RAI for nontoxic goiter, the estimated incidence of malignant tumors, other than thyroid cancer, suggests that the mortality rate is the same as that of nontoxic goiter after surgical treatment (14). At present, the indications for RAI treatment of Hashimoto’s thyroiditis should be limited to elderly patients with large goiters whose thyroiditis is refractory to TSH suppression therapy and who refuse surgery.

Indications for surgery in patients with Hashimoto’s thyroiditis include: 1) pressure symptoms or dysphagia, 2) hyperthyroidism, 3) a growing diffusely enlarged goiter that is unresponsive to TSH suppression therapy, 4) a cosmetic deformity, 5) history and/or physical findings suggesting malignancy, and 6) indeterminate findings on fine needle aspiration biopsy (15, 16). Shimizu et al. (17) reported surgery to be an effective therapy for patients with Hashimoto’s thyroiditis who had persistent compressive symptoms and/or an unsightly cosmetic appearance due to a large goiter despite long-term T4 treatment. However, surgery may not be suitable for elderly patients because of concomitant disorders such as heart or liver disease.

Although few in number, patients with Hashimoto’s thyroiditis with goiters larger than 100 g do present at the author’s clinic. Long-term thyroid hormone administration should be avoided because of the risk of osteoporosis in postmenopausal women. In addition to the risk of osteoporosis, the risk of arrhythmias such as atrial fibrillation increases in people of advanced age.

In administering RAI to patients with Hashimoto’s thyroiditis, questions arise as to how long it takes for efficacy to be observed and the optimal RAI dose. The dose of RAI could be lowered, considering that, in nine of our 13 patients, a gradual reduction in size continued for 23–61 months. The author hopes to further examine alternative administration methods, for example, the use of recombinant human (rh) TSH. Recently, Nieuwlaat et al. (18) reported that, in patients with nodular goiters, pretreatment with a single, low dose of rh-TSH allowed an approximately 50–60% reduction of the therapeutic dose of radioiodine without compromising the efficacy of thyroid volume reduction. For Hashimoto’s thyroiditis patients with a large goiter, the use of rh-TSH may also allow the dose of radioiodine to be reduced without loss of the efficacy of thyroid volume reduction.

In conclusion, RAI is effective in Hashimoto’s thyroiditis with a large goiter. It is hoped that the efficacy of this treatment will be confirmed in future studies.


   Footnotes
 
Disclosure statement: The author has nothing to declare.

First Published Online August 8, 2006

Abbreviations: FT4, Free T4; MCHA, microsomal hemagglutination antibody; RAI, radioactive iodine; RAIU, RAI uptake; rh, recombinant human; TGHA, thyroglobulin hemagglutination antibody.

Received May 30, 2006.

Accepted August 2, 2006.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. LiVolsi VA 1994 The pathology of autoimmune thyroiditis: a review. Thyroid 4:333–339[Medline]
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  4. Hegedus L, Hansen JM, Feldt-Rasmussen U, Hansen BM, Hoier-Madsen M 1991 Influence of thyroxine treatment on thyroid size and anti-thyroid peroxidase antibodies in Hashimoto’s thyroiditis. Clin Endocrinol (Oxf) 35:235–238[Medline]
  5. Sostre S, Reyes MM 1991 Sonographic diagnosis and grading of Hashimoto’s thyroiditis. J Endocrinol Invest 14:115–121[Medline]
  6. Nordmeyer JP, Shafeh TA, Heckmann C 1990 Thyroid sonography in autoimmune thyroiditis: a prospective study on 123 patients. Acta Endocrinol (Copenh) 122:391–395[Medline]
  7. Bogazzi F, Bartalena L, Brogioni S, Burelli A, Manetti L, Tanda ML, Gasperi M, Martino E 1999 Thyroid vascularity and blood flow are not dependent on serum thyroid hormone levels: studies in vivo by color flow Doppler sonography. Eur J Endocrinol 140:452–456[Abstract]
  8. Meier DA, Brill DR, Becker DV, Clarke SEM, Silberstein EB, Royal HD, Balon HR 2002 Procedure guideline for therapy of thyroid disease with 131I. J Nucl Med 43:856–861[Free Full Text]
  9. Hegedus L, Hansen BM, Knudsen N, Hansen JM 1988 Reduction of size of thyroid with radioactive iodine in multinodular non-toxic goitre. BMJ 297:661–662[Medline]
  10. Wesche MF, Tiel-V Buul MM, Lips P, Smits NJ, Wiersinga WM 2001 A randomized trial comparing levothyroxine with radioactive iodine in the treatment of sporadic nontoxic goiter. J Clin Endocrinol Metab 86:998–1005[Abstract/Free Full Text]
  11. Yokozawa T 1997 Thyroid weight. In: Atlas of thyroid and parathyroid ultrasound. ed 2. Chap 1. Tokyo: Vector Core; 25 (in Japanese)
  12. Nygaard B, Farber J, Veje A, Hansen JE 1997 Thyroid volume and function after 131I treatment of diffuse non-toxic goitre. Clin Endocrinol (Oxf) 46:493–496[CrossRef][Medline]
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  18. Nieuwlaat WA, Huysmans DA, van den Bosch HC, Sweep CG, Ross HA, Corstens FH, Hermus AR 2003 Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter. J Clin Endocrinol Metab 88:3121–3129[Abstract/Free Full Text]




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