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Thyroid Storm in a Child following Radioactive Iodine (RAI) Therapy: A Consequence of RAI Versus Withdrawal of Antithyroid Medication

Departments of Pediatrics (P.M.K., C.M.B., G.G., P.A.G.) and Diagnostic Imaging (R.B.N.), Rhode Island Hospital and Brown University, Providence, Rhode Island 02903

Address correspondence and requests for reprints to: Philip A. Gruppuso, M.D., Department of Pediatrics, Rhode Island Hospital, 593 Eddy Street, Providence, Rhode Island 02903.

	Abstract

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A 7.5-yr-old boy with Graves’ disease, difficult to control with antithyroid medication and radioactive iodine (RAI) therapy, developed thyroid storm encephalopathy on day 13 after withdrawal of methimazole therapy, 4 days after iodione-131 treatment. We attributed his thyroid storm to withdrawal of antithyroid medication as opposed to RAI therapy. We interpret this case as indicating that there may be a need to reevaluate the duration of antithyroid medication withdrawal before RAI therapy for hyperthyroid children at increased risk for thyroid storm.

	Introduction

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RADIOACTIVE IODINE (RAI) therapy and withdrawal of antithyroid medications are two well described causes of thyroid storm (1). Although much speculation exists regarding the pathophysiology of thyroid storm, an acute increase in thyroid hormone release probably plays a role in both of these precipitating factors. Reported cases of thyroid storm in 10- to 19-yr-old patients occurred 2–8 days after iodine-131 (¹³¹I) treatment. In these cases, thyroid storm was attributed to the RAI therapy (2, 3). Previous reports of thyroid storm in children have not attributed this complication to antithyroid medication withdrawal.

	Case Report

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GR is a Hispanic boy who presented at 4.8 yr of age with Graves’ disease in impending thyroid storm. On admission he was febrile to 38.5 C with a heart rate of 160 beats/minute, blood pressure of 154/62, but had normal mental status. Thyroid lobes measured 4 cm bilaterally. He had a hyperdynamic precordium, a 3/6 holosystolic murmur at the left sternal border radiating to the apex, sweaty palms, and warm skin. Thyroid function studies revealed a suppressed TSH (<0.03 mU/L; <0.03 µU/mL) and elevated T₄ (242 nmol/L; 18.8 µg/dL), T₃ (5.8 nmol/L; 377 ng/dL), and thyroid-stimulating immunoglobulin (271% of control). He was treated with propranolol and propylthiouracil (PTU) to control his hyperthyroidism. For 2.5 yr his hyperthyroidism was difficult to control medically, and he required methimazole (50 mg/day) and levothyroxine to maintain biochemical euthyroidism. After several discussions with the family, it was decided that GR would undergo RAI therapy.

Five days after discontinuing methimazole in preparation for a RAI uptake and scan, GR developed loose bowel movements and a temperature of 38.3 C. On physical examination he had a heart rate of 128 beats/minute, blood pressure of 120/60, 3/6 systolic murmur throughout his precordium, and an enlarged firm thyroid gland with bruits. The estimated weight of his thyroid was 70 g. Propranolol (3.3 mg/kg·day) was started, and a 24-h RAI uptake revealed 98% uptake. On day 9 after discontinuing the methimazole he was treated with 7 mCi ¹³¹I (100 µCi ¹³¹I/g thyroid tissue). Four days after treatment with ¹³¹I, GR vomited and had a brief generalized tonic-clonic seizure. In the emergency room, he was postictal and afebrile with a heart rate of 104 beats/minute and blood pressure of 120/70. GR was diagnosed as having thyroid storm encephalopathy. After 5 days of medical therapy he had no further seizures, and he was discharged on propranolol and PTU. The patient’s laboratory data and treatment are summarized in Table 1.

	Discussion

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Thyroid storm following RAI therapy has generally been attributed to increased thyroid hormone release from degenerating follicles. Brooks et al. (4, 5) showed that patients with thyroid storm and uncomplicated thyrotoxicosis had comparable T₄ and T₃ levels, but that free T₄ and dialyzable T₄ levels were significantly higher in the patients with thyroid storm. Although we did not measure GR’s free T₄ and dialyzable T₄ levels, his total T₄ and total T₃ during thyroid storm were 10% lower than his levels before RAI therapy.

Studies have shown that after RAI therapy patients pretreated with antithyroid medications have lower serum T₄ and T₃ levels than nonpretreated patients (6, 7). These studies also show that serum T₄ and T₃ levels increase significantly after withdrawal of antithyroid medication in preparation for RAI therapy. Our patient’s markedly elevated thyroid hormone levels clearly resulted from discontinuing the methimazole. Therefore, we suspect that withdrawal of antithyroid medication, not RAI therapy, precipitated GR’s thyroid storm, because his T₄ and T₃ levels during thyroid crisis were comparable with his levels before RAI therapy.

Retrospective studies have shown a lower success rate of RAI therapy in patients pretreated with PTU, but not methimazole (8, 9, 10). In addition, studies have also demonstrated lower RAI efficacy in patients treated with PTU and methimazole after RAI therapy (8, 11). Imseis et al. (10) compared the cure rate of RAI therapy in patients treated with RAI alone with those patients pretreated with PTU or methimazole. In their study, all patients received 120 µCi ¹³¹I/g thyroid tissue, and their hyperthyroidism was considered cured if 6–8 months after RAI they demonstrated clinical and laboratory evidence of euthyroidism or hypothyroidism without antithyroid medication. The cure rate in the group treated with RAI alone was 66% whereas the pretreated group, whose PTU and methimazole were discontinued 5–14 days before RAI therapy, achieved a cure rate of 38% and 69%, respectively.

Marcocci et al. (8) also showed that pretreatment with methimazole up to 5–7 days before ¹³¹I did not affect the efficacy of RAI therapy. Their study did demonstrate an increased prevalence of hyperthyroidism in patients treated for 3–4 months with methimazole starting 7 days after ¹³¹I administration. Although they showed that within 2 yr after RAI therapy hypothyroidism occurred more frequently in patients who did not receive post-RAI methimazole therapy, the overall cumulative incidence of hypothyroidism was similar in untreated and treated patients. These studies show that treatment with methimazole before RAI therapy is beneficial because it does not affect the overall efficacy of RAI and pretreated patients have lower thyroid hormone levels than patients treated with RAI alone.

Allahabadia et al. (12) determined that male gender and younger age of onset of Graves’ disease are associated with a higher failure rate of treatment with antithyroid medication. They also found that male gender, independent of radioiodine dose and treatment with antithyroid medication before and after RAI, is associated with a higher failure rate after a single dose of RAI therapy. The impact of goiter size on the outcome of medical and radioactive iodine therapy remains controversial (12). Our patient’s male gender and very young age at disease onset placed him at a significant risk for failing both medical and RAI therapy. GR’s hyperthyroidism was very difficult to control with medical therapy, and twice he failed RAI therapy, necessitating a third ablative dose of ¹³¹I. Our experience with this patient is not surprising considering the study by Cheetham et al. (13), in which eight pediatric patients with Graves’ disease, age 3.6–14.2 yr, relapsed after their hyperthyroidism was controlled with a combination of antithyroid medication and levothyroxine for a median of 4.5 yr. Following treatment with an initial dose of 8 mCi ¹³¹I, only three patients developed hypothyroidism. Four of the remaining five patients became hypothyroid after a second dose of ¹³¹I.

The dose of ¹³¹I is calculated by a standard formula that uses the estimated weight of the thyroid gland and the 24-h RAI uptake to determine the dose required for the delivery of 50–200 µCi ¹³¹I/g thyroid tissue (14). Hamburger’s (15) retrospective study showed that within 6 months of receiving a single dose of 200 µCi ¹³¹I/g thyroid tissue, 88% of the children were euthyroid or hypothyroid. Rivkees et al. (16) recommend that a single dose of 150–200 µCi ¹³¹I/g thyroid tissue will cure 85–90% of pediatric hyperthyroidism. Although GR received only 100 µCi ¹³¹I/g thyroid tissue for his initial ablation, he required two additional ablative doses of RAI (12.7 and 20.2 mCi), which demonstrates that his hyperthyroidism was radioresistant.

We recommend that, in children with a significant risk for developing thyroid storm, consideration be given to limiting withdrawal of methimazole to no more than 3 days before ¹³¹I treatment with resumption of the medications 3 days after RAI therapy. Studies show that patients pretreated with methimazole until 5–7 days before RAI do not require an increased dose of ¹³¹I to achieve cure, but that post-RAI treatment with methimazole is associated with an increased failure rate of RAI therapy (8, 10). Therefore, a shorter duration of methimazole withdrawal and resumption may necessitate higher doses of RAI to maintain efficacy.

Received September 11, 2000.

Revised November 6, 2000.

Revised January 12, 2001.

Accepted January 29, 2001.

	References

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