Delayed Presentation of Thyroid Storm Postradioiodine Ablation: Case Report and Review of Literature

Introduction

Thyroid storm is an acute life-threatening complication of thyrotoxicosis characterized by excess circulating thyroid hormone-induced multiorgan dysfunction and systemic decompensation.[1] It is usually associated with poorly controlled hyperthyroidism and a precipitating event or illness including radioactive iodine (RAI) therapy.[2]

Acute complications of radioiodine therapy include radiation thyroiditis and mild exacerbations of thyrotoxic symptoms.[3] However, frank thyroid storm precipitated by radioiodine therapy although rarely reported is often fatal.[4] McDermott et al. in 1983 were the first to review the etiopathogenetic basis of thyroid storm probably induced by radioiodine therapy. Several risk factors such as elderly, cardiovascular morbidity, multinodular goiter, and prolonged thyrotoxic phase were implied.[5]

Here, we report the successful management of an elderly female with thyroid storm postradioiodine ablation to emphasize the challenges in prompt diagnosis, multidisciplinary management, and future prevention of this rare clinical entity.

Case Report

A 73-year-old female presented to our center with a history of insidious onset, gradually progressive swelling in the anterior neck region, associated with palpitations, and significant weight loss for 2 years. Reports of her thyroid function test (TFT) were unavailable; however, she had been previously treated with oral medications (carbimazole [10 mg thrice daily] and propranolol [40 mg once daily]) and reported symptomatic improvement. She was referred to the department of nuclear medicine for RAI ablation therapy.

At presentation, she had a firm bosselated nodular goiter (3 cm × 2 cm) moving with deglutition without bruit. There were no palpable lymph nodes. On auscultation, no abnormal murmur and adventitious breath sounds were noted. There was no pedal edema. She had no signs of clinically active ophthalmopathy. On ultrasonography neck, both lobes of the thyroid and isthmus were bulky and replaced by multiple variable-sized nodules with cystic changes suggestive of multinodular goiter. Baseline TFT as in Table 1.

Carbimazole was stopped for 1 week, and she underwent an RAI uptake scan. The 2- and 24-h uptake was 49.1% and 54.7%, hence planned for RAI ablation. Due to the nonavailability of I-131 from the supplier, the patient was counseled to continue carbimazole and stop it 5 days before the rescheduled therapy. However, the patient self-discontinued medication for 14 days, a fact that was not revealed before therapy. Thus, the patient had been off antithyroid drugs (ATDs) for a total duration of 3 weeks and treated with a dose of 12 mCi. She was well till day 30 postablation when she developed acute-onset, watery diarrhea (stool frequency 15–20 times/day) associated with multiple episodes of vomiting and one episode of high-grade fever. Altered mental status with involuntary passage of urine and stool was noted. She also had shortness of breath progressing from New York Heart Association Grade 1 to Grade 3 and bilateral pedal edema (pitting) which progressed to knee level over 10 days. She was treated symptomatically at a local hospital but showed no improvement. She presented to the emergency room at our hospital on postablation day 40 [Table 2].

Given acute decompensated heart failure, she was treated with intravenous furosemide and diltiazem. After a detailed evaluation at our institute, the patient has a high-grade fever, tachycardia, and deranged TFT with a history of radioiodine ablation, hence a differential diagnosis of thyroid storm was considered. The Burch-Wartofsky Point Scale (BWPS) score was 75 (highly suggestive of thyroid storm) with deranged TFT [Table 1]. She was treated with intravenous hydrocortisone, propylthiouracil 200 mg every 6 h, and saturated potassium iodide 6 drops thrice daily after an endocrinology consult. The patient was afebrile with improvement in cardiopulmonary and neurological status by day 3. Hydrocortisone and propylthiouracil were gradually tapered and stopped. TFT improved, and she was shifted to carbimazole 10 mg every 8 h. The patient was discharged on day 8 in hemodynamically stable condition.

Discussion

Radioiodine has been used for the therapy of hyperthyroidism since 1946 and is currently the treatment of choice for the majority of thyrotoxic patients.

Thyroid storm is diagnosed based on clinical signs and symptoms of severe thyrotoxicosis and the presence of functional decompensation of one or more organ systems (BWPS and Japanese scoring system).[2,3] The clinical manifestations include high-grade fever, cardiovascular dysfunction (tachycardia, congestive heart failure, or atrial fibrillation), gastrointestinal dysfunction (nausea, vomiting, diarrhea, or occasionally jaundice), and central nervous system dysfunction (including hyperirritability, anxiety, confusion or apathy, and even coma).[1] The most frequent causes of death include shock, disseminated intravascular coagulation, and multiple organ failure.[4]

The precipitating factors in our patient include the 3-week discontinuation of ATD, elderly age, prolonged thyrotoxic phase, and multinodular goiter. Serum total and free T3 and T4 are usually high in patients with thyrotoxic storms. However, serum T3 was within normal limits in our patient, which may happen in patients who have been sick for more than a few days due to a decrease in the extrathyroidal conversion of T4 to T3.[6] The use of ATDs for 2 weeks to 2 months before RAI is usually recommended to render the patient euthyroid and to deplete the stored thyroid hormone.[7] In the reported literature, patients usually present with thyroid storm from day 3 to day 14, our patient had an unusual presentation after 30 days of radioiodine therapy.[5,8]

The pathophysiology of thyrotoxic crisis after radioiodine therapy includes injury to thyroid follicular cells and acute release of stored thyroid hormone into the circulation.[3] Histopathologic examination of the thyroid gland within the first 2 weeks after radioiodine administration has confirmed the presence of epithelial swelling and necrosis, disruption of follicular architecture, edema, and infiltration with polymorphonuclear cells.[5]

The Journal of Nuclear Medicine and the Society of Nuclear Medicine recommend a 3-day withdrawal as it is effective in treating Graves’ disease without exacerbating hyperthyroidism. Yet, controlled clinical trials and comparative studies show that a 2-day withdrawal is sufficient to restore the efficacy of radioiodine for thyroid ablation.[9101112] In the comparative study, patients in a 2-day antithyroid withdrawal regimen were examined prospectively using radioiodine uptake, serum-free T4, and an outcome of therapy. These parameters were compared to those in a 7-day withdrawal regimen retrospectively. The results showed no statistically significant difference in radioiodine uptake in the 2-day withdrawal group compared to the 7-day withdrawal group. The mean serum-free T4 measured 24 h after radioiodine therapy revealed that the 7-day group had significantly higher levels than the 2-day group. Thus, this study shows that the 2-day withdrawal period had similar results for uptake and did not exacerbate hyperthyroidism when compared to the 7-day withdrawal period.[12] In the controlled clinical trial, radioiodine kinetics was studied under continued thiamazole medication and after discontinuation for 1–2 days in 316 patients. The results showed that when the antithyroid medication was discontinued for at least 2 days, radioiodine uptake was near normal; however, uptake within 1 day of discontinuation was reduced. Patients in the continued thiamazole medication group showed a decreased uptake by a factor of 2.5.[9] Guidelines from the American Association of Clinical Endocrinologists also state that “elderly or cardiac patients with Graves’ disease may require ATD therapy before treatment with RAI to deplete the thyroid gland of stored hormone and reduce the risk of excessive posttreatment hyperthyroidism as a result of I-131-induced thyroiditis.”[13] No relation has been found between the dose of radioiodine and the magnitude of the increase in thyroid hormone levels after RAI.[14]

Prevention of thyroid storm after RAI in patients at high risk, i.e., elderly, severe, or prolonged thyrotoxic phase, significant weight loss, underlying cardiovascular or cerebrovascular disease, chronic illnesses, significant dehydration, active infection, and patients with very large goiter or multinodular goiter is fundamental.[15] The minimum duration of withdrawal of ATDs before RAI, adequate treatment of underlying illness, and restarting ATD 3–5 days post-RAI may prevent the thyrotoxic crisis.[8] Beta-adrenergic blockers should be used pre- and post-RAI to reduce the risk of thyroid storm.[16]

Conclusion

Thus, this case highlights the underlying potential for thyroid storm should be acknowledged in patients undergoing RAI treatment for hyperthyroidism, and appropriate precautions should be taken in the at-risk patients. Early recognition of this uncommon complication allows prompt implementation of lifesaving treatments.