A Case of Amiodarone Induced Thyrotoxicosis

A 69 year old male presented to the hospital due to worsening back pain and lower extremity weakness.  He had a medical history of follicular thyroid cancer and underwent lobectomy back in 2016. After admission, patient was found to have multiple metastasis of follicular thyroid cancer with lesion in the lumber spine, and his serum thyroglobulin level was elevated at 1,500 ng/mL (1.3 – 31.8 ng/mL) without thyroglobulin antibody detected. Patient did not present hyperthyroidism symptoms. TSH and total T4 were normal, and free T4 was slightly decreased. During hospitalization, patient was prescribed with Amiodarone, to control atrial fibrillation. Amiodarone is an antiarrhythmic drug used for severe ventricular arrhythmias, paroxysmal atrial tachycardia, and atrial fibrillation. It has high content of iodine and a direct toxic effect on thyroid gland, resulting in thyroid dysfunction in 3-5% of patients. In this case, severe hyperthyroidism was observed after amiodarone administration.

Patient’s FT4 level significantly elevated to >5.2 ng/dL (0.9-1.7ng/dL), total T4 was increased to 21.8 ug/dL (4.5-11.7 ug/dL), and TSH was suppressed to below the detection limit. The sudden increase of FT4 suggested Amiodarone induced thyrotoxicosis (AIT). High content of iodine in Amiodarone could raise blood iodine concentration up to 40 folds and enhance thyroid hormone biosynthesis in thyroid cells. This is the main cause of type 1 AIT, which is more common in patients with underlying thyroid diseases, such as Graves’ disease, or autonomous nodular goiter. Type 2 AIT typically happens in patients without underlying thyroid diseases and is caused by a direct toxic effect of amiodarone on thyroid follicular cells. Pre-formed T4 and T3 in thyroid cells are released into the circulation due to destructive thyroiditis in type 2 AIT. Differentiating these two types is important because it has therapeutic implications. However, the distinction may be difficult because patients may have a mixture of both mechanisms. Thyroid function tests are usually not helpful in the differentiation, but ultrasonography and thyroid scan with iodine uptake can help differentiate type 1 from type 2 AIT. 

In this case, thyroid scan with technetium showed reduced thyroid uptake in thyroid lobe, and mild uptake within metastatic lesions, suggesting possible thyroiditis due to amiodarone. Type 2 AIT develops as an inflammatory process and anti-inflammatory glucocorticoids are used in the treatment. Amiodarone was discontinued in this patient and his thyroid function tests indicated improvement of thyroid dysfunction. Amiodarone and its metabolites have a long half-life and accumulate in adipose tissues due to its lipophilic property. Therefore, in some cases, amiodarone toxicity effect can last for months, even after drug withdrawal. To be noted, amiodarone can also induce hypothyroidism, especially in patients with underlying Hashimoto’s thyroiditis or positive antithyroid antibodies.

Xin-small

-Xin Yi, PhD, DABCC, FACB, is a board-certified clinical chemist, currently serving as the Co-director of Clinical Chemistry at Houston Methodist Hospital in Houston, TX and an Assistant Professor of Clinical Pathology and Laboratory Medicine at Weill Cornell Medical College.

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