Chorea Associated with Thyrotoxicosis Due to Toxic Multinodular Goiter

Dear Editor:

Thyroid disease is associated with movement disorders. Tremors are relatively common in thyrotoxicosis. However, choreoathetosis is an uncommonly reported manifestation of hyperthyroidism. We describe here a patient with chorea associated with thyrotoxicosis and its response to treatment.

A 23-year-old female patient presented with involuntary, writhing, symmetrical movements involving arms, legs, neck, tongue, and face starting 10 days following delivery of her second child. Her medical history was significant for uncontrolled hyperthyroidism due to toxic nodular goiter diagnosed 3 years previously during her first pregnancy. At that time, she was started on propylthiouracil (PTU). She was noncompliant regarding follow-up and management. She reported taking PTU throughout her second pregnancy but stopped it following delivery. There was a history of emotional lability and 80 pound weight loss in the 2 months following delivery. On examination she appeared anxious but was alert and had a clear sensorium. Her heart rate was 130. Neurologic examination revealed large amplitude, writhing, symmetrical, and continuous choreiform movements involving both arms and legs. She also had difficulty speaking due to involuntary movements involving her mouth and tongue. The left thyroid lobe was enlarged on palpation without a bruit. She had no thyroid orbitopathy.

Laboratory data showed suppressed thyrotropin (TSH) <0.008 (normal range, 0.370–4.420 mIU/mL), elevated free thyroxine (T4) 3.32 (normal range, 0.75–2.00 ng/dL), and elevated free triiodothyronine (T3) 11.83 (normal range, 2.3–4.2 pg/dL). Thyroid-stimulating immunoglobulin, thyroid peroxidase, and antithyroglobulin antibodies were normal.

Radioactive iodine-123 thyroid uptake and scan showed an elevated uptake of 60% (normal, 10%–30%). The distribution of uptake was asymmetric and inhomogeneous with absence of uptake in right lobe and presence of a “cold” nodule in left lower thyroid lobe. Thyroid ultrasound confirmed the presence of a multinodular goiter.

Neurology consultation was obtained and a comprehensive workup for secondary causes of chorea including Wilson's disease, Sjogren's syndrome, neuroacanthocytosis, Sydenham's chorea, and other infectious and autoimmune disorders were negative. A magnetic resonance imaging study of the brain was normal.

It was felt that her choreiform movements were related to her uncontrolled hyperthyroidism. She was started on Methimazole, which was later switched to PTU because of development of skin rash. She was discharged home on PTU, Atenolol, Quetiapine, and a short Prednisone taper. Quetiapine was used because of its dopamine blocking actions in an attempt to control the abnormal movements but the patient stopped it after a few days. She was seen 4 months later in the neurology clinic. She reported resolution of choreiform movements within a few days after her hospital discharge. On a subsequent follow-up at the endocrine clinic, 6 months following the initial consultation, she was clinically euthyroid with resolution of chorea, tachycardia, and weight loss. She was still taking PTU. Her TSH was 0.012 mIU/mL, free T3 was 4.5 pg/dL, and free T4 was 0.78 ng/dL.

Choreoathetosis is a syndrome comprising of distinctive involuntary, purposeless, or quasi-purposeless movements characterized by emotional instability and absence of marked progressive deterioration. Previously reported cases of hyperthyroidism-induced chorea have described both unilateral and generalized occurrence. It is usually reversible with treatment with beta-adrenergic blockers, dopamine antagonists, and antithyroid drugs but persistent cases have been reported (1).

The pathogenesis of hyperthyroid-related movement disorders is poorly understood. It is believed to have biochemical rather than structural basis. Hypersensitivity of dopaminergic receptors to dopamine in the corpus striatum is suspected as underlying mechanism of hyperthyroidism-induced chorea (2). Alterations in thyroid function has been found to influence the sensitivity of adrenergic and dopaminergic receptors to noradrenaline and dopamine. Others have suggested that a preexisting structural lesion of the basal ganglia might be necessary for thyrotoxicosis to induce involuntary movements (3). However, in most of the reported cases including ours, various neuroimaging studies failed to identify a consistent structural abnormality in the basal ganglia.

Previously published reports have described cessation of chorea with successful treatment of hyperthyroidism in most cases. However, the longer the patient remains thyrotoxic, the more difficult it becomes to reverse the chorieform movements. Some investigators have reported a return of choreiform movements with recurrence of hyperthyroidism, thus establishing causality of thyrotoxicosis for these movements (4).

The resolution of our patient's choreoathetosis, with improvement of her hyperthyroidism in the absence of any visible abnormality in the basal ganglia, supports a biochemical or metabolic rather that structural basis for her neurological features. Further research in this area is needed to elucidate the etiology and pathogenesis of hyperthyroidism-induced chorea.