Hypothyroidism Secondary to Hashimoto’s Thyroiditis Presenting After Acute Phenytoin Overdose

Antiepileptics are associated with thyroid abnormalities. Phenytoin has the highest risk of hypothyroidism, although often subclinical. Rare cases of symptomatic hypothyroidism from phenytoin toxicity have been reported with chronic use. We present a case of acute-onset hypothyroidism due to Hashimoto’s thyroiditis likely triggered by phenytoin overdose.

Case Description:

A 56-year-old man with history of depression and seizures presented with ataxia and agitation after attempting suicide with phenytoin overdose. Initial evaluation revealed phenytoin level of 64.8 mg/L (range 10-20) and thyroid-stimulating hormone (TSH) of 2.91 mIU/L (range 0.47-4.68). An emergent whole-body computed tomography (CT) with intravenous contrast ruled out acute structural abnormalities. Eleven days later, the patient was transferred to an inpatient psychiatric service. A routine laboratory test then found a markedly elevated TSH at 22.9 mIU/L. Further testing revealed low free thyroxine (T4) 0.46 ng/dL (range 0.78-2.19) and triiodothyronine (T3) 92 ng/dL (range 97-169). The patient reported severe depression and constipation with no bowel movement for ten days. Therapy with levothyroxine 50 μg daily was started. Repeat thyroid function testing five days later revealed mildly improved free T4 (0.56 ng/dL) and total T3 (139 ng/dL), with up-trending TSH (45.9 mIU/L) and elevated thyroid peroxidase (TPO) antibodies (1360 IU/ml, range: < 9). In view of the diagnosis of Hashimoto’s thyroiditis and symptomatic hypothyroidism, levothyroxine was increased to 100 μg daily, closer to a full weight-based replacement dose.

Discussion:

Antiepileptics have been associated with thyroid function test abnormalities- most commonly, decreased T4 levels with or without elevated TSH. Chronic use of phenytoin has been associated with overt hypothyroidism. Proposed mechanisms involve the induction of hepatic enzymes by phenytoin, which causes increased T4 clearance and T4 to T3 conversion, as well as competitive binding of phenytoin to thyroxin-binding globulin.

Our patient had a normal TSH just eleven days prior and had never been diagnosed with hypothyroidism before. To our knowledge, this is the first case of hypothyroidism associated with acute phenytoin toxicity. Given the high TPO antibodies, this is a case of hypothyroidism due to Hashimoto’s thyroiditis exacerbated by phenytoin overdose. The iodine load from CT imaging may have contributed, however the standard contrast dose of intravenous iohexol 120 mL (350 mg/mL) is unlikely to have led to this presentation of persistently high TSH levels with symptomatic hypothyroidism. The patient’s constipation and mood both improved after starting levothyroxine. High suspicion for hypothyroidism is warranted for patients with supratherapeutic phenytoin levels.