Endocrine Abstracts

Introduction: Persistent symptoms of hypothyroidism or raised levels of thyroid stimulating hormone (TSH) despite adequate levothyroxine replacement (>1.6 µg/kg body weight) suggest treatment-refractory hypothyroidism. Adherence to treatment and conditions that might impair absorption or increase demand for levothyroxine should be explored.

Case: A 51-year-old man presented with raised TSH levels despite being on 425 mg daily of levothyroxine. He had total thyroidectomy performed for follicular thyroid cancer 14 months prior. He took his levothyroxine regularly before breakfast. Other medical history included epilepsy and hypertension, for which he took phenytoin 400 mg daily and ramipril 10 mg daily. He had been seizure-free since childhood. He weighed 114 kg.

Investigations and management: His serum TSH level was 17.1 mU/l (normal range: 0.3-4.1), free thyroxine of 16.7 pmo/l (12-22), and free triiodothyronine of 3.4 pmo/l (3.1-6.8): similar results for the past year. Other blood results, including malabsorption screening were normal. There was no assay interference. A supervised levothyroxine administration test did not demonstrate any improvement. The timing of levothyroxine administration was changed to bedtime but did not make any difference. The patient would not consider an alternative anti-epileptic because he feared a seizure relapse and losing his driving license. While on 600 mg daily of levothyroxine, his TSH was 18.4 mU/l. The patient decided to change the timing of levothyroxine administration to 02:00 in the morning and keep his phenytoin to 07:00. His TSH level improved to 4.91 mU/l at three months and to 0.29 mU/l a year later.

Discussion: The elimination half-life of phenytoin is about 22 hours. Phenytoin is a potent inducer of hepatic cytochrome P450 enzymes responsible for thyroid hormone metabolism. Phenytoin may also displace thyroid hormones from the binding globulins. Patients need advice concerning timing of levothyroxine administration when co-administered with phenytoin.