Endocrine Abstracts

Since the observation in 1961, that phenytoin treatment caused a reduction in protein bound iodine, the effect of various anticonvulsants on the thyroid hormones and in causing sub clinical and overt hypothyroidism has been a matter of debate. There are no reports linking newer antiepileptics like lamotrignine to thyroid hormone abnormalities. We report three patients who developed overt hypothyroidism while on treatment with Primidone, Lamotrignine and Carbamazepine respectively requiring supplemental thyroxine replacement.

The first patient is an 83-year-old male who was a known epileptic on primidone 750 mg/day and phenytoin 600 mg/day. Thyroid functions showed FT₄ 9 pmol/l and TSH 2.58 mU/l. Thyroxine replacement with gradual titration of the dose up to 100 mcg daily achieving biochemical levels of FT₄ 14, FT₃ 4.1 and TSH 1.73.

The second patient is a 41-year-old woman with a diagnosis of epilepsy on Carbamazepine 1200 mg/day, Valproic acid 3 g/day and Gabapentin 1800 mg/day. She was noted to have FT₄ 12 FT₃ 3.7 and TSH 0.98.The carbamazepine was reduced to 800 mg/day with addition of Lamotrignine 75 mg/day. Thyroid function 3 months later revealed central hypothyroidism with FT₄ 9 FT₃ 3.5 and TSH 1.23 possibly related to lamotrignine-induced effect requiring supplemental thyroxine at dose of 50 mcg daily.

The third patient is a 29-year-old lady with a background of hypothalamic teratoma diagnosed in 1988 and panhypopituitarism requiring full hormonal replacement. She was also on Carbamazepine 600 mg daily. She was noted to have suboptimal thyroid function (FT₄ 4 TSH 6.88) eventually requiring 200 mcg daily for adequate replacement (FT₄ 16 TSH<0.05).

Mechanisms implicated include increase in the extrathyroidal metabolism of thyroid hormones leading to low FT₄ and FT₃ levels or central hypothyrodism by interfering with the hypothalamic pituitary axis and inhibiting hypothalamic TRH release.

Anticonvulsants can induce central hypothyroidism, which can be adequately supplemented by thyroxine treatment improving patient symptomatology and seizure threshold. To the best of our knowledge, this is the first report, which might indicate that newer antiepileptics like Lamotrignine might demonstrate a similar effect on thyroid functions.