To the Editor: Repetitive transcranial magnetic stimulation (rTMS) is efficacious in treatment-resistant depression when applied with high-frequency stimulation (HF-rTMS: 5 Hz to 25 Hz) over the left dorsolateral prefrontal cortex (PFC) and with low-frequency stimulation (LF-rTMS≤1 Hz) over the right dorsolateral PFC.¹ rTMS is known to be painless and well-tolerated, and does not require, as a rule, either premedication or special biological monitoring.

However, rTMS seems to influence the hypothalamo-pituitary-thyroid axis. We report, here, the first case of thyroid-stimulating hormone (TSH) increase occurring during LF-rTMS for treatment of depression.

A 60-year-old woman was hospitalized for a treatment-resistant depression lasting for 2 years. She was treated with T₄, 100 μg/day, after complete thyroidectomy for a multinodular goiter 13 years ago. Her plasma TSH levels had been stable, between 1 and 2 mU/liter (normal range: 0.4–3.4) for a long time, as were her thyroid hormone levels. Antidepressants previously prescribed to the patient never affected her thyroid function. On admission, levels of TSH and free T₄ were 1.560 mU/L and 13.3 pmol/liter (normal range: 9.8–18.8), respectively.

For her treatment-resistant depression, daily rTMS sessions from Monday through Friday were delivered over 6 weeks in addition to her latest antidepressant (venlafaxine). The patient received LF-rTMS (1 Hz) to the right dorsolateral PFC (360 pulses per session, 120% motor threshold), and blood thyroid levels were obtained each Wednesday at 7 A.M.

Her serum TSH rapidly increased after beginning rTMS, up to 5.19 mU/L, and remained abnormally elevated during the whole rTMS period. When rTMS treatment was stopped 6 weeks later, plasma TSH returned to normal. In this patient treated with T₄, after thyroidectomy, free T₄ levels remained unchanged during the rTMS treatment period.

So far, very little is known on the impact of rTMS on hypothalamo-pituitary-thyroid axis.² A slight increase in plasma TSH level, remaining in the normal ranges, has been reported in healthy volunteers and in depressed patients with HF-rTMS (5 Hz to 20 Hz).^1,3,4 In our present case, we report a significant increase in plasma TSH, above normal range, during LF-rTMS (1 Hz) treatment. Because our patient had a history of thyroidectomy, this rise in TSH did not induce any increase in plasma T₄ level. In patients with a normal thyroid gland, we may expect an increase in plasma T₄ secondary to the LF-rTMS-induced rise in plasma TSH. Such an increase in plasma T₄ level has been recently suspected by Osuch et al.⁵ during treatment of anxiety disorders by LF-rTMS. Thus, rTMS can have significant effects on the pituitary-thyroid axis that may potentially induce hyperthyroidism. Further studies are needed to assess the effects of rTMS on thyroid function.