Fine-needle aspiration cytology of the thyroid gland was performed on 219 patients complaining of fatigue of more than one year’s duration. Eighty-seven patients (40%) were found to have definite histological evidence of chronic lymphocytic (autoimmune) thyroiditis. TSH levels were widely scattered, with a median of 3.8 mU/L and a range of less than 0.9 to greater than 15 mU/L (normal range, 0.1 to 5.0 mU/L). The clinical response to thyroxine therapy was equally favorable among patients with lymphocytic thyroiditis, irrespective of their initial TSH level. In a follow-up letter (Lancet 2003;361:1305), the writers point out that thyroid autoantibodies (peroxidase, thyroglobulin, or both) were present in only half of the patients with definite lymphocytic thyroiditis.

Comment: Although hypothyroidism is a well-recognized cause of fatigue, there is a great deal of controversy about how best to diagnose this condition. Most doctors will rule out a diagnosis of hypothyroidism if the TSH level is normal. The results of this study, however, suggest that chronic autoimmune thyroiditis is associated with clinical hypothyroidism, even in the presence of normal TSH values. Furthermore, fine-needle aspiration cytology of the thyroid gland is a more sensitive method of identifying thyroid autoimmunity than are measurements of thyroid autoantibodies. The results of this study suggest that approximately 40% of patients with chronic fatigue will benefit from thyroid-replacement therapy, and that standard thyroid-function tests are not sensitive enough to identify who will respond to such therapy. In lieu of an invasive biopsy of the thyroid gland, a careful therapeutic trial of thyroid hormone seems warranted for patients with chronic fatigue who have clinical evidence of hypothyroidism.

Wikland B, et al. Fine-needle aspiration cytology of the thyroid in chronic fatigue. Lancet 2001;357:956-957.