We strongly disagree with Dr. Di Poala's presumption that cold thyroid nodules are "totally asymptomatic and truly benign" and also with his misleading assertion that "untreated thyroid nodules disappear in 38% of cases, and only 13% of nodules increase in size."

Solitary benign cold nodules of the thyroid are not asymptomatic, and their presence may affect both quality and duration of life. Although these nodules rarely grow large enough to cause compression signs, patients feel uncomfortable because of aesthetic problems or fear of malignancy. The presence of malignancy cannot be completely ruled out by fine-needle aspiration biopsy, which, even in experienced hands, has a false-negative rate of 1% to 10% [1].

Further, most studies indicate that only a few solid nodules shrink by 50% or more, let alone disappear, without treatment (range, 0% to 20%) [2, 3]. To support his thesis, Dr. Di Poala quotes the work of Kuma and colleagues [4]. However, he fails to say that an invited commentary at the end of that report underlines the possible selection bias of the study—only 140 (85 with solid nodules) of 2609 invited patients were actually examined. Should new nodules appear during follow-up, malignancy will become more difficult to exclude. For these reasons, many untreated patients eventually have prophylactic thyroidectomy and bear the costs, morbidity, and mortality associated with this procedure. Dr. Di Poala does not inform the reader that in the study he cites, 68% of examined patients developed multiple nodules and 36.3% of patients who responded had had surgery.

In our study [2], L-thyroxine administration not only prevented nodule growth and the appearance of new nodules but also induced a substantial shrinkage in 40% of solid solitary cold benign nodules. Small nodules are more sensitive to thyroid-stimulating hormone (TSH) suppression; however, L-thyroxine therapy may also be beneficial in large nodules because it may prevent further nodule growth. For this reason, growth of a nodule during L-thyroxine treatment is a strong indication for surgical removal of the nodule, regardless of the cytologic diagnosis. Thyroxine treatment therefore improves diagnostic accuracy and avoids long-term anxiety and unnecessary surgery. These favorable results can be obtained using a L-thyroxine dose that decreases but does not fully suppress serum TSH levels and therefore does not induce subclinical hyperthyroidism. Even if subclinical hyperthyroidism is temporarily present in some patients, this intermittent condition is not associated with harmful cardiac or bone effects [5].

Finally, follow-up laboratory testing does not add cost because repeated procedures (cytologic testing, ultrasonography) are also advisable for untreated nodules. The adjunctive cost of L-thyroxine medication, therefore, is very low and favorably balanced against the benefits.