Why Do Clinicians Continue to Debate the Use of Levothyroxine in the Diagnosis and Management of Thyroid Nodules?

Why do clinicians still debate whether thyroid nodule volume decreases in response to therapy with levothyroxine, given that many types of nodules do not get smaller and that the therapy could have adverse effects [1]? The reasons include the enormous number of patients with enlarged thyroids, the myriad clinical variations of the condition, insecurity about clinical findings, exceptions to current diagnostic guidelines that identify malignancy, and questions about the long-term management of benign nodules or the contralateral lobe after surgery.

Suppressive therapy, in which thyroid hormone is administered to reduce the concentration of thyroid-stimulating hormone (TSH) to a level below normal (as opposed to replacement levothyroxine therapy, which normalizes the TSH level), had been used for years in the nonsurgical management of nodular thyroid disease [2-4]. However, this treatment is no longer popular: Recent studies failed to show efficacy [5, 6]; other studies showed an increased risk for osteoporosis as a consequence of thyrotoxicosis [7-9]; and fine-needle aspiration biopsy can better ascertain malignancy than can a therapeutic trial [10].

Although many patients do not need suppressive therapy, there are four main concerns about how the lack of suppressive therapy for cytologically benign disease may affect thyroid lesions or the patient's prognosis: First, in the past the clinician was alerted that a nodule might be malignant if it grew during treatment with levothyroxine. Enlargement of an untreated nodule is less informative. Second, because sampling errors from fine-needle aspiration biopsy may occur and negative or inconclusive cytologic findings do not exclude malignancy, it is uncomfortably open-ended to not treat patients who have “negative” cytologic findings and some clinical concern about malignancy but …