Recommendations for the Use of Thyroxine in the Solitary Thyroid Nodule

Given that the expected nodule response rate slightly exceeds the reported natural regression rate, suppression therapy may be considered to be of slight benefit. If it is to be used (perhaps in the context of an institutional trial), it must be for the proven solitary nodule that has unequivocally negative cytology, is homogeneously solid on ultrasonography, and has normal or reduced uptake on technetium 99m pertechnetate scanning (Fig. 8-1).

These nodules ideally should be associated with a normal thyroid profile and negative thyroglobulin and thyroid peroxidase autoantibody status. Patients with a large nodule, particularly if it possesses echogenic heterogeneity or has been present for longer than 2 years, or in whom there is a history of head and neck irradiation, should not be treated in this manner. One may aim for a TSH suppression level of 0.05 to 0.10 mU/L in premenopausal patients without cardiac risk factors and for a level of 0.1 to 0.3 mU/L in postmenopausal women, particularly those with a known history of osteoporosis, and in men older than 65 years with a recognized cardiac history.

Treatment is continued for 6 months to 1 year with clinical and ultrasonographically calculated nodular volume based on anteroposterior length and width, assuming the nodule to be a spherical ellipsoid. This is complemented by assessment of the contralateral thyroid lobar volume to gauge response to suppression.102 Ultrasonography is essential in the follow-up of these patients because of its greater accuracy in nodule assessment and because it eliminates patients' and clinicians' bias.103 If the nodule regresses, treatment may be stopped after 6 to 12 months of therapy and reinstituted if it remains stable or gradually enlarges after 6 months of therapy cessation. If the nodule actually enlarges with compliant therapy, repeated fine-needle aspiration cytology or thyroidectomy is mandatory to exclude

Clinical solitary nodule

High-resolution ultrasonography

Confirmed solitary-

-T4 T3 TSH

Thyroglobulin autoantibodies


^^TSH suppression^^ Premenopausal Postmenopausal

<60 years of age Prior cardiac disease

Follow-up sensitive TSH assay

Contralateral thyroid volume and nodule volume assessed by ultrasonography

Serum thyroglobulin measurement

Nodule enlarges FNA repeat

FIGURE 8-1. An algorithm for the use of thyroxine (T4) in a solitary thyroid nodule. FNA = fine-needle aspiration; T3 = triiodothyronine; TSH = thyroid-stimulating hormone.

the possibility of malignant degeneration. This phenomenon, however, although well recognized, is relatively infrequent.

In treating such patients with thyroid hormone, more questions are raised than are answered. Most notably, what are the desired endpoints in the treatment of patients with a benign thyroid nodule? Is mere regression acceptable, or is complete nodular disappearance required? What is the mechanism behind spontaneous nodule regression? Is the treatment cost-effective? Is there a nodule limiting size? Finally, how does TSH suppressive therapy work if it works at all?



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