Differentiated Thyroid Cancer in Two Patients with Resistance to Thyroid Hormone

Background: Resistance to thyroid hormone (RTH) is a genetic disease characterized by a reduced responsiveness of the pituitary and peripheral target tissues to TH. We describe two patients with RTH in whom differentiated thyroid cancer was diagnosed. Patient Findings: In both patients, RTH was unequivocally diagnosed and both underwent thyroidectomy for multinodular goiter. In Patient 1, histology showed a papillary thyroid carcinoma pT2. Because serum thyrotropin (TSH) levels were elevated even while the patient was taking 150 mu g daily of levothyroxine (LT4), the patient was treated with I-131 100 mCi for ablation of the thyroid remnant without discontinuing his LT4 therapy. We obtained a clinically adequate response by administering LT4 175 mu g/day (2.18 mu g/kg), but the serum TSH was persistently elevated on this dose. The patient was considered "free of disease'' after 8 years of follow-up. In Patient 2, histology revealed a papillary microcarcinoma (0.6 cm). Diagnostic whole-body scan was performed while the patient was taking 100 mu g/day LT4, a time that his serum TSH was 38 mu U/mL. Only a small remnant was revealed, so I-131 remnant ablation was not performed. While taking LT4 at a dose of 175 mu g/day (3 mu g/kg), the serum TSH was persistently high, serum TH levels were in the normal-high range, and he appeared to be clinically euthyroid. There has been no evidence of persistent or recurrent thyroid carcinoma in ultrasonography and thyroglobulin measurements that have been performed on a yearly basis for 3 years. Conclusion: Patients with thyroid carcinoma and RTH are a unique model of thyroid cancer in which follow-up likely occurs in the setting of constantly elevated serum TSH concentrations. The concern in these patients is that their persistent elevation of serum TSH may have an adverse effect on their thyroid cancer, and management choices in terms of the dose of LT4 that provides the optimum lowering of serum TSH without toxicity are difficult, particularly in the situation wherein, as was the case with one of our patients, there is cardiac disease.