Differentiated thyroid cancer in two patients with resistance to thyroid hormone

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.

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 μg daily of levothyroxine (LT(4)), the patient was treated with (131)I 100 mCi for ablation of the thyroid remnant without discontinuing his LT(4) therapy. We obtained a clinically adequate response by administering LT(4) 175 μg/day (2.18 μg/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 μg/day LT(4), a time that his serum TSH was 38 μU/mL. Only a small remnant was revealed, so (131)I remnant ablation was not performed. While taking LT(4) at a dose of 175 μg/day (3 μg/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.

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 LT(4) 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.