Effect of thyroid hormone suppression on control of advanced well-differentiated thyroid cancer

Excerpt

A 69 year old woman with long-standing diagnosis of radioactive iodine-refractory differentiated (papillary) thyroid cancer (DTC) was referred for consideration of initiation of kinase inhibitor therapy. She had been treated with 6 prior neck surgeries (initial thyroidectomy and consecutive central and lateral lymph node dissections over the years), but her disease progressed including in the thorax and yet remained asymptomatic. Supra-physiologic doses of levothyroxine were administered for the purpose of TSH suppression, since DTC is known to express the TSH receptor in the cell membrane and can respond to TSH stimulation with cell growth [1]. The current American Thyroid Association (ATA) guidelines [1] suggest that high-risk thyroid cancers patients, such as this case, should be maintained at a goal of TSH suppression of below 0.1 mU/L, as relapse free survival is lower compared to patients with non-suppressed TSH [2, 3]. When our patient was first seen, however, her TSH was suppressed to 0.2 mIU/L. The patient herein presented showed structural disease response (Fig. 1, representative metastasis circled in red, red arrows indicate the passage of time) attained 3 months after adjusting levothyroxine from 125 to 150 mcg per day, wherein her TSH decreased from 0.2 to 0.02 mU/L (her thyroglobulin level was not assessable due to high level of thyroglobulin antibodies). By RECIST 1.1 (response evaluation in solid tumors) criteria, a partial response was attained (RECIST measurements 66.3% baseline), confirmed upon later imaging 4 months thereafter. This case illustrates the exquisite sensitivity of some DTCs to aggressive TSH suppression, something that is sometimes neglected in the setting of newly approved and effective, but more toxic and much more expensive, kinase inhibitors (e.g. lenvatinib, sorafenib).

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