Endocrine Abstracts

Sunitinib and sorafenib are orally active tyrosine kinase inhibitors which have recently been developed as therapy for renal cell cancer and gastro-intestinal stromal tumours. Changes in thyroid function are frequently found during sunitinib therapy, typically occurring 7–24 months into therapy; the mechanism is not clear, though inhibition of iodine uptake, thyroid follicular cell apoptosis and thyroiditis have all been proposed. In contrast, thyroid dysfunction is reported to be unusual with sorafenib; if it occurs it is generally early (2–4 months) subclinical and mild (TSH <10 mU/l). We report here a patient with marked acute changes in thyroid function during sorafenib therapy. A 48-year-old man was found to have metastatic renal cancer following biopsy of a mass in the neck. After nephrectomy he was treated with sorafenib. Thyroid function was normal prior to treatment; 12 months after starting sorafenib he developed changes of mild hyperthyroidism (TSH 0.04 & 0.07 mU/l, fT4 20.5 and 23.4 pmol/l) which rapidly progressed to marked hypothyroidism over the following 2 months (TSH 0.02 & 51.4 mU/l, fT4 8 & 1.5 pmol/l). Further metastases have developed in the thyroid and spinal muscles, and sorafenib therapy has been changed to sunitinib. The rapid changes in thyroid function, which occurred during sorafenib therapy, suggests that sorafenib may cause a disturbance in thyroid function which is more marked and clinically significant than has been hitherto recognised. The pattern of thyroid dysfunction seen in this case is typical of acute thyroiditis, and contrasts with the progressive hypothyroidism which is most commonly seen with sunitinib. Both these tyrosine kinase inhibitors act at the VEGF receptor; VEGF and its receptor are expressed in thyroid follicular cells, and may play a role in angiogenesis in the thyroid gland. Further work is needed to clarify the mechanism by which sorafenib alters thyroid function.