Thyroid imaging in the management of anti-PD1/PD-L1 induced thyrotoxicosis

Context: Thyrotoxicosis is the most common endocrine adverse event due totreatment with anti-PD1 and anti-PD-L1. The most common form is destructive thyrotoxicosis whereas persistent, supposedly autoimmune hyperthyroidism (Graves’ hyperthyroidism) is rare. The possible role of thyroid imaging (neck ultrasound and scintigraphy) in the differential diagnosis has never evaluated. Aim: To evaluate the usefulness of neck ultrasound and 99Tc- scintiscan in patients with thyrotoxicosis induced by anti-PD1 and anti-PD-L1 therapy. Patients and methods We retrospective analyzed clinical, biochemical and imaging data of 15 consecutive patients who were referred to our department for thyrotoxicosis (high levels of FT4 and FT3 and low-to-undetectable level of TSH) ensued during immunotherapy. All patients underwent neck ultrasound and 99Tc-scintiscan at the onset of thyrotoxicosis and periodical tests of thyroid function (15, 30, 45, 60, 90 and 120 days). Results: All patients were euthyroid before starting immunotherapy. At the onset of thyrotoxicosis median FT4 was 3.05 ng/dl (normal range 0.7–1.7) median FT3 was 6.30 ng/l (normal range 2.7–5.7)At 99Tc- scintiscan 11 patients presented no uptake (Sci-) whereas 4 patients presented diffuse uptake (Sci+).Sci-patients had absent vascularization whereas Sci+ patients had hypervascular pattern at neck ultrasound. No differences in thyroid function tests were observed at the onset of thyrotoxicosis between the two groups. At 30 and 60 days Sci+ patients showed higher levels of FT4 and FT3 compared to Sci- patients (P < 0.005).All Sci- patients underwent spontaneous remission, whereasall Sci+ patients required treatment with methimazole in order to control thyrotoxicosis. Among Sci- patients, a lower (< 20 ml) thyroid volume was associated with a faster remission. TSH-receptor antibodies, measured as TBI,were negative throughout the follow-up in all patients. Conclusions: While Sci- patients showed a self limited course of thyrotoxicosis with a remission time inversely related to thyroid volume,Sci+ patients required treatment with methimazole in order to control thyrotoxicosis induced by PD1 and PD-L1 therapy.