Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade

Context: Thyrotoxicosis is a common immune-related adverse event in patients treated with PD1 or PD-L1 checkpoint inhibitors. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy is missing, as are data on response to treatment and follow-up. Objectives: To better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and informing management. Methods: We conducted a prospective cohort study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, scintigraphy, and longitudinal thyroid function tests. Results: Five patients had normal scintigraphic uptake (Sci+), no serum antibodies against the TSH receptor, and remained hyperthyroid throughout follow-up. The other 15 patients had no scintigraphic uptake (Sci-) and experienced destructive thyrotoxicosis followed by hypothyroidism (N= 9) or euthyroidism (N= 6). Hypothyroidism was more readily seen in those with normal thyroid volume than in those with goiter (P= 0.04). Among Sci- subjects, a larger thyroid volume was associated to a longer time to remission (P<0.05). Methimazole (MMI) was effective only in Sci+ subjects (P<0.05). Conclusions: Administration of PD1 or PD-L1 blocking antibodies may induce two different forms of thyrotoxicosis that appear similar in clinical severity at onset: a type 1 characterized by persistent hyperthyroidism that requires treatment with MMI, and a type 2 characterized by destructive and transient thyrotoxicosis that evolves to hypo- or eu-thyroidism. Thyroid scintigraphy and ultrasound help differentiating and managing these two forms of iatrogenic thyrotoxicosis