Journal of the Endocrine Society Journal Article

Thyrotoxicosis Due to Immunotherapy

August 30, 2021
 

Alessandro Brancatella, Isabella Lupi, Lucia Montanelli, Debora Ricci, Nicola Viola, Daniele SgrĂ², Lucia Antonangeli, Chiara Sardella, Sandra Brogioni, Paolo Piaggi, Eleonora Molinaro, Francesca Bianchi, Michele Aragona, Andrea Antonuzzo, Andrea Sbrana, Maurizio Lucchesi, Antonio Chella, Alfredo Falcone, Stefano del Prato, Rossella Elisei, Claudio Marcocci, Patrizio Caturegli, Ferruccio Santini, Francesco Latrofa
Journal of the Endocrine Society, Volume 5, Issue 9, September 2021, bvab093
https://doi.org/10.1210/jendso/bvab093

Abstract

Context

Thyrotoxicosis is a common immune-related adverse event in patients treated with programmed cell death protein-1 (PD1) or programmed cell death protein ligand-1 (PD-L1) blockade. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy, is lacking, as are data on response to treatment and follow-up.

Objective

The aim of this study was to better characterize the thyrotoxicosis secondary to immune checkpoint inhibitors, gaining insights into pathogenesis and treatment.

Methods

We conducted a retrospective study of 20 consecutive patients who had normal thyroid function before starting immunotherapy and then experienced thyrotoxicosis on PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, 99mtechnecium scintiscan, and longitudinal thyroid function tests.

Results

Five patients had normal or increased scintigraphic uptake (Sci+), no serum antibodies against the thyrotropin 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 = .04). Among Sci– individuals, a larger thyroid volume was associated with a longer time to remission (P < .05). Methimazole (MMI) was effective only in Sci+ individuals (P < .05).

Conclusion

Administration of PD1- or PD-L1–blocking antibodies may induce 2 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 hypothyroidism or euthyroidism. Thyroid scintigraphy and ultrasound help in differentiating and managing these 2 forms of iatrogenic thyrotoxicosis.

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immuno-endocrinology
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