Background Thyrotoxicosis is a common immune-related adverse event in patients treated with PD1 or PD-L1 blockade. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy is lacking, as are data on response to treatment and follow-up. 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 upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, 99mTechnecium scintiscan 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). Conclusion 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 euthyroidism. Thyroid scintigraphy and ultrasound help differentiating and managing these two forms of iatrogenic thyrotoxicosis.

Management of thyrotoxicosis induced by PD1 or PD-L1 blockade

Brancatella, Alessandro
Primo
;
Montanelli, Lucia;Ricci, Debora;Viola, Nicola;Sgrò, Daniele;Piaggi, Paolo;Molinaro, Eleonora;Bianchi, Francesca;Antonuzzo, Andrea;Sbrana, Andrea;Lucchesi, Maurizio;Falcone, Alfredo;Del Prato, Stefano;Elisei, Rossella;Marcocci, Claudio;Santini, Ferruccio;Latrofa, Francesco
2021-01-01

Abstract

Background Thyrotoxicosis is a common immune-related adverse event in patients treated with PD1 or PD-L1 blockade. A detailed endocrinological assessment, including thyroid ultrasound and scintigraphy is lacking, as are data on response to treatment and follow-up. 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 upon PD1 or PD-L1 blockade. Clinical assessment was combined with thyroid ultrasound, 99mTechnecium scintiscan 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). Conclusion 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 euthyroidism. Thyroid scintigraphy and ultrasound help differentiating and managing these two forms of iatrogenic thyrotoxicosis.
2021
Brancatella, Alessandro; Lupi, Isabella; Montanelli, Lucia; Ricci, Debora; Viola, Nicola; Sgrò, Daniele; Antonangeli, Lucia; Sardella, Chiara; Brogioni, Sandra; Piaggi, Paolo; Molinaro, Eleonora; Bianchi, Francesca; Aragona, Michele; Antonuzzo, Andrea; Sbrana, Andrea; Lucchesi, Maurizio; Chella, Antonio; Falcone, Alfredo; Del Prato, Stefano; Elisei, Rossella; Marcocci, Claudio; Caturegli, Patrizio; Santini, Ferruccio; Latrofa, Francesco
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/1103274
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