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Brancatella A, Lupi I, Montanelli L, et al. Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade. J Endocr Soc. 2021;5(9):bvab093doi: 10.1210/jendso/bvab093.
Brancatella, A., Lupi, I., Montanelli, L., Ricci, D., Viola, N., Sgrò, D., Antonangeli, L., Sardella, C., Brogioni, S., Piaggi, P., Molinaro, E., Bianchi, F., Aragona, M., Antonuzzo, A., Sbrana, A., Lucchesi, M., Chella, A., Falcone, A., Del Prato, S., Elisei, R., Marcocci, C., Caturegli, P., Santini, F., & Latrofa, F. (2021). Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade. Journal of the Endocrine Society, 5(9), bvab093. https://doi.org/10.1210/jendso/bvab093
Brancatella, Alessandro, et al. "Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade." Journal of the Endocrine Society vol. 5,9 (2021): bvab093. doi: https://doi.org/10.1210/jendso/bvab093
Brancatella A, Lupi I, Montanelli L, Ricci D, Viola N, Sgrò D, Antonangeli L, Sardella C, Brogioni S, Piaggi P, Molinaro E, Bianchi F, Aragona M, Antonuzzo A, Sbrana A, Lucchesi M, Chella A, Falcone A, Del Prato S, Elisei R, Marcocci C, Caturegli P, Santini F, Latrofa F. Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade. J Endocr Soc. 2021 May 15;5(9):bvab093. doi: 10.1210/jendso/bvab093. eCollection 2021 Sep 01. PMID: 34337277; PMCID: PMC8317632.
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J Endocr Soc. 2021 May 15;5(9):bvab093. doi: 10.1210/jendso/bvab093. eCollection 2021 Sep 01.

Management of Thyrotoxicosis Induced by PD1 or PD-L1 Blockade.

Journal of the Endocrine Society

Alessandro Brancatella, Isabella Lupi, Lucia Montanelli, Debora Ricci, Nicola Viola, Daniele Sgrò, 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

Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Pisa 56126, Italy.
  2. Endocrinology Unit, Azienda Ospedaliero-Universitaria Pisana, University Hospital of Pisa, Pisa 56124, Italy.
  3. Department of Information Engineering, University of Pisa, Pisa 56126, Italy.
  4. Nuclear Medicine Unit, Azienda Ospedaliero-Unuversitaria Pisana, University Hospital of Pisa, Pisa 56124, Italy.
  5. Metabolic Diseases and Diabetes Unit, Azienda Ospedaliero-Universitaria Pisana, University Hospital of Pisa, Pisa 56124, Italy.
  6. Oncology Unit, Azienda Ospedaliero-Universitaria Pisana, University Hospital of Pisa, Pisa 56126, Italy.
  7. Oncology Unit, Azienda Ospedaliero-Universitaria Pisana and Department of Translational Research and New Technologies in Medicine and Surgery, University Hospital of Pisa, Pisa 56126, Italy.
  8. Pneumology Unit, Azienda Ospedaliero-Universitaria Pisana, University Hospital of Pisa, Pisa 56124, Italy.
  9. Oncology Unit, Azienda Ospedaliero-Univeritaria Pisana and Department of Translational Research and New Technologies in Medicine abd Surgery, University Hospital of Pisa, Pisa 56126, Italy.
  10. Metabolic Diseases and Diabetes Unit, Azienda Ospedaliero-Universitaria Pisana and Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa 56124, Italy.
  11. Endocrinology Unit, Azienda Ospedaliero-Universitaria Pisana and Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa 56124, Italy.
  12. Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

PMID: 34337277 PMCID: PMC8317632 DOI: 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,

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 (

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.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Keywords: immune check point inhibitors; immune related adverse event; immunotherapy; thyroid; thyroid dysfunction

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