Immunotherapy-Associated Hypothyroidism: Comparison of the Pre-Existing With De-Novo Hypothyroidism

Megan M. Kristan, David Toro-Tobon, Nnenia Francis, Sameer Desale, Athanasios Bikas, Jacqueline Jonklaas, Rachna M. Goyal

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1 Scopus citations


Background: Immunotherapy has revolutionized the treatment of solid malignancies, but is associated with endocrine-related adverse events. This study aims to dissect the natural course of immunotherapy-induced hypothyroidism and provide guidance regarding diagnosis and management in patients with and without pre-existing hypothyroidism.

Methods: A retrospective analysis was conducted using patients who received immunotherapy between 2010-2019 within a multicenter hospital system. Participants were separated in three groups-those with pre-existing hypothyroidism, those who developed primary hypothyroidism and those with hypophysitis within a year of their first immunotherapy. Serial effects of immunotherapy on thyroid function tests (TFTs) and levothyroxine dosing were evaluated.

Results: 822 patients were screened, with 85 determined to have pre-existing hypothyroidism, 48 de-novo primary hypothyroidism and 12 de-novo hypophysitis. All groups displayed fluctuations in TFTs around weeks 6-8 of treatment. In the pre-existing hypothyroidism group, the levothyroxine dose was higher at 54 weeks than at baseline with the difference showing a trend towards statistical significance (p=0.06). The observed mean levothyroxine dose was significantly lower than the mean calculated weight-based dose for all groups. This finding was most clinically significant for the de-novo hypophysitis group (mean difference: -58.3 mcg, p<0.0001). The mean 0.9 mcg/kg levothyroxine dose at week 54 for the de-novo hypophysitis group was statistically lower than the other groups (p=0.009).

Conclusion: It is reasonable to screen with TFTs every 4 weeks, and space out TFTs surveillance to every 12 weeks after week 20. Our findings suggest a more conservative approach for levothyroxine dosing in those developing de-novo hypothyroidism, especially hypophysitis, such as initiating at 0.9-1.2 mcg/kg.

Original languageEnglish (US)
Article number798253
JournalFrontiers in Endocrinology
StatePublished - Mar 11 2022
Externally publishedYes

Bibliographical note

Funding Information:
Support for the current project was provided by a pilot grant from the Department of Medicine entitled ‘Effect of Immune Checkpoint Inhibitors on Thyroid Function: an Institutional Experience’ that was awarded to RG by the Department of Medicine at MedStar Georgetown University Hospital. The statistical analyses utilized in this publication were performed by the Biostatistics, Epidemiology, and Research Design core supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001409. Data were presented in the form of an oral abstract entitled “Immunotherapy-associated Thyroid Disorders: Comparison of the Course of Pre-existing Hypothyroidism Compared with De Novo Hypothyroidism” at the 89th Annual American Thyroid Association Meeting (Chicago, IL – 11/2019).

Publisher Copyright:
Copyright © 2022 Kristan, Toro-Tobon, Francis, Desale, Bikas, Jonklaas and Goyal.


  • check point inhibitor
  • hypophysitis
  • hypothyroidism
  • immunotherapy
  • thyroiditis
  • Hypothyroidism/chemically induced
  • Immunotherapy/adverse effects
  • Thyroid Function Tests
  • Humans
  • Retrospective Studies
  • Thyroxine/adverse effects

PubMed: MeSH publication types

  • Multicenter Study
  • Journal Article


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