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Peer-reviewedCC BY 4.0Frontiers in Psychiatry

Case Report: Hyperactive delirium with psychotic symptoms associated with severe hypothyroidism during pembrolizumab therapy. Complete remission after levothyroxine and no recurrence after pembrolizumab rechallenge

  • Eduardo Vieira Fregolente1
  • Sabine Bühler2
  • Jacob Lahr1
  1. 1University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern
  2. 2Prolindo Oncology and Hematology Practice
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Abstract

Thyroid dysfunction is a common adverse event during pembrolizumab therapy, but severe hypothyroidism accompanied by acute neuropsychiatric symptoms is rare. We present the case of a 78-year-old woman with metastatic colorectal cancer who developed agitation, hallucinations, and confusion three months after initiation of Pembrolizumab. Evaluation revealed profound hypothyroidism (TSH 37.9 mU/L, free T3 <0.60 pmol/L and free T4 <0.5 pmol/L) and moderate hyponatremia without acute findings on neuroimaging. Levothyroxine therapy led to complete remission of neuropsychiatric symptoms, and pembrolizumab was safely restarted with close monitoring and no recurrence. This case underscores the importance of assessing thyroid function in acute psychiatric presentations during immune checkpoint inhibitor therapy and supports cautious rechallenge after stabilization. Severe hypothyroidism was considered a major contributor, although a multifactorial delirium, including the contribution of hyponatremia and the absence of CSF/EEG evaluation, cannot be excluded.

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Cite

BibTeXRIS
BibTeX
@article{fregolente2026case,
  title = {{Case Report: Hyperactive delirium with psychotic symptoms associated with severe hypothyroidism during pembrolizumab therapy. Complete remission after levothyroxine and no recurrence after pembrolizumab rechallenge}},
  author = {Eduardo Vieira Fregolente and Sabine Bühler and Jacob Lahr},
  journal = {Frontiers in Psychiatry},
  year = {2026},
  month = oct,
  doi = {10.3389/fpsyt.2026.1905725},
  url = {https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1905725/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Case Report: Hyperactive delirium with psychotic symptoms associated with severe hypothyroidism during pembrolizumab therapy. Complete remission after levothyroxine and no recurrence after pembrolizumab rechallenge
AU  - Eduardo Vieira Fregolente
AU  - Sabine Bühler
AU  - Jacob Lahr
PY  - 2026
DA  - 2026/10/27
JO  - Frontiers in Psychiatry
DO  - 10.3389/fpsyt.2026.1905725
UR  - https://www.frontiersin.org/articles/10.3389/fpsyt.2026.1905725/full
AB  - Thyroid dysfunction is a common adverse event during pembrolizumab therapy, but severe hypothyroidism accompanied by acute neuropsychiatric symptoms is rare. We present the case of a 78-year-old woman with metastatic colorectal cancer who developed agitation, hallucinations, and confusion three months after initiation of Pembrolizumab. Evaluation revealed profound hypothyroidism (TSH 37.9 mU/L, free T3 <0.60 pmol/L and free T4 <0.5 pmol/L) and moderate hyponatremia without acute findings on neuroimaging. Levothyroxine therapy led to complete remission of neuropsychiatric symptoms, and pembrolizumab was safely restarted with close monitoring and no recurrence. This case underscores the importance of assessing thyroid function in acute psychiatric presentations during immune checkpoint inhibitor therapy and supports cautious rechallenge after stabilization. Severe hypothyroidism was considered a major contributor, although a multifactorial delirium, including the contribution of hyponatremia and the absence of CSF/EEG evaluation, cannot be excluded.
SN  - 1664-0640
ER  -