Probable Hypophysitis Recognized More Than Two Years After Pembrolizumab Discontinuation
- 1Hospital Medicine, Faith Regional Health Services, Norfolk, USA
Abstract
Immune checkpoint inhibitor-associated hypophysitis is an uncommon but clinically important endocrine immune-related adverse event. We report a 70-year-old man with a history of non-small cell lung cancer previously treated with approximately two years of pembrolizumab, with his last dose administered approximately 28 months before presentation. He developed progressive fatigue, anorexia, hypotension, functional decline, and confusion and was subsequently hospitalized with multifocal pneumonia and septic shock. Although the infection and hemodynamic instability improved, encephalopathy, weakness, poor oral intake, and dysphagia persisted. Brain magnetic resonance imaging demonstrated new pituitary enlargement compared with imaging obtained approximately three months earlier. Dedicated pituitary imaging showed enlargement measuring approximately 1.5 × 2.0 cm without definite differential enhancement to suggest a pituitary adenoma. Endocrine testing demonstrated a cortisol level of 3.3 µg/dL with an inappropriately low adrenocorticotropic hormone level of 6.5 pg/mL, free thyroxine of 0.36 ng/dL with thyroid-stimulating hormone of 2.0 µIU/mL, suppressed gonadotropins, and testosterone <10 ng/dL, supporting central adrenal insufficiency and central hypothyroidism with marked gonadal-axis suppression. Cerebrospinal fluid cytology and paraneoplastic studies were unrevealing. The patient was treated with hydrocortisone before thyroid hormone replacement and subsequently showed progressive improvement in mental status, oral intake, and participation in rehabilitation. This case highlights that pituitary immune-related adverse events may be recognized long after pembrolizumab discontinuation and emphasizes the importance of considering prior immune checkpoint inhibitor exposure in patients with unexplained endocrine and constitutional decline.
Related
- Isolated Adrenocorticotropic Hormone Deficiency Secondary to Pembrolizumab-Induced Hypophysitis: A Case of Life-Threatening Adrenal Crisis in a Patient With Metastatic Melanoma
- Arginine vasopressin deficiency following pembrolizumab-induced hypophysitis: a case report and review of the literature
- Outcomes in KEYNOTE-355 after chemotherapy discontinuation before pembrolizumab discontinuation and with immune-mediated adverse events
- Discontinuation of statins for primary prevention of atherosclerotic cardiovascular disease in adults aged 75 years or older (SAGA/SITE): a multicentre, open-label, pragmatic, non-inferiority randomised trial
- Case Report: Immune checkpoint inhibitor–induced hypophysitis presenting as acute paralytic ileus mimicking mechanical bowel obstruction in a patient affected by advanced non-small cell lung cancer
BibTeX
@article{adhikari2026probable,
title = {{Probable Hypophysitis Recognized More Than Two Years After Pembrolizumab Discontinuation}},
author = {Bibek Adhikari and Sushil Rayamajhi and Sneha Dhakal},
journal = {Cureus},
year = {2026},
month = sep,
doi = {10.7759/cureus.117267},
url = {https://europepmc.org/article/PMC/PMC13722840},
note = {CC BY},
}
RIS
TY - JOUR
TI - Probable Hypophysitis Recognized More Than Two Years After Pembrolizumab Discontinuation
AU - Bibek Adhikari
AU - Sushil Rayamajhi
AU - Sneha Dhakal
PY - 2026
DA - 2026/09/30
JO - Cureus
DO - 10.7759/cureus.117267
UR - https://europepmc.org/article/PMC/PMC13722840
AB - Immune checkpoint inhibitor-associated hypophysitis is an uncommon but clinically important endocrine immune-related adverse event. We report a 70-year-old man with a history of non-small cell lung cancer previously treated with approximately two years of pembrolizumab, with his last dose administered approximately 28 months before presentation. He developed progressive fatigue, anorexia, hypotension, functional decline, and confusion and was subsequently hospitalized with multifocal pneumonia and septic shock. Although the infection and hemodynamic instability improved, encephalopathy, weakness, poor oral intake, and dysphagia persisted. Brain magnetic resonance imaging demonstrated new pituitary enlargement compared with imaging obtained approximately three months earlier. Dedicated pituitary imaging showed enlargement measuring approximately 1.5 × 2.0 cm without definite differential enhancement to suggest a pituitary adenoma. Endocrine testing demonstrated a cortisol level of 3.3 µg/dL with an inappropriately low adrenocorticotropic hormone level of 6.5 pg/mL, free thyroxine of 0.36 ng/dL with thyroid-stimulating hormone of 2.0 µIU/mL, suppressed gonadotropins, and testosterone <10 ng/dL, supporting central adrenal insufficiency and central hypothyroidism with marked gonadal-axis suppression. Cerebrospinal fluid cytology and paraneoplastic studies were unrevealing. The patient was treated with hydrocortisone before thyroid hormone replacement and subsequently showed progressive improvement in mental status, oral intake, and participation in rehabilitation. This case highlights that pituitary immune-related adverse events may be recognized long after pembrolizumab discontinuation and emphasizes the importance of considering prior immune checkpoint inhibitor exposure in patients with unexplained endocrine and constitutional decline.
SN - 2168-8184
ER -