{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:59:32Z","timestamp":1790657972197,"version":"4.1.0"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) have significantly improved outcomes in advanced non-small cell lung cancer (NSCLC) but may induce immune-related adverse events (irAEs), including hypophysitis. Although endocrine irAEs usually present with nonspecific constitutional symptoms, atypical manifestations may delay diagnosis and expose patients to unnecessary invasive procedures. We report the case of a 76-year-old man with metastatic NSCLC receiving first-line nivolumab, ipilimumab, carboplatin, and pemetrexed who developed profound asthenia, altered mental status, bilious vomiting, and severe gastrointestinal dilation suggestive of acute mechanical bowel obstruction after two treatment cycles. Computed tomography demonstrated marked gastric and intestinal distension, and surgical management was initially considered. Endocrine evaluation subsequently revealed central hypothyroidism and secondary adrenal insufficiency, consistent with ICI-induced hypophysitis. Prompt initiation of physiological hormone replacement with intravenous hydrocortisone followed by thyroid hormone supplementation resulted in rapid neurological and systemic recovery, complete restoration of gastrointestinal motility, radiological resolution of bowel dilatation, and avoidance of surgery. Follow-up imaging also demonstrated a partial tumor response, which has remained durable for more than two years without additional anticancer treatment while the patient continues long-term endocrine replacement therapy. This case expands the clinical spectrum of ICI-induced hypophysitis by describing an unusual presentation as acute paralytic ileus mimicking mechanical bowel obstruction. It underscores the importance of maintaining a high index of suspicion for endocrine irAEs in patients receiving ICIs who develop unexplained multisystem deterioration or apparent surgical abdomen. Early hormonal assessment and timely replacement therapy can be lifesaving, prevent unnecessary surgical interventions, and allow optimal multidisciplinary management without compromising oncologic outcomes.<\/jats:p>","DOI":"10.3389\/fonc.2026.1934901","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:47:41Z","timestamp":1790657261000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Immune checkpoint inhibitor\u2013induced hypophysitis presenting as acute paralytic ileus mimicking mechanical bowel obstruction in a patient affected by advanced non-small cell lung cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Alice","family":"Baggi","sequence":"first","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Adriani","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca Carlofrancesco","family":"Ammoni","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgia","family":"Carola","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Morocutti","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara Colombo","family":"Zefinetti","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Marzani","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Berruti","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]},{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Grisanti","sequence":"additional","affiliation":[{"name":"Medical Oncology, Comprehensive Cancer Center, Azienda Socio-Sanitaria Territoriale (ASST) Spedali Civili","place":["Brescia, Italy"]},{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia","place":["Brescia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1811169","article-title":"The application and challenges of immune checkpoint inhibitors in lung cancer therapy","volume":"17","author":"Li","year":"2026","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-021-00484-3","article-title":"Endocrine toxicities of immune checkpoint inhibitors","volume":"17","author":"Wright","year":"2021","journal-title":"Nat Rev Endocrinol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0218-0","article-title":"Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance","volume":"16","author":"Martins","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12103468","article-title":"Progress and challenges of immune checkpoint inhibitor-induced hypophysitis","volume":"12","author":"Chen","year":"2023","journal-title":"J Clin Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad670","article-title":"Risk and incidence of endocrine immune-related adverse effects under checkpoint inhibitor mono- or combination therapy in solid tumors: A meta-analysis of randomized controlled trials","volume":"109","author":"Vardarli","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-015-0301-z","article-title":"Ipilimumab-induced hypophysitis: review of the literature","volume":"38","author":"Araujo","year":"2015","journal-title":"J Endocrinol Invest"},{"key":"B7","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1001\/jamaoncol.2017.3064","article-title":"Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens","volume":"4","author":"Barroso-Sousa","year":"2018","journal-title":"JAMA Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2022.7098","article-title":"Hypophysitis and secondary adrenal insufficiency from immune checkpoint inhibitors: Diagnostic challenges and link with survival","volume":"21","author":"Johnson","year":"2023","journal-title":"J Natl Compr Cancer Network"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2023.11.003","article-title":"Primary adrenal insufficiency induced by immune checkpoint inhibitors: biological, clinical, and radiological aspects","volume":"50","author":"Martella","year":"2023","journal-title":"Semin Oncol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1007\/s12020-024-03718-2","article-title":"Thyroid disorders induced by immune checkpoint inhibitors","volume":"85","author":"Karaviti","year":"2024","journal-title":"Endocrine"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.50799","article-title":"Hypothyroidism presenting as adynamic ileus mimicking a mechanical small bowel obstruction: A diagnostic and management dilemma","volume":"15","author":"Kubiszewski","year":"2023","journal-title":"Cureus"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.2174\/1871530320666200506075958","article-title":"Characteristics of patients with hypopituitarism having onset symptoms of pseudo-intestinal obstruction: A case report","volume":"21","author":"Yuan","year":"2021","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4236\/crcm.2013.22029","article-title":"Adrenal insufficiency and bowel obstruction: An overlooked association","volume":"2","author":"Kunjal","year":"2013","journal-title":"Case Rep Clin Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1530\/EC-25-0697","article-title":"A systematic review of ipilimumab-induced hypophysitis","volume":"15","author":"Kim","year":"2026","journal-title":"Endocr Connect"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.10.001","article-title":"Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"33","author":"Haanen","year":"2022","journal-title":"Ann Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2024.0057","article-title":"NCCN Guidelines\u00ae Insights: Management of immunotherapy-related toxicities, Version 2.2024","volume":"22","author":"Thompson","year":"2024","journal-title":"J Natl Compr Cancer Network"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2025.2453829","article-title":"High-dose glucocorticoid treatment vs. glucocorticoid replacement in immune checkpoint inhibitor associated hypophysitis (CORTICI): an open, randomised controlled trial","volume":"57","author":"Theiler-Schwetz","year":"2025","journal-title":"Ann Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1281645","article-title":"Immune-related adverse events and their effects on survival outcomes in patients with non-small cell lung cancer treated with immune checkpoint inhibitors: a systematic review and meta-analysis","volume":"14","author":"Liang","year":"2024","journal-title":"Front Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1402017","article-title":"Association between immune-related adverse events and prognosis in patients with advanced non-small cell lung cancer: a systematic review and meta-analysis","volume":"14","author":"Ma","year":"2024","journal-title":"Front Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2023.100787","article-title":"Immune-related adverse events as potential surrogates of immune checkpoint inhibitors\u2019 efficacy: a systematic review and meta-analysis of randomized studies","volume":"8","author":"Amoroso","year":"2023","journal-title":"ESMO Open"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1934901\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:48:07Z","timestamp":1790657287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1934901\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,29]]},"references-count":20,"alternative-id":["10.3389\/fonc.2026.1934901"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1934901","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,29]]},"article-number":"1934901"}}