{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:17:45Z","timestamp":1784557065087,"version":"3.55.0"},"reference-count":34,"publisher":"Bioscientifica","license":[{"start":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T00:00:00Z","timestamp":1521590400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/deed.en_GB"}],"content-domain":{"domain":["edm.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,3,21]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47\u2009mmol\/L, blood ketones of 7.5\u2009mmol\/L, pH of 6.95 and bicarbonate of 6.6\u2009mmol\/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1\u2009mmol\/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12\u2009kIU\/L (0\u20135\u2009kU\/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18\u2009U\/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy.<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Learning points:<\/jats:title>\n                    <jats:list list-type=\"bullet\">\n                      <jats:list-item>\n                        <jats:p>Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.<\/jats:p>\n                      <\/jats:list-item>\n                      <jats:list-item>\n                        <jats:p>Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.<\/jats:p>\n                      <\/jats:list-item>\n                    <\/jats:list>\n                  <\/jats:sec>","DOI":"10.1530\/edm-18-0111","type":"journal-article","created":{"date-parts":[[2018,3,21]],"date-time":"2018-03-21T09:53:52Z","timestamp":1521626032000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-2","source":"Crossref","is-referenced-by-count":13,"title":["Nivolumab-induced fulminant diabetic ketoacidosis followed by thyroiditis"],"prefix":"10.1530","volume":"2018","author":[{"given":"Ploutarchos","family":"Tzoulis","sequence":"first","affiliation":[{"name":"1Department of DiabetesThe Whittington Hospital, Whittington Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W","family":"Corbett","sequence":"additional","affiliation":[{"name":"2Department of MedicineImperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarupini","family":"Ponnampalam","sequence":"additional","affiliation":[{"name":"1Department of DiabetesThe Whittington Hospital, Whittington Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elly","family":"Baker","sequence":"additional","affiliation":[{"name":"1Department of DiabetesThe Whittington Hospital, Whittington Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Heaton","sequence":"additional","affiliation":[{"name":"1Department of DiabetesThe Whittington Hospital, Whittington Health NHS Trust, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triada","family":"Doulgeraki","sequence":"additional","affiliation":[{"name":"3Medical SchoolUniversity of Athens, Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Stebbing","sequence":"additional","affiliation":[{"name":"4Department of Surgery and CancerImperial College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref91","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1084\/jem.20022125","article-title":"The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice","volume":"198","year":"2003","journal-title":"Journal of Experimental Medicine"},{"key":"ref171","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/s40425-017-0245-2","article-title":"Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer","volume":"5","year":"2017","journal-title":"Journal for ImmunoTherapy of Cancer"},{"key":"ref41","first-page":"1","article-title":"Precipitation of autoimmune diabetes 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