Reactions 2001, p219 - 30 Mar 2024 1

Multiple drugs S

Immune-mediated euglycaemic diabetic ketosis, adrenal Insufficiency, drug misuse and treatment non-
compliance
A 74-year-old man developed immune-mediated euglycaemic diabetic ketosis during treatment with canagliflozin and
following dulaglutide misuse and treatment non-compliance. Additionally, he developed adrenal Insufficiency during treatment with
nivolumab and ipilimumab for non-small cell lung cancer [NSCLC; routes and durations of treatments to reaction onsets not stated;
not all dosages stated].
The man suffering from type 2 diabetes mellitus at the age of 58 years. He had been receiving canagliflozin 100 mg/day. His other
medications included basal-bolus unspecified insulin, glimepiride, metformin and dulaglutide 0.75 mg/ week.His glucose control
was poor. Based on the findings, he had a normal to mild decrease in insulin secretion. He was diagnosed with NSCLC. He
received chemotherapy with carboplatin and paclitaxel.Nivolumab and ipilimumab were given as maintenance therapy. During 3rd
cycle, he developed fatigue, excessive daytime sleepiness and appetite loss. After 13 days, his symptoms further worsened. He self-
discontinued dulaglutide (intentional drug misuse and treatment-non-compliance). On day 19th of 3rd cycle, he reffered
to emergency room with a high fever and a depressed level of consciousness with Glasgow Coma Scale (E4V3M5). On admission,
his vitals were as follow: BP was 118/79 mm Hg, pulse rate was 130/min and respiratory rate was 24/min and percutaneous oxygen
saturation was 97% on room air. Laboratory tests revealed the following: serum glucose was 121 mg/dL; HbA1c was 9.3%;
acetoacetic acid was 2076 μmol/L; β-hydroxybutyric acid was 4995 μmol/L; urinary ketone body was (3+); venous blood gas with a
pH was 7.40 and C-reactive protein was 16.6 mg/dL. Non-contrast CT scan did not reveal any infection. Based on the various
findings, he was diagnosed with canagliflozin and immunotherapy-related euglycaemic diabetic ketosis. The euglycaemic diabetic
ketosis also considered due to self-discontinuation of dulaglutide (intentional drug misuse and treatment non-compliance).
The man started receiving IV rehydration containing glucose and insulin for euglycaemic diabetic ketosis. However, he
developed severe unconsciousness and hypovolemic shock on day 3 of hospitalisation. Hence, he was suspected of euglycaemic
diabetic ketosis followed by adrenal insufficiency. He started receiving hydrocortisone therapy and his clinical condition drastically
improved. Urine analysis showed negative results for ketone bodies on day 7 of hospitalisation. A rapid ACTH test. A corticotropin-
releasing hormone loading test confirmed the diagnosis of adrenal insufficiency. His euglycaemic diabetic ketosis
and ACTH deficiency was graded as grade 4 immune-related adverse events. On day 23, he was discharged on hydrocortisone
supplementation. His diabetes was well-controlled on insulin and unspecified glucagon-like peptide-1 receptor agonist therapy.
Shibasaki S, et al. A Case of Type 2 Diabetes Mellitus with Lung Cancer Suffered from Euglycemic Diabetic Ketosis Accompanied by Adrenal Insufficiency after Immune
Checkpoint Inhibitors. Case Reports in Endocrinology 2024: Jan 2024. Available from: URL: https://dx.doi.org/10.1155/2024/9982174 803849767