Diabetic ketoacidosis following immunotherapy for lung cancer

A man in his sixties was treated with pembrolizumab for non-small cell lung cancer and developed diabetic ketoacidosis. Pembrolizumab is a monoclonal antibody approved for treating several types of cancer. Diabetes mellitus type 1 is a rare adverse reaction to immunotherapy for cancer, and in the following we describe the first case reported in Norway of diabetic ketoacidosis resulting from this treatment.

A man in his sixties was admitted to the Medical Department with suspected sepsis after being found with altered consciousness and tachypnoea with a respiratory rate of 33 breaths/min. On admission he was confused and had Kussmaul respiration with ketone odour and a blood sugar concentration of 69.7 mmol/l. His blood pressure was 172/97 mm Hg, pulse 99 beats/min. and rectal temperature 36.8 °C. Laboratory tests showed pH 7.18 (reference range 7.37–7.45), pCO₂ 2.5 kPa (4.7–6.0 kPa), bicarbonate 7 mmol/l (22–27 mmol/l), sodium 118 mmol/l (136–146 mmol/l), potassium 8.2 mmol/l (3.5–5.0 mmol/l), creatinine 141 μmol/l (60–105 μmol/l), CRP 33 (< 5), Hb 12.3 g/dl (13.4–17 g/dl) and leukocytes 17.5 ∙ 10⁹/l (3.5–11 ∙ 10⁹/l). His pancreatic amylase level was normal (45 U/l, reference range 10–65 U/l), while his lipase level was elevated (749 U/l, < 300). Urine dipsticks showed 3+ for ketones. In light of clinical examinations and supplementary tests, we concluded that the most probable diagnosis was ketoacidosis, and not sepsis. Blood cultures were therefore not ordered.

The patient was treated with fluids and an insulin drip in accordance with the department's procedure for treating ketoacidosis. His blood sugar concentration fell nicely with satisfactory correction of the acidosis. A switch to subcutaneous insulin treatment was possible after a while. On discharge the patient was taking 55 U insulin degludec once a day and 15 U insulin aspart with meals. Three months after the hospitalisation in question, the patient was well regulated on one dose of insulin degludec daily and insulin aspart with meals.

Tests associated with type 1 diabetes, such as s-anti-GAD, s-anti-IA2 and s-insulin antibody, were all negative. C-peptide level measured five weeks after hospitalisation was under 7 pmol/l (370–1 470 pmol/l). HbA1c on admission was 8.4 %. Thyroid tests were normal.

It emerged that the patient had received a diagnosis of adenocarcinoma in the right lung about two months earlier. PET-CT had showed signs of several metastases, and a lung biopsy had detected PD-L1 expression in 95 % of the cells. He had no known diabetes and HbAlc% was 5.7 % at the time. Treatment with pembrolizumab 200 mg had started. The first dose had been administered a month earlier, and the second dose 16 days before the hospitalisation in question with ketoacidosis. After radiotherapy for the lung tumour he will continue on pembrolizumab.