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Diagnosis and Treatment > Signs and Symptoms

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Ploutarchos Tzoulis Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

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Richard W Corbett Department of Medicine, Imperial College London, London, UK

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Swarupini Ponnampalam Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

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Elly Baker Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

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Daniel Heaton Department of Diabetes, The Whittington Hospital, Whittington Health NHS Trust, London, UK

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Triada Doulgeraki Medical School, University of Athens, Athens, Greece

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Justin Stebbing Department of Surgery and Cancer, Imperial College London, London, UK

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Summary

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 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/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 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/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 U/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.

Learning points:

  • Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.

  • Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.

  • Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.

  • Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.

Taxonomy:
Clinical Overview, Gland/Organ, Pancreas, Thyroid, Topic, Diabetes, Hormone, Insulin, Thyroxine (T4), TSH, Condition/ Syndrome, Adenocarcinoma, Diabetes mellitus type 1, Diabetic ketoacidosis, Hyperglycaemia, Hypothyroidism, Metabolic acidosis, Metastatic carcinoma, Thyroiditis, Patient Demographics, Age, Adult, Gender, Female, Ethnicity, White, Country of Treatment, United Kingdom, Diagnosis and Treatment, Signs and Symptoms, Aggression, Agitation, Cold intolerance, Confusion, Diabetes mellitus type 1, Diabetic ketoacidosis, Fatigue, Hyperglycaemia, Hypothyroidism, Metabolic acidosis, Polydipsia, Polyuria, Weight gain, Investigation, Bicarbonate, C-peptide (blood), C-reactive protein, Creatinine (serum), FT4, GADA, Glucose (blood), Haemoglobin A1c, Ketones (plasma), TSH, Urea and electrolytes, White blood cell count, Medication, Insulin, Insulin Aspart, Insulin glargine, Levothyroxine, Nivolumab, Saline, Related Disciplines, Oncology, Publication Details, Case Report Type, Unusual effects of medical treatment
DOI:
https://doi.org/10.1530/EDM-18-0111
Volume/Issue:
Volume 2018: Issue 1
Open access