Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICI) are anti-cancer drugs associated with adverse events that results from releasing the immune system against self-antigens while attacking cancer cells. Multiple endocrine dysfunctions have been associated with administration, including hypophysitis, thyroid disorders and diabetes.

Case report: We report the case of a 57-year-old female, diagnosed with melanoma of the left arm Barlow Depth 2 mm, receiving treatment with combined therapy (nivolumab and ipilimumab) from March 2023, who presented in the Emergency Department with nausea, vomiting, and low blood pressure (BP 90/70 mmHg). Blood tests showed TSH 33.6 mUi/ml (<3.6), ft4 0.2 ng/ml (0.8-1.7), ACTH <1.5 pg/ml, plasmatic cortisol level 8 am 0.6 mg/dl. Pituitary MRI showed no tumoral mass and normal visual field. Rapid volemic correction and hemisuccinate hydrocortisone iv were started with improvement of symptomatology. After two days, oral treatment with prednisone and levothyroxine substitution treatment, with immediate improvement. After four months, the patient presents to the Emergency Department for vomiting and diarrhea. Blood tests showed increased glucose level (523 mg/dl), ketoacidosis (pH 7.1, HCO3=9.3 nmol/l, Peptid C <0.03 ng/ml, HBA1c 9%, anti-GAD antibodies < 5 UI/ml). Insulinotherapy was initiated, with rapid improvement of her state.

Conclusion : ICI-related fulminant diabetes is associated with an incidence of <1% in PD1 inhibitors. Rapid elevation of HBA1c and the presence of ketoacidosis, even in the presence of negative anti-GAD antibodies in this patient, were suggestive of ICI diabetes. The particularity of the case is the presence of secondary cortical insufficiency, primary hypothyroidism, and diabetes induced by ICI.