Endocrine Abstracts

Introduction: Endocrinopathies are one of the most common autoimmune adverse events (AIAEs) causing severe toxic complications during the use of checkpoint inhibitor therapy (CPI).

Clinical Case: A patient with complaints of hyperpigmentation of the skin of the back in August 2022 an excisional biopsy was performed and pigmented epithelioid cell melanoma with tumor growth along the resection margin was verified. In December 2022, CT revealed metastases in the right axillary and supraclavicular lymph nodes, the right lung, the right scapula and the right groin area - mts skin melanoma of the back T4aN3M1 b (R1), and therefore therapy with pembrolizumab (a human monoclonal antibody IgG4 kappa that selectively blocks PD-1) was initiated. In August 2023 with manifestations of asthenic syndrome, dyspepsia (nausea, vomiting), an increase in venous blood glucose to 14-16 mmol/l, an endocrinologist at the place of residence diagnosed type 2 diabetes mellitus and recommended taking metformin and glimepiride. Due to the lack of improvement in general well-being the patient was hospitalized to an emergency department with diabetic ketoacidosis where insulin therapy was initiated (insulin glargine 14 units at night, short-acting insulin 3-4 units before main meals) with subsequent stabilization of the condition, but continuous persistence of asthenia and hypotension\. Subsequently, based on low values of ACTH and blood cortisol as well as 24-hour urine cortisol, secondary adrenal insufficiency was identified, for which hydrocortisone was prescribed. Due to the lack of compensation for adrenal insufficiency, the drug was replaced with prednisolone at a dose of 7.5 mg→5 mg/day. Later, due to severe hypotension on either glucocorticoid therapy (BP 80/40 mm Hg), fludrocortisone 0.05→0.1 mg was added to therapy. In November 2023 during hospitalization in the endocrinology hospital, his lab tests showedlow levels of C-peptide – 0.0035 ng/ml (1.1-4.4), insulin – 1.42 mU/ml (2.6-24.9), absense of antibodies to GAD – 0.2 U/ml (0-10), insulin – 2.68 U/ml (0-10), tyrosine phosphatase <1 U/ml (0-10) and positive islet cell antibodies – 2.6 U/ml (0-1). Insulin therapy was optimized, glycemic levels were stabilized within individual target values. According to hormonal analysis: ACTH – 2.77 pg/ml (7.2-63.3), cortisol – 41.42 nmol/l (171-536). MRI of the brain visualized heterogeneity of the adenohypophysis and the developing “empty” sella turcica.

Conclusion: Considering the etiological features of the occurrence of AIAEs during the use of CPI, a multidisciplinary approach is required for comprehensive and effective management of patients, minimizing complications and fully implement the therapeutic potential of this treatment method.