Endocrine Abstracts

Background: Immune checkpoint Inhibitors (ICIs) have revolutionized the treatment of vast array of cancers. Despite their efficacy, ICIs can cause various side effects related to the mechanism of action. Immune-related endocrine events (irEEs) are one of the most common immune-related adverse events (irAEs), accounting for 8.1% of all cases. We report two patients with durable responses to ICIs and concurrent serious irEEs.

Case 1: A 58-year-old woman with metastatic non-small cell lung cancer has been receiving nivolumab for 13 months after 4 previous lines of systemic therapy were ineffective. The patient developed primary hypothyroidism after 14 weeks of ICIs (TSH 82 mIU/l, FT4 0.67 pmol/l) and levothyroxine 100 μg/d was prescribed. After 4 weeks, she noted an episode of hypotension (90/60 mmHg), general weakness, nausea and vomiting. Lab tests showed low morning cortisol 2.8 nmol/l, Na 135 mmol/l with high ACTH 827 pg/ml, renin 184 μIU/ml, K 5.1 mmol/l. Primary adrenal insufficiency was diagnosed and all symptoms resolved after hydrocortisone 25 mg/d and fludrocortisone 0.1 mg/d treatment. To date, the patient has received 26 nivolumab infusions 240 mg/2weeks, with complete metabolic response according to 18F-FDG PET/CT.

Case 2: A 55-year-old woman with localized cutaneous melanoma, which was surgically resected and 6 months later recurred with jugular lymph nodes and liver metastases. Combination ICIs therapy was initiated (nivolumab+ipilimumab), then switching to nivolumab, which she has been receiving for 13 months. Within 4 weeks after ICIs were initiated, she noticed frequent episodes of hypoglycemia (up to 3.0 mmol/l), severe weakness, hypotension (80/60 mmHg), nausea and vomiting. Lab tests showed low morning cortisol 6.4 nmol/l, ACTH 2.1 pg/ml, renin 2.78 μIU/ml, Na 124 mmol/l, C-peptide 0.83 ng/ml, insulin 1 μU/ml, TSH 0.12 μIU/ml, FT4 8.98 pmol/l with normal-range K4.27 mmol/l. Central hypothyroidism and adrenal insufficiency were diagnosed. MRI scan identified empty sella. Symptoms of ICI-induced hypophysitis resolved after initiation of hydrocortisone 20 mg/d and levothyroxine 75 μg/d. The patient has received 26 nivolumab infusions 240 mg/2 weeks. Last 18F-FDG PET/CT confirmed complete metabolic response.

Conclusion: Increased overall survival and progression-free survival have been reported in cancer patients with ieEEs. However, causes of this correlation remain unknown, which warrants further research. Our cases demonstrate the importance of vigilant monitoring of endocrinopathies among cancer patients receiving ICIs in order to diagnose life-threatening complications in time.