Endocrine Abstracts

JOINT1558

Introduction: In recent years, immune checkpoint inhibitors (ICI) have emerged as a powerful innovative therapeutic strategy in the treatment of various types of cancer. They exert their effect by targeting the immune response towards malignant cells, blocking the usual inhibitory pathways of T-cell regulation, thereby allowing T-cell mediated destruction of cancer cells. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its associated ligand (PD-L1) are major immune checkpoints that serve as targets for inhibition.

Case report: A male with known type 2 diabetes mellitus on treatment with metformin, SGLT-2 inhibitors, and GLP-1 receptor agonists, was diagnosed with poorly differentiated non-small cell lung carcinoma (T2N3M0) at 45 years of age. After chemotherapy and radiotherapy, immunotherapy with Ipilimumab (CTLA-4 inhibitor) and Nivolumab (PD-L1 inhibitor) was initiated. After the 5th cycle of immunotherapy, laboratory and imaging findings indicated autoimmune thyroiditis with hormonal constellation suggestive of secondary hypothyroidism (TSH 0.818 mIU/L; FT4 6.7 pmol/L; anti-TPO 68.97 IU/ml (<12)). Levothyroxine treatment was started with gradual dose titration up to 100 mg. After the 6th cycle of immunotherapy, the patient reported general fatigue, easy tiring with minimal physical effort, and dizziness. Laboratory tests revealed evidence of immune-mediated hepatitis and hypoglycemia, and hormonal analysis showed uncontrolled hypothyroidism and secondary hypocorticism, but with no data of hypogonadism and hyposomatotropism (ACTH <5.00 pg/ml, Cortisol 08:00h: 22.22 nmol/L; TSH 61.05 uIU/ml, FT4 5.69 pmol/L; LH 8.38 mIU/ml; FSH 6.48 mIU/ml; Total testosterone 12.5 nmol/L; Growth hormone 0.27 ng/ml (0.05 - 3.0); IGF-I 154.0 ng/ml (48 - 209)). MRI of the pituitary shows mild general non-homogeneity of the gland, suggestive of hypophysitis. Treatment with intravenous methylprednisolone at a dose of 20 mg daily was initiated until clinical stabilization, followed by oral hydrocortisone with gradual dose reduction to 20 mg daily. Additionally, after initiating corticosteroid replacement therapy, the dose of Levothyroxine was increased to 150 mg and switched to liquid form.

Conclusions: Immune checkpoint inhibitors have rapidly become an integral part of many cancer treatment regimens. These new drugs can significantly improve survival rates for several forms of cancer. However, these benefits come with the cost of autoimmune side-effects (especially when immunotherapy is combined) that affect a number of tissues, including the endocrine glands. Keywords: cancer, checkpoint inhibitors, autoimmune side-effects, endocrine glands.