SUN-354 - Hypothyroidism and Extreme Hyperlipidemia Following Nivolumab Therapy: A Case Report

Introduction:
Incidence rates for hypothyroidism in patients treated with nivolumab range from 8-15%, with onset typically occurring within the first few months of starting therapy (1,2). The relationship between hypothyroidism and hyperlipidemia is well established and is mediated by reduced LDL receptor–dependent clearance and altered cholesterol metabolism (3). However, this case is notable for an extreme rise in LDL from 163 to 418 mg/dL following nivolumab, an exceptional degree of dyslipidemia.

Case:
A 36-year-old man with metastatic melanoma was started on adjuvant nivolumab. Family history was notable for hyperlipidemia in his father and paternal grandfather. Fifteen days after his fifth cycle, he developed fatigue, polydipsia, blurred vision, and a 10-lb weight loss. Labs revealed glucose >500 mg/dL, A1c 9%, and metabolic acidosis, and he was admitted for DKA due to immunotherapy-induced type 1 diabetes. Nivolumab was discontinued.

Eight months later, he developed fatigue, constipation, and facial edema. Labs demonstrated TSH 245 mIU/L, and levothyroxine was initiated with symptom improvement. Concurrent labs showed marked hypercholesterolemia: TC 589 mg/dL, LDL 418 mg/dL, HDL 118 mg/dL, and TG 240 mg/dL. His baseline LDL prior to immunotherapy was 163 mg/dL, consistent with underlying polygenic hypercholesterolemia. He was started on a high-intensity statin.

Discussion:
Immune checkpoint inhibitors such as nivolumab enhance antitumor immunity by blocking PD-1–mediated T-cell inhibition but may also provoke autoimmune endocrine injury. Thyroiditis progressing to hypothyroidism is among the most common endocrine toxicities. In this patient, the temporal association between a profoundly elevated TSH and extreme LDL elevation strongly suggests immune-related hypothyroidism as the precipitating factor that amplified an underlying genetic susceptibility. This case highlights the potential for immune checkpoint inhibitor–related endocrine toxicity to cause secondary metabolic derangements and emphasizes the importance of routine monitoring of thyroid function and lipid profiles in patients receiving or previously exposed to PD-1 inhibitors.

References:
1. A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated With Immune Checkpoint Inhibitors.
de Filette J et al.
Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme. 2019;51(3):145-156. doi:10.1055/a-0843-3366.

2. Clinical determinants and outcomes of hypothyroidism in immune checkpoint inhibitor (ICI) therapy.
Syed F et al.
Journal of Clinical Oncology. 2025;43(Suppl 16):e14623. doi:10.1200/JCO.2025.43.16_suppl.e14623.

3. Hyperlipidemia and Hypothyroidism.
Su X et al.
Clinica Chimica Acta; International Journal of Clinical Chemistry. 2022;527:61-70. doi:10.1016/j.cca.2022.01.006.

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