Endocrine Abstracts

Introduction: Immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death ligand 1, and its ligand (PD-1/PD-L1) have become the current standard of care for many cancers. The mechanism of action of these drugs results in some new types of adverse events related to the immune system, most frequently involving the pituitary and thyroid glands.

Case report: We present a case of mixed hypothyroidism (primary and secondary) induced by Durvalumab (PD-L1 inhibitor) that is associated with immune-mediated endocrinopathies. A 64-years female, ex-chronic smoker with a medical history since March 2022 of small cell lung carcinoma of the left superior lobe with secondary cerebral, peritoneal, and lymphatic involvement, has been transferred in October 2023 from the oncology department to the endocrinology ward for facial and bilateral leg edema, fatigue, and shortness of breath. The patient was started on Durvalumab in 04/2022 after chemotherapy and radiation treatment. Physical examination showed facial, bilateral leg edema, hoarse voice, slurred speech, and bradypsyhia. She was afebrile, normotensive, and bradycardic. Laboratory analysis detected mildly elevated TSH=9.21 uUI/ml with undetectable free T4 levels (0.1 ng/ml-n=0.8-1.7). Further investigation revealed normal prolactin levels (17.1 ng/ml-n=4.79-23.3) and normal corticotrope (cortisol=10.1 ugdl-n=4.82-19.5; ACTH=14.16 pg/ml -N:7.2-63.3) and somatotropic axes. The pituitary gonadotropin levels indicated menopause, consistent with age. Ultrasonography showed a hypoechoic shrunken thyroid gland consistent with chronic autoimmune thyroiditis. Thus far, thyroid antibody tests were negative. Based on laboratory tests, thyroid ultrasound findings, and clinical symptoms, the patient was diagnosed with severe hypothyroidism of mixed etiology (primary and secondary) associated with Durvalumab, and treatment with levothyroxine (1 mg) has been initiated. Symptoms worsened after initiating treatment with levothyroxine, leading to suspicion of secondary adrenal insufficiency. We didn’t perform stimulated tests for adrenal insufficiency in the acute phase and we preferred to initiate GC therapy replacement, following to be retested after treating thyroid insufficiency. Hydrocortisone hemisuccinate IV was initiated for 2 days with the improvement of symptoms. After two days, HC was switched to prednisone (1 mg/day), and the levothyroxine treatment was gradually increased to 1 mg/day. Follow-up after 2 months was recommended.

Conclusion: The case described the potential complications associated with the PD-L1 inhibitor Durvalumab, in the context of mixed hypothyroidism. Thyroid dysfunction occurs primarily with PD-1/PD-L1 blockade, and the pattern of inflammatory, destructive thyroiditis is observed, which evolves into hypothyroidism. In a minority of cases, central hypothyroidism can develop (TSH deficiency), mostly along with ACTH deficiency which should not be missed. Prompt management is crucial for mitigating adverse events.