Thomsen Marco Juul, Andersen Stine Linding, Torp Nanna Maria Uldall, Andersen Stig, Carlé Allan
Department of Clinical Biochemistry, Aalborg University Hospital, Hobrovej 18-22, Aalborg, 9000, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, 9000, Denmark.
Thyroid Res. 2025 Jul 15;18(1):35. doi: 10.1186/s13044-025-00254-7.
Immune checkpoint inhibitor (ICI) therapy is used in the management of advanced malignancies. Thyroid function abnormalities have been reported, but more evidence is needed to substantiate the subtypes and course of thyroid disease associated with this treatment.
A 51-year-old woman with metastatic pancreatic cancer and no previous history of autoimmune disease was referred to the Endocrine Department six days after the initiation of combined treatment with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). At the initial endocrinologic assessment, the patient had biochemical overt thyrotoxicosis with suppressed thyroid stimulating hormone < 0.01 mIU/L (reference range (RR), 0.3-4.5 mIU/L), elevated total thyroxine (TT4) > 309 nmol/L (> 24.0 µg/dL) (RR, 60-140 nmol/L; 4.7-10.9 µg/dL), and total triiodothyronine (TT3) 7.0 nmol/L (454.5 ng/dL) (RR, 1.1-2.5 nmol/L; 71.4-162.3 ng/dL). Despite marked biochemical thyrotoxicosis, the patient presented with few symptoms. TSH-receptor antibodies (TRAb) were negative, as were thyroid peroxidase antibodies, whereas elevated levels of thyroglobulin antibodies were found. Thyroid ultrasound revealed an enlarged, heterogeneous hypoechoic gland with increased vascularity. High-dose antithyroid drug (ATD) therapy were followed by a decline in thyroid hormone levels (after one week of treatment: TT4: >309 nmol/L (> 24.0 µg/dL); TT3: 1.8 nmol/L (116.9 ng/dL); after two weeks: TT4: 164 nmol/L (12.7 µg/dL); TT3: 0.9 nmol/L (58.4 ng/dL)). After five weeks, the patient developed biochemical hypothyroidism. Thus, ATD therapy was discontinued, and levothyroxine was initiated.
This case report illustrates with a short time frame from the initiation of ICI therapy the onset of thyrotoxicosis, followed by the development of thyroid insufficiency. This case highlights the challenges associated with subtyping the cause of thyroid dysfunction in patients treated with ICIs. Further, this case highlights the importance of clinical awareness and close monitoring of thyroid function in patients receiving immunotherapy.
免疫检查点抑制剂（ICI）疗法用于晚期恶性肿瘤的治疗。已有甲状腺功能异常的报道，但需要更多证据来证实与该治疗相关的甲状腺疾病亚型和病程。
一名51岁转移性胰腺癌女性，既往无自身免疫性疾病史，在开始使用伊匹单抗（抗CTLA-4）和纳武单抗（抗PD-1）联合治疗6天后转诊至内分泌科。在初始内分泌评估时，患者出现生化显性甲状腺毒症，促甲状腺激素水平降低<0.01 mIU/L（参考范围（RR），0.3 - 4.5 mIU/L），总甲状腺素升高（TT4）>309 nmol/L（>24.0 μg/dL）（RR，60 - 140 nmol/L；4.7 - 10.9 μg/dL），总三碘甲状腺原氨酸（TT3）7.0 nmol/L（454.5 ng/dL）（RR，1.1 - 2.5 nmol/L；71.4 - 162.3 ng/dL）。尽管有明显的生化甲状腺毒症，但患者症状较少。促甲状腺激素受体抗体（TRAb）为阴性，甲状腺过氧化物酶抗体也为阴性，而甲状腺球蛋白抗体水平升高。甲状腺超声显示甲状腺肿大、不均匀低回声，血管增多。高剂量抗甲状腺药物（ATD）治疗后甲状腺激素水平下降（治疗1周后：TT4：>309 nmol/L（>24.0 μg/dL）；TT3：1.8 nmol/L（116.9 ng/dL）；2周后：TT4：164 nmol/L（12.7 μg/dL）；TT3：0.9 nmol/L（58.4 ng/dL））。5周后，患者出现生化性甲状腺功能减退。因此，停用ATD治疗，开始使用左甲状腺素。
本病例报告显示，从ICI治疗开始后的短时间内，先是出现甲状腺毒症，随后发展为甲状腺功能不全。该病例凸显了对接受ICI治疗的患者甲状腺功能障碍原因进行亚型分类的挑战。此外，该病例强调了临床意识以及对接受免疫治疗患者密切监测甲状腺功能的重要性。
