Carril-Ajuria Lucia, Jiménez-Aguilar Elisabeth, Gómez-Martín Carlos, Díaz-Pedroche Carmen
Medical Oncology Department, Hospital Universitario 12 de Octubre and Instituto de Investigación i+12, Madrid, Spain.
Internal Medicine Department, Hospital Universitario 12 de Octubre, Madrid, Spain.
J Med Case Rep. 2018 Sep 4;12(1):246. doi: 10.1186/s13256-018-1782-0.
Immunotherapy treatment with immune-checkpoint blockade has become a new paradigm in cancer treatment. Despite its efficacy, it has also given rise to a new class of adverse events, immune-related adverse events, which may affect any organ, including the thyroid and the pituitary.
We present a case of a 77-year-old Caucasian man with metastatic renal cell carcinoma on immunotherapy treatment who was admitted to our hospital with a severe persistent headache of sudden onset. He had been on corticosteroid therapy for 10 days for suspected immune-related thyroiditis. The patient had tachycardia and mild diarrhea, and his thyroid function tests were compatible with subclinical hyperthyroidism with a suppressed thyroid-stimulating hormone level of 0.01 μIU/ml (0.4-4.5), a raised free T4 level of 2.17 ng/dl (0.7-1.9), and a free T3 level of 4.66 pg/ml (2.27-5). Computed tomography and magnetic resonance imaging revealed an enlargement of the pituitary gland compatible with macroadenoma. In the face of a probable immune-related hypophysitis, high-dose corticosteroid treatment was started. A posterior hormonal evaluation revealed secondary hypothyroidism with a suppressed thyroid-stimulating hormone level of 0.11 μIU/ml (0.4-4.5) and low thyroid hormones, a normal free T4 level of 1.02 ng/dl (0.7-1.9), and a low free T3 level of 1.53 pg/ml (2.27-5). These new findings suggested central hypothyroidism possibly due to pituitary apoplexy as a complication of the macroadenoma. Therefore, levothyroxine substitution was started along with the previously started corticosteroid therapy. The patient's headache and asthenia gradually resolved, and after a few days, he was released from the hospital with levothyroxine substitution and corticosteroid tapering.
This case emphasizes the importance of the differential diagnosis when dealing with patients on immune checkpoint inhibitors because other non-immune-related events may present. Our patient was finally diagnosed with immune-related hyperthyroidism and a concurrent pituitary macroadenoma. This case also highlights the importance of a prompt start of corticosteroid therapy once immune-related adverse events such as hypophysitis are suspected, because otherwise the outcome would be fatal.
免疫检查点阻断免疫疗法已成为癌症治疗的新范例。尽管其疗效显著，但也引发了一类新的不良事件，即免疫相关不良事件，可能影响包括甲状腺和垂体在内的任何器官。
我们报告一例77岁的白人男性，患有转移性肾细胞癌，正在接受免疫治疗，因突然出现严重持续性头痛而入住我院。他因疑似免疫相关甲状腺炎已接受皮质类固醇治疗10天。患者有心动过速和轻度腹泻，其甲状腺功能检查结果与亚临床甲状腺功能亢进相符，促甲状腺激素水平被抑制至0.01 μIU/ml（0.4 - 4.5），游离T4水平升高至2.17 ng/dl（0.7 - 1.9），游离T3水平为4.66 pg/ml（2.27 - 5）。计算机断层扫描和磁共振成像显示垂体增大，符合大腺瘤表现。鉴于可能存在免疫相关垂体炎，开始给予高剂量皮质类固醇治疗。后续的激素评估显示继发性甲状腺功能减退，促甲状腺激素水平被抑制至0.11 μIU/ml（0.4 - 4.5），甲状腺激素水平低，游离T4水平正常为1.02 ng/dl（0.7 - 1.9），游离T3水平低至1.53 pg/ml（2.27 - 5）。这些新发现提示中枢性甲状腺功能减退可能是由于垂体卒中，这是大腺瘤的一种并发症。因此，在继续之前开始的皮质类固醇治疗的同时，开始给予左甲状腺素替代治疗。患者的头痛和乏力逐渐缓解，几天后，他在接受左甲状腺素替代治疗和逐渐减少皮质类固醇剂量后出院。
该病例强调了在处理接受免疫检查点抑制剂治疗的患者时进行鉴别诊断的重要性，因为可能会出现其他非免疫相关事件。我们的患者最终被诊断为免疫相关甲状腺功能亢进并伴有垂体大腺瘤。该病例还突出了一旦怀疑出现如垂体炎等免疫相关不良事件，迅速开始皮质类固醇治疗的重要性，因为否则后果将是致命的。
