Bexarotene-induced central hypothyroidism (CH), for which levothyroxine (LT4) replacement is recommended, has been shown to be caused by pituitary but not hypothalamic disorder experimentally, though the underlying mechanism in humans remains unclear. Here, the pathophysiology of bexarotene-induced CH was examined using a TRH stimulation test in cutaneous T-cell lymphoma (CTCL) patients. In this retrospective longitudinal observational study, serum TSH and free T4 (F-T4) levels were measured in 10 euthyroid patients with CTCL during 24 weeks of bexarotene treatment. TRH stimulation testing was performed following CH diagnosis, with LT4 replacement dosage adjusted to maintain F-T4 at the pre-treatment level. After one week of bexarotene administration, all 10 patients developed CH, based on combined findings of low or low-normal F-T4 with low or normal TSH levels. TSH peak response after a stimulation test at one week was reached at 30 minutes. However, that was <4 μIU/mL in all patients, indicating a blunted though not exaggerated and delayed TSH response. In eight who continued bexarotene for 24 weeks, median LT4 replacement dosage was 125 (range, 75–150) μg/day. TSH level at 30 as well as 15, 60, 90, and 120 minutes after TRH stimulation was significantly correlated with LT4 replacement dosage (ρ = –0.913, p = 0.002), whereas TSH and F-T4 basal levels at one week were not. These results suggest that pituitary hypothyroidism is responsible for bexarotene-induced CH, while TSH levels after TRH stimulation precisely reflect residual pituitary-thyroid function in patients receiving bexarotene.

贝沙罗汀诱导的中枢性甲状腺功能减退症 (CH) 建议使用左甲状腺素 (LT4) 替代疗法，但实验表明它是由垂体而非下丘脑疾病引起的，尽管人类的潜在机制仍不清楚。在这里，使用皮肤 T 细胞淋巴瘤 (CTCL) 患者的 TRH 刺激试验检查了贝沙罗汀诱导的 CH 的病理生理学。在这项回顾性纵向观察研究中，在贝沙罗汀治疗 24 周期间测量了 10 名甲状腺功能正常的 CTCL 患者的血清 TSH 和游离 T4 (F-T4) 水平。在 CH 诊断后进行 TRH 刺激测试，调整 LT4 替代剂量以将 F-T4 维持在治疗前水平。贝沙罗汀给药一周后，所有 10 名患者均出现 CH，基于低或低正常 F-T4 与低或正常 TSH 水平的综合发现。刺激试验一周后的 TSH 峰值反应在 30 分钟达到。然而，所有患者的 TSH 反应均小于 4 μIU/mL，表明 TSH 反应迟钝但并未夸大和延迟。在 8 名继续使用贝沙罗汀 24 周的患者中，LT4 替代剂量的中位数为 125（范围，75-150）μg/天。TRH 刺激后 30 分钟以及 15、60、90 和 120 分钟的 TSH 水平与 LT4 替代剂量显着相关。ρ = –0.913, p = 0.002)，而一周时的 TSH 和 F-T4 基础水平则不然。这些结果表明，垂体甲状腺功能减退是贝沙罗汀诱导的 CH 的原因，而 TRH 刺激后的 TSH 水平准确地反映了接受贝沙罗汀的患者残留的垂体 - 甲状腺功能。