Fiore Roberto, La Rosa Stefano, Uccella Silvia, Marchiori Deborah, Kopp Peter A
Division of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne and University of Lausanne, Hôtel des Patients, Lausanne, Switzerland.
Unit of Pathology, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Eur Thyroid J. 2022 Sep 27;11(5). doi: 10.1530/ETJ-22-0006. Print 2022 Oct 1.
Consumptive hypothyroidism is a rare paraneoplastic condition most commonly associated with infantile hemangiomas. It is caused by overexpression of deiodinase type 3 (D3), which leads to preferential conversion of thyroxine to the metabolically inactive reverse triiodothyronine (rT3), paralleled by a decrease of the biologically active T3.
A 46-year-old male patient with previously normal thyroid function was diagnosed with a renal carcinoma with rhabdoid differentiation. He was treated with sunitinib, followed by the immune checkpoint inhibitors ipilimumab and nivolumab, and he developed primary hypothyroidism secondary to thyroiditis. Substitution with unusually high doses of levothyroxine as high as 4.3 µg/kg/day did not normalize his thyroid function. Poor compliance was refuted because there was no improvement after observed administration. He had no malabsorption. Although tyrosine kinase inhibitors can increase the expression of D3, this effect tends to be modest. Therefore, the suspicion of tumor-related consumptive hypothyroidism was raised and supported by low free T3 and elevated rT3 levels. The therapy could not be further modified because the patient opted for palliative care and passed away 12 days later. Immunohistochemistry of the tumor from a sample obtained prior to systemic therapy documented abundant expression of D3, corroborating the diagnosis of consumptive hypothyroidism.
This observation extends the spectrum of malignancies overexpressing D3. Although rare, increased awareness of this paraneoplastic syndrome is key, if persistent hypothyroidism cannot be explained by compliance issues or malabsorption. Substitution with high doses of levothyroxine, and combination therapy with liothyronine, can correct hypothyroidism in these patients.
消耗性甲状腺功能减退是一种罕见的副肿瘤性疾病，最常与婴儿血管瘤相关。它是由3型脱碘酶（D3）过度表达引起的，这导致甲状腺素优先转化为代谢无活性的反式三碘甲状腺原氨酸（rT3），同时生物活性T3减少。
一名46岁男性患者，既往甲状腺功能正常，被诊断为具有横纹肌样分化的肾癌。他接受了舒尼替尼治疗，随后使用免疫检查点抑制剂伊匹木单抗和纳武单抗，之后因甲状腺炎继发原发性甲状腺功能减退。使用高达4.3μg/kg/天的异常高剂量左甲状腺素替代治疗未能使他的甲状腺功能恢复正常。排除了依从性差的因素，因为在观察给药后没有改善。他没有吸收不良。虽然酪氨酸激酶抑制剂可增加D3的表达，但这种作用往往较小。因此，怀疑是肿瘤相关性消耗性甲状腺功能减退，并得到低游离T3和升高的rT3水平的支持。由于患者选择姑息治疗并在12天后去世，无法进一步调整治疗方案。全身治疗前获得的肿瘤样本的免疫组织化学显示D3大量表达，证实了消耗性甲状腺功能减退的诊断。
这一观察结果扩展了过度表达D3的恶性肿瘤谱。虽然罕见，但如果持续性甲状腺功能减退不能用依从性问题或吸收不良来解释，提高对这种副肿瘤综合征的认识是关键。使用高剂量左甲状腺素替代治疗以及与碘塞罗宁联合治疗，可以纠正这些患者的甲状腺功能减退。
