Roti E, Minelli R, Giuberti T, Marchelli S, Schianchi C, Gardini E, Salvi M, Fiaccadori F, Ugolotti G, Neri T M, Braverman L E
Centro per lo Studio, Prevenzione, Diagnosi e Cura delle Tireopatie, Universita degli Studi di Parma, Italy.
Am J Med. 1996 Nov;101(5):482-7. doi: 10.1016/s0002-9343(96)00259-8.
Recombinant human interferon-alpha (r-IFN-alpha) is often successfully used in the treatment of patients with chronic viral hepatitis B and C. Thyroid dysfunction has been reported to occur with variable frequency during r-IFN-alpha therapy especially in patients with preexisting thyroid autoimmunity. We have prospectively evaluated the effect of r-IFN-alpha on various aspects of thyroid function in patients with HCV chronic hepatitis.
Thirty-two patients with HCV chronic active hepatitis were studied prospectively before and during r-IFN-alpha therapy. Serum TSH, FT4, FT3, and thyroid receptor (TSR) and thyroid peroxidase (TPO) antibodies, and the iodide-perchlorate discharge test (I-C10(4)) to detect subtle defects in the thyroid organification of iodide were carried out during the study. Thyroid radioactive iodine uptakes (RAIU) were obtained in patients who developed thyrotoxicosis.
All patients were clinically and biochemically euthyroid prior to r-IFN-alpha therapy with negative I-C10(4) discharge tests. Four patients became thyrotoxic, 3 secondary to destructive or inflammatory thyroiditis with a low thyroid RAIU, and 1 patient developed hypothyroidism. The I-C10(4) discharge test became positive in 7 of the 32 patients studied prospectively; 5 of these patients did not develop other evidence of thyroid dysfunction and did not have positive TPO antibodies. In these 5 patients the test became negative after r-IFN-alpha was discontinued. Appropriate therapy of the patients with thyrotoxicosis (methylprednisolone for 3 patients with destructive thyroiditis and methimazole for 1 patient with hyperthyroidism) or with hypothyroidism (L-thyroxine) was successful.
Thyroid dysfunction, especially destructive or silent thyroiditis resulting in thyrotoxicosis, is not infrequently observed in patients receiving r-IFN-alpha therapy for chronic active hepatitis. Although underlying autoimmune thyroid disease appears to predispose patients to develop thyroid dysfunction, other patients become thyrotoxic or hypothyroid in the absence of baseline positive TPO-Ab. Subtle defects in the thyroidal organification of iodine as determined by the I-C10(4) discharge test, in the absence of autoimmune thyroid disease, was observed in 5 patients who remained euthyroid, suggesting that r-IFN-alpha directly reduces the intrathyroidal organification of iodine.
重组人干扰素-α（r-IFN-α）常用于成功治疗慢性乙型和丙型病毒性肝炎患者。据报道，在r-IFN-α治疗期间，甲状腺功能障碍会以不同频率发生，尤其是在已有甲状腺自身免疫的患者中。我们前瞻性地评估了r-IFN-α对丙型肝炎慢性肝炎患者甲状腺功能各方面的影响。
对32例丙型肝炎慢性活动性肝炎患者在r-IFN-α治疗前和治疗期间进行前瞻性研究。在研究期间进行血清促甲状腺激素（TSH）、游离甲状腺素（FT4）、游离三碘甲状腺原氨酸（FT3）、甲状腺受体（TSR）和甲状腺过氧化物酶（TPO）抗体检测，以及碘-过氯酸盐释放试验（I-C10(4)）以检测甲状腺碘有机化的细微缺陷。对发生甲状腺毒症的患者进行甲状腺放射性碘摄取（RAIU）检测。
所有患者在r-IFN-α治疗前临床和生化甲状腺功能正常，I-C10(4)释放试验阴性。4例患者发生甲状腺毒症，3例继发于破坏性或炎性甲状腺炎，甲状腺RAIU较低，1例患者发生甲状腺功能减退。在32例前瞻性研究的患者中，7例I-C10(4)释放试验呈阳性；其中5例患者未出现其他甲状腺功能障碍证据，且TPO抗体阴性。在这5例患者中，停用r-IFN-α后试验转为阴性。对甲状腺毒症患者（3例破坏性甲状腺炎患者用甲泼尼龙，1例甲状腺功能亢进患者用甲巯咪唑）或甲状腺功能减退患者（左甲状腺素）进行适当治疗均获成功。
在接受r-IFN-α治疗慢性活动性肝炎的患者中，甲状腺功能障碍，尤其是导致甲状腺毒症的破坏性或无症状性甲状腺炎并不少见。虽然潜在的自身免疫性甲状腺疾病似乎使患者易发生甲状腺功能障碍，但其他患者在基线TPO-Ab阴性的情况下也会发生甲状腺毒症或甲状腺功能减退。在5例甲状腺功能正常的患者中观察到，在无自身免疫性甲状腺疾病的情况下，由I-C10(4)释放试验确定的甲状腺碘有机化存在细微缺陷，提示r-IFN-α直接降低甲状腺内碘的有机化。
