Uy H L, Reasner C A, Samuels M H
University of Texas Health Science Center at San Antonio, Department of Medicine 78284-7877, USA.
Am J Med. 1995 Aug;99(2):173-9. doi: 10.1016/s0002-9343(99)80137-5.
To characterize the time course of recovery of the hypothalamic-pituitary-thyroid (HPT) axis by determining the frequency, onset, duration, and clinical attributes of the central hypothyroid phase following 131I therapy for Graves' disease and to examine whether the central hypothyroid phase is due to direct pituitary thyrotroph suppression or to hypothalamic thyrotropin-releasing hormone (TRH) deficiency.
Twenty-one hyperthyroid patients with Graves' disease evaluated at a university endocrine clinic and treated with radioactive iodine were prospectively studied. Serial thyroid function levels (serum thyroxine [T4], free thyroxine [free T4], triiodothyronine [T3], and thyroid-stimulating hormone [TSH]) were measured and TRH stimulation tests were performed at 2 to 4 week intervals for all subjects following 131I treatment. None of the patients was treated with thionamides after receiving 131I therapy.
Nineteen (90%) of the patients with Graves' disease experienced a transient central hypothyroid phase defined as the presence of a suppressed or inappropriately normal TSH level despite a low free T4 level following 131I treatment. This phase occurred a mean of 62.8 +/- 5.1 days following 131I treatment, persisted for an average of 24.7 +/- 2.4 days, and was not predictive of eventual treatment outcome. All patients had concordantly low T4 and T3 levels during this period and exhibited a blunted TSH response to TRH compared to 29 euthyroid control subjects, suggesting primary feedback suppression at the level of the pituitary thyrotrophs. The suppressed thyrotrophs required a minimum of 2 weeks to recover once patients became hypothyroid. The length of preexisting hyperthyroidism, basal free T4 elevation, and administered dose of 131I failed to predict the duration of the central hypothyroid phase, although a higher dose of 131I was associated with an earlier onset of central hypothyroidism (r = -.51, P < 0.05).
Clinicians should be aware of the delay in the recovery of the HPT axis that occurs in the majority of patients with Graves' disease treated with 131I and is manifested by a transient central hypothyroid phase. The blunted TSH response to TRH stimulation during this period suggests that suppression occurs primarily at the level of the pituitary thyrotrophs. The use of sensitive TSH measurements alone to monitor these patients during this period is not helpful and may be misleading.
通过确定131I治疗格雷夫斯病后中枢性甲状腺功能减退期的频率、起始时间、持续时间和临床特征，来描述下丘脑-垂体-甲状腺（HPT）轴的恢复时间进程，并研究中枢性甲状腺功能减退期是由于垂体促甲状腺细胞直接受抑制还是下丘脑促甲状腺激素释放激素（TRH）缺乏所致。
对在大学内分泌诊所评估并接受放射性碘治疗的21例格雷夫斯病甲亢患者进行前瞻性研究。在131I治疗后，对所有受试者每隔2至4周测量一次系列甲状腺功能水平（血清甲状腺素[T4]、游离甲状腺素[游离T4]、三碘甲状腺原氨酸[T3]和促甲状腺激素[TSH]），并进行TRH刺激试验。所有患者在接受131I治疗后均未接受硫代酰胺治疗。
19例（90%）格雷夫斯病患者经历了短暂的中枢性甲状腺功能减退期，定义为131I治疗后尽管游离T4水平较低，但TSH水平受到抑制或处于不适当的正常水平。此阶段在131I治疗后平均62.8±5.1天出现，平均持续24.7±2.4天，且不能预测最终治疗结果。在此期间，所有患者的T4和T3水平均一致降低，与29例甲状腺功能正常的对照受试者相比，其对TRH的TSH反应减弱，提示垂体促甲状腺细胞水平存在原发性反馈抑制。一旦患者出现甲状腺功能减退，受抑制的促甲状腺细胞至少需要2周才能恢复。尽管131I给药剂量较高与中枢性甲状腺功能减退的较早起始相关（r = -0.51，P < 0.05），但既往甲亢的持续时间、基础游离T4升高情况和131I给药剂量均无法预测中枢性甲状腺功能减退期持续时间。
临床医生应意识到，大多数接受131I治疗的格雷夫斯病患者会出现HPT轴恢复延迟，表现为短暂的中枢性甲状腺功能减退期。在此期间对TRH刺激的TSH反应减弱表明抑制主要发生在垂体促甲状腺细胞水平。在此期间仅使用敏感的TSH测量来监测这些患者并无帮助，且可能产生误导。
