Department of Clinical and Experimental Medicine, Endocrinology Units, University of Pisa and University Hospital of Pisa, Via Paradisa 2, 56124, Pisa, Italy.
Department of Pathology, Division of Immunology, The Johns Hopkins School of Medicine, Baltimore, MD, USA.
J Endocrinol Invest. 2020 Dec;43(12):1759-1768. doi: 10.1007/s40618-020-01341-2. Epub 2020 Jun 25.
The insulin-like growth factor-1 receptor (IGF-1R) is a key element in the pathogenesis of Graves' Orbitopathy (GO), but the role of IGF-1R autoantibodies (IGF-1RAbs) has not been established.
We designed a cross-sectional investigation to measure IGF-1RAbs in patients with Graves' disease (GD), with or without GO, who underwent radioiodine therapy followed by glucocorticoids (GC). Twenty-nine patients were included, 15 of which with GO. Patients were evaluated at baseline and three and 6 months after radioiodine. The primary objective was the prevalence of positive tests for IGF-1RAbs. The secondary objectives were: (1) IGF-1RAbs concentrations and their variations; (2) relationship between IGF-1RAbs and the features of GO; (3) relationship between IGF-1RAbs and anti-thyroid autoantibodies.
IGF-1RAbs above the cut-off value were found only in one patient with GD without GO. IGF-1RAb levels were greater in patients with GD without GO, at baseline (P < 0.0001), and after three (P < 0.0001) and six (P = 0.0001) months. No correlations were observed between IGF-1RAbs and the features of GO, nor between IGF-1RAbs and anti-thyroglobulin or anti-thyroperoxidase autoantibodies. There was an inverse correlation between anti-TSH receptor autoantibodies (TRAbs) and IGF-1RAb levels in GD patients with GO at 6 months (P = 0.03).
IGF-1RAbs appear to be greater in patients with GD without GO compared with those with GO, suggesting a putative protective role of IGF-1RAbs on the development of GO, in line with the beneficial effects of Teprotumumab on GO. The inverse correlation between IGF-1RAbs and TRAbs 6 months after radioiodine may reflect antigen spreading and/or GC treatment.
胰岛素样生长因子-1 受体（IGF-1R）是格雷夫斯眼病（GO）发病机制的关键因素，但 IGF-1R 自身抗体（IGF-1RAbs）的作用尚未确定。
我们设计了一项横断面研究，以测量接受放射性碘治疗后接受糖皮质激素（GC）治疗的格雷夫斯病（GD）患者（有或无 GO）的 IGF-1RAbs。共纳入 29 例患者，其中 15 例有 GO。患者在基线和放射性碘治疗后 3 个月和 6 个月进行评估。主要目的是检测 IGF-1RAbs 阳性的患病率。次要目标是：（1）IGF-1RAbs 浓度及其变化；（2）IGF-1RAbs 与 GO 特征的关系；（3）IGF-1RAbs 与甲状腺自身抗体的关系。
仅在一名无 GO 的 GD 患者中发现 IGF-1RAbs 超过临界值。无 GO 的 GD 患者基线时（P<0.0001）、治疗后 3 个月（P<0.0001）和 6 个月（P=0.0001）时 IGF-1RAb 水平更高。IGF-1RAbs 与 GO 特征之间无相关性，与抗甲状腺球蛋白或抗甲状腺过氧化物酶自身抗体之间也无相关性。在有 GO 的 GD 患者中，6 个月时抗促甲状腺激素受体自身抗体（TRAbs）与 IGF-1RAb 水平呈负相关（P=0.03）。
与有 GO 的患者相比，无 GO 的 GD 患者的 IGF-1RAbs 似乎更高，这表明 IGF-1RAbs 对 GO 的发生可能具有保护作用，与 Teprotumumab 对 GO 的有益作用一致。放射性碘治疗后 6 个月 IGF-1RAbs 与 TRAbs 之间的负相关可能反映了抗原扩散和/或 GC 治疗。
