Colao A, Lastoria S, Ferone D, Pivonello R, Macchia P E, Vassallo P, Bonavolonta G, Muto P, Lombardi G, Fenzi G
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Naples, Italy.
J Clin Endocrinol Metab. 1998 Nov;83(11):3790-4. doi: 10.1210/jcem.83.11.5274.
Corticosteroid treatment is successfully used in Graves' ophthalmopathy, and its effect varies according to the phase of the disease. The infiltration of the orbit by activated lymphocytes may explain the effectiveness of corticosteroid therapy. Scintigraphy with [111In-DTPA-D-Phe1]-octreotide was recently used to reveal the presence of activated lymphocytes in foci of autoimmune diseases, because elevated amounts of somatostatin receptors are expressed in the surface of these cells. The aim of the current study was to evaluate whether the degree of orbital [111In-DTPA-D-Phe1]-octreotide uptake is able to predict the response to corticosteroid therapy in patients with Graves' ophthalmopathy. Ten patients with Graves' ophthalmopathy entered the study. In all patients scintigraphy was performed, and subsequently, corticosteroid therapy (methylprednisolone, 1 g i.v. for 2 consecutive days a week for 6 weeks) was given. Clinical activity of Graves' ophthalmopathy was evaluated before and after treatment by calculating the ophthalmopathy index (OI). Planar and single photon emission computed tomography (SPECT) images of the head were obtained 24 h after the i.v. injection of 120-190 MBq of [111In-DTPA-D-Phe1]-octreotide. Radioligand uptake within each orbit (O) and brain (B) was measured using the region of interests (ROI) method and the O-to-B ratio was determined. According to the O-to-B ratio, the images were classified using the following three points score: 0 = O-to-B ratio < or =1; 1 = O-to-B ratio between 1 and 2.5; 2 = O-to-B ratio > or =2.5. The value of OI, measured before and after corticosteroid treatment, was correlated to the scintigraphic score. A significant change of OI was observed between posttreatment and pretreatment evaluation both in orbits with score 2 (OI: 15.4 +/- 1.5 vs. 9.6 +/- 0.5, P < 0.005) and in those with score 1 or 0 (OI: 12.9 +/- 1.5 vs. 11.5 +/- 1.4, P < 0.05) at the scintigraphy. However, when the OI was calculated excluding the changes in the soft tissue, which generally occur in all patients independently from the phase of the disease, a significant change of OI was observed only in the orbits with score 2 (OI: 12.9 +/- 1.3 vs. 8.3 +/- 0.5, P < 0.01) but not in those with score 0 or 1 (OI: 11.2 +/- 1.3 vs. 10.4 +/- 1.3). In particular, 6 weeks after corticosteroid treatment, the patients with orbital score 2 at the scintigraphy had a significant improvement of soft tissue changes, proptosis, lagophthalmos, extraocular muscle movements impairment, and diplopia, whereas patients with score 0 or 1 had only a significant improvement of the soft tissue inflammation. In conclusion, the current preliminary data suggested that [111In-DTPA-D-Phe1]-octreotide scintigraphy is able to predict the clinical response to corticosteroid treatment in patients with Graves' ophthalmopathy, and may be considered an useful approach to select the patients for the proper treatment.
皮质类固醇治疗在格雷夫斯眼病中得到了成功应用,其效果因疾病阶段而异。活化淋巴细胞对眼眶的浸润可能解释了皮质类固醇治疗的有效性。最近,[111In-DTPA-D-Phe1]-奥曲肽闪烁扫描被用于揭示自身免疫性疾病病灶中活化淋巴细胞的存在,因为这些细胞表面表达有大量的生长抑素受体。本研究的目的是评估眼眶[111In-DTPA-D-Phe] -奥曲肽摄取程度是否能够预测格雷夫斯眼病患者对皮质类固醇治疗的反应。10例格雷夫斯眼病患者进入本研究。对所有患者均进行了闪烁扫描,随后给予皮质类固醇治疗(甲泼尼龙,每周连续2天静脉注射1 g,共6周)。通过计算眼病指数(OI)评估治疗前后格雷夫斯眼病的临床活动度。在静脉注射120 - 190 MBq的[111In-DTPA-D-Phe1]-奥曲肽24小时后,获取头部的平面和单光子发射计算机断层扫描(SPECT)图像。使用感兴趣区(ROI)方法测量每个眼眶(O)和脑(B)内的放射性配体摄取,并确定O与B的比值。根据O与B的比值,使用以下三分制对图像进行分类:0 = O与B的比值≤1;1 = O与B的比值在1至2.5之间;2 = O与B的比值≥2.5。皮质类固醇治疗前后测量的OI值与闪烁扫描评分相关。在闪烁扫描中,评分2的眼眶(OI:15.4±1.5对9.6±0.5,P < 0.005)以及评分1或0的眼眶(OI:12.9±1.5对11.5±1.4,P < 0.05)在治疗后与治疗前评估之间均观察到OI有显著变化。然而,当计算OI时排除软组织的变化(软组织变化通常在所有患者中都会出现,且与疾病阶段无关),仅在评分2的眼眶中观察到OI有显著变化(OI:12.9±1.3对8.3±0.5,P < 0.01),而评分0或1的眼眶中未观察到(OI:11.2±1.3对10.4±1.3)。特别是,皮质类固醇治疗6周后,闪烁扫描眼眶评分为2的患者在软组织改变、眼球突出、兔眼、眼外肌运动障碍和复视方面有显著改善,而评分0或1的患者仅在软组织炎症方面有显著改善。总之,目前的初步数据表明,[111In-DTPA-D-Phe1]-奥曲肽闪烁扫描能够预测格雷夫斯眼病患者对皮质类固醇治疗的临床反应,并且可被视为选择合适治疗患者的一种有用方法。