甲狀腺疾病的偵測記錄、療效預測與預後評估：遠紅外線熱影像與細胞影像分析

Abstract

甲狀腺功能和結構異常是內分泌系統中最常見的疾病。在功能方面，葛雷夫氏症是造成甲狀腺亢進最主要原因之一，它的特徵是甲狀腺腫與機能亢進，病人可能合併有甲狀腺眼病變或脛前黏液水腫。目前並沒有好的工具可以研究記錄脛前黏液水腫或客觀描述眼病變的發炎程度，這對治療方式的選擇和發展是一大限制。在構造異常方面，甲狀腺乳突癌是最常見的甲狀腺癌，目前所有的預後評估工具都需要等到術後根據手術觀察記錄和病理報告才有辦法使用，這對手術本身甲狀腺切除範圍、淋巴節廓清與否的選擇並沒有幫助。本研究嘗試解決這些重要的臨床問題。 在葛雷夫氏症方面，電腦化遠紅外線熱影像可以度量局部的溫度，我們嘗試用它來協助觀察記錄發炎程度。脛前黏液水腫方面收納了87個有或沒有脛前黏液水腫的葛雷夫氏症病人與14個正常人，以遠紅外線熱影像觀察其前脛。遠紅外線熱影像顯示在脛前黏液水腫處和某些以肉眼觀察無脛前黏液水腫的葛雷夫氏症病人的前脛有異常的局部低溫。抗甲狀腺刺激素抗體值與溫度降低的程度有正相關(p=0.033)。此研究顯示遠紅外線熱影像有助於記錄脛前黏液水腫，並且可能有助偵測早期脛前黏液水腫的發生。 另一研究收納了46個接受大劑量類固醇治療甲狀腺眼病變的病人，以遠紅外線熱影像觀察眼睛溫度的變化。在大劑量類固醇治療後眼睛溫度平均來說會下降，溫度下降的程度與治療前的眼睛溫度成正相關(p= 0.004)。此研究顯示遠紅外線熱影像的溫度測量有助於預測大劑量類固醇治療甲狀腺眼病變的效果。 在甲狀腺乳突癌方面，我們嘗試用電腦程式分析術前以細針穿刺取得的甲狀腺乳突癌細胞型態，共迴溯性地收納研究了142個乳突癌病人的癌細胞，多變項迴歸分析發現病人在10年內復發的可能性與核質比、細胞核面積變異度、腫瘤大小、和病人年齡有統計顯著相關。此研究顯示以型態分析程式分析細針穿刺取得的甲狀腺乳突癌細胞，有助於在術前預測病人的預後。 總之，根據目前初步的研究成果顯示：遠紅外線熱影像有助於記錄葛雷夫氏症脛前黏液水腫及預測大劑量類固醇治療眼病變的效果，型態分析程式分析有助於預測甲狀腺乳突癌的預後。希望將來有更深入的研究並實際運用在臨床上。

Dysfunction and anatomic abnormalities of the thyroid are among the most common diseases of the endocrine glands. On the aspect of thyroid dysfunction, Graves’ disease (GD) is the most common form of throtoxicosis. It is characterized by thyrotoxicosis and goiter. Patients may have ophthalmopathy and pretibial myxedema (PM). Currently, there is no satisfactory tool to record and investigate PM, and to describe the inflammatory status of Graves’ ophthalmopathy (GO). It limits the choice and development of therapy. As to the anatomic abnormality of the thyroid, papillary thyroid carcinoma (PTC) is the most common thyroid malignancy. Currently, prognostic evaluation tools can be performed only after surgery because they depend on the observation and records of operation and pathology reports. They are not helpful for the operation planning for the extent of thyroidectomy and lymph node dissection. This study aimed to solve these important clinical issues. Digital infrared thermal imaging (DITI) detects surface temperature. We tried to appliy it to help observe and record GD complications. On the aspect of PM, eighty-seven GD patients with or without PM and 14 normal volunteers were recruited for observation of lower legs with DITI. DITI showed abnormally low focal temperature over PM lesions and in some GD patients without obvious PM. Thyrotropin receptor antibody level correlated positively and significantly with adjusted temperature difference between the center of temperature defect and the surrounding skin (p=0.033). We demonstrated that DITI is helpful in recording and may be a useful tool to detect early changes of PM. On the aspect of GO, forty-six patients with GO receiving intravenously methylprednisolone pulse therapy (MPT) were included for observation of the eye temperature with DITI. Local temperatures of the eyes decreased after MPT. Temperature difference (△T) significantly negative-correlated with basal mean temperature (MT) (p= 0.004). We demonstrated that DITI is valuable in the prediction of prognosis after MPT. As to PTC, we tried to analyze cytologic features with computerized morphometry (CM) to help predicting prognosis preoperatively. Cytologic features of 142 patients with usual-type PTC were studied with CM retrospectively. Multivariate logistic analysis indicated that nucleus-to-cell ratio, variation of nuclear area, tumor size, and patients’ age were significantly related to cancer recurrence in 10 years. We demonstrated that CM helped to predict prognosis preoperatively. In summary, according to current preliminary reports, DITI is useful in recording PM and predicting the prognosis of GO after MPT; and CM is useful in predicting the prognosis of PTC. Further large scale studies are necessary to help applying these methods clinically.