重组人促甲状腺激素和促再分化药物在分化型甲状腺癌中的应用

131Ⅰ去除术后残留甲状腺组织和131I治疗转移灶是分化型甲状腺癌(DTC)联合治疗方案中的重要组成部分。治疗前,最关键的准备是使促甲状腺激素(TSH)升高到适合的水平。重组人促甲状腺激素(rhTSH)可以有效地使血清TSH水平升高,rhTSH与内源TSH有相同的结构和生物活性,应用rhTSH副作用轻微,并可避免因停用甲状腺激素治疗而使患者出现的甲减症状。部分DTC患者的癌灶会发生失分化,造成病情恶化、预后变差,并对131Ⅰ治疗不再敏感。以异维甲酸为代表的促进再分化药物的研究已进入Ⅱ期临床阶段,取得了一定的突破,成为失分化DTC患者131Ⅰ治疗前准备的重要手段。     

Recombinant human TSH for the treatment of differentiated thyroid cancer metastatic to the spine

The diagnostic use of recombinant human TSH (rhTSH) in follow- up of differentiated thyroid cancer (DTC) is already approved, however its application in (131)I therapy is still to be evaluated. We report results obtained in four patients with DTC metastatic to central skeleton, in whom 5 courses of rtTSH aided 131I therapy were administered.     

Changing concepts in the management of differentiated thyroid cancer

The management of patients with differentiated thyroid cancer has changed significantly over the last few decades. Mortality has decreased as the result of earlier detection, refined surgical approaches, subsequent radioiodine ablation, and the development of more sensitive methods for detecting and monitoring disease recurrence. The latter has been facilitated by serum thyroglobulin measurements, the use of recombinant human thyrotropin, and the use of 18F-deoxyglucose/positron emission tomography in selected instances where radioiodine imaging fails to locate known or suspected recurrent or metastatic disease.     

重组人促甲状腺激素在甲状腺疾病诊治中的应用

重组人TSH (rhTSH)于1998年在国外进入临床应用,其临床适应证由辅助DTC患者的随访检查和检测逐渐扩展到辅助131I清除手术后残留甲状腺组织.近期研究表明,rhTSH在辅助131I治疗DTC转移灶、辅助131I治疗非毒性结节性甲状腺肿、提高18F-FDG PET对甲状腺癌的诊断效能及对先天性甲状腺功能减退症的病因鉴别诊断等多方面亦有应用潜力.     

Tumour dosimetry and response in patients with metastatic differentiated thyroid cancer using recombinant human thyrotropin before radioiodine therapy

The development of recombinant human thyrotropin (rhTSH) has given clinicians new options for diagnostic follow-up and treatment of patients with differentiated thyroid cancer (DTC). This paper evaluates the tumour dosimetry and response following -iodine-131 treatment of metastatic thyroid cancer patients after rhTSH stimulation instead of classical hormone withdrawal-induced hypothyroidism. Nineteen consecutive (131)I treatments in 16 patients were performed after rhTSH stimulation. All patients had undergone a near-total thyroidectomy followed by an ablative dosage of (131)I. They all suffered from metastatic or recurrent disease showing tumoral (131)I uptake on previous post-treatment scintigraphy. Dosimetric calculations were performed using (131)I tumour uptake measurements from post-treatment (131)I scintigrams and tumour volume estimations from radiological images. Response was assessed by comparing pre-treatment serum thyroglobulin (Tg) level with the Tg level 3 months post treatment. In 18 out of 19 treatments, uptake of (131)I in metastatic or recurrent lesions was seen. The median tumour radiation dose was 26.3 Gy (range 1.3-368 Gy), and the median effective half-life was 2.7 days (range 0.5-6.5 days). Eleven of 19 treatments (10/16 patients) were evaluable for response after 3 months. (131)I therapy with rhTSH resulted in a biochemical partial response in 3/11 or 27% of treatments (two patients), biochemical stable disease in 2/11 or 18% of treatments and biochemical progressive disease in 6/11 or 55% of treatments. Our study showed that although tumour doses in DTC patients treated with (131)I after rhTSH were highly variable, 45% of treatments led to disease stabilisation or partial remission when using rhTSH in conjunction with (131)I therapy, without serious side-effects and with minimal impact on quality of life. RhTSH is therefore adequately satisfactory as an adjuvant tool in therapeutic settings and is especially suitable in advanced recurrent or metastatic DTC patients who may be intolerant to TSH stimulation by levothyroxine withdrawal.     

rhTSH stimulation before radioiodine therapy in thyroid cancer reduces the effective half-life of (131)I.

Recombinant human thyroid-stimulating hormone (rhTSH) is effectively used for exogenous thyroid-stimulating hormone (TSH) stimulation before diagnostic (131)I scintigraphy. It is not yet widely used for preparation of patients receiving a therapeutic amount of radioiodine. METHODS: The results of 64 consecutive therapeutic applications of rhTSH with regard to clinical tolerance and side effects were evaluated in comparison with 163 radioiodine therapies (RITs) done on patients with hypothyroidism after thyroxine withdrawal during the same period. All therapies-applying 1.1-10 GBq of (131)I-used a standardized protocol of patient preparation and activity application. RITs were followed by daily whole-body uptake measurements for 2-6 d, and a biexponential curve fit was used to obtain a short initial and afterward a long effective half-life of (131)I. Patients after rhTSH were evaluated as a whole group (group A, n = 64) and as a subset of that group with normal thyroglobulin (hTG) levels (group D, n = 18). Patients after endogenous TSH stimulation were evaluated as a whole group (group B, n = 163), as a subset of that group excluding all ablative RITs (group C, n = 113), and as a subset of that subset with normal hTG levels (group E, n = 87). RESULTS: rhTSH-stimulated patients showed significantly higher TSH values than did endogenously stimulated patients (P < 0.001). Furthermore, the effective half-life of (131)I was significantly prolonged after endogenous stimulation (e.g., 0.43 d for group A vs. 0. 54 d for group B, P < 0.001). All rhTSH applications were tolerated well and without serious side effects. The only side effects were 2 cases of nausea and headache. CONCLUSION: The use of rhTSH for stimulation of TSH before RIT is safe but also significantly reduces the effective half-life of (131)I. This is mainly due to a reduced renal iodine clearance in the hypothyroid state, but the bioavailability of radioiodine may be slightly overestimated because of larger amounts of intestinal (131)I after endogenous TSH stimulation.     

Recombinant thyrotropin versus thyroid hormone withdrawal in evaluating patients with thyroid carcinoma

Patients with previously treated thyroid carcinoma require lifelong monitoring for recurrent disease. Two diagnostic tests that play a central role in follow-up of these patients--radioiodine whole body scanning and serum thyroglobulin measurement--are most accurate during thyroid-stimulating hormone (TSH) stimulation. Temporary discontinuation of thyroid hormone therapy was previously the sole effective approach for TSH-stimulated testing. However, hormone withdrawal was associated with the morbidity of hypothyroidism and occasional tumor progression. The introduction of recombinant TSH (rTSH)-stimulated testing offers an alternative therapy. Recent clinical trials have shown that the sensitivity of combined rTSH-stimulated radioiodine scanning and serum thyroglobulin measurement has equivalent sensitivity to testing after thyroid hormone withdrawal. Furthermore, measurement of the rTSH-stimulated thyroglobulin concentration is a more sensitive way to detect residual thyroid cancer or normal tissue than thyroglobulin measurement on thyroid hormone therapy alone. The results of these trials are reviewed and strategies for implementing rTSH-mediated testing are presented.