Follow-up and long-term results of radioiodine therapy in immune hyperthyroidism

Follow-up and long-term results of 131-I treatment in Graves' disease are mainly influenced by the initial therapy. In Austria 131I-dose is estimated mostly as a result of thyroid uptake and volume, with the aim to restore euthyroidism. Methimazole or Propanolol pretreatment is performed in more than half of the patients. In Salzburg fixed dosis of 185 MBq 131-I are delivered until euthyroidism is achieved. Follow-up is done in 3 to 6 monthly intervals, later on once a year. Long-term results of 131-I-therapy are rare, because of the difficulty in discriminating Graves' disease from hyperthyroidism due to thyroid autonomy in the years before antibodies could be evaluated. Results are also quite uncertain, when obtained before the age of TSH- and TRH-test, because mild hyperthyroidism and hypothyroidism might have been overlooked. Early hyperthyroidism after 131-I-treatment can occur in 7% to 40% within the first year, raising with 2% to 5% each year. Hypothyroidism seems to depend on the dose, but may be caused even by low doses. This difficulty in finding the "ideal" dose might be due to stimulating, blocking and destroying antibodies with differences in the sensitivity of the thyroid tissue. The goal should be, to attain euthyroidism by radioiodine therapy, but hyperthyroidism should not be prolonged over a long period by delivering too small doses in order to avoid hypothyroidism.     

A NTCP approach for estimating the outcome in radioiodine treatment of hyperthyroidism

Radioiodine has been in use for over 60 years as a treatment for hyperthyroidism. Major changes in clinical practice have led to accurate dosimetry capable of avoiding the risks of adverse effects and the optimization of the treatment. The aim of this study was to test the capability of a radiobiological model, based on normal tissue complication probability (NTCP), to predict the outcome after oral therapeutic 131I administration. Following dosimetric study, 79 patients underwent treatment for hyperthyroidism using radioiodine and then 67 had at least a one-year follow up. The delivered dose was calculated using the MIRD formula, taking into account the measured maximum uptake of administered iodine transferred to the thyroid, U0, and the effective clearance rate, Teff and target mass. The dose was converted to normalized total dose delivered at 2 Gy per fraction (NTD2). Furthermore, the method to take into account the reduction of the mass of the gland during radioiodine therapy was also applied. The clinical outcome and dosimetric parameters were analyzed in order to study the dose-response relationship for hypothyroidism. The TD50 and m parameters of the NTCP model approach were then estimated using the likelihood method. The TD50, expressed as NTD2, resulted in 60 Gy (95% C.I.: 45-75 Gy) and 96 Gy (95% C.I.: 86-109 Gy) for patients affected by Graves or autonomous/multinodular disease, respectively. This supports the clinical evidence that Graves' disease should be characterized by more radiosensitive cells compared to autonomous nodules. The m parameter for all patients was 0.27 (95% C.I.: 0.22-0.36). These parameters were compared with those reported in the literature for hypothyroidism induced after external beam radiotherapy. The NTCP model correctly predicted the clinical outcome after the therapeutic administration of radioiodine in our series.     

Analysis of demographic and clinical factors affecting the outcome of radioiodine therapy in patients with hyperthyroidism

Introduction

The influence of demographic and clinical factors on the outcome of ¹³¹I therapy in hyperthyroid patients has been examined, based on a retrospective evaluation of results obtained in patients submitted to ¹³¹I treatment at the Department of Nuclear Medicine and Oncological Endocrinology, Medical University of Lodz (Province Hospital, Zgierz). The goal of the study was to analyse such factors as the age and sex of patients, disease duration, as well as the hormonal status before ¹³¹I application, which could have an influence on the effects of therapy with radioiodine ¹³¹I.

Material and methods

The study involved 500 randomly selected patients with hyperthyroidism, treated with ¹³¹I radioiodine. The following 3 groups were defined: group 1 – patients with multinodular goitre (MNG), n = 200; group 2 – patients with a single autonomous nodule of the thyroid (AFTN), n = 100; group 3 – patients with Graves’ disease (GD), n = 200. The local ethics committee (in the Polish Mother''s Memorial Hospital – Research Institute, Lodz) approved the study.

Results

The obtained results indicate that the efficacy of therapy with ¹³¹I applied in patients with MNG, AFTN and GD does not depend on either patient sex or patient age. The length of antithyroid treatment before ¹³¹I therapy onset does not appear to have any effect on the therapy outcome, and the baseline thyrotropin concentration seems to be significant only in the case of GD.

Conclusions

The analysed demographic factors do not affect the outcome of ¹³¹I therapy in hyperthyroidism.     

Influence of thyroid volume reduction on calculated dose in radioiodine therapy of Graves' hyperthyroidism

Administration of radioactive iodine (131I) is an effective treatment for hyperthyroidism due to Graves' disease. Recently several investigators have shown that the success of this therapy may depend on the absorbed dose to the thyroid. Thyroid dose varies inversely with the mass of the gland. Much experimental evidence demonstrates that a reduction of the thyroid volume (mass) may occur after radioiodine therapy. In this work we evaluate the influence of the volume reduction on the calculation of the absorbed dose to the thyroid. A mathematical model of thyroid mass reduction after 131I therapy is presented, based on masses evaluated with ultrasonography of ten patients treated in the endocrinology department of our hospital. This model was applied to the general formula for calculation of the thyroid doses in these patients. The dose values obtained considering a reduction of thyroid mass after the treatment are often quite different from those obtained without considering change in mass (from 9% to 30% greater). We conclude that the consideration of thyroid mass reduction is important for an accurate estimation of the calculated dose.     

Use of corticosteroids to prevent progression of Graves' ophthalmopathy after radioiodine therapy for hyperthyroidism

We studied the effects of radioiodine treatment of hyperthyroidism due to Graves' disease on Graves' ophthalmopathy and the possible protective role of corticosteroids. Between June 1985 and June 1988, 26 patients were randomly assigned to treatment with radioiodine alone (group 1) and 26 to treatment with this agent and concomitant administration of systemic prednisone for four months (group 2). The initial dose of prednisone was 0.4 to 0.5 mg per kilogram of body weight for one month; the drug was gradually withdrawn over the next three months. All patients were evaluated at 3-month intervals for 18 months after they underwent radioiodine therapy. Ocular changes were assessed with the ophthalmopathy index; patients with moderate-to-severe changes (scores greater than or equal to 4) were excluded from the study. Before treatment, 10 patients in group 1 and 5 in group 2 had no evidence of ophthalmopathy: in none of them did ocular symptoms appear after radioiodine therapy. Among the patients in group 1 with an initial ophthalmopathy index greater than or equal to 1, ocular disease worsened in 56 percent (mostly involving soft-tissue changes and extraocular-muscle function) and did not change in 44 percent. In contrast, ophthalmopathy improved in 52 percent and did not change in 48 percent of group 2. The mean ophthalmopathy index increased from 1.5 to 3.0 in group 1 (P less than 0.005) and decreased from 2.2 to 1.3 in group 2 (P less than 0.05). We conclude that systemic corticosteroid treatment prevents the exacerbations of Graves' ophthalmopathy that occur after radioiodine therapy in a substantial proportion of patients with hyperthyroidism who have some degree of ocular involvement before treatment.     

CT引导水冷循环微波消融在肺癌治疗方面的应用

肺癌的发病率及死亡率居各种恶性肿瘤首位,并且有逐渐上升趋势,手术是主要的治疗手段。但大多数患者确诊时已是中晚期,失去手术机会而采用化疗放疗等其它方法,由于其毒副反应及耐药等原因使治疗有一定局限性。我院于2008年采用微波消融术治疗肺癌,利用微波对蛋白质的热凝固作用,使肿瘤细胞凝固坏死,操作简单,拓展了肿瘤治疗的新途径。现将CT引导水冷循环微波消融在肺癌治疗方面的应用报告如下。     

Treatment of a Down's syndrome patient for hyperthyroidism with radioactive iodine

A Down''s syndrome patient was hospitalized for evaluation of vomiting, abdominal pain, and a history of weight loss. A subsequent workup revealed that she had hyperthyroidism. The treatment of choice was radioactive iodine therapy. The patient had a history of consistent nausea and incontinence for urine and feces. Special problems posed by the patient and radiation safety are discussed.     

Feasibility study of hydrolyzable polyrotaxanes aiming at implantable materials

Hydrolyzable polyrotaxanes, in which many α-cyclodextrins (α-CD) are threaded onto a poly(ethylene glycol) (PEG) chain capped withl-phenylalanine via ester linkages, were synthesized to estimate the supramolecular dissociation via terminal ester hydrolysis. The polyrotaxane showed unique thermoresistant properties due to the supramolecular structure. The supramolecular structure was completely dissociated by terminal ester hydrolysis. PEG hydrogels cross-linked with the polyrotaxane were prepared as new candidate implantable materials for tissue engineering. It is suggested that controlling the rate of terminal ester hydrolysis and the following supramolecular dissociation may dominate the disappearance of the hydrogel. These findings will be of great importance for designing a scaffold based on the primary structure of the polyrotaxane that shows dual characteristics of excellent mechanical properties and perfect disappearance from an implanted site.     

clock基因干扰质粒的构建及干扰效率测定

目的：构建clock基因的干扰质粒，为深入研究clock基因在信号转导通路中的作用提供有效手段。方法：采用M-folder生物软件选择2个clock基因干扰位点，并根据3个干扰片段及一个阴性对照片段，定向克隆到pGenesil-1干扰载体并测序验证。将干扰质粒及对照质粒分别转染至NIH3T3细胞，并通过检测RT-PCR产物量以获得干扰效率。结果：RT-PCR产物捡测结果显示干扰质粒pGenesil-1／clock-Ⅱ干扰效率最高，其clock表达量降低了74％，而pGenesil-1／clock-Ⅰ干扰组clock表达量只降低了2％。结论：成功构建了对clock基因具有显著干扰效率的pGenesil-1／clock-Ⅱ干扰质粒，为进一步研究clock基因的功能奠定了基础。     

Treatment of pyruvate carboxylase deficiency with high doses of citrate and aspartate

A patient with severe pyruvate carboxylase deficiency presented at age 11 weeks with metabolic decompensation after routine immunization. She was comatose, had severe lactic acidemia (22 mM) and ketosis, low aspartate and glutamate, elevated citrulline and proline, and mild hyperammonemia. Head magnetic resonance imaging showed subdural hematomas and mild generalized brain atrophy. Biotin-unresponsive pyruvate carboxylase deficiency was diagnosed. To provide oxaloacetate, she was treated with high-dose citrate (7.5 mol/kg(-1)/day(-1)), aspartate (10 mmol/kg(-1)/day(-1)), and continuous drip feeding. Lactate and ketones diminished dramatically, and plasma amino acids normalized, except for arginine, which required supplementation. In the cerebrospinal fluid (CSF), glutamine remained low and lysine elevated, showing the treatment had not normalized brain chemistry. Metabolic decompensations, triggered by infections or fasting, diminished after the first year. They were characterized by severe lactic and ketoacidosis, hypernatremia, and a tendency to hypoglycemia. At age 3(1/2) years she has profound mental retardation, spasticity, and grand mal and myoclonic seizures only partially controlled by anticonvulsants. The new treatment regimen has helped maintain metabolic control, but the neurological outcome is still poor.     

The dynamics of reciprocal aiming with a steering wheel

The study of speed–accuracy trade-offs has a long history in scientists’ attempts to understand human movement control. In most such studies of reciprocal aiming, participants have been required to make reaching or pointing movements in space to targets of varying size. We wished to extend this body of work to a situation in which participants had to use a steering wheel in order to move a cursor on a computer monitor. Our results revealed a positive linear relationship between movement times and movement difficulty. We also observed an increased contribution of nonlinear dynamical terms as the movement difficulty increased. These results are consistent with the claim that a linear speed–difficulty relationship is a general feature of human motor control and one which is effector-independent. These results have relevant application to the study of human driving performance.