Literature
Home医学教育学术活动

第12届国际甲状腺大会热点 （2000-10）

来源：医业网
摘要：第12届国际甲状腺大会热点2000年10月22-27日日本京都ConferenceReportHighlightsofthe12thInternationalThyroid......

点击显示 收起

 

第12届国际甲状腺大会热点

2000年10月22-27日

日本京都

Conference Report
Highlights of the 12th International Thyroid Congress
October 22-27, 2000
Kyoto, Japan

Leonard Wartofsky, MD

 

Introduction

The 12th International Thyroid Congress in Kyoto, Japan, was a joint meeting of the American Thyroid Association, the Asia & Oceania Thyroid Association, the European Thyroid Association, and the Latin American Thyroid Society. Each of the 4 sister world thyroid associations presented their highest awards for outstanding research. The winner of the Van Meter Prize of the American Thyroid Association was Dr. A.N. Hollenberg; Dr. R. DiLauro was awarded the Merck Prize of the European Thyroid Association; Dr. S. Yamashita presented the Award Prize Lecture for the Asia & Oceania Thyroid Association, and Dr. A. Bianco gave the Prize Lecture for the Latin American Thyroid Society. This report will provide highlights of the latest clinical research on thyroid disease presented at the conference.

Subclinical Hypothyroidism

Subclinical hypothyroidism is generally defined as mild thyroid failure. It is characterized by normal values for total and free thyroxine (T4) or triiodothyronine (T3) and elevated serum thyrotropin (TSH) levels. However, since the thyroid affects so many bodily systems, patients often exhibit other, seemingly unrelated symptoms that may in fact be linked to the hypothyroidism.

Gasparyan and colleagues,[1] evaluated 160 patients, all of whom had "masked" hypothyroidism, but fit the above clinical definition. In addition, all of the patients demonstrated evidence of myocardial dysfunction, 90% demonstrated a form of vasomotor rhinitis, and 38% demonstrated ventilation abnormalities. All of the symptoms improved with L-thyroxine therapy.

L-thyroxine was also used by Brenta and coworkers[2] to normalize the time to peak diastolic filling. Multigated radionuclide ventriculography found it to be significantly delayed in patients with mild thyroid failure compared with controls, but restored to normal values with L-thyroxine therapy. Similarly, Monzani and colleagues[3] studied ventricular function before and after L-thyroxine therapy in 20 patients with a mean TSH of 5.32 +/- 1.80 using echocardiogram Doppler and ultrasonic videodensitometry. The abnormal findings correlated with TSH levels and were reversible in the thyroxine-treated group but not in the placebo treated group.

By contrast, Kamel and colleagues[4] Turkey, observed no improvement in serum lipids in 15 patients with mild thyroid failure (mean TSH = 8.3 mU/L) after L-thyroxine treatment. Rosenson and associates[5] compared lipoprotein subclasses in a group of 50 patients with those in age- and sex-matched data from the Framingham Study. Patients were found to have an increase in small, dense low-density lipoprotein (LDL), which is a dyslipidemia associated with atherogenesis. Finally, Weycker and coworkers[6] from Policy Analysis, Inc, calculated the risk for coronary artery disease in patients with mild thyroid failure. Approximately 3% of men and 6% of women in the study group had an elevated TSH level and were found, respectively, to have a 1.16-1.24 and 1.01-1.28 fold risk of coronary artery disease over 10 years.

Given the known association of hypothyroidism with hypercholesterolemia, Fatourechi and associates[7] explored whether patients with atherosclerotic coronary artery disease might have a higher prevalence of elevated TSH levels. Although the data indicated a very slight increase in prevalence, it was unclear whether this increase was a risk-related phenomenon, or if it resulted from the tendency of physicians to refrain from prescribing L-thyroxine to patients with coronary disease and only mild increases in TSH.

Following in the theme of detecting and treating mild disease, Lankarani and colleagues,[8] attempted to determine the likelihood of progression from mild thyroid failure to overt hypothyroidism. They found that initial TSH was a strong predictor, with disease progression seen in 36% of patients with TSH > 6.0 mU/L, in 48% of patients with TSH > 7.0 mU/L, and in 67% of those with TSH > 9.0 mU/L. Positive antimicrosomal antibodies to thyroid peroxidase (TPO) were another strong predictor of progression. Progression to overt hypothyroidism was also examined by Pankiv and coworkers[9] who found that 36% of 105 women in their cohort progressed to hypothyroidism, 15% normalized their TSH levels, and 49% remained unchanged. Confirming the results of Lankarani and colleagues, Dr. Pankiv found that TSH > 5-10 mU/L and the presence of antibodies were predictive of progression.

Graves' Ophthalmopathy and/or Thyrotoxicosis

Diagnosis and Pathogenesis

One of the difficulties in the diagnosis of Graves' ophthalmopathy is distinguishing between active and inactive ophthalmopathy. Rendl and coworkers[10] proposed that because of the involvement of cytokines in the orbital inflammatory process, 123-iodine radiolabeled interleukin-2 (123I IL-2) may prove to be an effective imaging agent to distinguish between active and inactive ophthalmopathy. In addition, 123I provides approximately half of the radiation exposure as 111-indium-octreotide scanning. Although results on only 4 patients were reported, the 2 with active disease showed significantly more 123I IL-2 uptake than the 2 patients with less active ophthalmopathy. The researchers concluded that the technique may be useful in determining which patients might benefit from anti-inflammatory therapy, such as corticosteroids or orbital irradiation.

The pathogenesis of Graves' disease also remains controversial. Working under the theory that intraorbital alterations in T4 to T3 conversion resulting in lower free T3 might be involved in the pathogenesis of ophthalmopathy, Molnar and colleagues[11] measured antibodies against the type 2 5'-deiodinase. Results were positive in 16 of 34 patients with ophthalmopathy, in 3 of 25 patients without ophthalmopathy, and in 0 of 13 control patients. Moreover, serum free-T3 levels were inversely related to the measured autoantibodies, suggesting a possible pathogenetic role for the type II 5'-deiodinase antibody.

Because adhesion molecules -- such as soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble endothelial leucocyte adhesion molecule-1 (sELAM-1) -- may be increased in inflammatory conditions, Wakelkamp and associates[12] compared levels of adhesion molecules in 62 patients with Graves' ophthalmopathy and 62 controls. Serum levels measured by enzyme-linked immunosorbent assay (ELISA) were higher in the Graves' patients. Smoking was associated with higher levels of sICAM-1 and lower levels of sVCAM, but there was no correlation between levels of adhesion molecules and the clinical activity score of the ophthalmopathy or the degree of control of thyrotoxicosis; however, the levels did correlate to the severity of ophthalmopathy.

It has been theorized that antigens shared by the thyroid and the orbit may play a role in the pathogenesis of ophthalmopathy. Several decades ago, Kriss and coworkers[13] hypothesized that transport of thyroglobulin occurs from the thyroid to the orbits via lymphatic channels. Evidence supporting this theory was presented by Marino and colleagues[14] of who found retrobulbar tissues from Graves' patients that contained thyroglobulin whereas tissue from control patients did not. Moreover, captured thyroglobulin was shown to contain thyroid hormone residues, thereby proving its origin from the thyroid gland.

Treatment: Orbital Irradiation

Standard therapeutic approaches to ophthalmopathy include corticosteroids given either orally, by retrobulbar injection, or by pulse intravenous injection. In some cases, greater benefit has been seen with combined oral steroids and external radiotherapy. Buescu and colleagues[15] studied 19 patients treated with combination pulse/oral steroids, 10 of whom failed to respond and were then treated with orbital irradiation. Significant improvement was seen in 6 of 10 patients and mild improvement was seen in 3 of the 10. The authors therefore recommend considering radiation for patients failing to improve after corticosteroids. When both treatments fail, however, switching to a more powerful steroid therapy may be warranted. Heufelder and colleagues[16] reported on a series of 16 patients treated with methotrexate who had previously failed on steroid or orbital radiation therapy. Of the 16 patients studied, 12 showed improvement based upon blinded analysis of a number of parameters.

The use of orbital radiation in severe ophthalmopathy has been generally accepted, but Prummel and coworkers[17] examined whether radiation treatment might also benefit patients with mild or early-stage ophthalmopathy. Eighty-eight patients who had been euthyroid for at least 2 months and had only mild ophthalmopathy were randomized to either orbital or sham radiation therapy. Response rates were clearly better in the radiated patients (52%) than in the controls or even as seen spontaneously in the natural history of the disease (27%). However, the improvements seen in most parameters were minimal, and, from the authors' perspective, routine use of orbital radiation for mild disease is not warranted.

Much better results with orbital irradiation for more severe ophthalmopathy have been previously reported by the Prummel and colleagues,[18] but the efficacy of this therapeutic modality even in severe disease has been called into question by Gorman.[19] In a randomized placebo-controlled study of 42 patients, one eye was irradiated with 20 Gy and the other eye served as the control; the sequence was reversed after 6 months. No significant differences between the irradiated and sham irradiated orbits were noted.

In the discussion after the paper presentation, Dr. Prummel emphasized the need to incorporate a quality of life (QOL) evaluation in assessing responses. Dr. Gorman's study, he noted, analyzed responses to therapy using objective criteria only. This sentiment was echoed by Terwee and associates[20] who described their use of an instrumental guide to assess QOL in patients with Graves' ophthalmopathy, particularly in regard to the patient's acceptance of physical appearance and visual function. With a change of 6 points, defined as significant improvement, treatment by orbital decompression, radiotherapy, and eye muscle surgery were associated with improved scores of 20.3, 8.1, and 2.8, respectively. The authors maintain that comparisons of various therapies are less than optimal unless QOL is taken into account.

Treatment: Anti-inflammatory Agents

Based upon the existence of an inflammatory response in ophthalmopathy, Stamato and colleagues[21] investigated whether treatment with anti-inflammatory agents such as colchicine might be beneficial. They treated a total of 20 patients with active inflammatory ophthalmopathy with 10 receiving colchicine and 10 receiving corticosteroids. All patients exhibited some clinical improvement on magnetic resonance imaging (MRI) and clinical activity scores, with amelioration of the inflammatory response in 100% of the colchicine-treated patients and in 85% of the steroid-treated patients.

Treatment: Radioactive Iodine Therapy

Walsh[22] of Nedlands, Australia, reported on the results of survey to assess clinicians regarding preferences for treating Graves' disease. The survey was modeled on those previously conducted Europe by Glinoer and colleagues[23] and in the United States by Wartofsky and colleagues.[24] The results from Australia were similar to those seen in Europe, but were in marked contrast to practice patterns in the United States. In Australia, 81% of respondents indicated they would treat a typical patient with antithyroid drugs, 19% would employ radioactive iodine (RAI), and none selected surgery as a standard therapy. For those patients with ophthalmopathy, respondents noted that RAI would likely be completely avoided.

It has been reported that thiourea pretreatment in Graves' disease has a radioprotective effect, and that subsequent RAI therapy would therefore be required in higher doses. This notion was disputed by Koerber and coworkers[25] who retrospectively compared 753 patients with autonomous nodular thyroid disease and 155 patients with Graves' disease variously treated with methimazole or carbimazole. They found that prior thiourea therapy had no effect on the success of RAI treatment.

The International Atomic Energy Agency in Vienna, Austria, sponsored an international multicenter randomized trial to assess the incidence of hypothyroidism after RAI therapy for Graves' disease using doses of either 60 Gy or 90 Gy. The ultimate goal is to develop a standardized treatment protocol. Kumar colleagues[26] described the results to date seen in 85 patients. There was no difference in the incidence of hypothyroidism at 2 years posttreatment, but therapy with 90 Gy tended to produce both an earlier clinical response and earlier hypothyroidism. In a separate study, Dr. Kumar[27] prospectively analyzed the effect of a variety of parameters on the propensity to develop post-RAI hypothyroidism in 104 patients with Graves' disease. The most significant influences were higher dosages of RAI, relatively younger age, or prior administration of lithium, which has been found to increase intrathyroidal RAI retention.

Treatment: Antithyroid Agents

Free radical overexpression is thought to be associated with a state of oxidative stress in Graves' disease. Abalovich and associates[28] found an abnormal oxidant/antioxidant balance in 69 patients with Graves' disease compared with that in 19 controls. Although indicators of abnormal oxidative status were restored toward normal after treatment with either methimazole (20 patients) or RAI (10 patients), methimazole was more effective.

On occasion, treating patients with thyrotoxicosis with propylthiouracil (PTU) or methimazole is not feasible because the patients are unable to swallow or are otherwise restricted from oral medications. However, thiourea treatment may still be highly desirable, especially in patients with thyroid storm. Although there are no intravenous preparations available, studies have indicated that rectal administration may be an effective way to deliver the drug.[29] In a study designed to compare the efficacy and bioavailability of a 400-mg dose of PTU given by either suppository or by enema, Jongjaroenprasert and coworkers[30] observed that either route would comparably reduce serum free T3. Nevertheless, earlier peak blood levels were seen with the enema.

In most centers, the duration of antithyroid drug therapy averages between 1 and 2 years, but some patients are treated for longer (or shorter) periods. Liu and colleagues[31] examined the effect of duration of treatment on remission rates and TSH receptor antibody titers. A higher relapse rate was seen in patients treated for only 6 months, but 36 months of treatment appeared to offer no advantage over 18 months of treatment. Although there was a reciprocal relationship between TSH-receptor titers and duration of therapy, with the lowest levels seen after 36 months, the authors suggest that treatment for longer than 18 months should not be necessary.

Glinoer and colleagues[32] examined the influence of smoking, thyroxine administration, and TSH-receptor antibody titers on relapse and remission rates after antithyroid drug therapy. Eighty-two patients were treated with thiourea for 15 months plus L-thyroxine for 12 months followed by continued thyroxine or placebo for another 12 months. Consistent with recent reports, recurrence rates were not altered by L-thyroxine therapy. By contrast, cigarette smoking and titers of TSH receptors were found to be independent predictors of recurrence after the withdrawal of thiourea.

Agranulocytosis is a dreaded and fortunately rare complication of antithyroid drug therapy. Kato and coworkers[33] described the characteristics of 17 patients and their responses to steroid or granulocyte-stimulating colony factor (G-CSF) therapy. Eight of 17 patients developed the complication upon resumption of medication following multiple discontinuations, indicating that poor compliance was a risk factor. On average, agranulocytosis occurred 48 and 16 days after initiation of methimazole or PTU therapy, respectively. Neither corticosteroids or G-CSF treatment accelerated the recovery of white blood cell counts.

Miscellaneous Findings

Thyrotoxic individuals are known to occasionally express personality disorders, and, rarely, sociopathic or criminal behavior. The clinical characteristics of 15 patients with Graves' disease and thyrotoxicosis who were referred by a correctional institution for evaluation were reported by Hennessey and colleagues.[34] Five of the 15 had committed violent crimes. Several of the individuals demonstrated a temporal relationship between onset of their disease and commission of their crimes, suggesting a relationship between the two.

Thyrotoxicosis, especially when untreated, is known to have an adverse effect on bone mineral density (BMD). Several published studies have shown that restoration of euthyroidism will have a salutary effect on bone density.[35] Arata and colleagues[36] examined the changes in BMD in a small group of 11 women aged 35-70 years. With attainment of euthyroidism, BMD peaked by 12-24 months and was restored to normal by 5 years. Notably, it does not seem to matter whether the treatment for thyrotoxicosis is medical or surgical. Ismailov and coworkers[37] reported that in 51 patients, BMD was restored to normal values 12 months after subtotal thyroidectomy.

Thyroid Cancer

Diagnosis: Detecting Thyroglobulin

Kloos and colleagues[38-41] reported on several different studies related to a comparison of the Nichols Institute Diagnostics (N) and Brahms Diagnostica (B) thyroglobulin (Tg) assays. One study examined detectability of serum Tg on thyroxine TSH suppression and found undetectable Tg in 98% of patients by the N assay compared with 90% of patients by the B assay in patients free of disease as indicated by negative radioiodine scans. However, in patients with demonstrated metastatic disease, detectable Tg was seen in 4% and 7% of samples by the N and B assays, respectively. In a study[41] that measured patients' sera after thyroxine withdrawal, the highest Tg levels seen in patients free of disease with negative radioiodine scans was 1.8 ng/mL by N assay and 1.0 ng/mL by the B assay. In patients with known metastatic disease, the lowest Tg levels noted were 8.2 ng/mL by N assay and 3.2 ng/mL by the B assay.

It had been proposed that the problem of interfering anti-Tg antibodies may be circumvented by loading the sera with known quantities of Tg and measuring the Tg before and after, known as the 'recovery' technique. Kloos and colleagues[39] spiked sera with either 1 or 50 ng/mL of Tg, but still found significant interference and difficulty assessing true Tg levels in the presence of anti-Tg antibodies.

The relative utility of the 2 assays measuring Tg after recombinant human TSH (rh-TSH) stimulation was also examined by Kloos and colleagues.[40] The lowest stimulated Tg levels were 4.4 ng/mL by N assay and 1.7 ng/mL by B assay in patients with known metastases; the highest values -- ie, 4.7 ng/mL by N assay and 2.2 ng/mL by B assay -- were seen in patients with negative rh-TSH scans. The B assay for Tg was cast in a more positive light by Rendl and associates[42] of Hennigsdorf, Germany, whose data demonstrated that the B assay showed improved precision at low Tg concentrations and was not as affected by the high-dose "hook effect"; they emphasized that the recovery method could obviate most problems with interfering anti-Tg antibodies. (Large amounts of antigen may produce falsely low values in immunoradiometric assays due to the so-called high-dose hook effect.)

It was proposed by Fatemi and coworkers[43] that monitoring anti-Tg antibodies may provide additional evidence of the presence of tumor, and may serve as a tumor marker as do the serum Tg levels themselves. Of 27 patients who were Tg-antibody-positive, 12 became Tg-antibody-negative during follow-up and were found to be free of disease, 7 had rising Tg-antibody and were found to have metastatic disease, and 7 others had persistent Tg-antibody levels and demonstrable residual disease. They concluded that when serum Tg is undetectable, the absence of anti-Tg antibodies can confirm the absence of disease, whereas measurable anti-Tg antibodies may serve as a tumor marker. Similarly, Park and colleagues[44] found evidence of recurrent disease in 63.6% (21/33) of patients with undetectable serum Tg but positive anti-Tg antibodies.

Diagnosis: Scanning

The utility of post-radioiodine treatment scans has been previously questioned by Cailleux and colleagues,[45] as they provide new information on metastases in only 10% of patients. Cailleux[46] further questioned whether pretreatment diagnostic scans were necessary if serum Tg was measurably elevated. This issue was studied by Ceccarelli and colleagues[47] who examined whether patients with undetectable Tg might show evidence of disease on a diagnostic scan. Of 662 patients being evaluated, 347 had detectable serum Tg; the remaining 315 patients served as the study group. All patients scanned negative for metastases, but 120 (38%) showed evidence of some uptake in the thyroid bed. Subsequent follow up demonstrated that 99.4% of the patients were disease-free, with 2 patients (0.6%) having positive disease in lymph nodes. In 29 patients, persistent faint thyroid bed uptake was dismissed as not significant because serum Tg was undetectable. The authors concluded that a finding of low serum Tg at the first annual follow-up evaluation was highly predictive of absence of disease, and that routine diagnostic scans could be omitted in these patients.

Park and Hennessey[48] examined the relative efficacy of a 1-week vs 2-week ambulatory low-iodine diet in sufficiently lowering the body's iodine pool to facilitate radioisotope scanning and potential therapy. The goal was an iodine/creatine (I/Cr) ratio of < 50 mcg/g. No patients achieved the goal ratio after 1 week, but 75% did achieve the goal after 2 weeks. The average ratios were 194 and 67 for 1 and 2 weeks, respectively. Nevertheless, 2 weeks may not be completely adequate preparation for scanning and therapy.

The utility of preoperative fluorodeoxyglucose-positron emission tomography (FDG-PET) to detect metastases in lymph nodes was examined by Lee and coworkers[49] in 22 patients with papillary carcinoma. Of the 85 surgically excised lymph nodes, 56 were positive for disease, and of the 56, the FDG-PET scan was positive in 45, providing a sensitivity of 80%.

The use of recombinant human (rh)-TSH to detect residual thyroid tumor in patients with undetectable serum Tg while on L-thyroxine suppression was reported by Wartofsky.[50] Serum Tg was measured 72 hours after injection of 0.9 mg rh-TSH on 2 successive days in patients with differentiated thyroid cancer thought to be free of disease. Patients who were 1-10 years postthyroidectomy and had no history of metastatic disease or anti-Tg antibodies. Serum Tg increased significantly in 15% of the patients, indicating that further evaluation was required. Lippi and associates,[51] using the same protocol in 40 patients, observed a response in serum Tg in 20 patients (50%); they demonstrated residual disease in 16 patients by radioiodine scanning, and in the remaining 4 patients by other imaging studies. Of the 20 patients with no Tg response to rh-TSH, the scan was negative in 17 with the remaining 3 showing a small amount of thyroid bed uptake. The use of rh-TSH in this manner appears to distinguish patients who are likely free of disease from those requiring further evaluation and continued follow-up.

Treatment

Given the dismal results of therapy for undifferentiated thyroid cancer, researchers have been exploring alternative experimental modes of treatment for these tumors. Pisarev[52] presented data on results achieved with boron neutron capture therapy. The approach relies on the uptake of boronated compounds followed by radiation with a neutron beam. This causes the radioactive boron to release alpha particles, which damage the host cells. The technique was applied to in vitro primary cultures of thyroid cells and a cell line of undifferentiated thyroid cancer, as well as to in vivo tumors transplanted to nude mice. Sufficient cellular concentration and probable radiation doses were achieved to warrant further study of these technique for undifferentiated thyroid tumors.

Besic and colleagues[53] achieved local control of undifferentiated anaplastic carcinoma in 15 patients using doxorubicin combined with hyperfractionated radiotherapy of either 1.2 or 1.6 Gy by 2 different regimens. Six patients died from failed therapy and the median survival was 3 months. The majority of patients did benefit from some local control, but neither radiation regimen demonstrated superiority.

Radiation-induced Thyroid Cancer

Genetic Rearrangements

Rearrangement of the RET proto-oncogene in papillary thyroid carcinoma (RET-PTC) was evaluated in 30 patients who had received radiation during childhood by Collins and coworkers.[54] Antibody against the RET-tyrosine kinase domain, which is highly correlated with RET arrangements, was determined in tissue samples. When compared with 34 patients with papillary cancer who had not received radiation, the radiation-exposed group was found to have a higher percentage of RET-positive cancers (87.7% vs 52.9%). In addition, the RET-positive tumors tended to be smaller and more multifocal. The effects of radiation exposure from nuclear accidents on gene rearrangements were evaluated by Figge and colleagues.[55] They examined the frequency of RET-PTC rearrangements over time by comparing 42 surgical specimens from 1998 to those seen after the 1986 Chernobyl accident. Using PCR primers for RET-PTC-1 and RET-PTC-3, 21% of the cases were positive for RET-PTC-1 and 15% were positive for RET-PTC-3, confirming the continuing influence of the radiation exposure. Lower doses of radiation exposure were seen in Belarus after the Chernobyl accident. However, when Saenko and associates[56] studied 38 Russian children, they found RET-PTC-1 rearrangements in 18.4% and RET-PTC-3 in 15.7% -- frequencies that were comparable to earlier reports of post-Chernobyl tumors. Similar results were seen by Tuttle and colleagues[57] in surgical specimens from patients in Bryansk, Russia, who were under age 18 in 1986. RET-PTC rearrangements were seen in 24% of the evaluable papillary tumors.

Radiation and Autoimmunity

There are an estimated 800-1000 cases of thyroid cancer in children resulting from the Chernobyl-Belarus exposure. Zvonova[58] analyzed the doses of radiation received by children and teenagers in the 13 years since April 1986. The average maximum dose received by children under age 3 was approximately 2 Gy, with children in the most contaminated areas receiving as much as 10 Gy.

Studies have suggested that the appearance of autoimmune thyroid disease after radiation exposure is strongly related to both the size of the radiation dose and to an iodine deficient milieu. Ostapenko and coworkers[59] reported on a cohort of children who were under age 18 at the time of the Chernobyl accident -- 8400 children had been exposed to > 1 Gy, 3500 exposed to 0.3 to < 1 Gy, and 3500 to < 0.3 Gy. Anti-Tg or antithyroid peroxidase (anti-TPO) antibodies were found in 6.3%, with the highest prevalence (13.2%) found in girls aged 15-18 years. The greatest prevalence was seen in girls 15 years post-Chernobyl, of whom 26.9% had positive antibodies.

The occurrence of post radiation autoimmune thyroid disease, as indicated by the appearance of anti-Tg or anti-TPO antibodies, was also evaluated. Petrenko and colleagues[60] found a frequency of 6.23% of positive anti-Tg or anti-TPO antibodies. Shilin and colleagues[61] presented a meta-analysis of 9 different reports encompassing approximately 25,000 blood samples. Children with a history of radiation exposure demonstrated a significantly higher frequency of antibodies, particularly of the anti-TPO type. The study highlights the importance of continuing surveillance for late appearance of clinical autoimmune thyroid disease. Indeed, Shinlin[62] also reported a 3-fold risk of Graves' disease in children from the radiation-exposed areas of Belgorod, Orel, and Voronej where iodine deficiency is endemic. They found that the younger the patient, the earlier the onset of Graves' disease.

Diagnostic Characterization

Abrosimov and associates[63] compared the frequency of various histologic types of thyroid cancer post-Chernobyl to those seen in England and Wales. Although the solid/follicular variant of papillary carcinoma was seen in 80% of children from the Ukraine, that tissue type was seen in fewer children from Belarus and in only 35% of the UK patients. This tumor tended to be more common in younger patients, with the more classic papillary pattern seen in older children or adolescents. Drozd and coworkers[64] compared 3-dimensional (3-D) ultrasound examination to traditional 2-dimensional (2-D) ultrasound in patients with radiation-induced thyroid abnormalities. They found the 3-D technique to be superior to the 2-D technique in detecting nodules and estimating thyroid size.

In a symposium on radiation-related neoplasia, Yamashita and colleagues[65] reviewed the incidence of various thyroid abnormalities reported from 5 different centers around Chernobyl. There was a 0.1% to 0.2% incidence of elevated TSH in children, with a 1% to 2% incidence of positive anti-Tg and anti-TPO antibodies. In Gomel, the incidence of thyroid nodules was 1.6% compared with 0.2% to 0.5% in the other regions. Between the years of 1991-1997, there was an increasing prevalence of abnormal echogenicity, with 2% to 3% of patients demonstrating abnormalities. Of those subjected to fine-needle-aspiration cytology, 10.3% of the abnormalities proved to be neoplasms, 26% chronic thyroiditis, 7% cancer, and 22% adenomatous goiter.

Treatment

The relative success of 2 surgical approaches to the management of post-Chernobyl thyroid cancer was reported by Roumiantsev and colleagues.[66] The tumors were 89% papillary and 11% follicular, and were treated by either near total thyroidectomy and radioiodine or by an "organ-sparing," more conservative surgery, which is typically done outside of the central major hospital. The group treated with the more aggressive approach demonstrated a 10.1% incidence of recurrent laryngeal nerve palsies compared with a rather astounding 20.3% in the conservative-surgery group. Notably, 1.3% in the more aggressively treated group demonstrated residual or metastatic disease, but 48.6% demonstrated residual or metastatic disease with the organ-sparing approach.

A relatively good prognosis with traditional therapy was also reported by Reiners and colleagues.[67] They evaluated 199 cases of thyroid cancer (99% of which were papillary) in children who received surgery and a total of 694 courses of radioiodine therapy. The incidence of thyroid cancer was 0.2 cases per 100,000 persons prior to 1986 and reached 10.7 per 100,000 persons in 1999. Overall, 84% (142/169) had achieved complete remission when re-evaluated.

References

  1. Gasparyan EG, Korovina OV, Linkov VI, et al. Clinical masks of subclinical hypothyroidism. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-339.
  2. Brenta G, Mutti LA, Schnitman M, Fretes O, Perrone A, Matute ML. Diastolic function in subclinical hypothyroidism before and after treatment with thyroid hormones. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-461D.
  3. Monzani F, Caraccio N, Di Bello V, et al. Effect of L-T4 therapy on left ventricular function in subclinical hypothyroidism. A randomized double-blind placebo controlled study. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-589.
  4. Kamel N, Gullu S, Sav H, Baskal N, Tonyukuk V, Erdogan G. Effects of levothyroxine treatment on biochemical parameters in patients with overt and subclinical hypothyroidism. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-463.
  5. Rosenson R, Miller TF Jr, Otvos J, Ladenson P, Wartofsky L, Ridgway EC. Atherogenicity of serum lipoproteins in mild thyroid failure (MTF). Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-477/D.
  6. Weycker DA, Nguyen M, Miller T, Oster G. Excess coronary heart disease risk among persons with elevated thyroid stimulating hormone levels. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-563.
  7. Fatourechi V, Schryver PG, Lankarani M, et al. Increased prevalence of mildly elevated serum TSH levels in patients with coronary heart disease compared to controls. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-347.
  8. Lankarani M, Klee GG, Schryver PG, et al. Progression of hypothyroidism in patients with mildly elevated TSH (5-10 mU/L). Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-348/D.
  9. Pankiv V, Havryliuk V, Vatseba, A, et al. Long-term study of subclinical hypothyroidism: psychopathological and cognitive features. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-480.
  10. Rendl JE, Guthoff R, Schirbel A, et al. Iodine-123-interleukin-2 (I-123-IL-2) scintigraphy in Graves' ophthalmopathy (GO): a new approach to assess disease activity. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-004.
  11. Molnar I, Csathy L. Autoantibodies against the type 2 5'-deiodinase are involved in the development of Graves' ophthalmopathy. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-281.
  12. Wakelkamp IMMJ, Gerding MN, van der Meer JWC, Prummel MF, Wiersinga WM. Serum adhesion molecule levels in graves' ophthalmopathy (GO): effects of smoking and disease severity. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-350/D.
  13. Konishi J, Herman MM, Kriss JP. Binding of thyroglobulin and thyroglobulin-antithyroglobulin immune complex to extraocular muscle membrane. Endocrinology. 1974;95:434-446.
  14. Marino M, Pinchera A, Latrofa F, et al. Identification of thyroglobulin in orbital tissues of patients with thyroid associated ophthalmopathy. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract 358/D.
  15. Buescu A, Soares DV, Violante AHD, Vaisman M. Steroid pulse therapy and adjunctive external irradiation in the treatment of Graves' ophthalmopathy. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-182.
  16. Heufelder AE, Schworm HD, Heufelder G. Methotrexate in the treatment of refractory Graves' ophthalmopathy. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-002.
  17. Prummel MF, Terwee CB, Gerding MN, et al. A randomized placebo-controlled study on radiotherapy for mild Graves' ophthalmopathy: effects on clinical severity and quality of life. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-311.
  18. Prummel MF, Wiersinga WM. Medical management of Graves' ophthalmopathy. Thyroid. 1995;5:231-234.
  19. Gorman CA. Radiation and thyroid diseases. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Symposium.
  20. Terwee CB, Dekker FW, Mourits MP, et al. How to interpret changes in quality of life in patients with Graves' ophthalmopathy? Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract 180/D.
  21. Stamato F, Manso P, Paves L, et al. Colchicine versus prednisone in the clinical treatment of Graves' ophthalmopathy. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-003.
  22. Walsh, JP. Management of Graves' disease in Australia. Effect of ophthalmopathy on physicians' choice of treatment. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-001.
  23. Glinoer D, Hesch D, Lagasse R, Laurberg P. The management of hyperthyroidism due to Graves' disease in Europe in 1986. Results of an international survey. Acta Endocrinol Suppl (Copenh). 1987;285:3-23.
  24. Solomon B, Glinoer D, Lagasse R, Wartofsky L. Current trends in the management of Graves' disease. J Clin Endocrinol Metab. 1990;70:1518-1524.
  25. Koerber C, Koerber-Hafner N, Schneider P, Reiners C. Influence of thyrostatic medication on the success rate of radioiodine therapy? Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-038.
  26. Kumar R, Pandey AK, Padhy AK, et al. Standardisation of I-131 treatment for hyperthyroidism with an intent to optimise radiation dose and treatment response. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-153.
  27. Kumar R, Pandey AK, Padhy AK, et al. Factors effecting radioiodine induced hypothyroidism in Grave's disease. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-152.
  28. Abalovich M, Repetto M, Loto M, Llesuy S, Alcaraz G, Gutierrez S. Peripheral parameters of oxidative stress in Graves' disease. The effects of methimazole and 131-Iodine treatments. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-158/D.
  29. Bartle WR, Walker SE, Silverberg JD. Rectal absorption of propylthiouracil. Int J Clin Pharmacol Ther Toxicol. 1988;26:285-287.
  30. Jongjaroenprasert W, Akarawut W, Chantasart D, Chailurkit L, Rajatanavin R. Comparative bioavailability and pharmacologic effect of propylthiouracil in thyrotoxic patients following rectal administration: enema vs. suppository. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-190.
  31. Liu C, Yu D, Wu X. Prospective study on the relationship between treatment duration of antithyroid drug and remission rate of Graves' disease. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-191/D.
  32. Glinoer D, Nayer DE, Bex M, The Belgian Collaborative Study Group on Graves' disease. Impact of thyroxine (T4) administration, TSH - receptor antibody (TSHR-Ab) and smoking, on the risk of recurrence in Graves' disease (GD) patients treated with antithyroid drugs (ATD): a prospective double-blind randomized trial. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-303.
  33. Kato K, Tushima T, Isozaki O, Megumi M, Mishimaki M, Takano K. Antithyroid agents induced agranulocytosis: analysis of the clinical characteristics of 17 cases treated in our institute. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. P-486.
  34. Hennessey JV, Tremont G, Hall K, Spaulding A. Characteristics of Graves' disease among incarcerated individuals. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-484.
  35. Langdahl BL, Loft AG, Eriksen EF, Mosekilde L, Charles P. Bone mass, bone turnover, body composition, and calcium homeostasis in former hyperthyroid patients treated by combined medical therapy. Thyroid. 1996;6:161-168.
  36. Arata N, Maruyama H, Saruta T. Longitudinal changes in bone mineral density (BMD) of thyrotoxic women following correction of thyroid function with antithyroidal drug treatment. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract 497/D.
  37. Ismailov SI, Babakhanov BK. Longitudinal changes in bone mineral metabolism and hormonal status in young surgically treated patients with Grave's disease. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-567.
  38. Kloos RT, Stewart J, Nagaraja NH, Mazzaferri EL. Comparison of Nichols and Brahms Diagnostica DYNOtest thyroglobulin plus assays in patients with thyroid carcinoma during TSH suppression. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-010.
  39. Kloos RT, Stewart J, Nagaraja NH, Mazzaferri EL. Low and high dose thyroglobulin recovery tests with Brahms diagnostica Bynotest thyroglobulin plus assay in thyroid cancer for interfering antithyroglobulin antibodies. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-114.
  40. Kloos RT, Stewart J, Nagaraja NH, Mazzaferri EL. Comparison of Nichols thyroglobulin and Brahms Diagnostica DYNOtest thyroglobulin plus assays after recombinant human TSH stimulation in thyroid cancer patients. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-113/D
  41. Kloos RT, Stewart J, Nagaraja NH, et al. Comparison of Nichols thyroglobulin assay and Brahms Diagnostica DYNOtest thyroglobulin plus assay in patients with differentiated thyroid cancer studied after thyroid hormone withdrawal. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-112D.
  42. Rendl J, Bergmann A, Froehlich J, et al. A new sensitive assay improves reliability of thyroglobulin determination in the follow up of patients with thyroid carcinoma. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-117/D.
  43. Fatemi S, Nicoloff J, LoPresti J, Guttler R, Carole S. Clinical significance of serial serum TG autoantibody (TGab) patterns in patients with differentiated thyroid carcinomas (DTC). Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-011.
  44. Park YJ, Kim TY, Lee SI, et al. Clinical significance of elevated level of serum anti-thyroglobulin antibody in patients with differentiated thyroid cancer after thyroid ablation. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-012.
  45. Cailleux AF, Baudin E, Travagli JP, Ricard M, Schlumberger M. Is diagnostic Iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer? J Clin Endocrinol Metab. 2000;85:175-178.
  46. Cailleux AF, Baudin E, Travagli JP, Ricard M, Schlumberger M. Is diagnostic iodine-131 scanning useful after total thyroid ablation for differentiated thyroid cancer? J Clin Endocrinol Metab. 2000 Jan;85(1):175-178.
  47. Ceccarelli C, Capezzone M, Sculli M, et al. After total thyroidectomy and thyroid residue ablation, routine diagnostic 131-I whole body scan may be omitted in thyroid cancer patients who have undetectable serum TG levels off L-thyroxine therapy. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-014.
  48. Park JT, Hennessey JV. Confirmation that a two-week low iodine diet is necessary for adequate preparation for 131-I scanning. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-102.
  49. Lee SJ, Yeo JS, Chung JK, et al. F-18-Fluorodeoxyglucose pet as a pre-surgical evaluation modality for I-131 scan negative thyroid carcinoma patients with local recurrence in cervical lymph nodes. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-103
  50. Wartofsky L. Clinical utility of rhTSH-stimulated thyroglobulin testing without scan in the follow-up of patients with well-differentiated thyroid cancer. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Short Call Abstracts SC-3.
  51. Lippi L, Molinaro E, Taddei D, et al. rhTSH stimulated thyroglobulin detects disease activity with high sensitivity in thyroid cancer patients. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-127/D.
  52. Pisarev MA. Perspective of a new treatment modality for undifferentiated thyroid cancer. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-098.
  53. Besic N, Auersperg M, Us-Krasovec M, Tomsic R. Local control rate in anaplastic thyroid carcinoma -- a combination of doxorubicin and radiotherapy performed three days a week versus five days a week. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-116.
  54. Collins BJ, Chiappetta G, Fogelfeld L, et al. RET expression in papillary thyroid cancer from patients irradiated in childhood for benign conditions. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract O-009.
  55. Figge JJ, Pisarchik AV, Ermak G, Kartel NA. The RET/PTC1 rearrangement is a common feature of papillary thyroid carcinomas from Chernobyl-contaminated regions of belarus twelve years after the accident. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. P-417.
  56. Saenko VA, Romei C, Elisei R, et al. Structural mutations of the RET gene in papillary thyroid carcinoma developed in children and adolescents of Russia after the Chernobyl accident. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-422.
  57. Tuttle RM, Fenton C, Lukes Y, et al. Activation of the RET/PTC oncogene in papillary thyroid cancer from Russian children exposed to radiation following the Chernobyl accident. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-437.
  58. Zvonova IA. Radioiodine impact on population of Russia after the Chernobyl accident: thyroid dose reconstruction, thyroid cancer morbidity and risk assessments. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-096.
  59. Ostapenko VA, Beebe G, Brill AB, et al. Prevalence of thyroid antibodies in the Belarus-USA study of thyroid cancer and other thyroid diseases following the Chernobyl accident. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-037.
  60. Petrenko S, Gomolko N, Daud A, Minenko V, Stezhko V, Ostapenko V. Humoral thyroid autoimmunity in the Belarus population affected by Chernobyl accident. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-061.
  61. Shilin DE, Petrova LM, Shilina SY, et al. Effects of iodine deficiency and different ways of its prevention on the thyroid status of newborns in Russia. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-222.
  62. Shilin DE. Some data about clinical state and history of radiation exposure in children with Graves' disease, residing at radiocontaminated due to Chernobyl accident areas of Russia. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-022.
  63. Abrosimov AY, Lushnikov EF. Histological characterization of papillary thyroid carcinoma in children and adolescents from Russia after the Chernobyl accident. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-074.
  64. Drozd VM, Lyshchik AP, Demidchik EP, Sidorov YD, Cherstvoy ED, Reiners C. 10 years of practical expiriense in diagnostic of radiation induced thyroid cancer in children of Belarus by ultrasound. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-080/D.
  65. Ishigaki K, Parshin V, Shklyaev S, et al. Urinary iodine levels and thyroid diseases in children; comparison between Nagasaki and Chernobyl. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-160/D.
  66. Roumiantsev PO, Vtyurin BM, Ilyin AA, et al. Efficacy of two different treatment strategies in young patients with well-differentiated thyroid carcinoma. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-075.
  67. Reiners C, Biko J, Demidchik YE, Drozd V. Results of treatment in 199 children from Belarus with advanced stages of thyroid cancer after the Chernobyl reactor accident. Program and abstracts of the 12th International Thyroid Congress; October 22-27, 2000; Kyoto, Japan. Abstract P-097/D.

作者：
医学百科App—中西医基础知识学习工具
  • 相关内容
  • 近期更新
  • 热文榜
    •
    医学百科App—健康测试工具