Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant TSH is effective in providing exogenous TSH stimulation for patients with differentiated thyroid cancer on thyroid hormone-suppressive therapy. It allows for detection of thyroid remnant and metastases by radioiodine scan and by serum thyroglobulin determination. The sensitivity and image quality of the WBS are similar after rTSH and after THSH withdrawal in the majority of patients. The equivalent 100% sensitivity of rTSH- and withdrawal-stimulated serum thyroglobulin measurement alone in identifying patients with radioiodine uptake outside the thyroid bed [38] may eventually lead to more extensive use of serum thyroglobulin testing after rTSH, with more selective application of radioiodine WBS [39]. Currently, a phase IV trial is in progress to evaluate the efficacy of rTSH-stimulated thyroglobulin levels as the primary modality for long-term follow-up of low risk thyroid cancer patients. The use of rTSH prevents the morbidity, metabolic impairment and the risk of tumor progression associated with THST withdrawal, because of shorter exposure time to elevated TSH [38]. Furthermore, it decreases the radiation exposure of healthy tissues due to faster iodine clearance in euthyroidism. rTSH is well tolerated, with transient nausea in 10.5% and headache in 7.3% of patients. No antibodies specific to rTSH were documented, even after multiple courses of the drug. Currently, rTSH is suggested for patients who do not respond to hormone withdrawal or cannot tolerate hypothyroidism. For patients with low risk of tumor recurrence, rTSH-stimulated testing may be used at 6-12 months after postoperative I-131 ablation and with a repeat cycle of rTSH one year later, followed by testing every 3-5 years. In high risk patients, one set of negative I-131 scan and thyroglobulin test results after hormone withdrawal are recommended before using rTSH testing, because of a greater sensitivity of the withdrawal scan and because rTSH is not currently approved for subsequent I-131 therapy often indicated in these patients [24]. Subsequently, two cycles of rTSH testing are recommended at 6-12 month intervals, followed by testing every 1-3 years for at least the first decade after initial diagnosis. The cost of this commercially available form of rTSH has been considered a major impediment to its common use; however, this should be weighed against the loss of productivity of working hours related to withdrawal [40]. In the therapeutic setting, rTSH is the only acceptable option in a subgroup of patients with hypopituitarism, ischemic heart disease, a history of "myxedema madness," debilitation due to advanced disease, or inability to elicit TSH elevation due to continued production of thyroxine by thyroid remnant or metastatic tumor [33,38]. In conclusion, recombinant TSH facilitates the management of patients with differentiated thyroid carcinoma. It increases the sensitivity of thyroglobulin testing during thyroid hormone suppression therapy and enables radioiodine uptake for whole-body scan and occasionally for radioiodine therapy, without the need for prolonged THST withdrawal and its associated hypothyroidism, reduced quality of life and risk of tumor progression.
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PMID:Recombinant thyroid-stimulating hormone in differentiated thyroid cancer. 1172 83

Treatment of persistent/recurrent differentiated thyroid cancer is based on surgery, when feasible, and malignant tissue ablation by 131I administration. This procedure requires levothyroxine withdrawal to obtain high levels of endogenous thyrotropin (TSH) to stimulate radioactive iodine uptake by the malignant tissue. Levothyroxine withdrawal may cause severe adverse effects and complications in patients with concomitant illness or advanced metastatic disease. The recent availability of recombinant human thyrotropin (rhTSH) allows diagnostic whole-body scan (WBS) and thyroglobulin testing without levothyroxine withdrawal. We describe six patients with metastatic differentiated thyroid cancer (DTC) and concomitant illness in whom the use of rhTSH was effective in preventing the complications that patients had previously experienced during hypothyroidism consequent to levothyroxine withdrawal. Our results indicate that rhTSH can be particularly advantageous to avoid signs and symptoms of hypothyroidism and complications because of associated diseases in view of 131I treatment of DTC metastases in selected cases in which levothyroxine withdrawal may be dangerous. Its efficacy to treat advanced metastatic disease should be further investigated.
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PMID:Usefulness of recombinant human thyrotropin in the radiometabolic treatment of selected patients with thyroid cancer. 1176 11

To determine whether (18)fluorodeoxyglucose-positron emission tomography (FDG-PET) for the detection of recurrences or metastases of differentiated thyroid carcinoma should be performed during thyrotropin (TSH) suppression or TSH stimulation, eight patients were studied sequentially. After the second FDG-PET scan, a therapeutic (131)I dose was administered with posttherapy scans obtained 10 days later. Both FDG-PET scans were compared with each other and with the (131)I posttherapy whole body scans by two independent observers. Findings were verified using other imaging modalities or biopsies. Median TSH was 0.04 mU/L during TSH suppression and 64 mU/L during TSH stimulation. The FDG-PET scans during TSH suppression showed abnormalities in four patients and the FDG-PET scan during TSH stimulation in five patients. One patient was only positive during TSH stimulation. In two other patients the FDG-PET scan during TSH stimulation clearly identified more lesions, and in all positive patients lesion contrast was better during TSH stimulation. In two patients FDG-PET findings during TSH stimulation led to a change in clinical management. Thus, the performance of FDG-PET during TSH stimulation was either superior or equal to FDG-PET during TSH suppression, but never inferior. To detect metastatic or recurrent differentiated thyroid carcinoma FDG-PET should be performed during hypothyroidism, leading to TSH stimulation.
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PMID:Better yield of (18)fluorodeoxyglucose-positron emission tomography in patients with metastatic differentiated thyroid carcinoma during thyrotropin stimulation. 1209 98

A case of a very rare combination of diffuse sclerosing variant of papillary thyroid carcinoma (DSPC) and primary squamous thyroid carcinoma (PSC) is presented. A 25-yr-old woman with right-sided neck mass and hypothyroidism was admitted. US showed that the right lobe of the thyroid gland was enlarged with irregular margins and heterogen echogenity and there were multiple small punctate echogenic foci in the central portion. A scintigraphy with 99mTc showed decreased uptake in the right lobe. FNA of the right lobe induced us to consider the presence of follicular neoplasm. Chest roentgenogram was normal. Total thyroidectomy with right-sided modified radical neck dissection was performed. Findings related to Hashimoto's thyroiditis and abundant psammoma bodies were observed in the frozen sections. Histopathologic findings demonstrated the coexistence of DSPC and PSC in both lobes and 16 lymph nodes metastases and soft tissue infiltration. Radioiodine was administered to ablate residual thyroid tissue. She was given T4 suppression therapy. At the 44th month of follow-up, she remains well without recurrences and metastases. The coexistence of DSPC and thyroiditis or PSC is still under debate. Very few cases with the combination of papillary thyroid carcinoma and PSC have been reported previously, thus we discuss the clinico-pathologic features and possible explanation for this unusual coexistence of malignancies.
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PMID:Diffuse sclerosing variant of papillary thyroid carcinoma with primary squamous cell carcinoma. 1224 Sep 7

The incidence of differentiated thyroid cancer (DTC) has increased in many places around the world over the past three decades, yet this has been associated with a significant decrease in DTC mortality rates in some countries. While the best 10-year DTC survival rates are about 90%, long-term relapse rates remain high, in the order of 20-40%, depending upon the patient's age and tumor stage at the time of initial treatment. About 80% of patients appear to be rendered disease-free by initial treatment, but the others have persistent tumor, sometimes found decades later. Optimal treatment for tumors that are likely to relapse or cause death is total thyroidectomy and ablation by iodine-131 ((131)I), followed by long-term levothyroxine suppression of thyrotropin (TSH). On the basis of regression modeling of 1510 patients without distant metastases at the time of initial treatment and including surgical and (131)I treatment, the likelihood of death from DTC is increased by several factors, including age >45 years, tumor size >1.0 cm, local tumor invasion or regional lymph-node metastases, follicular histology, and delay of treatment >12 months. Cancer mortality is favorably and independently affected by female sex, total or near-total thyroidectomy, (131)I treatment and levothyroxine suppression of TSH. Treatments with (131)I to ablate thyroid remnants and residual disease are independent prognostic variables favorably influencing distant tumor relapse and cancer death rates. Delay in treatment of persistent disease has a profound impact on outcome. Optimal long-term follow-up using serum thyroglobulin (Tg) measurements and diagnostic whole-body scans (DxWBS) require high concentrations of TSH, which until recently were possible to achieve only by withdrawing levothyroxine treatment, producing symptomatic hypothyroidism. New paradigms, however, provide alternative pathways to prepare patients for (131)I treatment and to optimize follow-up. Patients with undetectable or low Tg concentrations and persistent occult disease can now be identified within the first year after initial treatment by recombinant human (rh)TSH-stimulated serum Tg concentrations greater than 2 microg/l, without performing DxWBS. These new follow-up paradigms promptly identify patients with lung metastases that are not evident on routine imaging, but which respond to (131)I treatment. In addition, rhTSH can be given to prepare patients for (131)I remnant ablation or (131)I treatment for metastases, especially those who are unable to withstand hypothyroidism because of concurrent illness or advanced age, or whose hypothyroid TSH fails to increase.
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PMID:Management of papillary and follicular (differentiated) thyroid cancer: new paradigms using recombinant human thyrotropin. 1254 1

Thyroid carcinomas are fairly uncommon and include disease types that range from indolent localised papillary carcinomas to the fulminant and lethal anaplastic disease. Several attempts to formulate a consensus about treatment of thyroid carcinoma have resulted in published guidelines for diagnosis and initial disease management. Multimodality treatments are widely recommended, although there is little evidence from prospective trials to support this approach. Surgical resection to achieve local disease control remains the cornerstone of primary treatment for most thyroid cancers, and is often followed by adjuvant radioiodine treatment for papillary and follicular types of disease. Thyroid hormone replacement therapy is used not only to rectify postsurgical hypothyroidism, but also because there is evidence to suggest that high doses that suppress thyroid stimulating hormone prevent disease recurrence in patients with papillary or follicular carcinomas. Treatment for progressive metastatic disease is often of limited benefit, and there is a pressing need for novel approaches in treatment of patients at high risk of disease-related death. In families with inherited thyroid cancer syndromes, early diagnosis and intervention based on genetic testing might prevent poor disease outcomes. Care should be carefully coordinated by members of an experienced multidisciplinary team, and patients should be provided with education about diagnosis, prognosis, and treatment options to allow them to make informed contributions to decisions about their care.
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PMID:Thyroid carcinoma. 1258 60

The main steps in the management of differentiated thyroid cancer are thyroidectomy, treatment with iodine-131 ((131)I), and follow-up with whole-body scanning (WBS) and serum thyroglobulin (Tg) determination. Both (131)I treatment and follow-up require maximum stimulation of normal or pathological thyroid remnants by TSH. The use of recombinant human TSH (rhTSH) has been shown to be useful for follow-up, whereas previous reports are not univocal regarding the use of (131)I postsurgical ablation of thyroid remnants, at least when low doses (30 mCi) of (131)I are administered. A possible explanation for the diminished effectiveness of (131)I treatment after rhTSH may be the interference of iodine content of L-thyroxine (L-T4) therapy during the protocol of administration of rhTSH. We have evaluated the effectiveness of stimulation by rhTSH for radioiodine ablation of postsurgical remnants, stopping L-T4 the day before the first injection of rhTSH and restarting L-T4 the day after (131)I. The study included two groups of patients: group 1 included 16 patients with differentiated thyroid cancer (15 papillary cancers and 1 follicular cancer, stages I and II), who were treated with 30 mCi (131)I with the aid of rhTSH, using the standard protocol but stopping L-T4 as stated previously; and group 2 included 24 patients with the same features (histology and stage) of disease treated with 30 mCi in the hypothyroid state after L-T4 withdrawal. In both groups, serum TSH reached a very good stimulation level [76-210 U/liter (mean, 112 +/- 11 SE) and 38-82 U/liter (mean, 51 +/- 3 SE), respectively]. At the first WBS (after (131)I treatment), all patients showed thyroid remnants. Furthermore, two patients of the first group and three patients of the second group showed lymph node metastases. After 1 yr, all patients were studied again and underwent WBS with a tracer dose of (131)I and serum Tg measurement using rhTSH with the same protocol in both groups. The percentage of ablation (undetectable Tg and a negative WBS) was higher, although not reaching statistical significance, in patients treated with rhTSH: 81.2% in patients treated by rhTSH withdrawal and 75.0% in patients treated by L-T4 withdrawal, respectively. No patient experienced symptoms of hypothyroidism during the 4 d of L-T4 interruption, and serum T4 remained in the normal range. Urinary iodine was analyzed in both groups and compared with a control group of patients who received, for diagnostic purposes, rhTSH without stopping L-T4. In the first group, urinary iodine was 47.2 +/- 4.0 microg/liter (mean +/- SE; P = 0.21 vs. the second group, P = 0.019 vs. control group). In the second group, urinary iodine was 38.6 +/- 4.0 microg/liter (mean +/- SE; P < 0.001 vs. control group); urinary iodine in the control group was 76.4 +/- 9.3 microg/liter (mean +/- SE). Our data show that rhTSH, as administered in the protocol stated previously, allows at least the same rate of ablation of thyroid remnants when low doses (30 mCi) of (131)I are used. The possible role of interference of iodine content in L-T4 is not surprising if we consider that the amount of iodine in 30 mCi is negligible (5 microg) compared with the amount of iodine content in a daily dose of T(4) ( approximately 50 microg). The cost of rhTSH seems modest compared with the high cost of complex therapeutic regimens in other areas of oncology and in consideration of the well-being of patients and of the high level of effectiveness of the treatment.
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PMID:Radioiodine treatment with 30 mCi after recombinant human thyrotropin stimulation in thyroid cancer: effectiveness for postsurgical remnants ablation and possible role of iodine content in L-thyroxine in the outcome of ablation. 1297 Feb 72

As the function of the thyroid gland is the synthesis and secretion of thyroxin, a test which correctly measures this process is best for diagnosis of thyroid disorder and for determining the success of therapy. The rate of secretion can be measured with a Geiger counter which indicates what proportion of radioactive iodine in a serum specimen is in the form of thyroxin. The normal proportion is 2 to 10 per cent; in hyperthyroidism the proportion is 50 to 70 per cent, and in hypothyroidism less than 1 per cent. The same test has served to detect metastases of thyroid carcinoma following total thyroidectomy.
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PMID:Measurement of thyroxin synthesis with I131; a test for evaluation of thyroid function in equivocal states. 1304 58

Standard therapy for nasopharyngeal carcinoma (NPC) in children has generally followed the guidelines established for adults. We report here, the treatment outcomes in 32 children and adolescents with NPC and we discuss treatment approaches. Between 1993 and 1997, 32 NPC patients aged </=20 years (mean age 15 years) were treated in our institution; they represented 18% of all NPC cases seen during the same time period. 27 patients had no metastases at diagnosis; 26 of these were treated with primary chemotherapy combining epirubicin and cisplatin. Radiotherapy was then delivered to 22 patients at a mean dose of 70 Gy, either conventionally (6 patients) or bifractionated (16 patients). 5 patients had metastases at diagnosis and were treated with chemotherapy combining epirubicin, bleomycin and cisplatin before definitive radiotherapy. The objective response rate (OR) after chemotherapy was 90.9% at the primary site, with a 13.6% complete response (CR) rate. At nodal sites, the OR was 95.5% and the CR was 31.8%. Local control was obtained in all patients after definitive radiotherapy with a medium follow-up of 43.7 months. Late toxicity affecting quality of life was found in 26% of the children who were irradiated, especially among those under 15 years of age (skin fibrosis, 27%; trismus, 27%; hypothyroidism, 14%). No locoregional relapses were observed. Distant metastases occurred in 33% of cases, with a median delay of 4.7 months from the end of treatment. The 2- and 5-year overall survival (OS) rates were 76 and 56%, respectively. Disease-free survival (DFS) was 65% at 2 and 5 years. Therapeutic outcomes for childhood NPC were similar to those in adults, but with more radiotherapy-induced toxicity. New chemotherapeutic combinations and new radiotherapeutic techniques should be sought to improve both survival and quality of life.
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PMID:Nasopharyngeal carcinoma in childhood and adolescence: analysis of a series of 32 patients treated with combined chemotherapy and radiotherapy. 1455 27

Recombinant human TSH (rhTSH) is being widely used to monitor patients who were previously treated for differentiated thyroid cancers for evidence of recurrence. Its value lies in the avoidance of recurrent episodes of hypothyroidism in the follow-up protocols. rhTSH is also being evaluated as a potential therapeutic adjunct that would spare patients the experience of becoming hypothyroid when undergoing thyroid remnant ablation or treatment for metastases. In some centers, rhTSH is also used to support compassionate care of patients with advanced disease who cannot safely become hypothyroid. The (131)I uptake response to rhTSH, presently an off-label application, is expected to be similar to that of endogenously raised TSH levels. The two cases presented here are cautionary tales in which (131)I uptake by metastases was present under hypothyroid conditions, but absent in one patient and present in only a portion of the lesions in the other, with rhTSH stimulation.
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PMID:Two cases of thyroid carcinoma that were not stimulated by recombinant human thyrotropin. 1535 95


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