OncoLink
NCI CANCERLIT® Search: Thyroid Cancer - September 2001
Last Modified: November 1, 2001

Table of Contents

CancerMail from the National Cancer Institute

1
UI - 21066482
AU - Davies TF
TI - Analysis of the results of phase III controlled clinical trials with recombinant human thyrotropin: developing a clinical guide.
SO - Endocr Pract 2000 Sep-Oct;6(5):391-5
AD - Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
OBJECTIVE: To review two phase III clinical trials with recombinant human thyrotropin (rhTSH) in patients with treated thyroid cancer, which led to its approval by the Food and Drug Administration. METHODS: The trial designs, the results of radioiodine scanning, and the findings with use of both scanning and thyroglobulin (Tg) response are described. In the overall study design, the findings on whole-body radioiodine scanning were compared after use of two techniques--administration of rhTSH and withdrawal of thyroid hormone therapy. RESULTS: In the first phase III trial, two independent reviewers assessed 127 scan pairs and found 21 scan pairs to be discordant. In 18 of these cases, the scan after thyroid hormone withdrawal was judged as better than the scan after rhTSH administration. Subsequent analysis, however, revealed some problems with the protocol, and adjustments and standardizations were implemented for the second phase III trial, for which multiple blood samples were also obtained for serum Tg determinations. In this second study, 195 of 220 scan pairs were concordant, and only 25 pairs were discordant--17 were better after thyroid hormone withdrawal and 8 were better after rhTSH administration (P<0.1). The Tg response to rhTSH was not sufficiently reliable independently but was useful in combination with whole-body scanning (detection rate of 85 to 90%). CONCLUSION: The data indicate that rhTSH will be useful for investigation and long-term follow-up of patients with treated thyroid cancer.

2
UI - 21066481
AU - Haber RS
TI - Role of ultrasonography in the diagnosis and management of thyroid cancer.
SO - Endocr Pract 2000 Sep-Oct;6(5):396-400
AD - Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.
OBJECTIVE: To review the role of ultrasonography in the detection and management of thyroid cancer. METHODS: Viewpoints are presented on the appropriate applications and the advantages of ultrasonography, based on an extensive personal experience with more than 1,500 ultrasound examinations for assessment of thyroid nodules and for follow-up surveillance of patients with thyroid cancer. RESULTS: Ultrasonography is ideal for thyroid imaging because of the high echogenicity of thyroid tissue, the superficial site of the thyroid that allows the use of high-frequency transducers yielding high resolution, and the low expense compared with other techniques. In patients with a thyroid nodule, ultrasonography can assist in distinguishing benign from malignant disease. Ultrasound studies will characterize the presence of cystic versus solid elements, the degree of echogenicity of solid elements, the existence of calcifications, and the regularity and definition of the nodule borders. Although individual sonographic features of thyroid nodules are not specific for benign or malignant lesions, a constellation of typical features has more diagnostic value. Hypoechogenicity, poorly defined irregular margins, and microcalcifications are characteristics that should increase the index of suspicion for a malignant nodule. Cytologic examination of fine-needle aspirates is the optimal diagnostic test, and ultrasonographic guidance for performance of the aspiration biopsy is often helpful and sometimes critical. Ultrasonography is also useful for detection of cervical lymph node metastatic lesions. Lymph nodes involved with metastatic thyroid cancer tend to become rounded and bulging, and they lose their hilar echoes as their structure becomes disrupted. CONCLUSION: Because of its high resolution and relatively reasonable cost, ultrasonography is valuable in the diagnosis and management of thyroid cancer.

3
UI - 21066480
AU - Hurley JR
TI - Management of thyroid cancer: radioiodine ablation, "stunning," and treatment of thyroglobulin-positive, (131)I scan-negative patients.
SO - Endocr Pract 2000 Sep-Oct;6(5):401-6
AD - Division of Endocrinology, Diabetes and Metabolism, Joan and Sanford I. Weill Medical College of Cornell University, New York, New York 10021, USA.
OBJECTIVE: To present an overview of three controversial issues in the management of thyroid cancerradioiodine ablation, "stunning," and treatment of thyroglobulin-positive, (131)I scan-negative patients. METHODS: Pertinent studies from the literature and personal experience are reviewed. RESULTS: Radioiodine is commonly administered after thyroidectomy to destroy residual normal thyroid cells, a procedure known as thyroid ablation. Currently, use of radioiodine for ablation has been shown to decrease the risk of recurrence, increase the sensitivity of postablation whole-body scanning with radioiodine, and increase the sensitivity of serum thyroglobulin testing. With use of conventional criteria, administration of 30,000 rad to the thyroid remnant will successfully ablate approximately 95% of remnants that are 2 g or less, but the success rate is lower in patients with larger remnants. The same degree of success can be achieved by administration of 50 mCi of (131)I. The use of larger amounts of radioiodine does not increase the number of patients with successful thyroid ablation. If recurrence is used as the endpoint, no difference has been observed between patients who were given 29 to 50 mCi and those given 50 to 100 mCi for ablation. Stunning occurs when (131)I administered for preablation imaging causes a decrease in uptake of radioiodine subsequently given for ablation. Scanning doses of 2 mCi or less have not been shown to cause stunning, but the risk increases progressively with larger amounts. Therapeutic radioiodine is being given to patients with detectable thyroglobulin but negative (131)I whole-body scans with increasing frequency. Although posttherapy scans show abnormal uptake in most cases, no available evidence indicates that these patients benefit from treatment. CONCLUSION: Radioiodine ablation after thyroidectomy decreases the risk of recurrent thyroid cancer and facilitates subsequent radioiodine treatment. Stunning can be avoided by use of a maximal scanning dose of 2 mCi. It seems reasonable to treat patients who have progressively increasing thyroglobulin levels but to continue careful observation in those with stable or decreasing thyroglobulin concentrations.

4
UI - 21227882
AU - Hallquist A; Nasman A
TI - Medical diagnostic X-ray radiation--an evaluation from medical records and dentist cards in a case-control study of thyroid cancer in the northern medical region of Sweden.
SO - Eur J Cancer Prev 2001 Apr;10(2):147-52
AD - Department of Oncology-Pathology, Karolinska Institute, Radiumhemmet, Stockholm, Sweden. arne.hallquist@sos.se
The aim of this study was to evaluate the association between thyroid cancer and diagnostic X-ray radiation based on medical records. By using the Swedish Cancer Registry, 187 living cases with thyroid cancer (81%), aged 20-70 years at the time of their diagnosis in 1980-1989 were identified in the Northern Health Care Region of Sweden. Seven cases were reclassified as having a disease other than thyroid cancer and were excluded. The investigation included 180 living cases and 360 controls from the National Population Registry. In 132 cases and 251 controls data from X-ray records on earlier investigations > 5 years prior to diagnosis and corresponding years for the controls were analysed. The mean calculated thyroid dose for the cases was 7.0 mGy (median 1.1) and for the controls 7.4 mGy (median 1.0). This study showed no difference in the total material between calculated absorbed thyroid dose of medical diagnostic X-ray in cases versus controls. In younger women (< or = 50 years at diagnosis) with papillary thyroid cancer an association was found, however it was not significant. The results could be related to selective bias and should be treated with caution. Future studies require analysis of diagnostic medical X-ray investigations involving the thyroid gland including more specific data on sex and age of exposure in the whole study group.

5
UI - 21224265
AU - Mikosch P; Jauk B; Gallowitsch HJ; Pipam W; Kresnik E; Lind P
TI - Suppressive levothyroxine therapy has no significant influence on bone degradation in women with thyroid carcinoma: a comparison with other disorders affecting bone metabolism.
SO - Thyroid 2001 Mar;11(3):257-63
AD - Department of Nuclear Medicine and Special Endocrinology, State Hospital Klagenfurt, Austria. NuclMed.Abteilung@lkh-klu.at
The aim of this study was to examine different influences on bone degradation (estrogen status, thyroid function, parathyroid function, bone metastases) with special interest focusing on the significance of suppressive levothyroxine therapy (LT4) on bone degradation in patients with differentiated thyroid carcinoma (DTC). Two markers of bone degradation (ELItest NTx = U-NTx; Serum CrossLaps = S-CTx) were used (1) to quantify the influence of different metabolic influences on bone degradation and (2) to compare these two markers with each other. One hundred forty samples of 98 female patients ages 23-86 years were analyzed. The correlation between the two assays of bone degradation was high (r = 0.825; p < 0.001). Both assays demonstrated that estrogen deficiency, hyperparathyroidism, and bone metastases caused significant increases of bone degradation. A suppressive LT4 therapy, as used for patients with DTC, led to no significant increases of S-CTx and U-NTx. The study indicates that a well-controlled suppressive LT4 therapy has only a minor effect on the degree of bone degradation and that a possible estrogen deficiency in patients with DTC has a greater impact on bone degradation. Thus, female patients with DTC on suppressive LT4 therapy and estrogen deficiency may benefit from hormone replacement therapy, as patients with DTC and normal estrogen levels presented similar results to euthyroid controls.

6
UI - 21224267
AU - Kelman AS; Rathan A; Leibowitz J; Burstein DE; Haber RS
TI - Thyroid cytology and the risk of malignancy in thyroid nodules: importance of nuclear atypia in indeterminate specimens.
SO - Thyroid 2001 Mar;11(3):271-7
AD - Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Fine needle aspiration (FNA) cytology is the best test for malignancy in thyroid nodules. However, cytologic interpretation of FNA specimens is often difficult, especially in the presence of indeterminate microfollicular cytologic patterns, which are thought to suggest follicular neoplasm (adenoma or carcinoma). To assess the risk of malignancy associated with specific cytologic patterns, we correlated preoperative FNA cytologic patterns (n = 484 reports including repeat aspirations) with final histological diagnoses for 368 surgical thyroid specimens obtained during the period 1994-1998. The overall prevalence of malignancy in the surgical specimens was 31% (113 cancers, including 96 papillary and 9 follicular carcinomas). For nodules with benign FNA cytologic diagnoses of nodular goiter and chronic thyroiditis there was a low risk of malignancy (6/99, or 6.1%). Nodules with indeterminate cytologic patterns in the absence of nuclear atypia (i.e., microfollicles without nuclear atypia) had a similarly low malignancy risk (3/46, or 6.5%). In contrast, 31/52 nodules with cytologic nuclear atypia consistent with follicular neoplasm were malignant (60%), including specimens with or without microfollicular cytology. Nodules with frankly malignant cytologic patterns were almost invariably cancer (54/55), and cytologic diagnoses of papillary carcinoma were confirmed at surgery in all 49 cases. These results indicate that indeterminate microfollicular cytologic patterns in the absence of nuclear atypia are associated with a low risk of malignancy, at least in this series. This finding suggests that many nodules with such microfollicular cytology might be managed conservatively with observation. In contrast, cytologic nuclear atypia consistent with a follicular neoplasm confers a high risk of cancer. In addition, frankly malignant cytologic diagnoses, especially papillary carcinoma, are highly reliable, and thus may be used as a guide for planning surgery appropriate for thyroid cancer.

7
UI - 21260392
AU - Koren R; Yaniv E; Kristt D; Shvero J; Veltman V; Grushko I; Feinmesser R; Sulkes J; Gal R
TI - Capsular collagen staining of follicular thyroid neoplasms by picrosirius red: role in differential diagnosis.
SO - Acta Histochem 2001 Apr;103(2):151-7
AD - Department of Pathology, Hasharon Hospital, Petach Tikva, Israel. rumelia@isdn.mail.co.il
A key criterion in the diagnosis of thyroid follicular carcinoma is capsular invasion, but invasion cannot always be demonstrated histologically. Since invasion is likely to evoke reactions in the capsular collagen, we examined the effects of invasion on capsular collagen with the picrosirius orange-red (PSR) staining technique for collagen. Under polarized light, the color of PSR-stained collagen varies as a function of the structural and biochemical properties of the collagen fibers. Capsules of widely invasive carcinomas (n = 10), minimally invasive carcinomas (n = 10), and adenomas (n = 28) were stained with the PSR method. Carcinomas were assessed along the thickened capsule for sites of definite invasion, minimal invasion, and no evidence of invasion. In adenomas, sites of thickened capsules (similar to carcinomas) were compared to sites of thin capsules. All foci were evaluated for the color and color intensity of collagen fibers. We found a significantly higher frequency of yellow-green collagen fibers than of orange-red fibers at sites of invasion, whereas orange-red fibers significantly predominated at non-invaded sites. In a minority of cases both colors occurred but the non-dominant color was of lesser intensity in all but 1 case. There were no significant differences in staining between minimally and widely invasive carcinomas. Thick capsules of adenomas consistently stained with an intense orange-red color, although weakly stained yellow-green fibers were also observed in some of these cases. We conclude that PSR staining can provide diagnostically useful information in capsular samples of carcinomas, when both color and color intensity of PSR staining are evaluated at the same site. Specifically, intense yellow-green birefringence of collagen in a thickened capsule is additional evidence for capsular invasion.

8
UI - 21317180
AU - Aida N; Yamada N; Asano G; Tanaka S
TI - 3-D analysis of vascular and capsular invasion in thyroid follicular carcinoma.
SO - Pathol Int 2001 Jun;51(6):425-30
AD - Second Department of Pathology, Nippon Medical School, Tokyo, Japan. naritaka@nms.ac.jp
To clarify the mechanism of vascular invasion (VI) and capsular invasion (CI) in thyroid follicular carcinoma (FC), 3-D reconstruction of tumor tissues, vessels and capsules was performed from serial sections in five FC and three follicular adenomas (FA). Outflow veins in the lesions were well developed under the capsule, narrowed just beneath the capsule, and dilated within the capsule. Both VI and CI were observed at the poststenotic intracapsular dilated part of outflow veins. The tumor tissue extended along the intracapsular horizontal veins which flowed in parallel with the capsule in VI, or along the vertical veins which directly flowed outside the capsule in CI. There was tumor tissue in the subendothelial layer of the outflow veins within the capsule. Intravascular tumor nests and nodular lesions within the capsule continued from the main tumors. It can be concluded from these results that most VI and CI may not be true invasions but pre-invasive lesions.

9
UI - 21367598
AU - Belge G; Rippe V; Meiboom M; Drieschner N; Garcia E; Bullerdiek J
TI - Delineation of a 150-kb breakpoint cluster in benign thyroid tumors with 19q13.4 aberrations.
SO - Cytogenet Cell Genet 2001;93(1-2):48-51
AD - Center for Human Genetics, University of Bremen, Leobenerstrasse ZHG, D-28359 Bremen, Germany.
Structural rearrangements involving the long arm of chromosome 19 characterize a cytogenetic subgroup of benign thyroid tumors and constitute one of the most frequent specific chromosome abnormalities in epithelial tumors. Recently, we have been able to narrow down the breakpoint region affected in two cell lines to a region covered by a single PAC clone. Close to that region a candidate gene has been identified which we tentatively referred to as RITA (Rearranged In Thyroid Adenomas) now named ZNF331 according to HUGO nomenclature. However, the results had been obtained on two cell lines only making it necessary to extend the studies to a larger number of tumors including primary material. Herein, we have used four further primary tumors showing translocations involving 19q13 for fluorescence in situ hybridization (FISH) mapping studies using a variety of molecular probes from a 470-kbp cosmid/BAC contig. Ten new STSs were characterized and physically mapped within an EcoRI restriction map. The results enabled us to define an approximately 150-kbp breakpoint cluster region of the 19q13 aberrations in benign thyroid tumors flanked by two newly established STS markers. Copyright 2001 S. Karger AG, Basel

10
UI - 21384298
AU - Hinze R; Gimm O; Brauckhoff M; Schneyer U; Dralle H; Holzhausen HJ
TI - ["Physiological" and "neoplastic" C-cell hyperplasia of the thyroid. Morphologically and biologically distinct entities?]
SO - Pathologe 2001 Jul;22(4):259-65
AD - Institut fur Pathologie, Martin-Luther-Universitat Halle-Wittenberg. raoul.hinze@medizin.uni-halle.de
C-cell hyperplasia (CCH) occurs regularly in the setting of type 2 multiple endocrine neoplasia (MEN2), either separately or in association with medullary thyroid carcinoma (MTC). It can also accompany sporadic MTC and appear without any tumour association. To test the practicability of the terms "physiologic" and "neoplastic", 18 cases with incidental sporadic, non-MTC associated CCH were investigated and the morphological patterns were described. We found CCH of various degrees, including so-called neoplastic CCH. In 16 of the 18 cases, a MEN2 setting could be ruled out by mutation analysis of the RET proto-oncogene. Morphologically, one can not distinguish with certainty between sporadic and hereditary or reactive and tumour-associated CCH. While MEN2-associated CCH can be regarded as true preneoplasia, sporadic CCH possesses variable biologic potential. The preneoplastic potential of sporadic CCH is still obscure. A pure morphological distinction between "physiologic" and "neoplastic" CCH regardless of the RET status should not be used.

11
UI - 21395121
AU - Mai KT; Landry DC; Thomas J; Yazdi HM; Perkins DG; Odell PF
TI - Ret oncogene protein expression in papillary thyroid carcinoma and related lesions.
SO - Tumori 2001 May-Jun;87(3):166-72
AD - Department of Laboratory Medicine, Ottawa Hospital, Ontario, Canada. ktmai@civich.ottawa.on.ca
BACKGROUND: Activation of Ret oncogenes, particularly Ret/PTC, has been identified in papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the immunostaining pattern of Ret oncogene protein in PTC and nodular non-PTC lesions with a fine chromatin pattern. MATERIALS AND METHODS: Ninety-three PTC and 139 nodular non-PTC lesions were microscopically reviewed to identify the nuclear changes of "limited nuclear features of PTC" (focal nuclear grooves, nuclear inclusions or optically clear nuclei) and areas of infiltrating carcinoma (IC) and were submitted for immunostaining with Ret oncogene protein antiserum. RESULTS: Immunoreactivity for Ret protein ranged from negative in follicular adenoma (FA) with a coarse chromatin pattern, to negative or weak reactivity in FA with a fine chromatin pattern, to strong reactivity in PTC with areas of infiltrating carcinoma (IC). In FA with fine chromatin, FA and follicular carcinoma (FC) containing an admixture of areas of coarse and fine chromatin, areas with nuclear changes with "limited nuclear features of PTC" displayed varying degrees of immunoreactivity. The intensity of immunostaining varied with the degree of nuclear change. The noninvasive component of PTC with IC usually showed more extensive and stronger reactivity than PTC without IC. PTCs with and without IC were associated with a rate of lymph node metastasis of 48% and 3%, respectively. CONCLUSIONS: The expression of Ret oncogenes (Ret/PTC, other unknown variants or wild type) is focally or extensively present in all PTC with IC. The degree of immunoreactivity is likely to be proportional to the potential for lymph node metastasis of PTC. In the context of this study and due to the specificity of Ret oncogenes, it is likely that nodular non-PTC lesions with a fine chromatin pattern and focal positive reactivity for Ret oncogene represent PTC-related lesions.

12
UI - 21394061
AU - Morris LF; Waxman AD; Braunstein GD
TI - The nonimpact of thyroid stunning: remnant ablation rates in 131I-scanned and nonscanned individuals.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3507-11
AD - Department of Medicine, Cedars-Sinai Medical Center-University of California School of Medicine, Los Angeles, California 90048, USA.
Thyroid stunning has been reported as the temporary impairment of thyroid tissue after a 111-MBq or greater diagnostic 131I dose that decreases the final absorbed dose in ablative therapy. Concerns regarding the reality of stunning have arisen in part due to a flawed study design in prior reports. To assess whether a stunning effect has any impact on therapeutic outcomes, we compared initial treatment ablation rates in patients who received 111- to 185-MBq 131I diagnostic scans (n = 37) before ablative doses of 3700-7400 MBq with ablation rates in patients who did not receive any 131I before the initial treatment dose (n = 63). Ablation rates were 64.9% for scanned patients and 66.7% for nonscanned patients, a nonsignificant difference. Nonscanned patients with metastatic lesions (n = 23) were ablated at a higher rate (78.3%) than scanned patients (n = 9) (66.7%), but the difference was not significant (P = 0.50). It is possible that the reported stunning phenomenon, specifically its impact in temporarily impairing tissue, has been overemphasized.

13
UI - 21394062
AU - Ceccarelli C; Bencivelli W; Morciano D; Pinchera A; Pacini F
TI - 131I therapy for differentiated thyroid cancer leads to an earlier onset of menopause: results of a retrospective study.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3512-5
AD - Department of Endocrinology, University of Pisa, 56122 Pisa, Italy. claudia@endoc.med.unipi.it
Treatment with 131I for differentiated thyroid cancer may give a follicle-damaging radiation dose to the ovaries. This damage to the ovarian function could shorten the fertile life span and advance the natural menopause. To address this issue, we studied retrospectively the menopausal age of 130 women treated with 131I for differentiated thyroid cancer in our institution from 1974-1993. The menopausal age of women treated with 131I for differentiated thyroid cancer after total thyroidectomy and subjected to suppressive L-T4 therapy was compared with the menopausal age of a control group including 127 goitrous women who were treated with suppressive L-T4 for a comparable period of time. The cumulative therapeutic 131I dose to cancer patients ranged from 1,110-40,700 MBq (mean +/- SD, 5,308 +/- 5,483 MBq; median, 3700 MBq). All patients chosen for the study were younger than 45 yr when first treated (i.e. first administration of 131I and L-T4 for cancer patients, and institution of L-T4 therapy for goitrous patients), and older than 45 yr at the end of the study period. The menopausal status of both groups was assessed from the clinical records and compared using Kaplan-Meier survival analysis. The menopausal age of cancer women treated with 131I and suppressive L-T4 therapy was less than that of goitrous patients treated with suppressive L-T4 therapy (P < 0.001). We could not detect any relationship between menopausal age and the age at the first or last 131I dose or to the cumulative 131I dose received. These data indicate that 131I treatment is probably associated with an earlier ovarian failure in thyroid cancer patients. Conceivably, the ovarian irradiation by 131I might contribute to the process of the follicular atresia, thus inducing earlier menopause.

14
UI - 21394088
AU - Bevan S; Pal T; Greenberg CR; Green H; Wixey J; Bignell G; Narod SA; Foulkes WD; Stratton MR; Houlston RS
TI - A comprehensive analysis of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer: confirmation of linkage to TCO1.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3701-4
AD - Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom SM2 5NG.
About 5% of nonmedullary thyroid cancer is familial. These familial nonmedullary thyroid cancer cases are characterized by an earlier age of onset, more aggressive phenotype, and in some families a high propensity to benign thyroid disease. Little is known about the genes conferring predisposition to nonmedullary thyroid cancer. Three loci have been identified through genetic linkage: MNG1 on 14q32, TCO1 on 19p13.2, and fPTC on 1p21. In addition to these putative genes, a number of loci represent candidate familial nonmedullary thyroid cancer predisposition genes by virtue of their involvement in sporadic disease (TRKA), their role in benign disease (TSHR), and because they underlie syndromes with a risk of nonmedullary thyroid cancer (PTEN). To evaluate the roles of MNG1, TCO1, fPTC, PTEN, TSHR, and TRKA in familial nonmedullary thyroid cancer, we have carried out a comprehensive mutation and linkage analysis of these genes in 22 families. One family was linked to chromosome 19q13.2, confirming that TCO1 underlies a subset of familial nonmedullary thyroid cancer. None of the families was linked to MNG1 or fPTC, and there was no evidence to support the roles of PTEN, TSHR, or TRKA. Familial nonmedullary thyroid cancer is an emerging clinical phenotype that is genetically heterogeneous, and none of the currently identified genes accounts for the majority of families.

15
UI - 21394090
AU - Bucci A; Shore-Freedman E; Gierlowski T; Mihailescu D; Ron E; Schneider AB
TI - Behavior of small thyroid cancers found by screening radiation-exposed individuals.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3711-6
AD - Section of Endocrinology and Metabolism, University of Illinois College of Medicine, Chicago, Illinois 60612, USA.
Thyroid cancers detected by screening irradiated individuals are often small and of uncertain clinical significance. We retrospectively analyzed the effect of screening in a cohort of 4296 individuals exposed to radiation as children in the 1940s and 1950s and followed by us from 1974 until the present. We compared the thyroid cancers diagnosed before 1974 (122 cases, routine care) with the cancers found in subjects screened by us after 1974 (172 cases, screened), using cancer recurrence as the end point. Screening included a thyroid scan or, more recently, thyroid ultrasound. As expected, many of the cancers found by screening were very small (52% were <10 mm), but the range of tumor sizes overlapped those found by routine care. The recurrence rate was significantly lower in the cases found by screening, but when the comparison was limited to cancers 10 mm or larger, no difference in the recurrence rates was seen. This would suggest that the lower recurrence rate observed for small thyroid cancers detected at screening was due to earlier diagnosis rather than more effective treatment. By univariate analysis, four factors were associated with an increased risk of recurrence of small (<10 mm) thyroid cancers: short latency (i.e. a shorter time interval between the radiation exposure and the first thyroid surgery), lymph node metastases present at diagnosis, multifocal cancers, and higher radiation dose. In a multivariate analysis combining the four risk factors, only short latency was significant. As thyroid cancers that escape detection by routine means should be diagnosed at screening, and both large and small thyroid cancers have the potential to recur, screening may be of value, but only if groups with a sufficiently high prevalence of thyroid cancer can be identified to offset the adverse effects of unnecessary treatment due to false positive results.

16
UI - 21394096
AU - Niccoli-Sire P; Murat A; Rohmer V; Franc S; Chabrier G; Baldet L; Maes B; Savagner F; Giraud S; Bezieau S; Kottler ML; Morange S; Conte-Devolx B; The French Calcitonin Tumors Group (GETC)
TI - Familial medullary thyroid carcinoma with noncysteine ret mutations: phenotype-genotype relationship in a large series of patients.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3746-53
AD - Service d'Endocrinologie, CHU Timone, 13385 Marseilles, France. pniccoli-sire@ap-hm.fr
Familial medullary thyroid carcinoma only is related to germline mutations in the protooncogene RET, mainly in exons 10, whereas noncysteine mutations (exons 13-15) are considered infrequent. We analyzed 148 patients from 47 familial medullary thyroid carcinoma only families, and we found noncysteine RET mutations in 59.5% of these families. Of the index cases with noncysteine mutations, 43.4% presented with a multinodular goiter and high basal calcitonin; they were older at diagnosis than those with mutation in exon 10 and had more multifocal medullary thyroid carcinoma, but no difference in size, bilaterality, presence of C cell hyperplasia, or nodal metastases was found. Gene carriers with noncysteine RET mutations had a lower incidence of medullary thyroid carcinoma (78.2% vs. 94.1%) than those with mutation in exon 10; 20.2% had C cell hyperplasia only, although thyroidectomized at an older age. In conclusion, familial medullary thyroid carcinoma with noncysteine RET mutations are not infrequent and are overrepresented in presumed sporadic medullary thyroid carcinoma, suggesting that RET analysis should routinely be extended to exons 13, 14, and 15. The phenotype is characterized by a late onset of the disease, suggesting a delayed appearance of C cell disease rather than a less aggressive form. In familial medullary thyroid carcinoma gene carriers, the optimal timing for thyroidectomy remains controversial. Based on these data, we propose that surgery should be performed before elevation of the basal calcitonin level, potentially as soon as the pentagastrin test becomes abnormal.

17
UI - 21394101
AU - Hooft L; Hoekstra OS; Deville W; Lips P; Teule GJ; Boers M; van Tulder MW
TI - Diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography in the follow-up of papillary or follicular thyroid cancer.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3779-86
AD - Vrije Universiteit Medical Centre, Department of Nuclear Medicine, 1007 MB Amsterdam, The Netherlands. l.hooft@azvuv.nl
Positron emission tomography with 18F-fluorodeoxyglucose is a relatively new nuclear imaging technique in oncology. We conducted a systematic review to determine the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography in patients suspected of recurrent papillary or follicular thyroid carcinoma. Two reviewers independently selected, extracted, and assessed data from relevant literature found in computerized databases and by reference tracking. Prospective and retrospective studies with 10 human subjects, or more, that evaluated the accuracy of ring positron emission tomography, using 18F-fluorodeoxyglucose in follicular and papillary thyroid cancer, were included. Studies on 18F-fluorodeoxyglucose imaging using gamma cameras, reviews, case reports, editorials, letters, and comments were excluded. The methodological quality was assessed by applying the criteria for diagnostic tests recommended by the Cochrane Methods Group on Screening and Diagnostic Tests. A rating system was used for qualitative analysis consisting of four levels of evidence (1 = highest level; 4 = lowest level). Fourteen studies met the inclusion criteria. All studies claimed a positive role for positron emission tomography but, at evidence levels 3 or 4, precluding quantitative analysis. Methodological problems included poor validity of reference tests and a lack of blinding of test performance and interpretation. The reviewed material was heterogeneous with respect to patient variation and validation methodology. The most consistent data were found on the ability of 18F-fluorodeoxyglucose positron emission tomography to provide an anatomical substrate in patients with elevated serum Tg and negative iodine-131 scans. In conclusion, the results seem to support the potential of 18F-fluorodeoxyglucose positron emission tomography to identify and localize foci of recurrent cancer in the latter patient subset. However, implementation of positron emission tomography in a routine diagnostic algorithm requires additional evidence.

18
UI - 21394131
AU - Zafon C; Obiols G; Castellvi J; Tallada N; Galofre P; Gemar E; Mesa J; Simo R
TI - nm23-H1 immunoreactivity as a prognostic factor in differentiated thyroid carcinoma.
SO - J Clin Endocrinol Metab 2001 Aug;86(8):3975-80
AD - Division of Endocrinology, Hospital General i Universitari Vall d'Hebron, Barcelona 08035, Spain.
Several prognostic factors have been proposed to identify the patients at risk to develop metastases in differentiated thyroid carcinoma. Reduced nm23-H1 expression (a metastatic suppressor gene) has been correlated with high tumor metastatic potential in various human carcinomas, but the results obtained in differentiated thyroid carcinoma remain controversial. To elucidate the usefulness of nm23-H1 as a differentiated thyroid carcinoma prognosis factor, we evaluate the relationship between nm23-H1 immunoreactivity as well as both clinical status and patient outcome. For this purpose, thyroid resected specimens obtained from 94 differentiated thyroid carcinoma consecutive patients (64 papillary and 30 follicular) with at least 5 yr of follow-up were stained using monoclonal antibody to nm23-H1. We did not observe any relationship between nm23-H1 immunoreactivity and age, gender, initial differentiated thyroid carcinoma stage, local recurrence, or distant metastases in patients with papillary carcinoma. However, in patients with follicular carcinoma, a significant inverse association between metastatic disease and the expression of nm23-H1 product was obtained (P < 0.05). In addition, significant differences were found in the survival curves according to nm23-H1 immunoreactivity (log-rank P < 0.01). Finally, nm-23-H1 immunoreactivity was more specific but less sensitive than AMES score to predict metastases. In conclusion, our results suggest that nm23-H1 immunostaining could be added to the classic prognostic factors currently used to predict the outcome of patients with follicular thyroid carcinoma.

19
UI - 21347501
AU - Arturi F; Russo D; Bidart JM; Scarpelli D; Schlumberger M; Filetti S
TI - Expression pattern of the pendrin and sodium/iodide symporter genes in human thyroid carcinoma cell lines and human thyroid tumors.
SO - Eur J Endocrinol 2001 Aug;145(2):129-35
AD - Dipartimento di Medicina Sperimentale e Clinica, Universita di Catanzaro, 88100 Catanzaro, Italy.
OBJECTIVE: In the present study we analyzed the pattern of pendrin (PDS) and sodium/iodide symporter (NIS) gene expression in some thyroid carcinoma cell lines and a series of thyroid tumoral tissues. METHODS: Total RNA was extracted from all cell lines and from 53 tissues, and gene expression was examined by RT-PCR. Semiquantitative 'multiplex' RT-PCR was used to assess variations in PDS gene expression among various thyroid pathologies. Pendrin expression was determined in the thyroid cell lines by Western blot analysis. RESULTS: PDS mRNA was expressed in all the cells investigated; conversely, NIS mRNA was detectable only in the B-CPAP cells. Pendrin protein was expressed in B-CPAP and WRO cell lines, reduced in FRO and absent in ARO cells. PDS gene expression was not detected in 5 of 25 differentiated thyroid carcinomas (DTC) while NIS gene was not expressed in six carcinomas. A concordance expression of both PDS and NIS transcripts was found in 20 DTC. In contrast, 2 neoplastic thyroid tissues carrying undetectable PDS mRNA maintained NIS transcript, and 3 thyroid carcinomas negative for NIS mRNA retained the expression of PDS gene. A semiquantitative analysis showed that the mean PDS mRNA levels were significantly decreased in DTC tissues. CONCLUSIONS: Our data demonstrate that pendrin expression: (i) is present in the more differentiated thyroid carcinoma cell lines studied; (ii) is reduced or absent in DTC tissues; (iii) may not correlate with the NIS expression. These alterations may contribute to the loss of iodine concentration ability detected in thyroid tumors.

20
UI - 21347504
AU - Miedlich S; Lohmann T; Schneyer U; Lamesch P; Paschke R
TI - Familial isolated primary hyperparathyroidism--a multiple endocrine neoplasia type 1 variant?
SO - Eur J Endocrinol 2001 Aug;145(2):155-60
AD - Medical Department III, University of Leipzig, Germany.
OBJECTIVE: Familial isolated primary hyperparathyroidism (FIHP) is defined as hereditary primary hyperparathyroidism without the association of other diseases or tumors. Linkage analyses suggest that different genotypes can lead to the same phenotype of primary hyperparathyroidism. Hereditary syndromes associated with primary hyperparathyroidism are multiple endocrine neoplasia type 1 and type 2 (MEN 1 and MEN 2). In MEN 1, multiple parathyroid adenomas occur in more than 90% of the patients. Therefore, it has been suggested that FIHP could represent a variant or partial expression of MEN 1. DESIGN: We report on a large FIHP kindred with a MEN1 gene mutation. Nineteen family members (aged 10 to 87 years) were screened. Furthermore, statistical comparison by Fisher's exact tests of FIHP families with MEN1 gene mutations and MEN 1 families with two or more endocrinopathies was carried out to investigate genotype-phenotype correlations. METHODS: Mutational analysis of leucocyte DNA was carried out by direct sequencing of the complete coding region of the MEN1 gene. Screening of MEN 1 manifestations was carried out by determination of serum calcium, phosphate, parathyroid hormone, prolactin, ACTH, cortisol, IGF-I, gastrin, glucose, insulin, glucagon, serum potassium, aldosterone, plasma renin and urinary hydroxyindoleacetic acid. RESULTS: We detected an in-frame deletion mutation in exon 8 of the MEN1 gene resulting in the deletion of one glutamine acid residue at position 363. It was found in eight individuals. Two of these family members (aged 42 and 60 years) were operated for primary hyperparathyroidism, and three (aged 13 to 40 years) showed mild hypercalcemia and parathyroid hormone levels within the upper normal range or slightly elevated, without any clinical symptoms. Two individuals (aged 12 and 19 years) were normocalcemic. One could not be tested. None of them had clinical evidence of other MEN 1 manifestations. Statistical comparison of the mutation types in families with FIHP and families with two or more MEN 1-associated endocrinopathies reported in other studies reveals a significant difference. In families with FIHP, missense/in-frame mutations have been found in 87.5% of cases whereas in families with tumors in various endocrine glands these mutation types occur much less frequently (21-34%, P<0.05). CONCLUSIONS: These studies indicate that FIHP can represent a partial MEN 1 variant and is often caused by missense/in-frame mutations.

21
UI - 21347505
AU - Velin AK; Herder A; Johansson KJ; Trulsson LM; Smeds S
TI - Telomerase is not activated in human hyperplastic and adenomatous parathyroid tissue.
SO - Eur J Endocrinol 2001 Aug;145(2):161-4
AD - Department of Biomedicine and Surgery, University Hospital, Linkoping, Sweden.
BACKGROUND: Telomerase is a specific enzyme that appears to have a key role in cellular senescence and the progression of neoplastic tissue. High telomerase activity has been found in several cancers, but not in most normal and benign tissue. Little is known about the influence of telomerase on the abnormal growth associated with hyperparathyroidism. OBJECTIVE: To analyse telomerase activity in parathyroid tissue obtained from 29 patients undergoing surgery for primary hyperparathyroidism. DESIGN: Tissue for telomerase activity measurements was collected from six hyperplastic, 20 adenomatous and 22 normal parathyroid glands. METHODS: The highly sensitive PCR-based telomeric repeat amplification protocol, TRAP, combined with ELISA, was used to detect telomerase activity in tissue extracts containing 3.0 microg protein. RESULT: Telomerase was not activated in any of the analysed tissue by 3 microg protein. Reassay of 12 samples containing 6.0 microg protein verified these negative TRAP results. CONCLUSION: Our findings indicate that telomerase is not a part of the mechanism promoting parathyroid proliferation and the underlying conditions remain to be determined.

22
UI - 21397955
AU - Ringel MD; Hayre N; Saito J; Saunier B; Schuppert F; Burch H; Bernet V; Burman KD; Kohn LD; Saji M
TI - Overexpression and overactivation of Akt in thyroid carcinoma.
SO - Cancer Res 2001 Aug 15;61(16):6105-11
AD - Washington Hospital Center and MedStar Research Institute, Washington, DC 20010, USA. mxr9@mhg.edu
Enhanced activation of Akt occurs in Cowden's disease, an inherited syndrome of follicular thyroid, breast, colon, and skin tumors, via inactivation of its regulatory protein, PTEN. Whereas PTEN inactivation is uncommon in sporadic thyroid cancer, activation of growth factor pathways that signal through Akt is frequently identified. We hypothesized that Akt overactivation could be a common finding in sporadic thyroid cancer and might be important in thyroid cancer biology. We examined thyroid cancer cells lines and benign and malignant thyroid tissue for total Akt activation and isoform-specific Akt expression. In thyroid cancer cells, Akt 1, 2, and 3 proteins were expressed, total Akt was activated by insulin phosphatidylinositol 3'-kinase, and inhibition of phosphatidylinositol 3'-kinase reduced cell viability. In human thyroid tissue, increased levels of phosphorylated total Akt were identified in follicular but not papillary cancers compared with normal tissue. Levels of Akt 1 and 2 proteins and Akt 2 RNA were elevated only in the follicular cancers. In paired samples, Akt 1, 2, 3, and phospho-Akt levels were higher in five of six cancers, including three of three follicular cancers. These data suggest that Akt activation may play a role in the pathogenesis or progression of sporadic thyroid cancer.

23
UI - 21392396
AU - Pahlavan PS
TI - Hypercalcemia due to parathyroid adenoma.
SO - Saudi Med J 2000 Jun;21(6):596-7

24
UI - 21152859
AU - van Tol KM; de Vries EG; Dullaart RP; Links TP
TI - Differentiated thyroid carcinoma in the elderly.
SO - Crit Rev Oncol Hematol 2001 Apr;38(1):79-91
AD - Department of Endocrinology, University Hospital Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands. k.m.van.tol@int.azg.nl
The overall prognosis of patients with differentiated thyroid cancer is excellent, but the prognosis is rapidly worsening, when the disease is diagnosed in elderly patients. Old patients more often present with poor prognostic features, such as large tumors, follicular or Hurthle cell subtypes, extrathyroidal growth and distant metastases. Therefore, an optimal therapeutic approach is recommended. Current therapy includes a total thyroidectomy, if necessary combined with a lymph node dissection and followed by high dose radioiodine ablation. Radioiodine therapy in elderly patients meets specific problems, concerning thyroid hormone withdrawal, side effects of 131I and nursing problems. Additional treatment of residual, recurrent or metastatic disease must be tailored, according to the stage of the disease, and should not be denied on the basis of chronological age. Lifelong treatment with suppressive thyroid hormone therapy does not lead to important long-term side effects at old age.

25
UI - 21183439
AU - Bondarenko IuH
TI - [Peculiarities of clinical diagnosis of the thyroid gland cancer invading trachea and larynx]
SO - Klin Khir 2000 Jun;(6):21-2
The experience of diagnosis of the thyroid gland (TG) spreaded cancer in 153 patients was summarized. Optimal differentiated surgical methods were applied depending on the affection severity of the main respiratory ways. Combined resection TG with part of trachea (larynx) in 18 patients was done, in 96--thyroidectomy, in 39--palliative intervention.

26
UI - 21270323
AU - Thompson MA
TI - Radiation safety precautions in the management of the hospitalized (131)I therapy patient.
SO - J Nucl Med Technol 2001 Jun;29(2):61-6; test 74-5
AD - Division of Medical Imaging and Therapy, University of Alabama at Birmingham, 333 LRC, 1714 Ninth Avenue South, Birmingham, AL 35294-1270, USA.
OBJECTIVES: The patient who has been dosed with therapeutic activities of (131)I for thyroid carcinoma poses a unique set of problems for nuclear medicine technologists in their efforts to reduce personnel exposure and control contamination spread. It is the objective of this article to: (a) review practical radiation safety concerns associated with hospitalized (131)I therapy patients; (b) propose preventative measures that can be taken to minimize potential exposure and contamination problems; and (c) review pertinent federal regulations that apply to patients containing therapeutic levels of radionuclides.

27
UI - 21353432
AU - Aozasa K; Takakuwa T; Nakatsuka S
TI - [Malignant lymphoma developing with a background of inflammatory conditions]
SO - Nippon Naika Gakkai Zasshi 2001 Jun 10;90(6):1019-23

28
UI - 21365244
AU - Mihai R
TI - Molecular influences in thyroid and parathyroid surgery.
SO - Best Pract Res Clin Endocrinol Metab 2001 Jun;15(2):177-88
AD - University Department of Surgery, Bristol Royal Infirmary, Bristol, UK.
Recent progress in molecular biology and genetics has made a major impact on the management of patients with multiple endocrine neoplasia syndromes MEN-1 and MEN-2. The understanding of the mechanisms involved in inherited thyroid and parathyroid tumours also offered valuable answers for other models of neoplasia. In addition, parathyroid surgery has witnessed rapid progress, from the cloning of the calcium receptor to the development of calcimimetics, a new class of drugs that could shift the management of hyperparathyroidism from surgical intervention to medical treatment. Laboratory techniques initially designed for research are more and more being used for clinical diagnosis. For example, the use of the polymerase chain reaction is currently being evaluated in the early diagnosis of metastatic thyroid carcinoma by identifying specific gene products in the local lymph nodes. This chapter attempts to convince the reader that molecular biology is no longer restricted to the laboratory but has an increasing impact on clinical decisions to which an endocrine surgeon is exposed. Copyright 2001 Harcourt Publishers Ltd.

29
UI - 21374477
AU - Skinner MA
TI - Cancer of the thyroid gland in infants and children.
SO - Semin Pediatr Surg 2001 Aug;10(3):119-26
AD - Duke University Medical Center, Durham, NC 27710, USA.
Carcinoma of the thyroid gland is unusual in children and represents only about 3% of pediatric malignancies. Surgical management is the principa

About OncoLink  Contact OncoLink  Privacy statement   Disclaimer  Link to OncoLink  Home
For assistance please visit our HELP section
© Trustees of the University of Pennsylvania