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PubMed1998

The effects of radioactive iodine in thyroid remnant ablation and treatment of well differentiated thyroid carcinoma.

Although the use of radioactive iodine (131I) in the treatment of thyroid cancer is well established, treatment dose is not well standardized. In order to deduce the appropriate dose for thyroid remnant ablation and the effect of 131I in the treatment of distant metastases, data for 544 patients with papillary or follicular thyroid cancer were retrospectively reviewed. All patients received surgical treatment followed by post-operative 131I. If remnants were present in the 0.2 GBq 131I diagnostic scan, 1.1-3.7 GBq 131I were administered for ablation. For the treatment of distant metastases 3.7-5.6 GBq were used. Of 318 patients receiving 131I for thyroid remnant ablation, 290 were successfully ablated. After one dose of 1.1 GBq 131I, 82% (159/194) of thyroid remnants were ablated. During the follow-up period, two of 14 Stage IV patients with lung or mediastinal metastases at the time of operation achieved complete clinical remission. Factors identified as influencing response to 131I therapy included age, clinical stage, survival, recurrence, extent of surgery and the 1 month post-operative serum thyroglobulin (Tg) level. In conclusion 1.1 GBq 131I was adequate for thyroid remnant ablation unless distant metastases were present. Radioactive 131I has a role in the treatment of well differentiated thyroid carcinoma with pulmonary metastases but seems to be less effective for treatment of bone metastases.

Adenocarcinoma, Follicular↗
PubMed2003

Distinction between papillary thyroid hyperplasia and papillary thyroid carcinoma by immunohistochemical staining for cytokeratin 19, galectin-3, and HBME-1.

The histopathology of papillary thyroid hyperplasia and papillary thyroid carcinoma is similar enough to cause a diagnostic dilemma in a few cases. Both lesions may have papillary fronds with fibrovascular cores, nuclear crowding, and nuclear anisocytosis. Formalin- fixed paraffin-embedded tissues from 30 randomly selected patients with papillary thyroid hyperplasia and an equal number from patients with papillary thyroid carcinoma were analyzed for expression of cytokeratin 19 (CK19), galectin-3, and HBME-1. Cases of papillary thyroid carcinoma had moderate to strong CK19, galectin-3, and HBME-1 reactivity although both CK19 and galectin-3 showed positive staining in a significant number of nonneoplastic thyroid cases. HBME-1 was uncommon in the nonneoplastic cases. These results indicate that HBME-1 may be useful in helping to distinguish papillary thyroid carcinoma from hyperplasia in diagnostically difficult cases.

Adolescent↗
PubMed1991

[Studies on the iodide metabolism and the expression of thyroglobulin and thyroid peroxidase mRNA in the thyroid of BB/W rats].

BioBreeding/Worcester (BB/W) rats develop insulin dependent diabetes mellitus (IDDM) and lymphocytic thyroiditis (LT) spontaneously. Our previous studies have shown that BB/W (Saitama-Tokyo colony) rats develop LT at about 10 weeks of age. Their serum TSH values increase as LT extends, although their serum thyroid hormone levels remain normal. This indicates that BB/W rats suffer from subclinical hypothyroidism. To investigate whether BB/W rats have a defect in iodide metabolism, the thyroidal radioactive iodine uptake (RAIU) in BB/W rats was examined. Thyroidal RAIU at 3hr in both 8 and 16 week-old BB/W rats was significantly higher than that in age-matched normal Wistar rats. On the other hand, BB/W rats had significantly lower 48hr thyroidal RAIU than normal Wistar rats. This suggests that BB/W rats appear to have some defects in iodide metabolism, especially in iodide organification even before the development of LT. The expression of thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA in BB/W and Wistar rats was then examined using the Northern blot analysis. The expression of both TPO and Tg mRNA was greatly decreased in BB/W rats compared with that in Wistar rats despite the high serum TSH levels in BB/W rats. This indicates that BB/W rats may have pretranslational defects in TPO and Tg synthesis, resulting in the impaired thyroid hormone synthesis. In the present study, it has been demonstrated that BB/W rats appear to have a defect(s) in iodide metabolism possibly due to some abnormalities in TPO and Tg synthesis.

Animals↗
PubMed1991

[Incidence of abnormal thyroid function in patients with low titers of thyroid microsomal antibodies].

The incidence of abnormal thyroid function related to autoimmune disorders was examined in a district of Shimane Prefecture in 1988. Thyroid microsomal antibodies (MCPA) in sera were measured in a general population of 1,646, including 678 males and 968 females, aged 57.8 +/- 14.8 (mean +/- SD) yr. MCPA titer was defined as high (less than 1:128), low (1:16, 1:32, 1:64) or negative (less than 1:16) according to the highest dilution of test serum capable of agglutinating gelatin particles coated with the appropriate antigen. Test of MCPA revealed high titers in 141 subjects (group A), low in 43 subjects (group B) and negative in 1,462 (group C). Twenty-four patients with overt thyroid disorders were found in groups A and B: five with Graves' disease, two with Hashimoto's thyroiditis and 15 with goiter in group A, and two with goiter in group B. In the remaining 119 subjects in group A and 41 subjects in group B, serum free T4 (FT4) and TSH levels were measured. According to abnormalities in the levels of serum FT4 and/or TSH, their thyroid function was divided into the following 3 subgroups: 1) hyperthyroid (FT4 greater than 2.0 ng/dl, TSH less than 0.4 mu U/ml), 2) latent hypothyroid (0.8 less than FT4 less than 2.0 ng/dl, TSH greater than 5.0 mu U/ml) and 3) hypothyroid (FT4 less than 0.8 ng/dl, TSH greater than 5.0 mu U/ml). The hyperthyroid group consisted of two patients in group A and one in group B. Ten latent hypothyroid patients were found in group A and two in group B. Hypothyroidism was found in four patients in group A. The incidence of abnormal thyroid function was not different between group A (16 out of 119, 13.4%) and group B (three out of 41, 7.3%). Graves' disease and primary myxedema were found in one patient each in group B; these patients had no subjective symptoms but showed low titers of MCPA. These findings suggest that not only high titers of MCPA but also low titers of MCPA are closely related to abnormal thyroid function.

Adult↗
PubMed2005

Papillary thyroid carcinoma without metastases manifesting as an autonomously functioning thyroid nodule.

A 59-year-old woman with papillary thyroid carcinoma inside of an autonomously functioning thyroid nodule is described in this report. The patient was referred to our clinic because of rapid weight loss and swelling on the left side of the neck. Ultrasonography of the thyroid demonstrated a nonhomogeneous nodule in the lower part of an enlarged left lobe. Both 99mTc and 123I thyroid scintigraphic imaging showed a hot area corresponding to the nodule with lower uptake in the remaining thyroid tissue. Histopathological examination of the nodule revealed papillary adenocarcinoma, and the immunohistochemistry proved weak but positive staining for triiodothyronine and thyroxine. Based on these findings, the nodule was diagnosed as a functioning papillary adenocarcinoma. Although thyroid carcinoma manifesting as a hot nodule on the radionuclide isotope scan is an extremely rare occurrence, the current case is clinically important because it suggests that the diagnosis of a hot nodule cannot always rule out thyroid carcinoma in the nodule, and that even a hot nodule requires careful management so that the malignancy is not overlooked.

Adenocarcinoma, Papillary↗
PubMed1987

Adenylate cyclase stimulation and [3H]thymidine incorporation in human thyroid tissues and thyrocyte cultures: the effect of IgG preparation from patients with different thyroid disorders.

Primary cell cultures of normal and adenomatous human thyroid tissues were incubated with TSH or ammonium sulphate precipited IGG fractions (1 mg/ml) of sera from patients with different thyroid diseases (Graves' disease: active n = 7 in remission n = 12; thyroid autonomy n = 39; simple euthyroid goitre n = 15) and were compared to controls (n = 26). [3H]thymidine incorporation in primary thyrocyte cultures demonstrated a typical bell shape curve after incubation with EGF and TSH with a maximal effect at 10-100 microIU/ml. This effect, however, was inconsistent and positive only in 2 of 7 primary cultures. Only TSH positive cultures were used for IgG studies. 16-28% of IGG fractions from sera of thyroid patients caused high (more than X + 5 SD of controls) stimulation of [3H]thymidine incorporation. Dose response curves of IgG fractions of 19 additional patients (Graves' disease in remission n = 15; thyroid autonomy n = 4) showed an increase in [3H]thymidine incorporation at 0.1 mg protein/ml for 10 patients and at low concentrations of 10-5 mg/ml for 5 patients. There was a good correlation (r = 0.72) (P less than 0.0001) between positive findings in TSH-binding inhibition (TBII) and AC-stimulation (TSI) IGG fractions but none between stimulation of [3H]thymidine incorporation and any other thyroid specific immunoglobulin nor thyroid function nor any other available data. Immunoglobulins stimulating [3H]thymidine incorporation differ therefore from TBII and TSI. The growth effect of these immunoglobulins, however, has yet to be determined.

Adenoma↗
PubMed1988

Antibody-dependent cell-mediated growth inhibition of rat thyroid cells, FRTL-5, in patients with autoimmune thyroid diseases.

We studied antibody-dependent mononuclear cell-mediated growth inhibition of thyroid cells in 18 untreated patients with Graves' disease, 18 patients with chronic thyroiditis, and 15 normal subjects by measuring the ability of their sera to inhibit [3H]thymidine incorporation into DNA in a rat thyroid cell line, FRTL-5, in the presence of normal mononuclear cells. [3H]thymidine incorporation was significantly inhibited in the presence of sera from patients with Graves' disease and chronic thyroiditis (P less than 0.001), whereas it was not affected in normal subjects. A significant correlation was observed between the inhibition of [3H]thymidine incorporation and the titre of anti-microsomal antibodies (P less than 0.05). The inhibitory effect on [3H]thymidine incorporation was significantly abolished when serum pre-absorbed with human thyroid membranes was used (P less than 0.005). These inhibitory effects on [3H]thymidine incorporation significantly correlated with those obtained by using IgG fractions (P less than 0.01). These data indicate that antibody-dependent mononuclear cell-mediated growth inhibition may play a role in thyroid cell growth regulation in patients with autoimmune thyroid disease.

Adolescent↗
PubMed1983

Thyroid stimulation test with urinary T3 concentration as an index of thyroid response.

Ten USP units of TSH (thytropar) were administered intramuscularly daily for three days to five euthyroid controls, to thirteen patients with chronic thyroiditis [four clinically euthyroid patients with normal serum TSH (Group I), five clinically euthyroid patients with elevated serum TSH (Group II) and four clinically hypothyroid patients with high serum TSH (Group III)], and to five patients with primary hypothyroidism. Effects of TSH on the thyroid 24-hr uptake of 131I, 24-hr urinary T3 excretion and serum T3 concentration were assessed: In euthyroid controls, basal urinary T3 excretion was 0.76 +/- 0.26 (mean +/- S.D.) micrograms/day, increased to 1.31 +/- 0.16 micrograms/day on the first day, to 2.33 +/- 0.75 micrograms/day on the second day, and to a maximum of 2.78 +/- 0.65 micrograms/day on the third day of TSH administration. In Group I, basal urinary T3 excretion was normal (0.58 +/- 0.16 micrograms/day). Following TSH administration, the value increased to 1.60 +/- 0.62 micrograms/day, but the rate of increase was less than that in euthyroid controls. In Group II, basal urinary T3 excretion was normal (0.71 +/- 0.37 micrograms/day), but did not increase following TSH administration. In Group III, basal urinary T3 excretion was significantly low (0.32 +/- 0.07 micrograms/day), and did not increase after TSH administration. In patients with primary hypothyroidism, basal urinary T3 excretion, 0.12 +/- 0.10 micrograms/day, was lower than that of Group III, and did not increase after TSH administration. Positive correlations were found between urinary T3 excretion and serum T3 concentration before and after TSH administration. In contrast to basal serum T3 concentration and urinary T3 excretion, mean basal thyroid uptake of 131I in patients with chronic thyroiditis was higher than that of euthyroid controls. However, a positive correlation was found between the increased rate of urinary T3 excretion and the increase in thyroid 131I uptake after TSH administration. These observations indicate that the changes in urinary T3 excretion are reliable indices of the thyroid response to TSH administration in various states of thyroid function.

Humans↗
PubMed2002

Detection of thyroid peroxidase mRNA in peripheral blood of patients with malignant and benign thyroid diseases.

The aim of this study was to evaluate thyroid peroxidase (TPO) mRNA expression in peripheral blood of patients with benign and malignant thyroid disease. Included were 120 thyroid cancer patients, 85 patients with goitre or Graves' disease (GD) and 54 healthy volunteers. TPO mRNA expression was analysed in peripheral blood by nested RT-PCR. In cancer patients, RT-PCR results were compared with staging, grading and serum thyroglobulin (TG) measurement. TPO transcripts were detected in 7/10 (70%) patients with known metastases of thyroid cancer and in 39 of 110 (36%) patients without metastases (P<0.05), in 15/44 (34%) patients with goitre, in 17/41 (41%) cases with GD and in 4/54 (7.4%) subjects in the control group (P<0.05, controls vs all patients with thyroid disease). Among cancer patients without metastatic disease, RT-PCR results correlated positively with lymph node status (P=0.05), grading (P=0.01) and elevated serum thyroglobulin levels (P=0.03). This is the largest study investigating the use of the TPO-RT-PCR assay. Positivity in TPO-RT-PCR correlates significantly with metastatic disease in cancer patients and with the presence of thyroid disease in general. To date, TPO-RT-PCR cannot substitute for standard techniques in the diagnosis of local recurrence or metastatic spread in thyroid cancer patients. However, as results of TPO-RT-PCR correlate significantly with lymph node status, grading and serum TG measurements in patients with non-metastatic disease, TPO seems to be an interesting molecular marker to look at in follow-up studies.

Adult↗
PubMed1994

Consequences of thyroid hormone deficiency induced by the specific ablation of thyroid follicle cells in adult transgenic mice.

The herpes simplex type 1 virus thymidine kinase (HSV1-TK) reporter gene was coupled to a bovine thyroglobulin promoter (TG-tk construct). Within the thyroid glands of transgenic mice expression was confined to thyroid follicle cells. Infusion of Ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) to 8 to 12 week transgenic females led to the complete loss of thyroid HSV1-TK activity (at 3 to 4 days) and thyroid follicles (between 7 and 14 days). During the first 5 days of treatment a single reciprocal oscillation in circulating thyroxine (T4) and TSH levels occurred. By 14 days the circulating tri-iodothyronine (T3) and T4 levels of all treated animals were below the detection limits of the assays, while TSH levels were elevated ten-fold and continued to increase thereafter. During 14 days of treatment the thyroids regressed, protein content fell by 80-90% and the C cells, normally dispersed within the central region of each gland, came together in aggregates. Pituitary GH levels in females rose and fell back to normal within 14 days and between 14 and 28 days fell to a level comparable with that of GH-deficient lit/lit mice. The levels of hepatic GH receptor mRNA and the predominant 6.6 kb T3 receptor mRNA were unaffected by thyrocyte ablation. Thyrocyte ablation had no effect on the level of prolactin (Prl) receptor mRNA in females, but increased Prl receptor mRNA levels in males and eliminated group 1 major urinary protein (MUP).mRNA in females. T4 replacement reversed the effects of thyrocyte ablation on MUP mRNA in females and on Prl receptor mRNA in males.2+ Despite the many physiological changes induced by thyrocyte ablation, ablated mice have been maintained for up to 1 year without thyroid hormone supplementation. T4-deficient females were normally fertile and carried pups to term. Although transgenic males expressed HSV1-TK ectopically in spermatids and spermatozoa at levels similar to thyrocyte levels, a rate of Ganciclovir infusion which successfully ablated the thyrocytes did not affect the testis. As an alternative to infusion by minipump, thyrocyte ablation could be achieved by 6 twice-daily injections of Ganciclovir, at a level of 112 micrograms Ganciclovir/g body weight per day, and fetuses in utero could be thyrocyte ablated by administering 50 or 15 micrograms/g body weight per day to pregnant females between days 14 and 18 of gestation. These data demonstrate the potential value of transgenic thyrocyte ablation in the study of the effects of thyroid hormone deprivation.

Animals↗
PubMed1995

Apoptosis in thyroid tissue from patients with Hashimoto's thyroiditis.

To clarify whether apoptosis of thyroid follicular epithelial cells occurs at the tissue level in autoimmune thyroiditis, 17 specimens of thyroid tissues with Hashimoto's thyroiditis were stained for fragmented DNA. Almost all nuclei of follicular epithelial cells forming atrophic thyroid follicles surrounded by mononuclear cell infiltration and fibrosis showed positive staining. With increasing distance from lymphoid cell follicles, the percentage of follicular epithelial cells with DNA fragmentation-positive nuclei decreased (30-80%). Electron microscopic study revealed the existence of epithelial cells with shrunk and condensed nuclei. The frequency of those cells in different areas was almost compatible with that of cells with fragmentation-positive nuclei. These findings suggest that apoptosis plays an important role in the thyroid tissue injury in autoimmune thyroiditis.

Adult↗
PubMed1992

Evaluation of thyroid function and anti-thyroid autoantibodies in systemic sclerosis.

Parameters of thyroid metabolism, and the presence of anti-thyroid antibodies were investigated in 43 patients with systemic sclerosis. Anti-thyroid antibodies were detected in 14 cases. Elevated levels of anti-thyroglobulin antibodies were determined in 4 cases, anti-thyroid peroxidase (TPO) antibodies in 11, and anti-microsomal antibodies in 5. The detection of anti-TPO antibodies gave the most remarkable information about the presence of autoimmune thyroiditis. The patients with anti-TPO and/or reduced T3 concentration tended to have secondary Sjögren's syndrome. Our results provide further evidence that anti-thyroid antibodies might be responsible for the remarkable appearance of autoimmune thyroiditis in systemic sclerosis.

Adult↗
PubMed1999

[Differential diagnosis of Hashimoto's thyroiditis from thyroidal neoplastic diseases].

Thyroid lymphoma is a relatively rare disease, but has attracted the attention of many investigators because of its putative relationship with Hashimoto's thyroiditis. The definite diagnosis of thyroid lymphoma, especially the histologic distinction from small cell carcinoma or Hashimoto's thyroiditis, has been problematical and even regarded as impossible during the past decades. Recent progress in immunological methods including molecular biology has resolved many of the diagnostic problems in this field, thereby providing a scientific basis for approaching these diseases. In this review, we have discussed the important role of Hashimoto's thyroiditis in the etiology of thyroid lymphoma; the B-cell nature of proliferating cells in thyroid lymphoma; the histologic differential diagnosis.

Carcinoma, Small Cell↗
PubMed2000

[Effect of aceclofenac on thyroid hormone binding and thyroid function].

Influences of non-steroidal anti-inflammatory drugs (NSAID) on concentrations of thyroid hormones are known for a long time. These effects could be explained with interference between NSAIDs and thyroid hormone binding. We investigated the effects of a single dose of aceclofenac on thyroid function and thyroid hormone binding in 18 healthy volunteers. Serum levels of free thyroid hormones (FT3, FT4) and thyrotropin (TSH) were measured with commercial available kids and thyroid hormone binding was estimated with a specially modified horizontal argarose-gel-electrophoresis prior to and 2 hours after receiving a single dose of aceclofenac. We found a significant decrease in T3 binding on TBG and a significant increase of albumin-bound T3. All other investigated thyroid hormone binding parameters, FT3 and FT4, showed no significant changes. We conclude that aceclofenac leads to a significant redistribution of T3 protein binding. These effects seem to be explained by T3 displacement from TBG induced by aceclofenac.

Adult↗
PubMed2000

Correlation between clinical activity score and thyroid autoantibodies in patients with thyroid ophthalmopathy.

To investigate the relation between clinical activity score (CAS) and thyroid autoantibodies of thyroid ophthalmopathy, we measured the level of TSH receptor antibody (TRAb), antithyroglobulin antibody (ATA), and antimicrosomal antibody (AMA) in 41 patients with thyroid ophthalmopathy. The results of thyroid autoantibodies level were compared with CAS. Under the multiple regression and correlation analysis among CAS and the levels of TRAb, ATA, and AMA, no correlation was shown in this study. In conclusion, there is no correlation of thyroid ophthalmopathy among CAS and the levels of TRAb, ATA, and AMA in our study. If we use these three kinds of thyroid autoantibodies to match the activity of thyroid ophthalmopathy, it seems to be inappropriate. Further search of other simplified index to reflect the activity of ophthalmopathy should be encouraged.

Adult↗
PubMed2001

Immunohistochemical studies of Na+/I- symporter in human thyroid tissues--a correlation with clinical thyroid scintigraphy.

BACKGROUND: Thyroid Na+/I- symporter (NIS) is thought to play an important role in iodide uptake in thyrocytes. We hypothesize that there is correlation between the expression of NIS protein in the normal and diseased thyroid tissues and their clinical thyroid scintigraphy. METHODS: Twenty-seven patients, aged from 21 to 81, were studied from the surgical department of a tertiary referral center. Ten patients were with papillary carcinoma, 5 with follicular carcinoma, 5 with follicular adenoma, 5 with nodular goiter and 2 with Graves' disease. All the carcinoma patients underwent total thyroidectomy while others had lobectomy or subtotal thyroidectomy. The thyroid tissue sections prepared for study were stained with polyclonal hNIS antibody (SS Chiang, Ohio). RESULTS: Most of the nodular goiters were negatively stained except 2 samples that showed weak signal focally. All cases with follicular adenoma or follicular carcinoma were negative for NIS expression, while some with papillary carcinoma were stained positive at sporadic follicles with weak signal. The thyroid tissue of Graves' disease was stained positive for NIS expression. CONCLUSIONS: Thyroid tissues with hypofunctioning nodules displayed significantly reduced or undetectable level of NIS expression. It correlated well with pre-operative thyroid scans.

Adult↗
PubMed2003

[Thyroid nodules with calcification and thyroid carcinoma].

OBJECTIVE: To investigate the significance of thyroid calcification for diagnosis of thyroid carcinoma. METHODS: Retrospective analysis of 817 thyroid nodules' pre-operative ultrasonic and postoperative pathologic results. RESULTS: Total ultrasonic thyroid calcification ratio was 18.1% (148/817). Total pathologic thyroid calcification ratio was 19.6% (160/817), which in benign samples was lower than that in malignant samples (13.1% vs 53.5%, P < 0.01). Micro-calcification ratio in benign samples was lower than that in malignant samples (2.9% vs 38.6%, P < 0.01). CONCLUSIONS: Thyroid nodules with calcification especially micro-calcification is considered to be the most specific sign of thyroid carcinoma, so the detection of it should be an important diagnostic criterion.

Adolescent↗
PubMed2005

Serum levels of antibodies to thyroid peroxidase correlate with quantitative descriptors of thyroid ultrasound images in patients with breast cancer.

The aim of the study was to compare the structural changes in ultrasound image of the thyroid tissue in 12 women with breast cancer (BC) and 8 women with colorectal cancer (CC). MATLAB software was used to analyse the digitised images. As quantitative descriptors of thyroid ultrasound images (QDTI) were used raw grey scale values of individual image pixels (RAW) and the optimal one-dimensional discriminative texture features (F2, F6, F7). The possible relations between QDTI and thyroid laboratory parameters were tested. In the BC group serum levels of antibodies to thyroid peroxidase negatively correlated with feature RAW (multiple regression, beta coefficient -0.75, p=0.004) and positively with feature F2 (multiple regression, beta coefficient 1.44, p=0.04). In the BC group RAW negatively correlated with serum levels of tumour marker CA 15-3 (Pearson's correlation coefficient, r=-0.714, p=0.00917). No such correlations were found in CC group. The correlations between QDTI and serum levels of antibodies to thyroid peroxidase in patients with BC show that the positivity of antibodies to thyroid peroxidase is probably accompanied with structural changes in the thyroid tissue.

Aged↗