Increased Radioiodine Uptake Research Articles

Rexinoid therapy for poorly differentiated thyroid cancer: A pilot clinical phase II trial and correlation to retinoid and peroxisome-proliferator activated receptor gamma receptors expression.

TPS269 Background: Thyroid cancer causes over 1,600 deaths annually, mostly from poorly differentiated tumors that are radioiodine resistant. Cytotoxic chemotherapy has limited efficacy so alternative therapies are warranted. Retinoids are vitamin A derivatives that bind to retinoic acid and retinoid × receptors (RARs and RXRs), each with α, β, and γ isotypes. Retinoid receptors are present in thyroid tissue and the RXRγ isotype has been shown to be higher in thyroid cancer than matched normal tissue. RXRs can form a heterodimer partnership with PPARγ to enhance transcriptional activity upon DNA binding. Bexarotene is a selective RXR agonist approved for the treatment of cutaneous T-cell lymphoma. Preclinical in vitro and in vivo studies show that bexarotene reduces growth in RXRg expressing cells and xenograft tumor size, and this effect is enhanced when PPARγ is present. Additionally, bexarotene has been shown to increase radioiodine uptake in some patients with previously radioiodine-resistant thyroid cancer. Methods: Adult patients with radioiodine-resistant follicular-derived thyroid cancer and RECIST criteria disease progression and/or PET positive lesions will be enrolled. Eligible patients will receive open-label bexarotene at a dose of 300 mg/m2/day. Concomitant omega-3 fatty acids will be started two weeks before bexarotene. We propose a two-part, standard phase II trial where we will study 19 patients and if we see one response we will enroll 12 more for a total of 26 patients. With an anticipated 10-30% drop out this will allow for 14 initial patients and if a responder is found 23 patients total. Study drug will be given for one year and the primary end points are tumor response by RECIST criteria and correlation with primary thyroid cancer tissue expression of RXR and PPARy receptors. The secondary endpoint is radioiodine uptake at 6 months and 1 year. At weeks 8, 18, 24, 30, 38, 46, and 52 TSH, Free T4, total T4, total T3, thyroglobulin and thyroglobulin antibodies will be obtained. Neck ultrasound, PET-CT scan, and rhTSH-stimulated radioactive iodine whole body scan will be obtained on weeks 24 and 52. No significant financial relationships to disclose.

Single photon emission computed tomography (SPECT)/computed tomography using Iodine-123 in patients with differentiated thyroid cancer: additional value over whole body planar imaging and SPECT

The aim of the study was to assess the diagnostic performance of co-registered single photon emission computed tomography (SPECT)/computed tomography (CT) compared to Iodine-123 whole body gamma camera (WBGC) imaging and to SPECT alone in patients with differentiated thyroid cancer. WBGC and SPECT/CT (n=85) imaging of the neck and thorax was performed in 79 consecutive patients. Three experienced observers reviewed: i) WBGC images followed by ii) SPECT alone, and iii) co-registered SPECT/CT. Foci of increased radioiodine uptake were classified on a five-point scale. Biopsy, other imaging modalities, and clinical follow-up served as the reference standard. Twenty-two patients had local recurrence or metastatic thyroid cancer (11 were radioiodine negative), 9 had remnant thyroid tissue, and 54 had no evidence of disease. When classifying equivocal, probably, and definitely malignant findings as positive for malignancy, the sensitivity, specificity, positive predictive value, and negative predictive value were as follows: 41, 68, 31, and 77% for WBGC imaging; 45, 89, 59, and 82% for WBGC plus SPECT imaging; and 50, 100, 100, and 85% for WBGC plus SPECT/CT imaging respectively. The specificity was improved by the addition of SPECT (P=0.0002) and SPECT/CT (P<0.0001) than to WBGC imaging. SPECT/CT was also more specific than WBGC plus SPECT imaging (P=0.016). In a study-based analysis, SPECT/CT provided additional diagnostic information in 42% (36/85) of cases. SPECT/CT provided further characterization in 70% (63/90) of foci and improved the diagnostic confidence of all three observers. The addition of SPECT/CT significantly improved the diagnostic information over Iodine-123 WBGC imaging and WBGC plus SPECT imaging alone.

Recombinant Human Thyrotropin Administration Enhances Thyroid Uptake of Radioactive Iodine in Hyperthyroid Cats

Hyperthyroidism is the most diagnosed endocrine disorder in cats and radioiodine (131I) is the treatment of choice. The dose emission rate and radioactivity in urine, saliva, and on hair and paws are determined by the dose of administered 131I. A dose reduction of therapeutic 131I could possibly be achieved after recombinant human thyrotropin (rhTSH) administration as in humans with nodular goiter. rhTSH will increase radioiodine uptake in hyperthyroid cats. Five hyperthyroid cats. Twenty-five micrograms rhTSH (day 1) or 2 mL 0.9% sodium chloride (NaCl) (day 9) was injected IV. One hour later, 11.4 +/- 4.1 (mean +/- SD) MBq 123I was injected IV. Radioactive iodine uptake (RAIU) was measured 6, 12, and 24 hours after rhTSH (RAIU-rhTSH) or NaCl (RAIU-blanco) injection. Blood samples for measurement of TT4 were taken before injection of rhTSH or NaCl (TT4(0)) and at the time of imaging. Percentages of RAIU-rhTSH (and RAIU-blanco) at 6, 12, and 24 hours after administration of rhTSH were 34 +/- 18 (31 +/- 21), 46 +/- 20 (38 +/- 18), and 47 +/- 15 (36 +/- 14). There was a statistically significant effect of rhTSH administration on RAIU (P = .043) but not on serum TT4 concentration. Baseline serum TT4(0) concentration influenced RAIU-rhTSH significantly at 6 hours (P = .037). The increased RAIU observed after rhTSH administration in hyperthyroid cats could lead to a lower therapeutic dose of 131I after rhTSH administration in hyperthyroid cats and decreased risk of environmental and owner contamination during and after hospitalization.

Radioiodine Studies, Low Serum Thyrotropin, and the Influence of Statin Drugs

A low serum thyrotropin (TSH) concentration is an excellent predictor of hyperthyroidism, either overt or subclinical. Whether statin use influences the ability of a low serum TSH measurement to detect hyperthyroidism has not been evaluated. In a cohort of 307 patients with low or undetectable serum TSH concentrations suggestive of hyperthyroidism, we determined whether concurrent statin use influenced the results of radioiodine uptakes and scans. Participants included 29 patients taking a statin medication and 278 who were not taking a statin. Radioiodine uptakes and scans were interpreted by board-certified nuclear medicine physicians. Sixteen of the 29 patients who were taking a statin (55%) had normal radioiodine uptakes and scans despite their low serum TSH. The remaining 13 low-TSH patients who were taking a statin (45%) had abnormal uptakes and scans, most commonly showing diffuse thyroid hyperplasia with increased radioiodine uptake. In contrast, the vast majority of the 278 patients not taking a statin had abnormal uptakes and scans (84%), while only 16% of them had normal uptakes and scans (p < 0.001 vs. those on statins). The age- and sex-adjusted odds ratio of a statin user with a low serum TSH having normal radioiodine studies (as opposed to abnormal studies) was 3.6 (95% CI, 1.6-8.4). In patients with a low serum TSH concentration, normal thyroid function and morphology, as assessed by radioiodine studies, were much more common if the patient was taking a statin. Statins may falsely lower the serum TSH without altering thyroid function ("pseudohyperthyroidism") or, alternatively, statins may improve thyroid function in patients with hyperthyroidism.

Rosiglitazone Effect on Radioiodine Uptake in Thyroid Carcinoma Patients with High Thyroglobulin but Negative Total Body Scan: A Correlation with the Expression of Peroxisome Proliferator–Activated Receptor-Gamma

Thyroid carcinoma patients with high thyroglobulin (Tg) level but negative total body scan (TBS) are difficult to treat with radioiodine (RAI). The objective of this study was to determine if treatment with rosiglitazone (RZ), a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, was associated with an increase in RAI uptake in thyroid carcinoma patients with high serum Tg and negative TBSs. We also determined if there was a correspondence between the effect of RZ and the degree of staining for PPAR-gamma within thyroid cancer tissues. We prescribed 8 mg of RZ daily for 6 weeks in 23 patients with epithelial cell thyroid carcinoma who previously had negative posttherapeutic I-131 total body scans (post Rx TBSs) with high serum Tg concentrations. Diagnostic total body scans (Dx TBSs) before and 6 weeks after RZ treatment were compared. An ablative dose of I-131 was then given to all patients, and post Rx TBS was performed to evaluate RAI uptake. Immunohistochemical staining of PPAR-gamma expression in thyroid cancer biopsies was done to correlate this with possible effects of RZ on RAI uptake. Seven patients had strong PPAR-gamma-positive staining in thyroid biopsies, nine patients had weakly positive staining, and seven patients had negative staining. Five of seven patients with strong staining had either positive post Rx TBS, or both Dx TBS and post Rx TBS. One of nine patients with weak staining had positive Dx TBS and post Rx TBS. In contrast, none of the seven patients with negative staining had positive TBS. RZ can increase RAI uptake in thyroid tissue in the majority of patients with epithelial cell thyroid carcinoma whose previous posttherapeutic I-131 scans were negative provided they have high intensity and extent of PPAR-gamma expression in thyroid tissue. Few, if any, patients with weak or no PPAR-gamma expression in thyroid cancer tissue increase RAI uptake after RZ treatment.

The Comparative Effects of Gene Modulators on Thyroid-Specific Genes and Radioiodine Uptake

The aim of this study was to comparatively investigate the effects of 5-azacytidine-C (5-Aza), trichostatin-A (TSA), and all-trans retinoic acid (ATRA) on the mRNA expressions of the sodium and iodine (Na/I) symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO), and the thyroid-stimulating hormone receptor (TSH-R), as well as radioiodine (RAI) uptake in cancer (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines. Cell lines were treated with 10 ng/mL of TSA, 5 microM of 5-AZA, and 1 microM of ATRA, according to the MTT (methyl-thiazol-tetrazolium) test results. Additionally, recombinant thyroid-stimulating hormone (rTSH) was also applied, with a selected dose of 100 ng/mL. Following the treatment, NIS, Tg, TPO, and TSH-R mRNA levels were detected by real-time-polymerase chain reaction (RT-PCR) and RAI uptakes were measured by using a well counter as counts/cell number. 5-Aza increased TSH-R mRNA expression in both of the cell lines and decreased TPO, NIS, and Tg mRNA levels in the cancer cell line. In the normal thyroid cell line, 5-AZA increased TPO mRNA levels by 2-fold and made no differences in NIS and Tg mRNA levels. TSA treatment repressed NIS and Tg mRNA levels and made no change on other thyroid-specific genes that were investigated in the cancer cell line. In the normal thyroid cell line, TSA increased TSH-R mRNA levels in 72 hours and created no important difference in the other genes. ATRA repressed the TSH-R mRNA levels in the normal thyroid cell line and increased the TPO and Tg mRNA levels slightly in both the cell lines. Furthermore, in short-term treatment, ATRA repressed the NIS gene expression slightly, but in the long term, this repression turned to basal levels. 5-Aza, TSA, and ATRA did not make any changes in RAI uptake in the cancer cell line, but rTSH increased RAI uptake significantly. In the normal thyroid cell line, TSA and ATRA decreased RAI uptake (to 1/10 and 1/2, respectively), but 5-Aza and rTSH increased RAI uptake significantly (2- and 4-fold, respectively). In our study, we showed an increase in TSH-R gene expression and radioiodine uptake with 5-Aza. Further in vitro and in vivo studies are needed to support our findings and the potential clinical use of this agent.

Reinduction of Cell Differentiation and 131I Uptake in a Poorly Differentiated Thyroid Tumor in Response to the Reverse Transcriptase (RT) Inhibitor Nevirapine

Our recent findings have shown that the reverse transcriptase (RT) inhibitors, nevirapine and efavirenz, used for 10 years in human immunodeficiency virus (HIV) disease, act as cytostatic and differentiating agents by modulating gene expression in several human tumor cell models. In dedifferentiated thyroid cancer, they reestablish thyroid-stimulating hormone (TSH) signaling, Na/I symporter (NIS), thyroglobulin peroxidase (TPO) expression, and even radioiodine uptake (RIU). In this paper, we describe the case of a 76-year-old woman who was affected by thyroid papillary carcinoma and who underwent a total thyroidectomy and a debulking of the right laterocervical region for lymph-node metastases, vessel infiltration, and neoplastic thrombosis of the internal jugular vein, followed by 3 radioiodine treatments. At restaging, a computed tomography scan revealed that distant metastases were mostly not taking up the radioiodine at the 131I whole-body scan (WBS). An analysis of tumor cells obtained by fine-needle aspiration biopsy of a right laterocervical lymph-node revealed cell anisokaryosis, nuclear pleomorphism, and scanty colloid, as well as the undetectable expression of thyroglobulin and NIS proteins. After starting a nevirapine treatment (NT), higher thyroglobulin levels were observed and some metastases exhibited a significant increase in radioiodine uptake, which led us to again treat the patient with 131I. Five (5) months later, the 131I-WBS revealed the disappearance of RIU in some metastases and its significant reduction in other lesions, with a parallel drop in serum thyroglobulin. No new metastatic lesion was revealed by rh-TSH-stimulated 131IWBS and 18F-flourodeoxyglucose positron emission tomography scan. Cells obtained from the right laterocervical lymph-node 2 months after NT exhibited a reduced nuclear pleomorphism, an increase in colloid production, and a significant upregulation of thyroglobulin and NIS protein expression. This first in vivo molecular and morphologic evidence of cell differentiation in human cancer and low toxicity of nevirapine strongly encourage its use in dedifferentiated thyroid cancer treatment.

The Comparative Effects of Gene Modulators on Thyroid-Specific Genes and Radioiodine Uptake

The aim of this study was to comparatively investigate the effects of 5-azacytidine-C (5-Aza), trichostatin-A (TSA), and all-trans retinoic acid (ATRA) on mRNA expressions of Na/I symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO), and thyroid stimulating hormone receptor (TSH-R), and radioiodine (RAI) uptake in cancer (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines. Cell lines were treated with 10 ng/mL of TSA, 5 microM of 5-Aza, and 1 microM of ATRA, according to the MTT (methyl-thiazol-tetrazolium) test results. Additionally, recombinant thyroid stimulating hormone (rTSH) was also applied, with a selected dose of 100 ng/mL. Following the treatment, NIS, Tg, TPO, and TSH-R mRNA levels were detected by real-time-polymerase chain reaction (RT-PCR) and RAI uptakes were measured by using a well counter as the counts/cell number. 5-Aza increased TSH-R mRNA expression in both of the cell lines and decreased TPO, NIS, and Tg mRNA levels in the cancer cell line. In the normal thyroid cell line, 5-Aza increased TPO mRNA levels 2-fold and made no differences in NIS and Tg mRNA levels. TSA treatment repressed NIS and Tg mRNA levels, and made no differences on other thyroid specific genes investigated in the cancer cell line. In the normal thyroid cell line, TSA increased TSH-R mRNA levels in 72 hours and created no important differences in other genes. ATRA repressed the TSH-R mRNA levels in the normal thyroid cell line and increased the TPO and Tg mRNA levels slightly in both cell lines. Furthermore, in short-term treatment, ATRA repressed NIS gene expression slightly, but in the long term, this repression turned to basal levels. 5-Aza, TSA, and ATRA did not make any differences in RAI uptake in the cancer cell line, but rTSH increased RAI uptake significantly. In the normal thyroid cell line, TSA and ATRA decreased RAI uptake (to 1/10 and 1/2, respectively), but 5-Aza and rTSH increased RAI uptake significantly (2- and 4-fold, respectively). We have shown an increase in TSH-R gene expression and radioiodine uptake with 5-Aza. Further in vitro and in vivo studies are needed to support our findings and the potential clinical use of this agent.

A clinical study of all-trans-retinoid-induced differentiation therapy of advanced thyroid cancer

To evaluate the changes in differentiation markers and therapeutic effects in all-trans-retinoic acid (ATRA)-treated patients with dedifferentiated thyroid cancer. Between September 2001 and July 2004 eleven patients were analysed retrospectively. They had dedifferentiated thyroid cancers (DTC) (four follicular, five papillary, two oxyphilic) and were selected for treatment with ATRA (1.00+/-0.09 mg x kg x d) for 30 or 60 days. All patients had advanced stage tumours with prior operative and radioiodine treatment. Extensive tumour invasion, distant metastatic spread, and insufficient or non-existent uptake of radioiodine precluded conventional therapeutic options. Changes in I uptake, response of target lesions, and serum thyroglobulin (Tg) levels were measured and compared in these patients before and after ATRA therapy. In 11 patients with DTC, iodine uptake was increased in four and there was a partial response (PR) of target lesions in five patients as well as two patients with stable disease. Tg was assessed in eight patients, in whom two responders showed increased radioiodine uptake or no change and decreased Tg level, as well as PR after ATRA-induced differentiation therapy. ATRA has an effect on the differentiation status of DTC and deserves further investigation.

Reproducibility of whole-body 131I scan and serum thyrotropin and stimulated thyroglobulin values in patients studied twice after injection of recombinant human thyrotropin

Recombinant human TSH (rhTSH) is used to increase radioiodine uptake during imaging of thyroid cancer, obviating the need to render the patient hypothyroid. We assessed the reproducibility of radioiodine uptake, serum thyrotropin (TSH), and stimulated serum thyroglobulin (Tg) levels after rhTSH administration. A retrospective review was performed of patients at Stanford who underwent whole-body (131)I scanning for surveillance of thyroid cancer twice after thyroidectomy and (131)I ablation, with rhTSH prior to each scan. Forty-eight hour radioiodine uptake, peak serum TSH, and stimulated serum Tg levels for each study were recorded. Paired t tests and correlation analysis were used to assess interexamination repeatability. Twenty-three patients underwent two scintiscans with rhTSH, for a total of 46 exams. There was no significant difference between percent uptake at 48 h in the paired exams (p=0.40). Serum TSH level was measured in 45 of 46 exams; TSH exceeded 50 mIU/l in all cases, and there was no significant difference between paired TSH levels (p=0.93). All patients had stimulated serum Tg levels measured, with no significant difference between paired Tg levels (p=0.40); after excluding one patient whose Tg changed from 15.8 ng/ml to undetectable between scans without interval treatment, the p value rose to 0.95. There was a strong correlation among paired uptake values (r=0.85, p<0.0001), peak serum TSH (r=0.69, p=0.0003), and stimulated Tg levels (r=0.81, p<0.0001). No discordant scan interpretations were reported. Forty-eight hour radioiodine uptake, peak serum TSH, and stimulated serum Tg levels after administration of rhTSH are repeatable between studies, demonstrating reproducibility of diagnostic results without rendering patients hypothyroid.

Increased Radioiodine Uptake of Thyroid Cell Cultures after External Irradiation

Radioiodine uptake (RIU) is one of the main prognostic factors for curative results of radioiodine therapy in patients with differentiated thyroid cancer. Some days after application of (131)I, the uptake of a subsequent administration of radioiodine was found to be reduced. In contrast, early after irradiation with high-energy photons glucose and amino acid uptake were observed to be increased. Effects of external irradiation on RIU of thyrocytes using high-energy photons have not been investigated so far. Two different cell lines (FRTL-5 and ML-1 cells) derived from thyroid tissue were studied in vitro. Cell lines were either incubated with (131)I only (controls) or additionally irradiated with single doses of 6 or 10 Gy of high-energy photons using a linear accelerator. Cell number and RIU were determined 24-96 h after (131)I application. RIU measurements were repeated after application of sodium perchlorate in excess to investigate specificity of the uptake. Statistical analyses were performed using non-parametric tests. Incubation with radioiodine as well as irradiation with high-energy photons slowed down proliferation in investigated cell lines significantly. Irradiation with solely (131)I resulted in stable or slightly decreased iodide uptake. Compared to those cells, the RIU increased significantly in externally irradiated cells, i. e., additional irradiation with 10 Gy resulted in an almost threefold increase of RIU in FRTL-5 after 72 h. The increase of RIU after irradiation was dose-dependent in both cell lines and could be blocked by perchlorate excess. It could be demonstrated that external irradiation increases RIU in thyroid cell cultures early after irradiation. The increase was dose-dependent and specific, as it could be blocked by perchlorate. This effect appears to be similar to the increase of other actively transported substances after irradiation with high-energy photons. Therefore, the results of this study may contribute to the knowledge of a generalized irradiation-induced mechanism which causes the activation of different cellular transporters. The clinical impact of these findings on combined therapy concepts has to be investigated in further experiments.

Molecular nuclear medicine using sodium/iodide symporter

Iodide uptake occurs across the membrane of thyroid cells via an active transporter, sodium/iodide symporter (NIS). Decreased NIS expression levels account for the reduced iodide uptake in thyroid carcinomas. We found that thyroid cancer patients with positive immunostaining for NIS responded to I-131 therapy better than did the patients with negative immunostaining. Thus, NIS gene can be used for radionuclide gene therapy. Targeted expression of functional NIS in cancer cells would enable these cells to concentrate iodide from plasma and would, therefore, offer the possibility of radioiodine therapy. We and others have shown that gene transfer of NIS into a variety of cell types confers increased radioiodine uptake up to several hundred-fold that of controls. Imaging reporter gene is useful in noninvasively determining the location, duration and magnitude of transgene expression in living animal. We could monitor not only exogenous gene expression, but also endogenous gene expression such as p53 and nuclear receptor activity such as retinoic acid receptor using cis-NIS reporter imaging gene system. This reporter gene imaging can also be used for monitoring cancer cells, stem cells and immune cells. In conclusion, the NIS has the potential to expand molecular nuclear medicine in the near future.

Utility of Recombinant Human Thyrotropin for Augmentation of Radioiodine Uptake and Treatment of Nontoxic and Toxic Multinodular Goiters

To report our results in treating 16 patients with low radioiodine uptake (RAIU) multinodular goiter who had obstructive symptoms or suppressed thyroid-stimulating hormone (TSH or thyrotropin), indicating mild hyperthyroidism. Six patients were treated with 0.3 mg of recombinant human thyrotropin (rhTSH) followed by 30 mCi of (131)I 72 hours later. Ten patients were treated with 0.9 mg of rhTSH followed by 30 mCi of (131)I 24 hours later. Of the 16 treated patients, all 10 with compressive symptoms and both patients with weight loss had remission or improvement, as did 1 of 2 patients with atrial fibrillation. All patients with suppressed TSH had a return to normal levels or became hypothyroid. During the next 3 to 7 months, estimated gland size reduction was 30 to 40%. Three of the 6 patients who received 0.3 mg of rhTSH and 6 of the 10 patients who received 0.9 mg of rhTSH, in conjunction with (131)I therapy, ultimately had TSH levels indicative of hypothyroidism. Mild radiation thyroiditis developed in only one patient, and no other side effects occurred. The 0.3-mg dose of rhTSH seemed to be as efficacious as the 0.9-mg dose. The greater than fourfold increase in RAIU at 72 hours after administration of rhTSH in our study is more than twofold higher than the 24-hour RAIU results previously reported in normal subjects and in patients with multinodular goiter. These findings have implications for future expanded studies and alternative dosing regimens in treating patients with both multinodular goiter and subclinical hyperthyroidism.

Thyrotoxicosis Induced by Topical Iodine Application

We describe an elderly man who was admitted with congestive cardiac failure and found to have thyrotoxicosis. He did not have goiter, and he had normal radioiodine uptake in his neck. Serum iodine levels were elevated, explaining the lack of increase in radioiodine uptake in the thyroid gland. He had multiple pressure sores, which were treated with povidone-iodine (Betadine) soaks. Biochemical data were consistent with Graves' disease unmasked by topical iodine application. Povidone-iodine soaks are commonly used in decubitus ulcer care and warrant special attention in patients with preexisting thyroid disorders. We have reviewed the literature on this unusual complication.

Thyrotoxicosis induced by topical iodine application

• We describe an elderly man who was admitted with congestive cardiac failure and found to have thyrotoxicosis. He did not have goiter, and he had normal radioiodine uptake in his neck. Serum iodine levels were elevated, explaining the lack of increase in radioiodine uptake in the thyroid gland. He had multiple pressure sores, which were treated with povidone-iodine (Betadine) soaks. Biochemical data were consistent with Graves' disease unmasked by topical iodine application. Povidone-iodine soaks are commonly used in decubitus ulcer care and warrant special attention in patients with preexisting thyroid disorders. We have reviewed the literature on this unusual complication. (<i>Arch Intern Med.</i>1990;150:2400-2401)

IMMUNOHISTOCHEMICAL ASPECTS OF AUTONOMOUSLY FUNCTIONING THYROID NODULES (AFTNs)

The immunohistochemical aspects of 18 patients with autonomously functioning thyroid nodules (AFTNs) examined between 1984 and 1988 are investigated. The diagnosis of AFTN is made by the thyroid scintigraphy, which shows increased radioiodine uptake (hot nodule). Histologically, follicular adenoma was present in 5 patients and adenomatous goiter in 13.For the immunohistochemical investigations, paraffin sections were stained for thyroglobulin (Tg), thyroxine (T4), and triiodothyronin (T3) using the avidin-biotin peroxidase complex method. The positivity for Tg, T3 and T4 was found to be stronger in AFTN tissues than in the extranodular thyroid tissues. In particular, they were strongly positive in the areas of papillary structure and microfollicles, or some eosinophilic cells in the foci of lymphocyte infiltration associated with focal thyroiditis. In conclusion, the immunohistochemical examination of T3, T4 and Tg is useful for differentiating AFTN from a nonfunctioning nodule or carcinoma of the thyroid.

A simplified low iodine diet in I-131 scanning and therapy of thyroid cancer.

A simplified, low iodine diet was developed for outpatient use prior to I-131 scanning and therapy in thyroid cancer. Iodine intake of five subjects on the diet was approximately 50 micrograms a day and this level was maintained for four weeks. The diet required only minimal instruction to be followed reliably. This level of iodine intake may increase radioiodine uptake in thyroid carcinomas.

Lithium as an adjuvant of iodine-131 uptake when treating patients with well-differentiated thyroid carcinoma.

Differences in the I-131 uptake by 14 metastatic lesions from well-differentiated thyroid carcinoma and 12 local remnants of normal thyroid tissue before and after an adjuvant therapy with lithium carbonate, were observed. After the adjuvant treatment and administration of an I-131 tracer dose, a considerable increase of radioiodine uptake in all metastatic lesions was found (P less than 0.001), but only a slight increase was found in 50% of the normal tissue. The response to lithium carbonate by neoplastic tissue seems to be different than that of the normal thyroid tissue, and produces a lengthening of the average I-131 biologic life that could be helpful when treating well-differentiated thyroid carcinoma.

Serum-Thyroxine Levels in Microwave-Exposed Rats

The nature of the response of the thyroid gland in animals exposed to microwave irradiation is controversial. An enlarged thyroid and an increase of radioiodine uptake in microwave workers have been reported. Absence of thyroid disorders has also been reported in other exposed populations. Animal experimentation has contributed to the controversy because both increased and decreased thyroid functions have been reported. The thyroxine concentration in rats as representative of thyroid function in animals exposed to 2.45-GHz, 120-Hz amplitude-modulated microwaves has been studied. Comparison was made between thyroxine concentrations in microwave- and sham-exposed rats by Student's t test. After a 1-hr exposure, an increased thyroxine concentration was found in rats exposed at 40 and 70 mW/cm2, but not at 1, 5, 10, 20, 50, or 60 mW/cm2. After a 2-hr exposure, increased thyroxine concentration was noted in rats exposed at 25, 30, and 40 mW/cm2, but not at 1, 5, 10, and 20 mW/cm2. After a 4-hr exposure, thyroxine concentration increased in rats exposed at 1 mW/cm2 and decreased in rats exposed at 20 mW/cm2; but changes were not noted at 5 or 10 mW/cm2. Other experiments included animals that were exposed once for 4 hr (0.1, 1, 10, 25, and 40 mW/cm2), sampled 24 hr after a 4-hr exposure (0.1, 1, 10, 25, and 40 mW/cm2), or exposed for 4 hr 3 times (1, 10, 20, 30, 40, and 55 mW/cm2) and 10 times (1, 10, 20, 25, 30, and 40 mW/cm2), to evaluate the consistency of the thyroxine response. None of the rats in these experiments displayed any alteration of thyroxine concentration, except that decreased thyroxine was noted in rats exposed at 40 mW/cm2 for the third time. These studies covered a long time span; rats from two commercial sources (BS and CR) were used and subjected to different numbers of exposures, and therefore these data were evaluated for their stability. Two factors could influence the result significantly, i.e., source of animal and number of sham exposures. Rats used in the 2-hr exposures were from two different commercial sources; rats from CR had a higher (but normal) thyroxine concentration than did rats from BS. Therefore the data of these animals were separated by commercial source for reevaluation. Instead of increased thyroxine concentration in rats exposed at 25, 30, and 40 mW/cm2, changes were not noted in any microwave-exposed rats. The influence of sham exposure revealed that appropriate concurrent control and specification of animal source are needed in longitudinal studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Iodine metabolism and the effect of TSH in thyroid glands of early bovine embryos.

The ontogeny of the thyrotrophin-thyroid axis during the first trimester was studied in 104 bovine embryonic thyroids taken from foetuses of crown-rump length 1.4 to 19.2 cm (25-120 days). The uptake of labelled iodine in vitro in the absence or presence of TSH was measured. The per cent incorporation of radioiodine into iodotyrosines and iodothyronines in the presence and absence of TSH was also studied. It was found that the foetal tissue displayed radioiodine uptake by 25 days of foetal life and the uptake increased with age. TSH caused a further increase in radioiodine uptake in foetuses of 40 days or older. Incorporation of radioiodine into MIT and DIT was apparent at 25 days and into T3 and T4 by 40 days of foetal life. Addition of TSH increased the proportion of total radioiodine found as DIT and thyroxine in foetuses of 40 days older. This TSH stimulation of radioiodine incorporation increased with age. However, the proportion of radioiodine found as MIT and T3 was not affected before 120 days of foetal life. This was in marked contrast to the adult thyroid where the proportion of radioiodine found as T3 was increased by the addition of TSH. It is concluded that the foetal thyroid can respond to TSH by at least 40 days of foetal life and that this response differs from that seen in the adult.