131I therapy for pediatric thyroid cancer

Azido-3'-deoxy-thymidine (AZT) is a drug extensively used in the treatment of AIDS. AZT was incubated in vitro either with the pituitary-hypothalamus complex (PHc) or the intact pituitary (PI) of male rats. The PHc is comprised of the hypothalamus and the attached pituitary gland. After a preincubation period, the PHc or PI was incubated for 1 or 2 h with Krebs-Ringer bicarbonate buffer or either of two different concentrations of AZT (1 and 10 microM). In the control incubations, the PHc released less prolactin (PRL) and more follicle-stimulating hormone (FSH) and luteinizing hormone (LH) than the PI, indicating that hypothalamic control of the pituitary was exerted in vitro, presumably by diffusion of releasing and inhibiting hormones from the neurohypophysis to the anterior lobe of the hypophysis. Both concentrations of AZT evoked a significant increase in release of PRL and a decreased release of LH and FSH from the PHc. In the case of LH, the higher concentration of AZT partially suppressed LH release within 1 h. The other effects were not dose-related and were observed after incubating the tissue with AZT for 2 h. However, incubation of the PI with AZT failed to alter anterior pituitary hormone release, illustrating that the site of action of AZT is in the hypothalamus. We hypothesize that AZT blocks DNA synthesis resulting in suppression of synthesis and consequent release of hypothalamic hormones that control release of pituitary hormones in vitro. The results raise the possibility that AZT may alter hypothalamic-pituitary function in vivo.     

I-131 uptake in the breast for thyroid cancer surveillance with biopsy-proven benign tissue

A 37-year-old woman was seen for recurrent papillary carcinoma of the thyroid after thyroidectomy. After repeated surgery and I-131 therapy, follow-up I-131 scanning and thyroglobulin levels were negative. Subsequent I-131 surveillance, however, demonstrated bilateral breast uptake. A biopsy taken of this area in the right breast proved that the increased uptake was secondary to benign disease.     

Consensus proposal on the use of 131I in the treatment of thyrotoxicosis and thyroid cancer

A consensus meeting held by the Chilean Endocrinological Society reached to 22 consensus proposals on the use of iodine-131 in hyperthyroidism and thyroid cancer, that are reported in this paper. Some of these propositions are: 1) Hyperthyroidism: A previous 131I uptake test must be performed. A calculated or an ablative dose should be administered. Hypothyroidism must be considered an objective rather than a complication. In patients with cardiovascular risk, normal thyroid function must be attained with prophythioturacil. In cases of treatment failure, the dose should not be repeated before six months. It must be used with used with caution in children and teenagers. 2) Thyroid cancer: A iodine free diet is recommended prior to the therapeutic dose. A 100 mCi complementary ablative dose should be given after surgery, with a posterior exploration. This examination must not be done routinely, and if required, a 5 mCi dose should be used. For the treatment of metastases, a dose of 150 to 200 mCi is recommended. There is no radiation risk in hyperthyroidism or thyroid cancer. The only absolute contraindication is pregnancy. Recommendations for radiological protection are formulated. Hospitalization is suggested to protect other people from radiation exposure.     

The changing role of radioiodine in the management of differentiated thyroid cancer

Craniosynostosis occurs in one out of 2,000 births. It results in primary skull deformations requiring surgical repair, in infants with a body weight of less than 10 kg. Pure craniosynostosis is the most frequent situation, where the risk for cerebral compression during brain development is the lowest. Therefore the aim of surgical correction in this case is mainly cosmetic. Conversely, in syndromic craniosynostosis, associated malformations are more common and cerebral, visual and respiratory consequences of complex facio-craniosynostosis are usually severe. Current surgical techniques consist of a total skull vault reconstruction which carry a high risk of sudden and major blood losses. Intraoperatively, whatever the type of craniosynostosis, mean blood losses corresponding to 90% of estimated red cell mass have to be anticipated. These blood losses vary according to the type of skull deformation and the type of surgery. Accurate evaluation is usually difficult and must be based more on calculation of red cell mass variations than on simple monitoring of surgical drainage. Invasive haemodynamic monitoring is always required. To reduce the amount of homologous blood transfusion, peroperative haemodilution seems to be the most suitable technique, due to unresolved technical difficulties in autotransfusion practice in infants. Severe facial deformities are associated with chronic hypoxaemia and cerebral compression representing major risk for these children in poor condition undergoing such major surgical procedures. With experienced teams, this high-risk surgery carries a low peroperative mortality (less than 1%) and morbidity rate. The latter includes essentially transient peroperative hypotension. The excellent final cosmetic and functional results justify the practice of this surgery in children with a bodyweight of less than 10 kg.     

The role of iodine-131 and thallium-201 imaging and serum thyroglobulin in the management of differentiated thyroid carcinoma

BACKGROUND: A prospective study was conducted to evaluate the use of iodine-131 sodium scintigraphy, thallium-201 chloride scintigraphy, and quantitative serum thyroglobulin estimation in the detection of differentiated thyroid carcinoma after thyroidectomy and iodine-131 sodium ablative therapy. METHODS: Thirty-one patients with a median age of 45.6 years (range, 20-73 years) were included in the study. After optimal endogenous thyroid-stimulating hormone stimulation (> 50 mU/ml), 53 pairs of iodine-131 and thallium-201 scans were performed. Concomitant serum thyroglobulin levels were available for 32 pairs of scans. The presence or absence of thyroid cancer was established by clinical, radiologic, and/or biopsy findings. RESULTS: The concordance between iodine-131 and thallium-201 scan findings in the presence of disease (25 scan sets) was 36%. The concordance in the absence of disease (28 scan sets) was 82%. Iodine-131 scanning was found to be significantly better (P < 0.05) than thallium-201 scanning, in terms of sensitivity (0.8 versus 0.6), specificity (0.96 versus 0.82), accuracy (0.89 versus 0.72), and the predictive value of a positive test (0.95 versus 0.75). The measurement of serum thyroglobulin had a low sensitivity (0.3) in the study but had a specificity of 1.0. CONCLUSION: It was concluded that iodine-131 sodium scintigraphy is superior to thallium-201 scintigraphy and serum thyroglobulin estimation for the detection of residual or metastatic differentiated thyroid carcinoma. However, the use of combined modalities provides a higher diagnostic yield. Thallium-201 scintigraphy was especially useful in cases in which iodine-131 scintigraphy was negative and quantitative thyroglobulin levels were elevated.     

Effect of postoperative 131I treatment on thyroglobulin measurements in the follow-up of patients with thyroid cancer

Correlation of serum thyroglobulin (Tg) levels with recurrent cancer was performed in 200 patients who had undergone a subtotal thyroidectomy for well-differentiated thyroid carcinoma. Patients were divided into three groups: (1) those not treated postoperatively with radioactive iodine, (2) those treated with low dose (30 mCi) radioactive iodine, and (3) those treated with high dose (50-250 mCi) radioactive iodine. Tg levels proved to be reliable in detecting recurrent thyroid cancer regardless of the dose of radioactive iodine given postoperatively. These results reinforce the recommendation of using the Tg assay as the primary method of following these patients postoperatively, even when there was less than a total thyroidectomy and ablation with radioactive iodine.     

The comparative value of serum thyroglobulin measurements and iodine 131 total body scans in the follow-up study of patients with treated differentiated thyroid cancer

This study is an attempt to unify the evaluation of patients with well-differentiated thyroid cancer after ablative therapy. As such serum thyroglobulin determinations on and off thyroid hormone (T4) therapy and iodine 131 total body scans were examined in 53 patient studies. No metastases were found in patients whose thyroglobulin value was undetectable (less than 1 ng/ml). Values during T4 therapy that were detectable, even as low as 4.2 ng/ml, were occasionally associated with metastases. After T4 withdrawal, thyroglobulin value and scan were obtained. Neither metastasis nor clinically detectable cancer was found in patients whose thyroglobulin value was less than 10 ng/ml while off T4. Conversely, a value greater than 10 ng/ml was often associated with documented metastases even when the scan was negative. In summary, a thyroglobulin value less than 1 ng/ml during T4 therapy or less than 10 ng/ml off T4 therapy suggests successful therapy and a routine scan could be avoided unless clinically indicated. However, a value greater than 10 ng/ml suggests the presence of metastasis despite a negative scan. Thyroglobulin determination substantially improves the management of these patients.     

Iodine 131 uptake by primary lung adenocarcinoma. Misinterpretation of 131I scan

The effects of temperature (25 C) and time (2, 4, 6, 8, 12, 24, 48, 72, 96 hours and 5, 13, and 19 days) were determined on thawed samples of Anaplasma marginale-infected erythrocytes cryogenically preserved with dimethyl sulfoxide and frozen in liquid nitrogen. Inoculation into splenectomized calves indicated that infectivity was not destroyed by either time or temperature from 2 to 72 hours, but was destroyed at 96 hours. The incubation periods of the disease in inoculated splenectomized calves increased in proportion to the length of time the samples were held at 25C.     

Leukemia developing after 131I treatment for thyroid cancer in a patient with Werner's syndrome: molecular and cytogenetic studies

A 40-year-old female patient with Werner's syndrome (WS) suffering from thyroid cancer and myelodysplastic syndrome (MDS) is reported. She had been diagnosed as having WS complicated with thyroid cancer seven years previously. Total thyroidectomy and radioactive iodine (131I, 100 mCi/year) therapy for seven years had slowed the progression of thyroid cancer. She suffered a sudden onset of MDS at the age of 40 years. After six months she died from overt leukemia. We found an additional chromosome aberration of chromosome 10 in the progression of leukemia from MDS.     

Redifferentiation therapy-induced radioiodine uptake in thyroid cancer

Due to a dedifferentiation of tumor cells, some thyroid carcinomas lose their capability for radioiodine (RI) concentration. This phenomenon is associated with a worse prognosis and prevents effective treatment. Retinoic acid (RA) is known to induce redifferentiation in various kinds of tumors and has been used recently in thyroid cancer. METHODS: Twelve patients (9 women, 3 men) with 6 papillary, 4 follicular and 2 mixed-cell type tumors (including 4 Hurthle cell carcinomas) were treated orally with RA (dose: 1.18 +/- 0.37 mg/kg body weight) for at least 2 mo before RI therapy. None of the patients could be treated with any other modality (RI, surgery, external radiation) when RA administration was started. Initially, clinically important tumor sites did not take up significant amounts of RI. Changes of RI uptake and thyroglobulin (Tg) serum values were determined. Glucose metabolism was followed with fluorodeoxyglucose (FDG) PET imaging in 10 patients before and in 5 patients after RA treatment. RESULTS: In 2 patients, a significant RI uptake was induced by RA, and in another 3 patients a faint RI uptake was achieved (responder group). In 7 patients, no change of RI uptake was observed (nonresponder group). Median Tg was increased from 105-840 microg/liter during RA therapy in the responder group, which was significantly higher than the nonresponder group (173-134 microg/liter). FDG PET was positive in all 10 patients before RA therapy. PET showed variable patterns of changes (increase/decrease/disappearance) in glucose consumption related to RA response. CONCLUSION: RA can induce RI uptake in some patients with RI negative thyroid carcinoma tumor sites. Response to RA is associated with a significantly higher increase of Tg, suggesting that a restoration of Tg synthesis can be addressed as a redifferentiation parameter in these patients.     

131I treatment of 131I negative whole body scan, and positive thyroglobulin in differentiated thyroid carcinoma: what is being treated?

Several aspects of the management of differentiated thyroid cancer cause considerable controversy. Among these is the role of 131I therapy in patients after thyroidectomy. There is no controlled study to demonstrate whether this treatment reduces the recurrence rate or improves mortality. Because of the overall excellent prognosis, it is unlikely that a controlled study will ever be conducted. Most frequently, patients have a diagnostic scan with 131I to determine whether radioiodine would be an appropriate therapy and to judge much to be prescribed, based on the extent of abnormalities seen on the scintiscan. Serum thyroglobulin (Tg) has been found to be a valuable tumor marker, with very good sensitivity and specificity. In most patients, the result of whole-body 131I scintiscan and Tg measurement give concordant results. However, in some patients, Tg is measurable, but the diagnostic scan with 131 is normal. There has been data published about treatment of these patients with therapeutic doses of 131I. The author questions whether this treatment is appropriate, prompted by seeing and hearing of patients who were treated with therapeutic doses of 131I, but had no abnormal uptake of the therapeutic doses and who had no improvement in serum Tg level. These patients have no clinical evidence of disease, and the only abnormality is measurable Tg. Since large doses of radioiodine are not without problems, a controlled clinical trial should be developed to evaluate efficacy in this situation.     

Radiotherapy in the management of thyroid cancer

Surgery is the definitive and potentially curative treatment for the slow growing well-differentiated papillary and follicular carcinomas. Total (or near-total) thyroidectomy is required, together with excision of adjacent lymph nodes when involved, or a modified block dissection if there is extensive lymphatic involvement. Ablation of residual normal thyroid with radioactive iodine usually follows as this will permit subsequent whole-body I-131 scanning to exclude the presence of residual or metastatic disease. Normally such patients have an excellent prognosis and can be followed simply with serum thyroglobulin estimations. Occasionally therapeutic radioactive iodine is necessary to eradicate metastatic disease. The anaplastic carcinomas grow and metastasise with explosive rapidity. They are typically inoperable at presentation and have no ability to concentrate iodine. Prognosis is appalling with external beam radiotherapy providing only palliation. Medullary carcinoma is different again as it arises from the parafollicular or C-cells. Total thyroidectomy must be undertaken as these tumours may be multifocal; a central compartment neck resection is ideally undertaken at the same time, together with a formal block dissection if lymph node disease is found to be present. External beam radiotherapy is often required. These tumours can be inherited and produce the tumour marker calcitonin. The rarest group of thyroid cancer is the lymphomas. Like the anaplastic carcinomas, they grow very rapidly but, unlike the former, are radio-responsive. The additional use of chemotherapy is necessary when they are of advanced stage or demonstrate poor prognostic factors.     

Comparison of 4- and 24-hr thyroid scans with 123I: concise communication

Thyroid scans were performed at 4 and 24 hr after administration of Na123I solution in 124 examinations. The 4-hr and 24-hr scans were found to be of equal diagnostic value. Thus, in individuals with structural thyroid abnormalities, one can effectively reduce the time required for scan evaluation from the standard 24 hr to 4 hr.     

Cost minimization analysis and utility of pretreatment and posttreatment total body iodine-131 scans in patients with thyroid carcinoma

An on-line immunoaffinity extraction with liquid chromatography/membrane introduction mass spectrometry (IAE/LC/MIMS) method for the determination of BTEX compounds in complex sample matrixes is described. This method uses an immunoaffinity column (1 mm i.d. x 20 mm) for on-line sample cleanup and enrichment, a 5-micron C18 trapping column (2 mm i.d. x 20 mm) for analyte focusing, a 3-micron C18 analytical column (3.2 mm i.d. x 100 mm) for separation, and a membrane introduction mass spectrometer for quantitation. The immunoaffinity column was evaluated in terms of binding capacity, recovery, and enrichment factor. The method was optimized for the determination of BTEX compounds in a mixture of 30 volatile organic compounds, which showed no matrix interference and a dramatic improvement of the detection limit over that of the LC/MIMS method (up to 474-fold). This method was also used for the determination of BTEX compounds in several gasoline-contaminated water samples, and the results were compared with the EPA reference methods.     

131I dose-dependent thyroid autoimmune disorders in children living around Chernobyl

The nucleotide sequence of 35,400 bp at approximately 10 kb from the right telomere of chromosome VII was determined. The segment contains the MAL1 locus, one of the five unlinked loci sufficient for maltose utilization. Until now, each of these loci was considered to contain three genes (for regulator, permease and alpha-glucosidase), but a fourth gene, presumably an extra alpha-glucosidase gene, was found at MAL1 adjacent to the usual cluster of three genes. The two glucosidase genes are present in opposite orientation, forming an inverted repeat structure. In addition to the four genes at MAL1, there are 11 complete, non-overlapping open reading frames (ORFs) longer than 300 bp in the sequence presented here. A new ABC transporter gene (YGR281w), required for oligomycin resistance was found (YOR1; Katzman et al., 1995), and the previously sequenced BGL2 (YGR282c), ZUO1 (YGR285c) and BIO2 (YGR286c) genes were located. The sequence of BIO2, a biotin synthetase gene, required substantial correction and the size of Bio2p is 375, rather than 356, amino acids. Two ORFs show rather weak similarities to animal genes: YGR278w to an unknown ORF of Caenorhabditis elegans and YGR284c to the murine Surf-4, a member of a cluster of at least four housekeeping genes. The remaining five ORFs do not encode known functions, but three of these show weak to high similarities to other ORFs in the Saccharomyces cerevisiae genome and one (YGR280c) codes for a particularly lysine-rich protein.     

Leukaemias and cancers following iodine-131 administration for thyroid cancer

We studied 1771 patients treated for a thyroid cancer in two institutions. None of these patients had been treated with external radiotherapy and 1497 had received (131)I. The average (131)I cumulative activity administered was 7.2 GBq, and the estimated average dose was 0.34 Sv to the bone marrow and 0.80 Sv to the whole body. After a mean follow-up of 10 years, no case of leukaemia was observed, compared with 2.5 expected according to the coefficients derived from Japanese atomic bomb survivors (P = 0.1). A total of 80 patients developed a solid second malignant neoplasm (SMN), among whom 13 developed a colorectal cancer. The risk of colorectal cancer was found to be related to the total activity of (131)I administered 5 years or more before its diagnosis (excess relative risk = 0.5 per GBq, P = 0.02). These findings were probably caused by the accumulation of (131)I in the colon lumen. Hence, in the absence of laxative treatment, the dose to the colon as a result of (131)I administered for the treatment of thyroid cancer could be higher than expected from calculation of the International Commission on Radiological Protection (ICRP). When digestive tract cancers were excluded, the overall excess relative risk of second cancer per estimated effective sievert received to the whole body was -0.2 (P = 0.6).     

Hospital discharge policy in thyroid cancer patients treated with 131I: the effect of changing from fixed time to exposure rate threshold

Juvenile myelomonocytic leukemia (JMML) carries a poor prognosis. The endogenous production of cytokines by the JMML cells contributes to their growth and therapeutic resistance. Interleukin (IL)-4, IL-10, and IL-13 inhibit cytokine production in monocytes. We have now studied whether these cytokines can inhibit JMML cell cytokine production, thereby potentially reducing the malignant cell load in this disorder. We found that IL-10, but not IL-4 or IL-13, dose dependently inhibited JMML cell production of the hemopoietic growth factors granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and IL-1beta. Similarly, IL-10, but not IL-4 or IL-13, suppressed JMML colony formation and cell viability. This was not due to the absence of receptors because we could detect mRNAs for the IL-4 and the IL-13 receptor alpha subunits and the IL-2 common gamma subunit in JMML cells. Furthermore, the receptors were active since both IL-4 and IL-13 up-regulated surface expression of MHC class II and down-regulated CD14 antigens on JMML cells and monocytes. Unlike activated monocytes, the JMML cells did not produce IL-10. It is suggested that the loss of cytokine inhibitory effects of IL-4 and IL-13 could play a role in the pathogenesis of this disorder. On the other hand, the inhibition of cytokine production, growth, and viability of JMML cells by IL-10 suggests that this cytokine may have a therapeutic potential in JMML.     

Effectiveness of preoperative radioactive iodine (131I) therapy for locally advanced papillary thyroid cancer: a case report

We report here the effectiveness of preoperative radioactive iodine-131 (131I) therapy for locally advanced thyroid cancer. A 57-year-old woman demonstrated a hard neck tumor that markedly invaded the surrounding organs. The cytological diagnosis of the tumor using fine-needle aspiration biopsy was papillary carcinoma. Because curative resection of the tumor appeared difficult at her first visit, 131I therapy was performed prior to surgery and was more useful than expected. After 3 131I treatments, the tumor size was greatly reduced, and the patient underwent a curative operation. Histopathological diagnosis was well differentiated papillary carcinoma, pT4 and pN1b. The postoperative clinical course was uneventful. There have been no definitive reports using 131I as preoperative treatment for inoperable thyroid cancer. We suggest that 131I therapy may also be beneficial as neoadjuvant therapy for locally advanced thyroid carcinoma.