Therapeutic implications of thymic uptake of radioiodine in thyroid carcinoma

BACKGROUND: NPC18915, a member of new antiinflammatory agent called nactins (neutrophil activation inhibitors), has been shown to reduce reperfusion injury in rat lung transplantation at high dosage. In vitro studies have demonstrated effectiveness of this compound even at low dosage. We hypothesized that this compound ameliorates lung ischemia reperfusion injury even at low dosage levels if administration is optimally timed. The aim of this study was to determine the efficacy and the best timing for administration of low-dose NPC18915. METHODS: Forty syngeneic rat left lung transplantations were performed. All isografts were flushed with low-potassium dextran-1% glucose solution 20 ml and preserved for 18 hours at 4 degrees C. Animals were divided into four groups. Group I animals (n = 10) served as control subjects. In groups II (n = 10), III (n = 10), and IV (n = 10), NPC18915 (0.04 mg) was added to the flush solution and was administered intravenously (0.4 mg/kg) immediately before reperfusion (group II) and 60 minutes (group III) and 120 minutes (group IV) after reperfusion. Pulmonary function was assessed 24 hours after reperfusion. RESULTS: In group III, oxygenation improved in comparison to group I (247.2 +/- 59.8 versus 76.6 +/- 16.0 mm Hg, p < 0.002). Wet-to-dry weight ratio and graft myeloperoxidase activity were significantly improved (group III versus group I, 6.02 +/- 0.21 versus 7.19 +/- 0.41, p = 0.013) (group III versus group I, 0.093 +/- 0.019 versus 0.207 +/- 0.023 delta optical density/min/mg, p < 0.002). There were no significant differences in CD11b expression. CONCLUSION: These data suggest that delayed administration of NPC18915, 60 minutes after reperfusion, dramatically improves pulmonary graft function.     

Acute leukemias after treatment with radioiodine for thyroid cancer

Leukemia is an uncommon complication of exposure to radioiodine (131I), used in treatment of thyroid cancer, because low doses are now used. We report two cases of acute myelogenous leukemia developed after the treatment of a thyroid carcinoma with a small dose of 131I.     

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.     

Quantification of salivary gland function in thyroid cancer patients treated with radioiodine

PURPOSE: Damage to salivary gland function following external irradiation has been documented. However, the extent of damage following radioiodine (131I) therapy for thyroid cancer has not been adequately studied. We evaluated salivary dysfunction in Ca-thyroid patients treated with therapeutic doses of 131I. METHODS AND MATERIALS: A simple acquisition and analysis protocol using 99mTcO4- (pertechnatate) and a gamma camera computer system was planned. The uptake of 99mTcO4- by the salivary glands at 10 min and percent of excretion of 99mTcO4- from the glands in response to a sialogogue (lemon juice) was studied in 33 patients treated with 1.369-38.702 GBq of 131I (Mean = 10.16 GBq, standard deviation = 7.659 GBq) in addition to 14 athyreotic controls. RESULTS: Significant damage to the salivary gland in terms of abnormal percent uptake or excretion was noted in 72.73% of the patients. Forty-eight percent of the patients treated with 131I showed asymmetrical involvement of the salivary complexes as opposed to none of the controls. Reduction in uptake of 99mTc4- or response to sialogogue was dose dependent, being more marked with higher radioiodine doses. Parotid glands were more affected than submandibular glands following 131I therapy. CONCLUSIONS: 131I therapy produces a significant effect on salivary gland function that is dose related and becomes evident over a period of several months after treatment.     

Radioiodine uptake in rheumatoid arthritis-associated lung disease mimicking thyroid cancer metastases

Haemorrhagic infarction of the small bowel is a rare complication of warfarin therapy. We take this opportunity to report a case that needed a resection of the small bowel.     

Diagnosis, radioiodine and radiotherapy of thyroid carcinomas

The long-term prognosis of differentiated thyroid carcinoma depends on early diagnosis and treatment of metastases and local recurrences and is modulated by several factors, age and histology being the most relevant. This article summarizes current trends in the use of radioactive iodine (131J) and gives explicit advice on its use in the treatment of these cancers. Complications of therapy are discussed in detail. We currently recommend that all patients undergoing a subtotal or total thyroidectomy are followed up by 131J thyroid scanning approximately 4 weeks after surgery. The combined use of three diagnostic modalities (measurement of serum thyroglobulin, neck ultrasonography with ultrasound-guided biopsy for detecting recurrences of carcinoma in the neck region and 131J whole-body scintigraphy) appears to give the best results in the follow up of patients with differentiated thyroid carcinoma. If any residual uptake is detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation with 1,5-3 GBq of radioactive 131J. External radiotherapy is always indicated in papillary and folliculary carcinoma in the pT4 stage of pTNM classification but not in those in pT1-3 pN0 stage. In the presence of lymph-node metastases and distant metastases, an individual treatment concept is recommended regarding all risk factors, especially the age and sex of the patient, the histology and grading of the tumor and the completeness of tumor resection. Finally, radiotherapy is usually not indicated in medullary carcinoma, whereas it is always indicated in anaplastic carcinoma.     

"High-dose" radioiodine therapy in advanced differentiated thyroid carcinoma

There is yet no consensus concerning the appropriate regimen of the application of [131I]sodium iodine (Nal) activities to patients suffering from advanced differentiated thyroid carcinoma. We report on a total of 167 applications of [131I]Nal, including 78 applications of 11.1 GBq. Response to high-activity radioiodine therapy (RIT) is correlated to the course of the disease as well as to the reaction of thyreoglobulin and acute/subacute side effects of radiation. METHODS: Following radioablation of thyroid remnants using 1.85 to 3.7 GBq[131I]Nal, 26 patients with advanced differentiated thyroid carcinoma (follicular, 11; papillary, 4;mixed-cell thyroid carcinoma, 11) were treated with repeated activities of 11.1 GBq[131I]Nal. Initial tumor staging according to UICC showed T4 in 54%, T3 in 19%, T2 in 19% and was not obtained in 8%. Differentiated thyroid carcinoma was multifocal in 23% of patients. Applied accumulated activities ranged from 14.8 to 99.9 GBq with a mean of 55.5 GBq per patient. RESULTS: Mean post-diagnostical follow-up was 73 mo, mean follow-up after diagnosis of metastatic spread was 48 mo. Follicular thyroid carcinoma remained as stable disease in 7 of 11 patients, 6 of whom showed metastatic disease after a mean of 20 mo, and only 1 complete remission was achieved using high-dose therapies, with progressive disease in the remaining patients. Overall, 73% of follicular thyroid carcinoma had progressive disease without major response to high-activity RIT. In contrast, only 20% of papillary thyroid carcinoma/mixed-cell thyroid carcinoma showed progressive disease, and complete remission was achieved in 47% of patients. Pulmonary and lymph node metastases in the majority of patients showed good response to therapy, whereas local recurrences and bone metastases showed minor reactions to RIT. After low-activity therapies 8% of patients showed WHO grade I hematotoxic reactions. After high-activity therapies, 38% of patients had WHO I, 8% WHO II and one patient had WHO III toxicity (4%). CONCLUSION: Use repetitive high-activity RIT with a maximum of 44.4 GBq applied during 1 yr and a maximum of 99.9 GBq accumulated activity resulted in a significant increase of hematotoxicity. However, during the follow-up period (mean, 4 yr), no clinical symptoms possibly related to low blood counts were seen in patients with advanced differentiated thyroid carcinoma. Initiation of high-activity RIT in reaction to metastatic tumor outspread to achieve complete remission was found to be useful in treating papillary thyroid carcinoma and mixed-cell thyroid carcinoma, but only in a minority of follicular thyroid carcinoma patients.     

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.     

Cytogenetic study of thyroid patients treated with external irradiation or radioiodine

Where clinically permitted, either external irradiation or radioiodine therapy is usually recommended for the treatment of differentiated thyroid cancer patients. This paper describes an attempt to clarify the radiation burden and the distribution of radiation doses on the lymphocytes in consequence of these two therapeutic modalities, and the circumstances of the applicability of biological dosimetry. Thyrotoxic patients with intact thyroid glands underwent 131I therapy were also analysed for this purpose. An analysis was made of the extent to which exposure to local neck irradiation (50 Gy) or radioiodine therapy (1734-2600 MBq) causes chromosomal aberrations in the lymphocytes of thyroid disease patients after total or subtotal thyroidectomy, or thyrotoxic patients with intact thyroid glands (185-595 MBq). The irradiated volume of lymphatic tissues played the most important role in the formation of chromosomal aberrations. External irradiation caused 10-times more aberrant cells than 131I therapy did in cancer patients. In thyrotoxic patients the lower therapy doses of radioiodine caused a significantly higher frequency of aberrations than that observed in thyroid cancer patients. Selective radiosensitivity of lymphocytes was supported by the analysis of the Poisson distribution of aberrations, which suggested a homogeneous dose distribution only in 131I-treated and thyroidectomized cancer patients. In conclusion, we suggest that the results of studies of the genetic alterations in the lymphocytes exposed to radioiodine, under well-defined circumstances should not be ignored before the mode of radiation treatment is chosen. On the other hand, in the modelling of accidental environmental radioiodine exposure, only thyrotoxic patients with an intact thyroid gland and heterogeneous dose-distribution are a suitable group.     

Outcome of 309 patients with metastatic differentiated thyroid carcinoma treated with radioiodine

From 1969 to 1990 there were 309 patients with differentiated thyroid carcinoma (241 papillary and 68 follicular) treated with radioactive iodine for functioning node metastases alone (n = 191) or distant metastases (n = 118) with or without node metastases. These patients represented 32.7% of 945 patients treated in our institution during the same period. Initial treatment included near-total thyroidectomy and 131I ablation of postsurgical thyroid residue, followed by L-thyroxine suppressive therapy. At the end of follow-up (mean 5.8 years), 146 patients (76.4%) in the group with nodal metastases were considered cured, as assessed by clinical and laboratory evaluation including whole body scan (WBS) and serum thyroglobulin (Tg) levels; 32 patients (16.7%) had persistent disease. Loss of 131I uptake in persistent metastatic lesions occurred in five patients (2.6%), and newly developed distant metastases occurred in eight patients (4.2%). Of the patients with distant metastases, 36.4% were cured by 131I. Distant metastases from papillary carcinomas had a higher cure rate than follicular carcinomas (p < 0.01). The metastases of four patients (5.2%) lost the property to take up radioiodine. Lung and bone metastases detectable by WBS but not by radiography were most likely to be cured by 131I. The overall survival at the end of follow-up was 95.8% in patients with only lymph node metastases and 76.0% in those with distant metastases. Tumor-related deaths were 3.6% and 23.7%, respectively. Our data indicate that 131I therapy is highly effective in the treatment of lymph node metastases from differentiated thyroid carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in radioiodine turnover in patients with autonomous thyroid adenoma treated with percutaneous ethanol injection

In 24 patients with autonomous thyroid adenoma, we studied the hormonal pattern (free thyroxine, free triiodothyronine and thyroid stimulating hormone) and markers of radioiodine turnover before and after nodule ablation with percutaneous ethanol injection. METHODS: The hormonal pattern was studied before treatment and at various intervals after nodule ablation. Changes in radioiodine turnover were studied measuring 131I protein-bound iodine and the biologic half-life of radioiodine in the thyroid (calculated from thyroid uptake at 24 and 48 hr) before and after ethanol treatment. RESULTS: The hormonal pattern was normalized by treatment in all patients and remained normal for the follow-up period. Before treatment, protein-bound 131I was elevated in all patients but 4; after treatment, it normalized in 15 patients with the disappearance of the adenoma on scintigraphy. In the remaining 9 patients with only partial nodule destruction on scintigraphy, protein-bound 131I remained elevated although markedly reduced. Biologic half-life was shortened in 18 of 24 patients before treatment; after treatment, it was normal in 18 of 24 patients (13 of 15 with complete nodule ablation and 5 of 9 with partial ablation). CONCLUSION: Ethanol treatment normalized the hormonal pattern in all patients. Measures of radioiodine turnover were better markers of residual disease in that they normalized in almost all patients with complete nodule ablation, whereas they remained abnormal in a high proportion of patients with incomplete ablation. Thyroid hormones remained normal over a follow-up period of 3-7 yr in all patients.     

Influence of compensated radioiodine therapy on thyroid volume and incidence of hypothyroidism in Graves'' disease

Postoperative thromboembolic complications were evaluated in 2578 patients undergoing elective abdominal surgery, all receiving prophylaxis with low molecular weight heparin. A positive fibrinogen uptake test (FUT) developed in 217 patients (8.4%), while 37 patients (1.4%) had major thromboembolism (TE, defined as proximal deep vein thrombosis and/or pulmonary embolism, verified with phlebography, pulmonary scintigraphy or autopsy). In only 14% a positive FUT was associated with a major TE event. In 19% of the patients with major TE the FUT was negative. In multiple logistic regression the independent predictors for major TE were partially different from those for positive FUT. Thirty day mortality was 3.0%. There were significant associations between both positive FUT and major TE on one hand and mortality on the other (relative risks 2.4 and 5.8, respectively). FUT is not a good predictor of major TE. Both positive FUT and major TE indicate a significant risk of postoperative death.     

Measurement of incorporation in family members of radioiodine therapy patients after therapy of benign thyroid diseases

The medical records of 190 patients with meningomyelocele operated on between 1979 and 1993 were reviewed. In 65 patients, psychometric tests were performed. The Denver Developmental Screening Test and the Wechsler Intelligence Scale for Children, Revised (WISC-R) were used in children under and over 6 years old, respectively. There were 82 boys (43.2%) and 108 girls (56.8%). The lumbar region was the site of the meningomyelocele in 113 patients (59.5%). Patients with cervical and sacral meningomyelocele had a higher rate of almost normal motor function than those with meningomyelocele at other levels (P=0.000). Only 36 (21.7%) of 166 patients followed up by us did not have hydrocephalus. We also noted that the higher the location of the meningomyelocele, the greater the control of both sphincters (P=0.014). Fifty-four percent of the hydrocephalic patients had a normal development or IQ. Psychometric tests were normal in 76% of those without hydrocephalus. Twenty-four patients were lost to follow-up. The follow-up of the remaining 166 patients ranged from 1 month to 180 months (mean 60.2 months). Fifty-three patients (32%) died, central nervous system infection being the most common cause of death (44%). The management of children with meningomyelocele needs a team approach.     

Follicular thyroid cancer

Follicular thyroid cancer is the second most common thyroid malignancy after PTC. There are marked geographical variations in the relative proportions of FTC and PTC, most likely related to dietary iodine content. In iodine-deficient areas, the relative rate of FTC tends to be increased. Other risk factors for FTC include age over 50 years and female sex. Genetic factors may also have a role in determining disease susceptibility but remain ill-defined. Histologically, FTC is characterized by follicle formation and the absence of any papillary elements in the tumor. Differential diagnosis from a benign adenoma can be difficult. The degree of vascular invasiveness seems to correlate with tumor aggressiveness, and two histologic subtypes, oxyphilic FTC and insular FTC, may be associated with increased morbidity and mortality. Primary treatment for FTC is complete surgical tumor removal. Extensive bilateral surgery beyond this goal may not confer additional benefit but can facilitate adjuvant treatment and follow-up. Postoperative levothyroxine treatment is almost universally used, and patients deemed at high risk of recurrence may benefit from radioiodine remnant ablation. Treatment of metastatic disease involves operation, radioiodine, and, in selected cases, external beam radiation and chemotherapy. Prognosis for patients with metastatic disease is guarded, but most other patients have good outcomes comparable to that in PTC. For nonoxyphilic FTC, high-risk features other than initial metastases include advanced age, locally extensive disease, and the presence of marked angioinvasion. In oxyphilic FTC, DNA aneuploidy is also important. Follow-up should be most intense during the first 5 years after primary treatment and needs to be tailored to the patient's risk of disease progression. For patients at low risk of recurrence (young, small lesions, minimally invasive tumor), serum thyroglobulin measurements may largely suffice, whereas higher risk patients with elevated serum thyroglobulin levels and patients with significant titers of interfering anti-thyroglobulin autoantibodies may also need to undergo periodic diagnostic radioiodine scanning.     

Radioiodine ablation of residual tissue in thyroid cancer: relationship between administered activity, neck uptake and outcome

A retrospective review was performed to evaluate the effectiveness of radioiodine in the ablation of residual thyroid tissue after surgery for differentiated thyroid cancer. 121 patients were treated at the Princess Margaret Hospital, Toronto, Canada between 1977 and 1989, with the activity of radioiodine determined empirically. Ablation of residual thyroid was determined by 131I nuclear scans, using absent visible uptake (compared with background) as the criterion for successful ablation. 97 patients (80%) had successful ablation of residual thyroid tissue after the first administration of radioiodine. Patients with higher iodine uptake in the neck had a tendency to receive higher activities of 131I. There were no statistically significant differences in age, sex, type of surgery, initial iodine uptake in the neck and administered radioiodine activity between those successfully ablated and those that were not. Patients receiving less than 3.7 GBq (100 mCi) tended to have lower iodine uptake (< 5% at 24 or 48 h), but their rate of thyroid ablation was just as high as those given 3.7 GBq or more. In order to take advantage of this, we have formalized our approach by deriving guidelines to the empiric determination of radioiodine activity based on the iodine uptake in the neck. Among the 11 patients treated with lobectomy only, the ablation rate was 64%. Although this was not significantly lower than for other forms of surgery, we continue to recommend completion thyroidectomy for this group of patients, if the goal of treatment is to ablate all thyroid tissue.     

Percent 131I uptake and post-therapy 131I scans: their role in the management of thyroid cancer

Renal disease in patients infected with human immunodeficiency virus (HIV) often presents with significant proteinuria and progressive renal failure; focal glomerulosclerosis is the most common renal pathology identified. To our knowledge, we report the first case of nephrotic-range proteinuria and preserved renal function in an HIV-infected patient in association with disseminated histoplasmosis. The initial level of proteinuria was 12.5 g/24 h. The patient developed a concomitant lesion on his neck, which was biopsied and identified as Histoplasma capsulatum by fungal stains and culture. The serum CF titer of antibody against yeast antigens of H. capsulatum was 1:8. The level of serum albumin decreased to 2.0 g/dL, and the level of serum cholesterol increased to 284 mg/dL. Immunohistochemical staining of renal biopsy tissue demonstrated immune complexes within the mesangium; H. capsulatum antigen was also demonstrated in the mesangium. Therapy with oral itraconazole resulted in marked clinical improvement. The findings in this case emphasize the need to rule out treatable causes of the nephrotic syndrome in AIDS, especially in cases of immune-complex glomerulonephritis.