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.     

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.     

Radioiodine I-31 therapy in the management of thyroid cancer. A prospective study

The therapeutic value of I-131 ablation therapy following thyroidectomy for thyroid cancer was evaluated in 54 patients in a prospective study of 25 years. Thirteen (24%) patients had follicular, 24 (44%) papillary, 13 (24%) mixed papillary-follicular, two (4%) Hurthle cell and two (4%) had undifferentiated cell type tumor. Twenty-four (44.5%) patients had metastases at the time of I-131 therapy mainly to cervical and mediastinal lymph nodes, and less frequently to bone, brain, lung, and liver. After surgical thyroidectomy, the mean cumulative dose of I-131 required to achieve therapeutic ablation of functioning post-surgical remnants or tumor metastases was 163.4 mCi. The recurrence rate for patients with metastases was 56% and those without metastases was 25%. Ten patients showed recurrence of I-131 accumulating tissue five to 10 years after initial total ablation. The total mean cumulative dose of I-131 administered for both followup diagnostic studies, and initial and follow-up therapy was 245.3 mCi. Seven deaths were attributable to thyroid cancer, five with differentiated and two with anaplastic cell type tumors. Three of the four patients with differentiated cell type tumors had metastases to brain or bone. Their response to therapy was similar to those patients with anaplastic cell type tumors. In contrast, there were no deaths due to thyroid cancer when total ablation was achieved and maintained. After ablation, all patients were maintained on maximum tolerated doses of thyroid extract or thyroxin. No significant complications attributable to the therapeutic doses of I-131 employed in this series were noted.     

Changes of angiogenin serum concentrations in the perinatal period

We report a 49-year-old woman with Marfan syndrome who underwent total thyroidectomy for follicular carcinoma. The patient was given 100 mCi of radioactive iodine (131I) followed by levothyroxine (LT4) 0.2 mg/day after surgery. The subsequent five total body scans were negative and thyroglobulin (TG) measurements ranged between undetectable levels to 12 ng/mL. Nine years after thyroidectomy the patient developed bilateral exophthalmos with markedly positive thyroid-stimulating immunoglobulins (TSI), indicating the presence of Graves' disease. TG levels increased and concurrently pulmonary metastases that did not concentrate radioiodine at tracer doses, were diagnosed. Due to these metastatic lesions, the patient received a therapeutic dose of 150 mCi of 131I 1 month after LT4 withdrawal, and a total body scan was made 10 days later. Slight uptake of 131I was found in the right side of the neck, whereas predominant uptake occurred in the right lung base. We suggest that the elevated TSI played a role in the growth of metastases.     

Thyroid cancer in children, pregnant women, and patients with Graves' disease

Differentiated thyroid cancer may have a different clinical course when it develops in children, pregnant women, and patients with Graves' disease. Thyroid nodules which develop in these patients appear to have a greater risk of malignancy and should be evaluated aggressively. Treatment in all cases includes operation followed by radioactive iodine ablation (in the nonpregnant patient) and thyroid hormone suppression. Follow-up, including serum Tg and yearly thyroid scans, should be continued as long as possible.     

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)     

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.     

Differentiated thyroid cancers. 20 years' results of a protocol based on simple prognostic criteria

OBJECTIVES: To study the long-term results of an aggressive management protocol based on a new-simple classification and to determine the duration for patient follow-up according to this classification. MATERIAL AND METHODS: For the 509 patients with differentiated thyroid carcinoma, the classification was: group 1: cancer < 1 cm (n = 117), group 2A: cancer without extension in patients of age less than 45 years (n = 100), group 2B: cancer without extension in patients aged more than 45 (n = 94), group 3: cancer with nodal extension alone (n = 102), group 4: high risk cancer in patients having either distant metastases or local tissular extension or in whom after iodine-131 ablation, Tg level was > 3 micrograms/l off hormone therapy (n = 96). Total thyroidectomy was the rule except for group 1 and some patients of group 2A in whom the tumor was solitary, relatively small, well-differentiated, with no capsular or capillary invasion. Iodine 131 ablation was carried out after a total thyroidectomy and repeat treatments with iodine 131 were given whenever necessary. RESULTS: In group 1, 2A and 3, the 20 years death rate of cancer was 0 p. 100. For group 2B, patients cancer death rate was 8 p. 100 and for group 4 it was 32 p. 100. Distant metastases were the cause of death except for one patient who died from local recurrence. Clinical inspection, Tg measurement, iodine 131 whole-body scan and chest X-ray were all useful in discovering local or distant recurrences. CONCLUSION: Our results justify the use of an aggressive initial management for differentiated thyroid carcinoma and an appropriate scoring system. When this protocol is applied, patients of group 1, 2 and 3 should have an excellent prognosis. However patients follow-up should not be shorter than 15 years for patients of group 1 and 2A and than 20 years for all other groups.     

Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS: In this phase I trial, eligible patients were treated with a single injection of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20-mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in the SCRC. Patients were followed up for toxicity and response until death or for a minimum of 1 year after treatment. The SCRC patients, who were previously irradiated, were followed up without additional treatment unless progressive disease was identified. RESULTS: We administered 36 treatments of 131I doses up to 120 mCi to 34 previously irradiated patients with recurrent or metastatic brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to neurologic or hematologic toxicity. None of the patients treated with less than 120 mCi developed significant neurologic toxicity; one patient developed major hematologic toxicity (MHT). The estimated median survival for patients with glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks, respectively. CONCLUSION: The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.     

Overexpression of CAF1 encoding a novel Ca2+-binding protein stimulates the transition of Dictyostelium cells from growth to differentiation

In Mexico, 39% of 158 patients operated on for thyroid cancer require reoperative thyroid surgery. We retrospectively reviewed the indications and histopathological findings of 60 patients reoperated on because of: a) suspected persistent or recurrent disease; b) high risk patients treated by lobectomy; c) different histology; d) complete lack of information, e) and distant metastasis. In 53 cases (88%), the initial surgery was nodulectomy or lobectomy, and in seven (11%) was subtotal or near-total thyroidectomy. Among the 60 reoperations, 50 were completion total thyroidectomy and 10 were near-total thyroidectomy. In 27 cases (45%) a neck dissection was additionally done. Histologic examination revealed thyroid carcinoma in 32 cases (53%) and neck node metastasis in 28 cases (47%). Complications included six cases (9%) of permanent palsy of the recurrent laryngeal nerve after the initial surgery outside of our hospital and two cases (1.75%) of reoperated cases. In four reoperated patients (6.6%), permanent hypoparathyroidism was developed. It is mandatory to complete thyroidectomy and neck dissection in a high proportion of patients initially treated in general hospitals due to an inadequate criteria in the selection of the extension of thyroidectomy and treatment of neck node metastases. Histologic findings of these patients support our indications to complete the surgical treatment.     

The correlation of the vasopressin- and oxytocin-producing activities of different nuclei in the hypothalamo-hypophyseal neurosecretory system]

Radioiodine long has proven to be a safe and effective treatment for thyroid disease. Nonetheless, persisting concerns regarding radiogenic stochastic risks (e.g., carcinogenesis) to patients, their families, and the general public have led regulators to establish criteria for release of 131I-containing patients from medical confinement, with limits ranging from as low as 2 mCi in some parts of Europe to as high as 30 mCi in the United States. To optimize clinical efficacy and cost-effectiveness of 131I therapy, such regulations should be based on logical dosimetric considerations. The thyroidal absorbed dose, proportional to maximum uptake and effective half-life and inversely proportional to mass, is typically approximately 1,500 rad/mCi of 131I administered to a euthyroid adult (based on a thyroid maximum uptake of 25%, effective half-life equivalent to the physical half-life of 131I (8.04 days), and mass of 20 g). As thyroid uptake increases from 0% to 100%, extrathyroidal absorbed doses range from a minimum of 0.15 to 0.5 rad/mCi for breast and gonads to a maximum of 1.5 to 2 rad/mCi for stomach and salivary glands; the absorbed doses of the urinary bladder wall, in contrast, decrease with increasing thyroid uptake, from 2 to 0.6 rad/mCi. In hyperthyroid patients (approximately 15%) with a small iodine pool (so-called small patients), the short effective half-life of radioiodine in the thyroid and high serum concentrations of long-lived protein-bound 131I result in a standard 7,000-rad absorbed dose for treatment of Graves' disease requiring an administered activity of 28 mCi of 131I and yielding a prohibitively high blood absorbed dose of 150 rad. Importantly, once the fetal thyroid begins to function and accumulate radioiodine at a gestational age of 10-12 weeks, fetal thyroid absorbed doses as large as 5,000 rad/mCi of 131I administered to the mother can result. Thus, pregnancy is an absolute contraindication to administration of 131I because of the risk of radiogenic cretinism. Based on actual measurements of thyroid activity and of external absorbed dose, the total thyroid and mean extrathyroidal absorbed doses to adult family members from immediately released 131I-treated patients are approximately 0.01 and approximately 0.02 rad/mCi administered, respectively, yielding an effective dose of approximately 0.02 rem/mCi. A maximum permissible effective dose of 0.5 rem for adults therefore is consistent with a release criterion of 30 mCi of retained 131I. Lower-activity release criteria therefore may be unnecessarily restrictive.     

Modern methods of wound treatment. 1. One wound is not the same as all the others

Papillary carcinoma, the commonest thyroid malignancy, has a good prognosis and low incidence of distant metastases. Brain metastasis is extremely rare with a frequency of about 1% in reported series. In this paper we present the clinical details of one case of histologically proven brain metastasis from papillary thyroid cancer, first presented with neurological symptoms, initially treated with excisional biopsy and radiotherapy in other hospital, without clinical response. The patient was then referred to our service, where he underwent a total thyroidectomy and modified radical neck dissection, with the aim of posterior radioactive iodine treatment for the brain lesion. Unfortunately, he died of neurological complications, two months after the neck treatment. Also presented is a review of the literature of this unusual clinical presentation.     

Struma ovarii or malignant ovarian goiter. A case

BACKGROUND: We report a case of follicular struma ovarii observed in an ovary teratoma without metastatic dissemination. CASE REPORT: A right ovarian tumor was discovered at ultrasound examination in a 31-year-old woman complaining of low abdominal pain. The patient underwent laparoscopic exploration and a 4-cm cystic mass of the right ovary was removed. Microscopic examination showed a malignant struma ovarii of the follicular type with vascular space invasion; other teratomous elements were identified. Immunohistochemical staining for thyroglobulin confirmed the nature of the tumor. The patient was treated by complete right ovariectomy followed by total thyroidectomy and administration of radioactive iodine (99 mCi I-131). Repeat I-131 body scan performed at 6 months was normal. DISCUSSION: Struma ovarii is a rare type of ovarian teratoma, consisting mainly of thyroid tissue. The incidence of malignant struma ovarii is below 1% and fewer than two dozen cases with distant metastases have been reported. The major problem associated with struma ovarii has been the establishment of criteria for malignancy.     

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.     

Iodothyronine content of human thyroid albumin

Stable thyroid hormones (T4 and T3)1) have been demonstrated in pure albumin isolated from normal human thyroid tissue iodinated in vivo. Five samples of albumin were separated from other thyroid proteins by acrylamide gel electrophoresis. After pronase hydrolysis, the content of Thyroid hormones was measured chemically (T4 + T3) as well as by competitive radioactive measurement (T4) and radioimmunoassay (T3). The purity of the albumin and validity of these measurements were confirmed by different techniques. The synthesis of thyroid hormones is not therefore a property unique to Tg and may occur in albumin. However the amount of iodothyronines in the albumin (average 0.004 residue per molecule) is much less than that found in Tg (0.5 residue per molecule). In the albumin as in Tg the number of hormone residues per molecule is proportional to the number of atoms of iodine. At an equivalent iodine concentration, the albumin seems capable of forming the thyroid hormones as well as Tg. The difference between these two proteins, in their capacity to synthesize thyroid hormones, seems to depend on their capacity for iodination. This difference of iodination does not seem to be linked with the number of tyrosyl residues, but might be related to the position of these residues.     

Outcome of differentiated thyroid cancer in Graves' patients

The clinical behavior and outcome was evaluated in 21 nonoccult differentiated thyroid carcinomas occurring in Graves' patients during the period 1982-94 and compared with that of matched tumors occurring in euthyroid controls (n = 70). At surgery, patients with Graves' disease showed distant metastases more frequently than euthyroid patients (3/21 = 14.3% vs. 1/70 = 1.4%, P = 0.0556). Graves' patients also showed a significantly higher cumulative risk of recurrent/progressive distant metastases or total adverse events (odd ratios = 3.14 and 2.07, respectively) as compared with euthyroid patients. At the last follow-up visit, persistence of distant metastases was also more frequent in the Graves' group (P = 0.007), although the cumulative individual dose of radioiodine administered was higher than in the control group (median dose = 805 mCi vs. 350 mCi). Two patients died in the Graves' group vs. none in the control group. Circulating thyroid stimulating antibodies were present in all patients but one and persisted as long as signs of disease were evident. These findings indicate that differentiated thyroid carcinomas in patients with Graves' disease are more aggressive than those occurring in matched euthyroid controls and should, therefore, be managed accordingly.     

Onset of the neuromuscular block simulated in an anatomical model

Radioiodine scintigraphy is the gold standard exploration for imaging metastases of differentiated thyroid cancer and enables the decision of therapy with 131 radioactive iodine to be made. However, other approaches may be of use for diagnosis when there is no visible uptake after the administration of 131I, while elevated thyroblobulin levels suggest the presence of metastatic tissue in one third of metastatic patients. In order to detect recurrences or metastases, in conjunction with conventional imaging techniques (cervical and hepatic ultrasonography, lung CT scan..), other scintigraphic explorations with various radiopharmaceutics may be used, although none of them has any specificity towards thyroid cancer. Tl201 and MIBI which are used as perfusion tracers for myocardial explorations, are also used for detection of various tumors and for metastatic thyroid cancer. The performances of both radiopharmaceutics in imaging metastases are differently evaluated between investigators with a sensitivity ranging from 45 to 94% while the specificity varies less (82-97%). 18-Fluoro-deoxyglucose is retained in malignant tissue depending on the grade of malignancy. It has been shown to accumulate in thyroid cancer and metastases. Its detection by whole body PETscan represents a limitation for use which will be modified by new techniques. 111In-octreotide which binds to somatostatin receptors located on tumor cell membranes is able to show thyroid cancer metastases in some instances. We report on the very preliminary results of these combined scintigraphic approaches, performed in a limited number of patients who had no radioiodine uptake and elevated Tg levels, in order to determine the most appropriate exploration in terms of performance and cost.     

Follicular adenocarcinoma of the thyroid in the maxillary sinus

No reports of metastatic thyroid carcinoma in the maxillary, ethmoid, or sphenoid sinuses can be found in the literature. A woman with severe posterior epistaxis was examined recently. She had undergone a partial lobectomy for a thyroid tumor 16 years previously. Hemorrhagic thyroid tissue was in the maxillary sinus. The results of subsequent examinations indicated thyroid deposits in the lung and spine. The patient received radioactive iodine, 100 MCi. Her lung and spine deposits lysed, and she experienced no further epistaxis. Thyroid carcinoma's ability to metastasize to a paranasal sinus is documented here. Epistaxis after a thyroidectomy for cancer now must be considered an unusual clinical manifestation of metastatic spread, unless otherwise proved. The differential diagnosis of epistaxis must now include thyroid carcinoma metastatic to the sinonasal tract.     

Surgical treatment of hyperthyroidism in children

During the past ten years, subtotal thyroidectomy for hyperthyroidism was performed upon 43 children at Childrens Hospital of Los Angeles. There were no deaths, no recurrent laryngeal nerve injuries and no permanent hypoparathyroidism. During the one to ten year follow-up period, one patient had recurrent hyperthyroidism develop and was treated with 131I. Twenty-five patients are hypothyroid and require thyroid supplement; 14 are euthyroid and receiv no medication. Postoperative thyroid function did not correlate well with gland remnant size, degree of fibrosis or the extent of lymphoid follicle formation. Lymphocytic infiltration was more severe in patients who had hypothyroidism develop postoperatively. Transient hypocalcemia developed in 22 patients. The effectiveness and safety of the surgical treatment for hyperthyroidism in children is reaffirmed, and it is advocated for consideration over 131I or prolonged medical therapy.     

Malignant tumors invading chest wall: treatment with CT-directed implantation of radioactive seeds

Computed tomography (CT) was used to direct permanent implantation of radioactive iodine-125 seeds in two patients with unresectable lung cancer and in one with recurrent breast cancer invading the chest wall. An average of 60 seeds were implanted, with a mean total radioactivity of 35.6 mCi (1,317 MBq). Tumor coverage was adequate and pain relief was good in all patients. One patient had histologically documented complete response and another had CT-documented partial response.