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.     

Placentas and foetal health

The placenta provides many critical services to the developing foetus. Proper placental implantation, growth and function are necessary for normal foetal growth and development. Placental structure varies widely among species but all mammalian placentas have a convoluted materno-foetal interface that may be quite simple or highly complex; the more complicated interdigitations tend to characterise smaller placentas that have limited areas of contact between the placenta and the endometrium. The intimacy of the contact between maternal and foetal tissue varies from apposition only, as in the equine placenta, to invasion of maternal vessels by foetal cells, as in man. Abnormalities identified in the human placenta provide insight into maternal and foetal diseases that affect pregnancy outcome.     

Advanced trauma life support versus Combat Trauma Life Support courses: a comparison of cognitive knowledge decline

Post-thyroidectomy I-131 whole-body scintigraphy is an important aspect in the management of patients with thyroid cancer. The scan is used to detect residual thyroid tissue and distant functioning metastases. Extrathyroid I-131 accumulation does not always denote metastatic disease, and several potential sources of false-positive I-131 scans have been identified. This report presents four cases of benign oral disease as a cause of false-positive I-131 uptake. Benign oral disease has not been documented previously as an important source of false-positive I-131 whole-body scans.     

Preferential renal excretion of iodide derived from thyroxine and triiodothyronine deiodination in man

Tracer doses of 131I- (Carrier free), 131I-T3 and 131-T4 were administered po to 19 healthy male volunteers at intervals 2 to 8 weeks to study whether or not part of the iodide generated in the kidney from T3 and T4 deiodination may enter the renal tubular lumen and be excreted in the urine without entering the blood stream. U(urine)/T(thyroid) ratios of the radioactivity from these materials were employed as the index of the comparison. U/T ratios were severalfold higher 24 h after 131I-T3 or 131I-T4 administration than after 131I-. The data indicate that the 131I- derived from T3 and T4 metabolism is more readily excreted into urine than 131I- which reaches the kidney as inorganic iodide.     

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.     

Reverse discordant scintigraphy in diffuse goiter

Both Tc-99m pertechnetate and radioactive iodine (I-123 NaI or I-131 NaI) are useful in thyroid scintigraphy. These radiopharmaceuticals yield similar functional information in most patients. Occasionally, however, discordant results have been reported in the literature (warm or hot on the pertechnetate image and cold on the radioiodide image). Most of these reports have concerned the solitary thyroid nodule. A case is presented here with diffusely decreased Tc-99m pertechnetate uptake and normal I-131 NaI uptake in a patient with a diffuse goiter and subclinical hyperthyroidism, so-called reverse discordant behavior.     

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.     

Role of technetium-99m sestamibi in localisation of thyroid cancer metastases

Technetium-99m sestamibi (MIBI) is a routinely used myocardial perfusion imaging agent. We have studied groups of patients with differentiated thyroid carcinoma, in order to evaluate the usefulness of this agent in localising regional neck and nodal disease and metastases. There are three groups of patients. Group 1 consisted of patients with known nodal disease or metastases (22 patients) and with raised serum thyroglobulin levels (Tg). Group 2 comprised patients with normal I-131 scans and normal Tg levels (nine patients). Non-thyroid malignancies (six patients) comprised an additional group 3. In group 1, the MIBI scan showed 47 sites of metastases, while the I-131 scan revealed 49 sites. The MIBI scan was positive in two patients where the I-131 scan was negative, while in two other patients, the MIBI study was negative whereas the I-131 scan was positive. In group 2, 6/9 patients had no disease, 2/9 had thyroid remnants, and 1/9 had a fresh primary lung tumour, unrelated to the earlier thyroid cancer. All of them had normal MIBI scans. In group 3, two patients with lung cancer and two with breast cancer and metastases had normal MIBI scans. A further two patients with nasopharyngeal cancer (NPC) had mildly increased MIBI localisation in neck nodes and bone metastases. In summary, Tc-99m sestamibi appears to be as good as I-131 in search for thyroid carcinoma metastatic spread, especially nodal disease and this tracer does not localise well in the primary or metastases of other cancers.(ABSTRACT TRUNCATED AT 250 WORDS)     

beta-Naphthoflavone- and self-induced metabolism of 3,3',4,4'-tetrachlorobiphenyl in hepatic microsomes of the male, pregnant female and foetal rat

1. The in vitro metabolism of 3,3',4,4'-tetrachloro-[14C]-biphenyl ([14C]-TCB) by hepatic microsomes from the Wistar rat was investigated with liver microsomes from the male, pregnant female and foetus. 2. Three hydroxylated metabolites (4-OH-3,3',4,5'-tetrachlorobiphenyl, 5-OH-3,3',4,4'-tetrachlorobiphenyl, and 6-OH-3,3',4,4'-tetrachlorobiphenyl) were identified by hplc and gc-ms after incubations of liver microsomes from the beta-naphthoflavone-pretreated male rat and TCB-treated pregnant rat. No metabolites of [14C]-TCB were found after incubation with foetal liver microsomes from dams pretreated with [14C]-TCB. The results indicate that the in vivo accumulation of 4-OH-tetraCB in the foetal compartment is probably due to transplacental transport rather than the formation of this metabolite in the foetus. 3. Pretreatment of the male rat with beta-naphthoflavone substantially induced the formation of hydroxylated metabolites, but pretreatment with phenobarbital and dexamethasone was without effect. Based on in vitro incubations of liver microsomes from the beta-naphthoflavone pretreated male rat, an apparent Km and Vmax of 4.5 microM and 240 pmol/mg protein/min respectively was determined for the metabolism of [14C]-TCB. The formation of phenolic metabolites of [14C]-TCB was most likely dependent on P4501A induction.     

Adrenal gland photoscanning by means of 131I-iodinated cholesterol

Photoscanning by means of 131I-19-iodinated cholesterol was performed on 10 patients with various diseases of the adrenal glands. The authors confirmed that the method was suitable for study of the morphology and function of the adrenal glands in disease, especially when combined with stimulation by ACTH or suppression by dexamethasone. The radiation dose absorbed by the thyroid and by the gonads can be controlled during the examination by blocking the iodine trapping and suppression of the gonado-stimulating action, respectively.     

Chernobyl accident: reconstruction of thyroid dose for inhabitants of the Republic of Belarus

The Chernobyl accident in April 1986 resulted in widespread contamination of the environment with radioactive materials, including (131)I and other radioiodines. This environmental contamination led to substantial radiation doses in the thyroids of many inhabitants of the Republic of Belarus. The reconstruction of thyroid doses received by Belarussians is based primarily on exposure rates measured against the neck of more than 200,000 people in the more contaminated territories; these measurements were carried out within a few weeks after the accident and before the decay of (131)I to negligible levels. Preliminary estimates of thyroid dose have been divided into 3 classes: Class 1 ("measured" doses), Class 2 (doses "derived by affinity"), and Class 3 ("empirically-derived" doses). Class 1 doses are estimated directly from the measured thyroidal (131)I content of the person considered, plus information on lifestyle and dietary habits. Such estimates are available for about 130,000 individuals from the contaminated areas of the Gomel and Mogilev Oblasts and from the city of Minsk. Maximum individual doses are estimated to range up to about 60 Gy. For every village with a sufficient number of residents with Class 1 doses, individual thyroid dose distributions are determined for several age groups and levels of milk consumption. These data are used to derive Class 2 thyroid dose estimates for unmeasured inhabitants of these villages. For any village where the number of residents with Class 1 thyroid doses is small or equal to zero, individual thyroid doses of Class 3 are derived from the relationship obtained between the mean adult thyroid dose and the deposition density of (131)I or 137Cs in villages with Class 2 thyroid doses presenting characteristics similar to those of the village considered. In order to improve the reliability of the Class 3 thyroid doses, an extensive program of measurement of (129)I in soils is envisaged.     

Thyroid malignant neoplasms. Therapeutic results in 305 patients

Between 1960 and 1972, 305 patients with malignomas of the thyroid gland were surgically treated, irradiated (megavoltage therapy and/or iodine-131), and treated with thyroid hormone according to principles formerly stated. Differentiated adenocarcinomas (34.4% of all the patients) were observed more frequently in women and younger patients, whereas dedifferentiated carcinomas (33.8%) are found relatively more often in men and in an advanced age. Only in 12% of the cases the tumor was discovered in an early stage; thus, an early diagnosis is much too rare so far. In almost two thirds of the patients a spread of metastases occurred. Of these, 11% grew manifest later than five years following the therapy. Distant metastases from differentiated adenocarcinomas accumulated I-131 in sixty per cent, those from undifferentiated carcinomas still in twenty per cent. Treatment results are influenced decisively by histology, tumor spread, age and sex, women less than forty years old with differentiated adenocarcinomas and a circumscribed extension of the tumor having the best prognosis. More prognostic importance is due to the extension of the primary tumor than to the presence of metastases to regionary lymph nodes. Patients with metastases accumulating I-131 have a better chance of survival than those whose metastases do not accumulate. By means of standardized therapeutic rules, utilizing modern therapeutic techniques and based on interdepartmental cooperation, it was possible to improve the results partly by the two- or threefold as compared to a previously treated group of patients.     

Neurological complications after autologous stem cell transplantation

Clinically detectable well-differentiated metastatic thyroid cancer to the kidney is rare, with only 12 cases reported in the medical literature. The authors report a case of metastatic thyroid carcinoma to the kidney in a patient with widespread dissemination. She underwent total thyroidectomy, radical left nephrectomy, radioactive ablation with I-131, radiotherapy, and thyroid suppression therapy. Well-differentiated thyroid metastatic cancer can be amenable to treatment with successful long-term results.     

Characterisation of erythrocyte shapes and sizes by NMR diffusion-diffraction of water: correlations with electron micrographs

Irradiation of the mammalian foetus produces a broad spectrum of congenital abnormalities, growth retardations, developmental delays, and functional deficits, depending upon the dose and the specific gestational phase of irradiation. The developing brain is particularly susceptible to production of deleterious effects, with decreased brain size, behavioural alterations, and mental retardation having been documented. Supplementing the limited human data, rodent models have been extensively used to investigate the specific processes by which relatively low doses, with correspondingly minor cellular damage to the developing neocortex, can produce dramatic postnatal consequences in brain structure and function. The effects of a variety of physical (dose, linear energy transfer, dose rate, fractionation) and biological (species, strain, gestational age, time course post-irradiation) parameters have been examined in an attempt to provide much needed information on such critical aspects as dose response, threshold doses for effect, and extrapolation to human risk estimates. Various acute cellular responses (e.g. appearance of pyknotic cells and macrophages) observed in the developing neocortex 0-24 h after in utero irradiation can be associated with postnatal effects. Moreover, it is possible to correlate thinning of specific layers of the cerebral cortex with specific behavioural aberrations, allowing prediction of brain structural changes from functional alterations, and vice versa. Thus, it is possible to speculate as to the mechanisms and targets for extremely sensitive, radiation-induced cellular damage in the developing foetal brain, that will interfere with the orderly and precisely programmed development of the mammalian brain, leading finally to postnatal expression as delays in growth and development, perturbations in behaviour, and alterations in brain structure.     

131 iodine: medical use. Carcinogenic and genetic effects

131 radioiodine is used for treating patients with thyrotoxicosis and differentiated thyroid carcinoma. Its therapeutic effect is related to the radiation dose delivered to the thyroid tissue. The radiation dose is related to its radioactive concentration (ratio between the radioactive uptake and the mass of functional tissue) and its effective half-life. Follow-up studies of patients exposed to 131I did not demonstrate any tumorigenic effect of 131I on the thyroid gland in adults, but do exclude such an effect in children. The dose delivered to other tissues is relatively low, and significant risk of cancer and leukemia has been found only in patients exposed to high cumulative activities of 131I (> 15 GBq). No genetic effect has been found in the studies of the outcome of pregnancies in women exposed to 131I for thyroid carcinoma. These data indicate that there is no scientific reason to avoid the use of 131I even in young patients when therapeutic benefits can be obtained.     

Changes in thyroid volume in response to radioactive iodine for Graves' hyperthyroidism correlated with activity of thyroid-stimulating antibody and treatment outcome

This study investigated 1) the relationship between thyroid volume and thyroid function in radioactive iodine (RAI) treatment for Graves' disease, and 2) the activity of thyroid-related Ig in serum on the responsiveness of thyroid tissue to RAI. The changes in thyroid volume per megabecquerel (MBq) of 131I retained in thyroid tissue was calculated by ultrasonography as a quantitative indicator of the effect of RAI on thyroid volume. Of the 52 patients treated with 131I (3.7 MBq retained/g thyroid tissue), 26 patients showed thyrotoxicosis, 20 patients became euthyroid, and 6 patients developed hypothyroidism 6 months after therapy. The change in thyroid volume per MBq 131I was lower (P < 0.01) in the hyperthyroid patients than in the euthyroid or hypothyroid patients. The activity of thyroid-stimulating antibody in serum immediately before the therapy was greater (P < 0.01) in the hyperthyroid patients than in the euthyroid patients and was greater (P < 0.05) in the euthyroid patients than in the hypothyroid patients; it was inversely correlated with the changes in thyroid volume per MBq 131I (r = -0.667; P < 0.01). Accurate measurement of changes in thyroid volume during the course of RAI treatment provides evidence of the responsiveness of Graves' disease thyroid tissue to RAI, which is related to the outcome of thyroid function. Thyroid-stimulating antibody determination may be useful in deciding the appropriate dose of RAI to obtain euthyroidism instead of hyperthyroidism.     

Foetal rat pancreatic transplantation: posttransplantation development of foetal pancreatic iso- and allografts and suppression of rejection with mycophenolate mofetil (MMF) and cyclosporine based immunesuppression

CONTEXT: High-dose iodine 131 is the treatment of choice in the United States for most adults with hyperthyroid disease. Although there is little evidence to link therapeutic (131)I to the development of cancer, its extensive medical use indicates the need for additional evaluation. OBJECTIVE: To evaluate cancer mortality among hyperthyroid patients, particularly after (131)I treatment. DESIGN: A retrospective cohort study. SETTING: Twenty-five clinics in the United States and 1 clinic in England. PATIENTS: A total of 35 593 hyperthyroid patients treated between 1946 and 1964 in the original Cooperative Thyrotoxicosis Therapy Follow-up Study; 91 % had Graves disease, 79% were female, and 65% were treated with (131)I. MAIN OUTCOME MEASURE: Standardized cancer mortality ratios (SMRs) after 3 treatment modalities for hyperthyroidism. RESULTS: Of the study cohort, 50.5% had died by the end of follow-up in December 1990. The total number of cancer deaths was close to that expected based on mortality rates in the general population (2950 vs 2857.6), but there was a small excess of mortality from cancers of the lung, breast, kidney, and thyroid, and a deficit of deaths from cancers of the uterus and the prostate gland. Patients with toxic nodular goiter had an SMR of 1.16 (95% confidence interval [CI], 1.03-1.30). More than 1 year after treatment, an increased risk of cancer mortality was seen among patients treated exclusively with antithyroid drugs (SMR, 1.31; 95% CI, 1.06-1.60). Radioactive iodine was not linked to total cancer deaths (SMR, 1.02; 95% CI, 0.98-1.07) or to any specific cancer with the exception of thyroid cancer (SMR, 3.94; 95% CI, 2.52-5.86). CONCLUSIONS: Neither hyperthyroidism nor (131)I treatment resulted in a significantly increased risk of total cancer mortality. While there was an elevated risk of thyroid cancer mortality following (131)I treatment, in absolute terms the excess number of deaths was small, and the underlying thyroid disease appeared to play a role. Overall, (131)I appears to be a safe therapy for hyperthyroidism.     

Screening for microalbuminuria by RIA in 131I-treated thyroid cancer patients

Thyroid cancer patients are treated with up to 9.9 GBq of 131I to ablate remnant thyroid tissue and/or any functioning metastases that may be present. Radioiodine therapy is repeated as often as required. However, only a small fraction of the 131I is taken up by remnant thyroid and metastases, the remainder being eliminated by the kidneys, which are therefore subject to irradiation. External radiation therapy to the kidneys is known to lead to nephritis and albuminuria. The study included 113 patients treated with one to four doses of 131I (1.1-9.9 GBq each dose) and followed up 1 month to more than 8 years later. Spot samples of urine were collected and microalbuminuria measured by in-house radioimmunoassay. Twelve patients had elevated levels (normal range up to 34 micrograms ml-1), but their clinical history revealed such predisposing factors as diabetes and/or hypertension and proteinuria before therapy commenced. The remaining patients had normoalbuminuria. Grouping the patients based on the total dose of 131I administered resulted in a median microalbuminuria of 2.4-12.9 micrograms ml-1. Hence, this study showed that the dose of 131I normally used in treating thyroid cancer does not increase microalbuminuria to any significant extent.     

Replication of influenza virus in organ cultures of human and simian urogenital tissues and human foetal tissues

A survey of human adult tissues in organ cultures showed that influenza viruses (A/Moscow/1019/65 (h2n2) or a recombinant virus virulent for man (PR/8-A/England/939/69 Clone 7a(H3N2)) could infect uterus, bladder and conjunctiva but not oesophagus under the conditions employed; simian bladder and uterus were also susceptible. These results were similar to those already described for corresponding ferret tissues. Organ cultures of human foetal nasal mucosa, trachea, oesophagus, small and large intestine, and bladder consistently supported replication over 4 days or more with high virus yields. Lung, conjunctiva and umbilical cord were less consistently susceptible and gave lower yields. Placenta and kidney cultures allowed replication of virus in one of 8 and one of 4 experiments respectively, the yields being low and of short duration. Organ cultures of neural tissue (meninges and brain), lymphopoietic tissue (spleen, liver and thymus) and amnion did not support significant viral replication. The results are discussed in relation to possible infection of the foetus in utero with influenza virus.     

Pattern of descent of foetal head in normal labour

The phenomenon of foetal head descent and the effect of station of foetal head at admission on the course of labour were studied on the basis of a prospective partographic study in 100 cases of normal labour. Only 16.9% of nulliparous women had engaged foetal head at admission in labour. Engagement of foetal head occurred during the period of maximum slope of cervical dilatation in nulliparous women and at the onset of deceleration phase in multiparous women. Parturients with unengaged foetal head entered hospital much earlier in labour than those with engaged foetal based. Course of labour was uninfluenced by the degree of engagement of foetal head. However, multiparous women showed faster rate of foetal head descent than nulliparous women (p < 0.001) and women with lesser haemoglobin concentration demonstrated slower rate of descent of foetal head (p < 0.01).