The use of radioactive iodine in the treatment of Graves disease

Fifty patients with uncomplicated Graves' disease were treated with radioactive iodine (I(131)). Twenty-six patients who were followed for one year or longer are the basis of this report. Twenty-five are now euthyroid; only one is not completely well. The total dose of radioiodine administered varied from 0.5 to 10 millicuries. The average length of time necessary for return to a euthyroid state was from three to four months. Hypometabolism developed in three patients, and in one the signs and symptoms of myxedema developed. No other complications ensued. One patient who apparently relapsed had complete return to normal after further iodine administration. The determination of the uptake of radioactive iodine by the thyroid gland is a useful diagnostic procedure in differentiating conditions simulating hyperthyroidism.Following treatment with radioactive iodine, the thyroid gland becomes smaller, the uptake of iodine by the gland is reduced, and the level of organic iodine in the plasma becomes normal. In acute thyroiditis, in spite of a high basal metabolic rate, high content of organic iodine in the plasma and other evidences of "hyperthyroidism," the uptake of I(131) has been very low.     

HYPERTHYROIDISM—Diagnosis by Failure of Triiodothyronine to Suppress Uptake of Iodine131

Sixty patients with abnormally high I¹³¹ uptake were treated with liothyronine (L-triiodothyronine) for seven or eight days and then tested again. Fifty-five patients showed a suppression of iodine uptake sufficient to eliminate the possibility of hyperthyroidism. Also the therapeutic trial of liothyronine indicated whether they were euthyroid, or hypothyroid with iodine deficiency. Six of the patients showed insignificant change in the I¹³¹ uptake after treatment with thyroid hormone—that is, the change from the original uptake was less than 30 per cent. These six patients were later confirmed to be hyperthyroid. In four patients the uptake at the second test was less by between 35 and 52 per cent than at the first. These four patients, like the remainder with even greater suppression in thyroid uptake, remained clinically euthyroid.The repeat I¹³¹ uptake test was thus seen to be considerably more accurate than the single test and well worth the time required to perform it.     

The Normal Thyroidal Uptake of Iodine

The range of values for the 24-hour thyroidal accumulation of radioactive iodine in euthyroid persons varies with geographic location. In the San Bernardino Valley region of Southern California the “normal range” is 6 percent to 33 percent in euthyroid subjects. This is lower than in studies from other areas of the United States. The urinary iodide excretion and the absolute iodine uptake of the thyroid are higher than in studies from many other areas of the United States, pointing to iodine abundance as the reason for this difference. The geographic variation and the possibility of changing dietary iodine intake of normal persons point to the necessity of current and local determinations of the “normal range” of the thyroidal uptake of radioiodine if the results of this thyroid function test are to be properly interpreted.     

Extensive scleral perforation with complete recovery

Sixty patients with abnormally high I(131) uptake were treated with liothyronine (L-triiodothyronine) for seven or eight days and then tested again. Fifty-five patients showed a suppression of iodine uptake sufficient to eliminate the possibility of hyperthyroidism. Also the therapeutic trial of liothyronine indicated whether they were euthyroid, or hypothyroid with iodine deficiency. Six of the patients showed insignificant change in the I(131) uptake after treatment with thyroid hormone-that is, the change from the original uptake was less than 30 per cent. These six patients were later confirmed to be hyperthyroid. In four patients the uptake at the second test was less by between 35 and 52 per cent than at the first. These four patients, like the remainder with even greater suppression in thyroid uptake, remained clinically euthyroid.The repeat I(131) uptake test was thus seen to be considerably more accurate than the single test and well worth the time required to perform it.     

Radioiodine treatment of multinodular non-toxic goitre.

OBJECTIVE--To investigate the long term effect of radioactive iodine on thyroid function and size in patients with non-toxic multinodular goitre. DESIGN--Consecutive patients with multinodular non-toxic goitre selected for radioactive iodine treatment and followed for a minimum of 12 months (median 48 months) after an intended dose of 3.7 MBq/g thyroid tissue corrected to a 100% uptake of iodine-131 in 24 hours. PATIENTS--69 patients with a growing multinodular non-toxic goitre causing local compression symptoms or cosmetic inconveniences. The treatment was chosen because of a high operative risk, previous thyroidectomy, or refusal to be operated on. MAIN OUTCOME MEASUREMENTS--Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 1, 2, 3, 6, and 12 months after treatment and then once a year. RESULTS--56 patients were treated with a single dose of 131I, 12 with two doses, and one with four doses. In 45 patients treated with one dose and remaining euthyroid the median thyroid volume was reduced from 73 (interquartile range 50-106) ml to 29 (23-48) ml at 24 months in the 39 patients in whom this was measured during follow up. The median reduction was 40 (22-48) ml (60% reduction, p < 0.0001), half of which occurred within three months. Patients treated with two doses as well as those developing hypothyroidism and hyperthyroidism had a significant reduction in thyroid volume. Eleven patients developed hypothyroidism (cumulative five year risk 22%, 95% confidence interval 4.8% to 38.4%). Side effects were few: three cases of hyperthyroidism and two cases of radiation thyroiditis. Only one patient was dissatisfied with the result; she was referred for operation six months after treatment. CONCLUSIONS--A substantial reduction in thyroid volume accompanied by a low incidence of hypothyroidism and few side effects makes the use of radioactive iodine an attractive alternative to surgery in selected cases of non-toxic multinodular goitre.     

食盐加碘后甲状腺摄131I 率的变化及其与尿碘的关系

目的：了解食盐加碘后健康人及甲亢患者甲状腺摄131I 率的变化及其与24 小时尿碘含量的相关性,探讨甲状腺摄131I 率与 碘营养状况的关系。方法：对比食盐加碘前后健康体检者及甲亢患者甲状腺摄131I 率的变化,分析健康体检者甲状腺摄131I 率、晨 尿碘浓度及经肌酐校正的尿碘含量与24小时尿碘含量的相关关系。结果：健康人及甲亢患者食盐加碘后3、6 及24 小时甲状腺 摄131I 率均显著降低;健康体检者甲状腺摄131I 率与24 小时尿碘含量呈负相关（r=－0.7651, P<0.001）,晨尿碘浓度与24 小时尿碘 含量呈正相关（r=0.8231, P<0.001）,经肌酐校正的尿碘含量与24 小时尿碘含量呈正相关（r=0.9054, P<0.001）。结论：食盐加碘对甲 状腺摄131I 率有显著影响,应重新确立甲状腺摄131I 率的正常范围及甲亢的诊断标准;经肌酐校正的尿碘含量较晨尿碘浓度能更 准确地反映碘营养状况;甲状腺摄131I率可作为评估个体碘营养状况的指标,可以稳定地反映近期的碘营养状况。     

食盐加碘后甲状腺摄 ~（131）I率的变化及其与尿碘的关系

目的：了解食盐加碘后健康人及甲亢患者甲状腺摄131I率的变化及其与24小时尿碘含量的相关性,探讨甲状腺摄131I率与碘营养状况的关系。方法：对比食盐加碘前后健康体检者及甲亢患者甲状腺摄131I率的变化,分析健康体检者甲状腺摄131I率、晨尿碘浓度及经肌酐校正的尿碘含量与24小时尿碘含量的相关关系。结果：健康人及甲亢患者食盐加碘后3、6及24小时甲状腺摄131I率均显著降低;健康体检者甲状腺摄131I率与24小时尿碘含量呈负相关（r=-0.7651,P〈0.001）,晨尿碘浓度与24小时尿碘含量呈正相关（r=0.8231,P〈0.001）,经肌酐校正的尿碘含量与24小时尿碘含量呈正相关（r=0.9054,P〈0.001）。结论：食盐加碘对甲状腺摄131I率有显著影响,应重新确立甲状腺摄131I率的正常范围及甲亢的诊断标准;经肌酐校正的尿碘含量较晨尿碘浓度能更准确地反映碘营养状况;甲状腺摄131I率可作为评估个体碘营养状况的指标,可以稳定地反映近期的碘营养状况。     

SCINTIGRAMS OF THE THYROID GLAND—The Diagnosis of Morphologic Abnormalities with I131

Functioning thyroid tissue containing sufficient radioiodine can be visualized by scanning the gland with a directional scintillation counter.⁴ This visual representation of the gland is called a “scintigram.” Scintigrams have been invaluable in the detection and study of both “toxic” and non-functioning nodules, diffuse enlargement in hyperthyroidism and the subsequent reduction in gland size after treatment, carcinoma, and aberrant thyroid tissue.     

THE USE OF ANTITHYROID DRUGS

The preoperative use of antithyroid drugs is mandatory if surgical treatment of complicated hyperthyroidism is contemplated. Six months to a year may be required for suitable preparation.The long-term use of antithyroid drugs is less effective for the “cure” of hyperthyroidism than is operation or the use of radioactive iodine.Propyl and methyl thiouracil are the antithyroid drugs of choice.Either of these thiouracil derivatives is capable of producing leukopenia.The antithyroid drugs exert no favorable effect on exophthalmos.The antithyroid drugs are suitable for the control of hyperthyroidism during pregnancy. The patient probably should not be kept hypothyroid during pregnancy but rather in a state of mild hyperthyroidism.     

SEVERE EUTHYROID CARDIAC DISEASE—Technique for Treatment with Radioiodine

It is possible to safely lower the basal metabolism of patients suffering from severe cardiac disease by administering multiple small doses of radioiodine in order to achieve symptomatic relief.From the present study, multiple small doses of I¹³¹ appeared to be as effective as single or multiple large doses of this material and complications such as thyroiditis, temporary thyrotoxicosis and bone marrow depression were almost always avoided. No damage to the parathyroid glands or the recurrent laryngeal nerve was observed. No radiation sickness developed after therapy.A scintigram of the thyroid gland was useful in determining the size, shape and function of the thyroid gland before and during radioiodine treatment and helped to determine the need for additional treatment. In order to prevent the distressing symptoms of the myxedema state, desiccated thyroid was administered when necessary.In the series of 278 euthyroid patients with severe cardiac disease who were treated with radioactive iodine, results were excellent in 35 per cent of cases and good in 44 per cent. In 21 per cent there was no improvement.     

Discriminant Value of Thyroid Function Tests

Different thyroid function tests permitted a final classification of 204 consecutive patients with suspected thyroid disorders into three populations (thyrotoxic, euthyroid, and hypothyroid). Linear discriminant analysis was applied to all test results (10 variates) on adjacent population pairs. Two invitro tests (serum protein bound iodine (P.B.I.) and tri-iodothyronine (T-3) uptake values) gave good separation of thyrotoxic from euthyroid patients and fairly good distinction of hypothyroid patients. If a ¹³¹I uptake figure was then added to the in-vitro results most patients (95·5%), including thse initially classified as equivocal, were correctly diagnosed. Other tests, including clinical questionnaires, were poor discriminants.Two new techniques of utilizing the test data were devised. Firstly, the data from the two in-vitro tests were also displayed graphically, and oblique boundary lines derived from the discriminant functions gave better separation of patients than previously used limits or mathematical expressions of “free thyroxine.” Secondly, a nomogram incorporating the best four discriminants was designed as a diagnostic aid and proved to be the best means of interpreting the tests.Discriminant analysis of this kind can be used in the interpretation of diagnostic tests in any branch of medicine, and it allows the best use to be made of the available data.     

Diazepam and Tests of Thyroid Function

The effect of diazepam on thyroid function tests was examined in 12 euthyroid patients requiring the drug for psychiatric reasons and in six patients with thyrotoxicosis. Assessment was made before and after four weeks'' therapy.There was no significant difference in results from tests of thyroid iodide trapping and binding (thyroid radioiodine uptake, thyroid clearance, and absolute iodine uptake) except in the one-hour thyroid uptake in the euthyroid group, which was increased after diazepam. This increase occurred without alteration in serum thyroid stimulating hormone levels. No change occurred in either group in tests of thyroid hormone release (protein-bound iodine, T-3 resin uptake, or Thyopac-3 and free thyroxine index).Patients with suspected thyroid disease who are taking diazepam do not need to stop therapy while their thyroid status is being determined.     

Iodinated phospholipids and the iodination of proteins of dog thyroid gland in vitro

Slices of dog thyroid gland were incubated with liposomes consisting of (125)I-labelled phosphatidylcholine (the iodine was covalently linked to unsaturated fatty acyl chains). The (125)I label of (125)I-labelled liposomes was incorporated into thyroid protein and/or thyroglobulin at a higher rate than was the (131)I label of either Na(131)I or (131)I(2). The iodine was shown to be protein-bound by the co-migration of the labelled iodine with protein under conditions where free iodine, iodide and lipid-bound iodine were removed from protein. The uptake of iodine from the iodinated phospholipid was probably due to phospholipid exchange between the iodinated liposomes and the thyroid cell membrane, since (a) (14)C-labelled phospholipid was metabolized to (14)CO(2) and (b) many lipids in the tissue slice became (14)C-labelled. A very strong inhibition of iodide ;uptake' from Na(131)I, caused by thiosulphate, produced only a minor inhibition of the incorporation of (125)I from (125)I-labelled liposomes into thyroid protein and/or thyroglobulin. This implies that free iodide may not necessarily be formed from the iodinated phospholipids before their entrance or utilization in the cell. Synthetic polytyrosine polypeptide suspensions showed some iodination by (131)I-labelled liposomes. In tissues with low tyrosine contents, such as liver and kidney, only a trace uptake was observed. Salivary gland showed some uptake. Endoplasmic reticulum of thyroid gland showed a higher iodine uptake than that of the corresponding plasma membranes. These experiments, together with the demonstration of the diet-dependent presence of iodinated phospholipids in dog thyroid, leads us to suggest that iodination of the membrane phospholipids of thyroid cells may be directly or indirectly involved at some stage in the synthesis of thyroglobulin, or exists as a scavenger mechanism, to re-utilize and/or recover released iodine from unstable compounds inside the thyroid cell.     

Effect of yogic exercises on thyroid function in subjects resident at sea level upon exposure to high altitude

Using radioactive iodine, the effect of 1 month's yogic exercises has been investigated on the thyroid function of subjects resident at sea level (SL) specially after their exposure to high altitude (HA). The results have been compared with a group of SL subjects who underwent physical training (PT) exercises for the same duration. Ten healthy male volunteers in the age range of 20–30 years were used as test subjects in this study with each serving as his own control. The subjects were randomly divided into two groups of 5 each. One group practised hatha yogic exercises, while the other group performed the regular PT exercises. The thyroidal accumulation and release of radioactive iodine have been measured in each of the subjects of both groups before and after 1 month of their respective exercises at SL. One month of yogic exercises at SL has been observed to cause a significant reduction in the trans-thy-roidal availability of radioiodine. The thyroid radioactivity in this group of subjects was always below normal levels with the exception of two peaks of radioactive iodine uptake, when the levels of radioactivity in the thyroid were similar to the control values of pre-yogic exercises. The release of radiolabel at 24–48 h was significantly increased after yogic exercises. In contrast, the subjects performing PT exercises for the same duration at SL showed significant thyroid uptake of radioactive iodine at 24 h. Subsequently their¹³¹I uptake continued to rise slowly until 72 h without any demonstrable thyroidal release of radiolabel. This indicated that increased thyroid activity was induced by conventional PT exercise. Exposure of SL residents to HA irrespective of their exercise regime altered the thyroidal handling of radioiodine. Thyroidal concentrations of freshly administered radioiodine at early and late sampling intervals were very high in both of the groups, especially the yogics, after their return to SL from HA. Possible mechanisms of the observed changes have been discussed.     

Occurrence of Goitre during Lithium Treatment

Of 330 patients given lithium for recurrent manic-depressive disorder 12 developed goitre after treatment periods of five months to two years. All the patients remained clinically euthyroid. Pressure symptoms necessitated subtotal thyroidectomy in two patients. In 9 out of 10 patients with goitre, and in two out of seven without goitre study with radioactive iodine showed abnormal findings in iodine metabolism. Discontinuance of lithium led to disappearance of goitres, while thyroid metabolism returned to normal. Thyroxine or desiccated thyroid produced shrinkage of the gland in spite of continued lithium medication.     

Function of the serotoninergic system of the thyrotoxic thyroid

The state of serotoninergic system in thyrotoxic and euthyroid gland were compared. It was shown that in patients with hyperthyroidism (diffuse toxic goiter) serotonin and 5-hydroxytryptophan content, velocity and the latter uptake were augmented. The authors stress the role of the delay in serotonin oxidative deamination as one of the reasons for increased serotonin content in thyrotoxic thyroid gland. Possible ways of increasing intrathyroid serotonin accumulation and its role in the development of thyroid hyperfunction are discussed.     

MATURATION OF THE RAT FETAL THYROID

Maturation of the rat fetal thyroid was studied with the aid of I¹³¹ and of fluorescence and electron microscopy. The I¹³¹ concentration of the fetal gland increased exponentially from day 17 to day 20 of gestation and was related to the weight of the fetus (and presumably the weight of the thyroid) and also to the quantity of I¹³¹ accumulated by the fetus. In the 17-day gland, thyroglobulin or immunologically similar material was sparsely present in the incipient lumens of some cell clusters. With maturation, this material increased and was also observed within follicular cells on days 18 to 19 of gestation. On day 20, the specifically reacting material was present in the follicular lumens and was absent from the cytoplasm of follicular epithelium. Ultrastructurally, the earliest thyroid cells examined were replete with all the organelles found in the more mature epithelium. No direct correlation could be made between the cytoplasmic structures and the presence of thyroglobulin, although the granular endoplasmic reticulum was most likely the organelle responsible for synthesis of thyroglobulin. Thyroglobulin or a precursor was found in fetal thyroid cells before measurable quantities of I¹³¹ were concentrated and before cytoplasmic droplets appeared.     

Severe euthyroid cardiac disease; technique for treatment with radioiodine

It is possible to safely lower the basal metabolism of patients suffering from severe cardiac disease by administering multiple small doses of radioiodine in order to achieve symptomatic relief. From the present study, multiple small doses of I(131) appeared to be as effective as single or multiple large doses of this material and complications such as thyroiditis, temporary thyrotoxicosis and bone marrow depression were almost always avoided. No damage to the parathyroid glands or the recurrent laryngeal nerve was observed. No radiation sickness developed after therapy.A scintigram of the thyroid gland was useful in determining the size, shape and function of the thyroid gland before and during radioiodine treatment and helped to determine the need for additional treatment. In order to prevent the distressing symptoms of the myxedema state, desiccated thyroid was administered when necessary. In the series of 278 euthyroid patients with severe cardiac disease who were treated with radioactive iodine, results were excellent in 35 per cent of cases and good in 44 per cent. In 21 per cent there was no improvement.     

The estimation of the goiter by means of ultrasonography and scintigraphy (SPECT) with using 131I

INTRODUCTION: Ultrasonography (US) and scintigraphy (SPECT) are used to evaluate the volume of thyroid glands. An accurate estimation of the thyroid volume, among other factors, is necessary to calculate the suitable radioactive iodine dose, which determines the success of the therapy. The aim of the study was to estimate the volume of the goiter by means of US and (131)I-SPECT. MATERIAL AND METHODS: A group of 80 patients with a thyroid disorder in their past medical history was examined. Patients were divided into two groups. The group A contained 50 patients (39 females, 11 males) with a goiter, where the volume of the thyroid was evaluated with the use of US and (131)I-SPECT. The group B contained 30 patients (21 females, 9 males) with a normal volume of the thyroid gland shown by US and (131)I-SPECT. US of the thyroid gland was made by means of an ALOKA SSD 500 device, with the linear head 7.5 MHz frequency. (131)I-SPECT was made by means of a one head gammacamera Diacam with a high energy collimator. RESULTS: In the group A, the average volume of the goiter was 44.55 ml in US and 49.67 ml in SPECT (p<0.001). In control group B the average volumes of the thyroid gland were respectively 13.83 ml vs. 16.19 ml (p<0.001). CONCLUSION: The results of the thyroid volume measurement was dependent on the method used in both the investigated and control groups.     

Iodine metabolism in the thyroid gland in chronic uranium poisoning]

The exchange of radioactive and stable iodine was studied for 21 days after the I131 injection in the thyroid gland and the blood of rats against the background of chronic uranium intoxication. The latter was accompanied by a decrease in the number of iodine-transport loci of the gland, as well as of the value of the intrathyroid iodine pool and of the stable iodine concentration in the thyroid tissue. The compensatory reaction of the thyroid gland was expressed in the increase of its mass and the rate of the thyroid metabolism as well.