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.     

Diurnal rhythms of thyroid hormones in rooster chicks (Gallus domesticus). 2. Studies on the protein-bound radioiodine and the "free" hormone portion]

In four week old cockerels the plasma was investigated for cyclic changes in total radioactivity, PB131I, PI131I, and "free" thyroid hormones 24 hours after injection of Na131I. Maxima in total radioactivity were observed at 3.00 am and 9.00 pm. They were significant different from the minima at noon (2P less than 0.005). At the same points of the day maxima, resp. minima were found in the PB131I and the "free" hormones. The "free" hormones expressed in per cent of total hormones showed low values at 6.00 am, 3.00 pm, and 9.00 pm. The diurnal changes in haematocrit and albumin concentration were not responsible for the variation of PB131I. In order to eleminate effects of isotope dilution by ingested iodine the PB131I was expressed in per cent of total radioactivity of plasma (= conversion rate) or resp. in per cent of thyroidal radioiodine uptake. The obtained values showed maxima at 6.00 am and 9.00 pm. From that we conclude again on a stimulation of the thyroid at these times.     

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.     

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。     

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.     

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。     

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.     

THE USE OF RADIOACTIVE IODINE IN THE TREATMENT OF GRAVES' DISEASE

Fifty patients with uncomplicated Graves'' disease were treated with radioactive iodine (I₁₃₁). 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 I₁₃₁ has been very low.     

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.     

Les métastases pulmonaires micronodulaires de type miliaire dans le cancer thyroïdien bien différencié (médullaires exclus) à propos de dix cas

Thyroid cancer is relatively a rare cancer; about 1% from all cancers; between 10 and 15% of patients with differentiated thyroid cancer develop micro or macronodular pulmonary metastases. In this study we examined the characteristics and evolution after treatment of 10 patients with micronodular or miliary metastases of well-differentiated thyroid carcinoma. Total body scintigraphy with 131 iodine, chest X-ray or CT scan, and thyroglobulin assay were performed for all patients. The treatment was iodine 131 (3, 7 GBq), therapeutic 131 iodine scan was done for all patients seven days after the 131 administration. The effect of 131 iodine treatment was evaluated by means of changes in the number and size of lung metastases on the total body scintigraphy with 131 iodine and by serum thyroglobulin levels six months after 131 iodine ablation, they all received L-thyroxin (2,4 μg/kg/j). The minimum duration of follow-up was 12 months. There were six females and four males within a range of 13–70 years old. Eight had papillary and two follicular thyroid cancer. These 10 patients benefited 131 iodine therapy. The effect of 131 iodine treatment and the prognostic values of the following variables were examined: age at the time of 131 iodine, treatment and histological findings. The miliary was rarely diagnosed on the initial investigation, only in two cases by 131 iodine scan after surgery, two cases by chest X-ray, and two cases by CT scan, the initial thyroglobulin levels was very high in seven cases, between 10 and 40 ng/ml in one case and less than 10 ng/ml in two cases. These results indicate that age, 131 iodine uptake, histological findings and the presence of other metastases are important factors in predicting the effects of 131 treatment for pulmonary metastases of well-differentiated thyroid carcinoma. Among all the variables studied, the best prognosis for survival was demonstrated by increased 131 uptake in pulmonary metastases and by early diagnosis during post surgery 131 iodine scanning of radiologicaly inapparent metastases.     

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.     

Effect of lithium on thyroidal 131iodine uptake, its clearance, and circulating levels of triiodothyronine and thyroxine in lead-treated rats

The influence of lead acetate (50 mg per kg body weight) on the 131iodine (131I) biokinetics (uptake and retention) in rat thyroid and serum levels of triiodothyronine (T3) as well as thyroxine (T4) was evaluated as a function of time and in combination with lithium treatment. The 2-h and 24-h uptake of 131I in the thyroid was stimulated significantly by lead treatment. The 24-h uptake showed a maximum stimulation after 4 months of lead treatment. Lithium supplementation, however, showed the opposite effect by reducing the iodine uptake whereby the maximum decrease was noticed after 2 months of treatment. Further, simultaneous lead and lithium treatment resulted in an even more pronounced increase of 2-h 131I uptake with a maximum after 3 months. However, the 24-h uptake after 3 months and 4 months of treatment did not differ significantly from the lead treated reference groups. The thyroidal biological half-life of 131I (Tbiol) was found to have clearly increased following the lead/lithium treatment. Interestingly, the combined lead/lithium treatment applied for 4 months caused a further growth of Tbiol, thus reflecting an increased retention of 131I. A maximum increase of Tbiol was seen after 2 months of combined treatment. A progressive decline of the circulating T3 and T4 levels following lead or lithium treatment was noticed and was more pronounced after combined treatment.     

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.     

Decreased thyroid hormone-stimulated oxygen consumption and glucose uptake in mononuclear blood cells from patients with autosomal dominant osteopetrosis type I

Nine patients, from four different families, with autosomal dominant osteopetrosis were investigated. They all had roentgenological type I disease, characterized by universal, symmetrical osteosclerosis and enlarged thickness of the cranial vault. All patients appeared clinically euthyroid. Thyroxine (T4) and tri-iodothyronine (T3) induced oxygen consumption and glucose uptake were studied in vitro in mononuclear blood cells from patients and control persons. Unstimulated oxygen consumption from patients and controls did not differ, and no difference in unstimulated glucose uptake was observed. The increase in T4 and T3 stimulated oxygen consumption was significantly lower in cells from patients with osteopetrosis (T4: 0.007 +/- 0.004 mumol/mg DNA per h, T3: 0.011 +/- 0.004 mumol/mg DNA per h) compared with controls (T4: 0.017 +/- 0.003 mumol/mg DNA per h, T3: 0.023 +/- -0.013 mumol/mg DNA per h; p less than 0.05, p less than 0.05). Cellular glucose uptake after T4 and T3 stimulation was significantly lower in patients (T4: 0.032 +/- 0.017 mmol/l per mg DNA per h, T3: 0.02 +/- 0.017 mmol/l per mg DNA per h) compared with controls (T4: 0.09 +/- 0.017 mmol/l per mg DNA per h, T3: 0.08 +/- 0.01 mmol/l per mg DNA per h; p less than 0.05, p less than 0.01). The reduced oxygen consumption and glucose uptake indicate thyroid hormone resistance which may be of pathogenetic importance for the development of autosomal dominant osteopetrosis type I.     

Ablative radioiodine therapy for hyperthyroidism: long term follow up study.

A total of 225 patients were treated for hyperthyroidism with 555 MBq (15 mCi) radioiodine to ablate the thyroid and induce early hypothyroidism. The efficacy of this treatment in eradicating hyperthyroidism and problems of follow up were assessed one to six years later from case records and questionnaires. Information was received from 197 out of 219 live patients (90%) and from 160 doctors concerning 207 patients (92%). Only three patients were not traced and six had died since treatment. The modal time to hypothyroidism was three months, and 64% of patients were hypothyroid at one year; 5.6% had failed to become euthyroid within one year. Ninety five per cent of patients had been seen by the doctor and 82% had had a thyroid test done within the past two years. Most doctors preferred patients to be returned to their care once thyroxine treatment was stabilised. An ablative dose of 131I is recommended as an effective means of treatment which has clear advantages over conventional methods. Good communications and effective follow up should ensure success.     

Thyrotropin receptor antibody activities significantly correlate with the outcome of radioiodine (131I) therapy for hyperthyroid Graves' disease.

The outcome of 131I therapy for 109 patients with Graves' disease was analysed according to pretreatment laboratory data including thyrotropin receptor antibody (TRAb) activities. Forty-five percent of patients became euthyroid, and 13% of patients became hypothyroid within one year after 131I therapy. Forty-two percent of patients remained hyperthyroid one year after 131I therapy. Pretreatment values for serum T4, T3, and the estimated weight of the thyroid were significantly higher in the hyperthyroid group. The mean for the TRAb index of the hyperthyroid group was significantly higher than that of the euthyroid group. Life table analysis revealed a significant effect of the TRAb index on the rate of hyperthyroidism after 3 months or later. These results appear to suggest that the TRAb index is one of the factors which influence the outcome of 131I therapy for Graves' disease.     

Over-the-Counter-Drug-Induced Thyroid Disorders

ObjectiveExcessive iodine ingestion may cause thyroid dysfunction. In this case series, we report four patients who developed significant thyroid dysfunction after ingesting over-the-counter (OTC) drugs containing large concentrations of iodine.MethodsFour patients from a tertiary medical center are reported.ResultsCase 1 involved acute exacerbation of thyrotoxicosis induced by taking OTC Tri-iodine™ in a 35-year-old woman while still on methimazole therapy. Case 2 involved thyroid-extract-induced thyrotoxicosis following ingestion of Thyromine™, and was confirmed by laboratory studies and 131I thyroid uptake. Cases 3 and 4 involved severe, symptomatic hypothyroidism induced in 2 patients with underlying autoimmune thyroiditis (Hashimotoဩs disease) following ingestion of Iodoral™. In all cases, thyroid dysfunction resolved with appropriate management and discontinuation of the OTC drugs.ConclusionThese case reports demonstrate the significant risks associated with OTC preparations containing iodine in patients predisposed to thyroid dysfunction. There is no valid reason for taking high-dose OTC iodine supplements, which have been shown to cause harm and have no known benefit.     

The treatment of multinodular large non-toxic goiter using repeated doses of radioiodine (preliminary report)

INTRODUCTION: The aim of study was to establish the effectiveness of radioiodine therapy using 131I in the group of patients with multinodular large non-toxic goiter. MATERIAL AND METHODS: Therapy was undertaken in female patients disqualified from surgery due to high risk and these patients who didn't agree to surgery. Studies were performed in 7 women (age range: 62-82 yrs) with large goiters (2nd degree according to WHO classification and goiter volume assessed by USG over 100 cm(3)). Serum TSH, fT4, fT3, antithyroid antibodies (TPOAb, TgAb, TRAb) levels, urinary iodine concentration (UIE) were estimated in all patients parallel with radioiodine uptake test (after 5 and 24 hours), 131I thyroid scintigraphy and fine needle biopsy to exclude neoplasmatic transformation. These studies and therapy with 22 mCi 131I were repeated every 3 months. RESULTS: Before therapy median thyroid volume was approximately 145 cm(3) and during therapy gradually decreased to 76 cm(3) after 6 months and to 65 cm(3) after 12 months. Increase of TRAb can be a inhibiting factor of thyroid volume reduction. Other antithyroid antibodies showed marked tendency to rise but without significant correlation with radioiodine uptake and goiter reduction. After 12 months we found 2 patients with clinical and laboratory hypothyroidism. CONCLUSIONS: In some cases of multinodular large non-toxic goiter, the radioiodine therapy can be the best alternative way for L-thyroxine treatment or surgery therapy. The fractionated radioiodine therapy of multinodular large non-toxic goiter is safe and effective method but continuation of nodules observation is necessary.     

Microscopic distribution of iodine radioisotopes in the thyroid of the iodine deficient new-born rat: insight concerning the Chernobyl accident.

Thyroid cancer markedly increased in children exposed to iodine radioisotopes following the Chernobyl accident. This increase exceeded predictions based on dose estimates to the whole organ. We sought to investigate whether iodine deficiency may have influenced the pattern of microscopic distribution of radioiodines, which may be important to interpretation of the observed effects. Iodine-deficient new-born rats were injected with iodine-129 (129I) and the microscopic distribution in the thyroid tissue was studied at 24 hr and at one week after administration, using secondary ion mass spectrometry (SIMS). Twenty-four hr after administration, SIMS images showed large differences in 129I uptake among thyroid follicles, with more than a factor ten variation in the local concentration. In addition, the distribution of 129I inside follicles varied with time. At 24 hr, the highest concentration was found at the periphery of the colloid, close to the thyroid cells. There also was enhanced concentration of 129I at one pole of follicles. Distribution inside follicles was homogeneous at 7 days. Conclusions: 1/Dosimetric models, which assume uniform iodine uptake by thyroid follicles, give an oversimplified picture of radiation dosimetry in cases involving iodine deficiency, which induces patchy tissue irradiation. 2/The dynamic pattern of iodine distribution within thyroid follicles suggests that decay events from short-lived iodines will occur closer to thyroid cells than events resulting from iodine-131.     

Diurnal rhythms of thyroid hormones in rooster chicks (Gallus domesticus). 1. Studies on the colloid epithelium portion, the radioiodine accumulation in the thyroid gland and the plasma radioiodide concentration]

Four and five week old White Leghorn cockerels were investigated concerning diurnal changes of thyroidal activity. They were kept under normal conditions, including the changes in day light (light from 5.00 am to 8.00 pm). In the thyroid maxima of the per cent amount of colloid were found at 3.00 am and at noon. The values differed significantly from the intermediate ones (2P less than 0.001) which reached only 22 per cent of the maxima. The thyroidal uptake of radioiodine had also a maximum at 3.00 am (51 percent and 78 percent resp., 90 min. or 24 hours p.i.). The 24-h uptake at 3.00 am was significant different from the corresponding uptakes between 6.00 am and 6.00 pm (53-61 percent; 2P less than 0.05). The plasma radioiodide increased at afternoon and in the evening. The 9.00 pm concentration differed significantly from the 9.00 am concentration (2P less than 0.001). Since in the afternoon most of the food is ingested the thyroid can take up a greater amount of untracered iodide and therefore the radioiodide concentration of plasma may remain high. The above observations may be explained in the following way: (1) The thyroidal iodine uptake is increased in the afternoon corresponding to the increase in colloid; however these increase is not detectable by measuring the radioiodine uptake because of dilution effects (during the night the increase in colloid coincidences with the increase in iodine uptake); (2) looking at the daily changes of colloid and radioiodine uptake the thyroid may be stimulated in the early morning and in the evening.