Radioactive Iodine Uptake Values Research Articles

Least Significant Changes and Reproducibility of 131I Uptake Test.

Radioactive iodine uptake (RAIU) is one of the important tests performed in the departments of nuclear medicine, testing thyroid function by measuring the amount of 131I uptake after oral administration. A RAIU value measured 4 and 24 h after administration has been widely used for differential diagnosis of thyroid function and for the calculation of treatment dose. This study was performed to define practical methods for reproducibility and least significant change (LSC) values replicating thyroid measurements. In the study were 119 patients referred to the nuclear medicine department for examination of thyroid gland function with the diagnosis of Graves' disease (60), toxic multinodular goiter (29), thyroiditis (10), thyroid cancer (6), and unknown etiology (14). The level of thyroid stimulating hormone (TSH) among the patients was 2.07 ± 6.74 μIU mL-1. RAIU measurements were carried out by two different technicians, who have performed an equal number of measurements from each diagnosis in reference to the clinical diagnosis. Measurement of each patient was performed twice at 4 and 24 h after the administration under stable geometry and counting conditions using a standard procedure. Data were evaluated using statistical methods. For assessment of the reproducibility, three parameters were used: reproducibility coefficient (RC), the root-mean-square standard deviation (SDRMS), and the least significant change values. The average RAIU values of the first and second measurements were found as 23.71 ± 16.52% and 23.94 ± 16.64% at 4 h (p >0.05), and 35.33 ± 19.22% and 35.49 ± 19.19% at 24 h (p >0.05), respectively. For thyroid uptake values repeated at 4 and 24 h after radioiodine administration, the mean difference was found to be -0.24 ± 0.62% [limits of agreement (%); -1.44 to 0.97] at 4 h and -0.16 ± 0.44% [limits of agreement (%); -1.02 to 0.70] at 24 h. Confidence intervals were within the limits of agreement (d̅-1.96 SD and d̅+1.96 SD). When the correlation between the repeated RAIU measurements was examined taking the differences and averages into account, there was a negative correlation between 4-h measurement pairs (r=-0.203, p <0.05). On the other hand, a significant correlation was not found between the 24-h measurement pairs (r=0.074, p >0.05). RC, SDRMS, and LSC were calculated as 0.70%, 0.46%, and 1.29% for the 4 h measurements and 0.54%, 0.33%, and 0.91% for the 24-h measurements, respectively. Although there was a minor difference between measurement pairs at 4 and 24 h post-administration, the difference appeared to be insignificant without an apparent effect in the clinical settings.

Multi-parametric Ultrasound Evaluation of Pediatric Thyroid Dyshormonogenesis

The aim of this study was to assess the diagnostic contribution of gray-scale ultrasonography, color Doppler, superb microvascular imaging and shear wave elastography in thyroid dyshormonogenesis (TD). From October 2017 to February 2018, the prospective study included 31 patients (13.6 y; 11–14 y) diagnosed with TD based on thyroid scintigraphy and perchlorate discharge tests and 40 healthy pediatric volunteers (12.8 y; 10–16 y). Median resistive indices (RIs), peak systolic and end-diastolic velocities, vascularity indices (VIs) via superb microvascular imaging and shear wave elastography parameters were evaluated. Median VI values were significantly higher and median RI values were significantly lower in the study group than the control group. No significant difference was found between shear wave elastography parameters of the TD and control group. VI was significantly correlated with median total thyroid gland volumes (p = 0.002, r = 0.28), medication dosage (p = 0.03, r = 0.48) and 2-h radioactive iodine uptake values (p = 0.008, r = 0.57). VI is a clinically significant and novel parameter useful for diagnosing TD.

Correlation of radioiodine doses for 6-hr and 24-hour iodine-131 thyroid uptake values for Graves' hyperthyroidism.

The destruction of thyroid follicular cells by iodine-131 treatment for Graves' hyperthyroidism to a large extent depends on the amount of intrathyroidal activity absorbed (IAA). A thyroid weighing 50 g should receive an iodine-131 therapeutic dosage of between 110 MBq and 350 MBq for the effective treatment of Graves' hyperthyroidism. An IAA received of more than 350 MBq to the thyroid will bestow an unnecessary high iodine-131 therapeutic dosage. The objective of the study was to determine if the IAA would remain between 110 MBq and 350 MBq if the calculated administered activity (CAA) has been used with the highest radioactive iodine uptake (RAIU) value. A retrospective analysis was made of the 6- and 24-hr iodine-131 RAIU results of Graves' hyperthyroid patients (n = 124). Male (n = 18) and female (n = 106) patients from different racial groups and ranging from 15 to 75 years of age were included in the study. Overall, the CAA using the 6-hr RAIU value was higher. The CAA by the 6-hr RAIU values was used with the 24-hr RAIU values to calculate the IAA. 53.3% (n = 66) of the study group would have received IAA higher than 350 MBq when the CAA by the 6-hr RAIU values was used with the 24-hr RAIU values to calculate the IAA. These results suggested that the 24-hr RAIU value was most valuable for the calculation of an administered activity so that IAA of between 110 and 350 MBq can be achieved.

The influence of position deviation on RAIU and the corresponding therapeutic dose calculations in patients with Graves hyperthyroidism

Objective To evaluate the influence of inappropriate position deviation on radioactive iodine uptake (RAIU),effective half-life (Teff) and the corresponding dose variances in patients suffering from Graves hyperthyroidism.Methods RAIU was examined in 20 patients with Graves hyperthyroidism (7 males,13 females,average age (46.60 ±9.55) years) 2,4,6,and 24 h after intake of the radioiodine capsule.A scintillation probe was positioned at the center of the inferior edge of the thyroid cartilage 25 cm away for 2 min,which was defined as the standard manipulation (test 1).Then,the probe was moved either 5 cm backward (test 2) or 5 cm higher (test 3) compared with test 1.Variants of RAIU,Teff as well as dose calculations were acquired by different combinations (CⅠ-Ⅸ) of 4 h and 24 h-RAIU,according to the above 3 manipulations (C Ⅰ-Ⅲ:test 1 for RAIU4 h,test 1,2,3 for RAIU24 h respectively ; C Ⅳ-Ⅵ:test 2 for RAIU4h,test 1,2,3 for RAIU24h respectively; CⅦ-Ⅸ:test 3 for RAIU4h,test 1,2,3 for RAIU24h respectively).Paired t test was used to compare the statistical differences between C H-Ⅸ to C Ⅰ.Results RAIU24 h of test 2 (68.08％ ± 7.88％) and test 3 (62.18％ ± 7.45％) were significantly lower than that of test 1 (78.05％ ± 8.31％ ;t =12.15,14.37,respectively,both P ＜ 0.01).Teffs of C Ⅱ (4.42 ± 0.73) d,CⅢ(3.76 ±0.53) d,CⅤ(5.59 ±0.46) d,CⅥ(4.47 ±0.44) d,CⅧ(5.94 ±0.54) d and CⅨ (5.45 ±0.66) d were significantly different from that of C Ⅰ (5.04 ±0.56) d which was defined as standard (t:3.86-13.64,all P ＜0.01).Among the 180 131I dose values calculated by different Teff and RAIU values induced from C Ⅰ-Ⅸ combinations,74.4％ (119/160) were over-calculated while 9.4％ (15/160) were under-calculated.Taking one patient as an example,the changes of RAIU24 h (decreased up to 26.0％) and the percentage of Teff deviation(66.9％,ranged from-47.5％ to 19.4％)led to an over-calculated 131 I dosage by as high as 129.8％ compared with CⅠ.Conclusions Incorrect positioning in RAIU detection could result in various false RAIU,Teff and 131I dose calculations.Such deviations could possibly exert an impact on the patients' therapeutic outcomes,thus influencing the efficacy of the iodine therapy.Optimization of RAIU positioning is essential for clinical practice to guarantee radioiodine dose management. Key words: Graves disease; Radiotherapy; Iodine radioisotopes; Radiotherapy dosage; Posture

The predictive role of 24h RAIU with respect to the outcome of low fixed dose radioiodine therapy in patients with diffuse toxic goiter

Radioactive iodine uptake (RAIU) is a test used to differentiate hyperthyroidism from thyroiditis and to calculate the radioiodine dose for treatment of Graves' disease. We aimed to evaluate the predictive role of 24h RAIU with respect to the outcome of radioiodine therapy in patients with diffuse toxic goiter (DTG). Case records of patients with DTG treated with radioactive iodine were reviewed retrospectively. Patients were divided into two groups based on 24h RAIU (normal range: 15% - 35% at 24 h): the first group included patients with 24h RAIU values equal to or less than 50%, while the second group included patients with 24h RAIU values of over 50%. Gland size, duration of disease, treatment with antithyroid drugs (ATD) and its duration were the other factors considered. Success of the first dose of 131I was defined as a euthyroid or hypothyroid status at 12 months post-therapy without the need for additional radioiodine or ATD therapy. Data were analyzed with 95% power and 1% type I error (α=0.01). Six hundred thirty-three (633) consecutive patients with DTG were given a fixed-dose (5mCi) of radioiodine between January 1987 and December 2006. One hundred seventy-five patients (175) had an RAIU ≤50% and 458 patients had an RAIU >50%. First-dose success rate in the former group was 81.7% and in the second group 68.6% (p=0.001). The overall first-dose success was 72%. Multivariate analysis confirmed the significant role of 24h RAIU data to predict a successful outcome. A 24h RAIU value of ≤50% appears to be associated with a significantly better outcome compared to that of a 24h RAIU value of >50% in patients with DTG given as treatment a fixed dose of 185 MBq radioiodine.

Radioiodine 131I Treatment for Large Nodular Goiter: Recombinant Human Thyrotropin Allows the Reduction of Radioiodine 131I Activity to Be Administered in Patients with Low Uptake

(131)I therapy is effective in reducing the volume of large nodular goiters (thyroid volume [TV]), mainly after stimulation with recombinant human thyrotropin (rhTSH). The amount of (131)I to be administered inversely depends on thyroid radioactive iodine uptake (RAIU). In patients with low RAIU, we evaluated the efficacy of (131)I treatment at lower doses with respect to those calculated on the basal RAIU, after rhTSH stimulation. Eighteen consecutive patients (17 women and 1 man, 49-83 years) with large nodular goiter were included in the study. At enrollment, 24th h RAIU, TSH, free thyroxine, free triiodothyronine, thyroglobulin antibodies, thyroid peroxidase antibodies, TSH receptors antibodies, urinary iodine, and TV were measured. RAIU was <40% in 11 patients (lower uptake group [LUG]) and >40% in 7 (higher uptake group [HUG]). RAIU difference in the two groups was significant (p < 0.0001). LUG patients were treated with rhTSH (0.03 mg i.m.) and RAIU was measured again after 24 hours. The administered amount of (131)I was aimed to give the thyroid a dose of 100 Gy, by the formula: (131)I activity = 370 MBq × TV (mL)/RAIU(%), taking into account RAIU value after rhTSH for LUG patients. Patients were re-evaluated 3 and 12 months after therapy. At enrollment, LUG and HUG patients did not differ for TV, free thyroxine, free triiodothyronine, TSH, and urinary iodine. LUG patients were older than HUG patients (p = 0.027). In LUG, the uptake increased after rhTSH (42.8% [36%-47.5%] vs. 30% [23.4%-31.6%], p = 0.0044). The (131)I activity was 1073 MBq (740-1103 MBq) in LUG and 851 MBq (677-918 MBq) in HUG (p = 0.22, NS), vs. 1300 MBq (1077-2150 MBq) in LUG, based on RAIU before rhTSH. At 3 and 12 months after radioiodine, TV was reduced to 74% [59%-84%] and 53% [42%-72%] in LUG and 75% [70%-77%] and 65% [54%-74%] in HUG, respectively. The reduction was significant with respect to the basal, both at 3 and 12 months, but not different between the two groups. One single dose of 0.03 mg of rhTSH increased the thyroid RAIU by 40% in patients with nodular goiter and low basal uptake. This allowed a mean reduction of 36% (26%-42%) in the administered (131)I activity without loss of effectiveness. In patients with low RAIU, rhTSH pre-treatment may optimize (131)I therapy.

Approach to the Patient with Amiodarone-Induced Thyrotoxicosis

Amiodarone, a benzofuranic iodine-rich antiarrhythmic drug, causes thyroid dysfunction in 15-20% of cases. Although amiodarone-induced hypothyroidism poses no particular problem, amiodarone-induced thyrotoxicosis (AIT) is a diagnostic and therapeutic challenge. There are two main forms of AIT: type 1, a form of iodine-induced hyperthyroidism, and type 2, a drug-induced destructive thyroiditis. However, mixed/indefinite forms exist that may be caused by both pathogenic mechanisms. Type 1 AIT usually occurs in abnormal thyroid glands, whereas type 2 AIT develops in apparently normal thyroid glands (or small goiters). Diagnosis of thyrotoxicosis is easy, based on the finding of increased free thyroid hormone concentrations and suppressed TSH levels. Thyroid radioactive iodine (RAI) uptake values are usually very low/suppressed in type 2 AIT, most commonly low or low-normal, but sometimes normal or increased in type 1 AIT despite the iodine load. Color flow Doppler sonography shows absent hypervascularity in type 2 and increased vascularity in type 1 AIT. Mixed/indefinite forms may have features of both AIT types. Thionamides represent the first-line treatment for type 1 AIT, but the iodine-replete gland is not very responsive; potassium perchlorate, by inhibiting thyroid iodine uptake, may increase the response to thionamides. Type 2 AIT is best treated by oral glucocorticoids. The response very much depends on the thyroid volume and the severity of thyrotoxicosis. Mixed/indefinite forms may require a combination of thionamides, potassium perchlorate, and steroids. RAI is usually not feasible in AIT due to low RAI uptake values. Thyroidectomy represents a valid option in cases resistant to medical therapy.

Comparison of four different protocols of I-131 therapy for treating single toxic thyroid nodule

To compare low and high doses as well as fixed and calculated doses of I-131 in treating toxic thyroid adenoma. In a prospective study, patients with hyperthyroidism and a single hot thyroid nodule and 24-h radioactive iodine uptake of more than 25% were randomly treated with one of four protocols: fixed low dose (FLD, 481 MBq), fixed high dose (FHD, 832 MBq), calculated low dose (CLD, 3.33-3.70 MBq/g), and calculated high dose (CHD, 6.66-7.4 MBq/g). The patients were asked to visit the endocrinologist 2 and 6 months after treatment and every 6 months thereafter. Clinical exam and laboratory tests were done in all patients during each follow-up. A curative effect was considered as absence of thyroid stimulating hormone suppression (thyroid stimulating hormone>0.3). An analysis of variance test was used for comparison of groups. 97 patients completed the follow-up, eight male, 89 female, with a mean age of 43.3 years (SD=13.4) and mean 24-h radioactive iodine uptake values of 48.07% (SD=14.07). No significant difference was noted in the four groups regarding age, sex ratio, thyroid uptake, and thyroid weight. About 10 months after therapy, cure of hyperthyroidism was higher in CHD group compared with other groups. Hypothyroidism was significantly higher in CHD and FHD groups compared with CLD and FLD groups in all follow-ups. No significant difference was noted in the cure of hyperthyroidism between CLD and FLD groups. Mean radioiodine dose administered in calculated groups was significantly less than fixed dose groups. CHD protocol is preferable in old patients with toxic adenoma whereas CLD is more appropriate in young patients.

Radioactive Iodine in the Treatment of Type-2 Amiodarone-Induced Thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) is usually classified into two types: type 1, in which a high iodine content triggers the autonomous production of thyroid hormone; and type 2, in which destructive thyroiditis causes the release of preformed thyroid hormone. AIT is a difficult management problem that sometimes requires ablative thyroid therapy. The use of radioactive iodine (RAI) therapy in patients with type-1 AIT who had a 24-hour radioactive iodine uptake (RAIU) value of >10% has been previously reported. Despite its documented efficacy at usual doses (10-30 mCi) in patients with type-1 AIT, the efficacy of RAI in those with type-2 AIT has never been questioned, because type-2 patients usually have low RAIU. We thought that high adjusted-dose RAI might be an attractive alternative to thyroid gland ablation in patients with type-2 AIT. Four patients with type-2 AIT who required thyroid ablation were included in the study. These individuals were either poor candidates for surgery or had refused surgery. The size of the thyroid gland in all subjects was within normal limits, and each thyroid was characterized by a homogenous echotexture on ultrasonography, the absence of vascularity on Doppler sonography, a low (<4%) 24-hour RAIU value and the absence of thyroid autoantibodies-all of which are characteristic of type-2 AIT. The patients were initially treated with thionamides and glucocorticoids. All patients except one achieved euthyroidism before RAI therapy. All four patients received one dose of RAI (range 29-80 mCi) and followed up for 12 months. No exacerbation of thyrotoxicosis was noted after RAI therapy. Hypothyroidism (in three patients) or euthyroidism (in one patient) was achieved in first six months. In patients with type-2 AIT, RAI treatment may be the therapy of choice for thyroid gland ablation.

Proportion of type 1 and type 2 amiodarone‐induced thyrotoxicosis has changed over a 27‐year period in Italy

Two main forms of amiodarone-induced thyrotoxicosis (AIT) exist. Type 1 AIT is a form of iodine-induced hyperthyroidism. Its management is complex and includes thionamides, potassium perchlorate and, occasionally, thyroidectomy. Type 2 AIT is a destructive thyroiditis, responds to glucocorticoids, and usually does not require further thyroid treatment once euthyroidism has been restored. To assess retrospectively the prevalence and relative proportion of type 1 and type 2 AIT over a 27-year period at a tertiary referral centre in Italy. Consecutive AIT patients (n = 215) seen at the department of endocrinology of the University of Pisa between 1980 and 2006. Type 1 AIT constituted the most frequent AIT form (60%) during the first years covered by this study. The annual mean number of type 1 AIT patients was 3.6 at the beginning of the study period, and 2.5 during the later years. In contrast, the mean annual number of new cases of type 2 AIT progressively increased from 2.4 to 12.5. Likewise, the proportion of type 2 AIT increased in a significant linear manner (P < 0.0001), currently accounting for 89% of AIT cases. Type 2 AIT patients showed a male preponderance, higher serum FT4/FT3 ratio (P < 0.002), lower 3-h and 24-h thyroidal radioactive iodine uptake values (P < 0.0001), and received a higher cumulative dose of amiodarone (P < 0.0001) than type 1 AIT patients. Over a 27-year period, the epidemiology of AIT changed, as the prevalence of type 2 AIT progressively increased and that of type 1 remained constant. Thus, under most circumstances, endocrinologists nowadays deal with type 2 AIT, which is a destructive thyroiditis, generally treated successfully with glucocorticoids. Although no additional treatment is usually required after the destructive process subsides, periodic assessment of thyroid function is warranted, because of the occurrence of hypothyroidism (up to 17%) during long-term follow-up of these patients.

Effect of Various Doses of Recombinant Human Thyrotropin on the Thyroid Radioactive Iodine Uptake and Serum Levels of Thyroid Hormones and Thyroglobulin in Normal Subjects

Recombinant human TSH (rhTSH), usually given as 0.9-mg doses im on 2 successive days, increases serum thyroglobulin (Tg) and radioactive iodine uptake (RAIU) in residual thyroid tissue in patients with thyroid cancer. We previously reported that a single, relatively low dose of rhTSH (0.1 mg im) is a potent stimulator of T(4), T(3), and Tg secretion in normal subjects. The present study describes the effects of higher doses of rhTSH on thyroid hormone and Tg secretion. Six normal subjects for each dose group, having no evidence of thyroid disease, received either 0.3 or 0.9 mg rhTSH by im injection. Serum TSH, T(4), T(3), and Tg concentrations were measured at 2, 4, and 8 h and 1, 2, 3, 4, and 7 days after rhTSH administration. The peak serum TSH concentrations were 82 +/- 18 and 277 +/- 89 mU/L, respectively, for the 0.3- and 0.9-mg doses of rhTSH. Serum T(4), T(3), and Tg concentrations increased significantly in subjects receiving 0.3 and 0.9 mg rhTSH, with significant increases in T(4) and T(3) being observed before significant increases in serum TG: Peak concentrations of serum T(4), T(3), and Tg, after 0.3 mg rhTSH administration, were 100 +/- 19, 131 +/- 14, and 1035 +/- 724% above individual baselines, respectively. Similarly, peak concentrations of serum T(4), T(3), and Tg, after 0.9 mg rhTSH administration, were 102 +/- 16, 134 +/- 7, and 1890 +/- 768% above individual baselines, respectively. These data, compared with previously reported data for the responses to 0.1 mg rhTSH, indicated that 0.1, 0.3, and 0.9 mg rhTSH had similar quantitative stimulatory effects on thyroid hormone and Tg secretion, except that the T(4) response was greater in groups receiving 0.3 and 0.9 mg rhTSH than in the group receiving 0.1 mg rhTSH. We also studied the effect of rhTSH on the thyroid RAIU in the group that received 0.9 mg rhTSH. The 6- and 24-h RAIU values were significantly higher after rhTSH (pre-rhTSH, 6-h value = 12.5 +/- 1.8%; 24 h value = 23 +/- 2.7%; post-rhTSH, 6 h value = 27 +/- 4.8%; 24-h value = 41 +/- 4.2%). The stimulating effects of 0.9 mg rhTSH on the 6- and 24-h RAIUs were similar. rhTSH is a potent stimulator of T(4), T(3), and Tg secretion and the RAIU in normal subjects. Single doses greater than 0.1--0.3 mg do not seem to further enhance thyroid hormone or Tg secretion.

Accuracy Considerations When Using Early (Four- or Six-Hour) Radioactive Iodine Uptake to Predict Twenty-Four-Hour Values for Radioactive Iodine Dosage in the Treatment of Graves' Disease

Although literature has offered methods to predict 24-hour radioactive iodine uptake values from early (4- to 6-hour) measurements, the resultant dosage errors have not been examined. Potential errors include underdosage, overdosage, and a failure to recognize rapid turnover patients (early-to-late uptake ratios > or = 1) who are at high risk for treatment failure and full-body radiation exposure. We developed and tested a novel method for minimizing error involved in using a single early uptake measurement to derive late uptake. From a retrospective analysis of 203 Graves' disease patients, receiver operating characteristic (ROC) curve analysis enabled us to identify patients likely to experience rapid turnover and therefore should receive 24-hour studies. Twenty-four-hour uptake measurements are necessary with 77% or more 4-hour uptake values and 80% or more 6-hour values. After eliminating these patients, we developed linear regression equations to predict the 24-hour uptake from 4-hour (n = 61) and 6-hour (n = 22) rule groups, testing their efficacy on separate 4-hour (n = 61) and 6-hour (n = 21) patient groups. We also used our test population to measure error in four early-to-late uptake conversion formulas presented in the literature. Error involved in these predictions ranged from a 10.6% overestimate for 4-hour calculations to a 5.9% underestimate for 6-hour calculations. When applied to two dosage formulas incorporating gland size, absorbed dose, and 24-hour uptake, average dosage error was 7%. In comparison to the other sources of error radioactive iodine (131I) dosimetry, potential error in predicting 24-hour uptake from 4- or 6-hour uptake values is low.

The change in 123I-uptake between 3- and 24-hours is useful in predicting early response to methimazole in patients with Graves' disease.

Some patients with Graves' disease respond well to anti-thyroid drug treatment but others do not. Factors determining the patient's responsiveness to the medical treatment are unclear, but the intrathyroidal iodine pool is believed one of the important factors. In this study, we found that delta radioactive iodine uptake (RAIU) (RAIU at 24 h-RAIU at 3 h) is useful in predicting early response to treatment with methimazole (MMI). Among 32 patients with Graves' disease, who were given 30 mg MMI as an initial dose, 11 patients responded quickly to MMI-treatment. Within one month, serum free T4 levels decreased to below the normal range in 6 patients (< 10.3 pmol/L) or decreased from beyond the highest level of the assay (> 125 pmol/L) to the normal range in 5 patients. When these rapid responders (group A) were compared with the remaining 21 patients who showed a more gradual response to MMI-treatment (group B), a different pattern of 123I-thyroid uptake was noted. RAIU at 3 h was significantly higher in group A than in group B, while RAIU at 24 h was similar in the two groups. As a result, rapid responders had a significantly lower delta RAIU value than gradual responders (-0.7 +/- 8.4% in group A, 14.2 +/- 8.2 in group B, P < 0.01). No significant difference was found between the two groups in various pre-treatment parameters such as severity and duration of thyrotoxicosis, the titer of TSH receptor antibodies (TRAb), frequency of positive antithyroglobulin antibodies (TGHA), urinary excretion of iodine and thyroid volume. The incidence of positive antithyroid microsomal antibodies (MCHA) was higher in group A than in group B, and thyroid ultrasonography showed a tendency to low echogenicity in group A. delta RAIU was negatively correlated with the reduction in the serum free T4 level during the first two weeks after MMI-treatment was initiated (r = -0.60, P < 0.01). Moreover, delta RAIU correlated positively with the biological half-life of the intrathyroidal iodine, calculated in a different series of 24 patients with Graves' disease who received radioisotope treatment (r = 0.54, P < 0.01). The low delta RAIU value is considered to reflect the rapid turnover of the intrathyroidal iodine, and may be related to the small intrathyroidal iodine pool. delta RAIU is useful in predicting early responsiveness of patients with Graves' disease to MMI-treatment.

Reevaluation of the thyroidal radioactive iodine uptake test, with special reference to reversible primary hypothyroidism with elevated thyroid radioiodine uptake.

The clinical significance of the thyroidal radioactive iodine uptake (RAIU) test was reevaluated in patients with various thyroid disorders. Compared with 262 normal subjects or 194 patients with euthyroid diffuse goiter with normal serum TSH levels, RAIU values were significantly higher in 100 patients with latent primary hypothyroidism (serum TSH, 5-40 mU/L). In 126 patients with overt primary hypothyroidism (serum TSH, greater than 40 mU/L), RAIU values were either extremely high (49 patients with reversible hypothyroidism and 10 patients with postpartum hypothyroidism) or low (67 patients with irreversible hypothyroidism). The increase in RAIU values in latent, or reversible overt hypothyroidism was TSH dependent, and there was a good correlation between RAIU values and serum TSH levels (r = 0.6203; P less than 0.001). In overt primary hypothyroidism, spontaneous recovery of thyroid function during iodide restriction alone occurred in 52 of 53 patients with RAIU values above 35%, in only 7 of 23 patients with RAIU values between 10-35%, and in none of 50 patients with RAIU below 10%. Thus, recovery was predicted by high RAIU values (P less than 0.001; prediction rate, 91.4%). Goiter was found in about 80% of the patients with reversible hypothyroidism, compared with only 34% of the patients with irreversible hypothyroidism. Recovery of thyroid function during iodide restriction also occurred in 71% of the patients with latent hypothyroidism. However, RAIU measurements did not predict the prognosis of patients with latent hypothyroidism. We conclude that iodine-induced reversible hypothyroidism is common in our patient population, and RAIU measurements may be helpful in determining the prognosis of patients with overt primary hypothyroidism.

Thyroid Amyloidosis With Recurrent Subacute Thyroiditis-Like Syndrome

We studied 2 men with a subacute thyroiditis-like syndrome (STLS) associated with systemic amyloidosis. Both had very tender, diffuse, firm goiters, low thyroidal radioactive iodine uptake values, and increased erythrocyte sedimentation rates. Glucocorticoid therapy resulted in dramatic improvement. Compared to 18 patients with subacute thyroiditis, these 2 men had 1) persistence of goiter even in remission, 2) repeated exacerbation of STLS, 3) pain always localized in the same site, and 4) gastrointestinal, renal, and cardiac abnormalities. Histological examination of the patients' thyroid glands revealed amyloid deposition and no evidence of subacute thyroiditis. In addition, 1 man had low T3 thyrotoxicosis with an elevated rT3/T3 ratio, suggesting impaired peripheral conversion of T4 to T3, and immunological and histological evidence of Hashimoto's thyroiditis. These findings suggest that thyroid amyloidosis may be associated with STLS. When patients with clinical features of subacute thyroiditis have an unusual course, the possibility of thyroid amyloidosis should be considered.

Graves' disease in pregnancy years after hypothyroidism with recurrent passive-transfer neonatal Graves' disease in offspring: Therapeutic considerations

Symptoms and signs of severe hypothyroldism developed in a young woman at age 15. These symptoms progressed for a year; at age 16, she was found to have a firm goiter, thyroid autoantibodies, very low serum thyroxine and high thyrotropin values, indicating autoimmune thyroiditis with hypothyroidism. She received l-thyroxine, 0.20 mg per day, and was well until age 24 when she became pregnant. In the first trimester, manifestations indicative of hyperthyroidism developed; these were only ultimately recognized immediately after delivery of a 32-week still-born goitrous baby. Despite the discontinuation of thyroxine therapy, the hyperthyroidism persisted and was confirmed as Graves' disease by elevated thyroxine, triiodothyronine, and radioactive iodine uptake values, a diffuse scanning result, and the presence of thyroid-stimulating antibody. The patient was treated with propylthiouracil and became pregnant while receiving that regimen. Later, several months after delivery, the patient was treated with radioactive iodine, ultimately became hypothyroid, and has been treated ever since with thyroxine. She became pregnant again and, because of the continuing high titers of thyroid-stimulating antibody, received propylthiouracil, 100 mg daily, commencing in the third trimester of pregnancy, to avoid probable fetal hyperthyroidism due to the transplacental transfer of thyroid-stimulating antibody. In each of the last two pregnancies, when the infants were born, they seemed normal (because of the transplacental effect of propylthiouracil), but passive-transfer neonatal hyperthyroidism developed in each within 10 days after delivery, ultimately requiring treatment by conventional means. This case illustrates the following points: (1) Hyperthyroidism occasionally develops years after hypothyroldism. (2) In young women, high titers of thyroid-stimulating antibody may produce fetal and neonatal passive-transfer hyperthyroidism even at a time when the mother herself is no longer hyperthyroid; transplacental treatment of the fetus by maternal propylthiouracil ingestion may thus be necessary during the last trimester, but only when there is a high degree of probability that the fetus is at risk. (3) Because the infants had been protected in utero by the placental transfer of propylthiouracil, neonatal hyperthyroidism did not develop until several days after delivery. However, the possible severe effects of fetal hyperthyroidism in utero may well have been avoided by such therapy.

Twelve-Year Experience of Radioactive Iodine Uptake in Hyperthyroid Patients

To the Editor.— Recent communications inThe Journal, an article by Wong and Schultz (238:1741, 1977) and a letter by Sostre (239:1035, 1978), have summarized data suggesting that the radioactive iodine uptake (RAIU) in normal persons declined during the 20 years from 1957 to 1977. Hooper and Caplan (238:411, 1977) indicate that increased dietary iodine content may be the cause of decreasing RAIU values in hyperthyroid patients as well as in normal persons. They found a notable change in hyperthyroid patients with toxic nodular goiter. However, they did not find an appreciable change in the RAIU values for patients with Graves' disease between 1970 and 1976. Between 1965 and 1977 we treated 466 patients for hyperthyroidism using radioactive iodine. During these years we found that the 24-hour RAIU values for hyperthyroid patients remained essentially unchanged, between 45% and 55% (Figure), within the usually accepted hyperthyroid range. Of these 466 patients,

Changing Values for the Normal Thyroid Radioactive Iodine Uptake Test

The normal range for thyroid radioactive iodine (RAI) uptake values in the Minneapolis area has shifted twice in the past 20 years. The mean 24-hour thyroid RAI uptake value in 29 normal subjects was 20.5% +/- 6.1% (SD) in 1975, whereas only four years previously it was found to be 11.5% +/- 4.4% (SD) in 51 normal subjects. In a previously published study, the mean thyroid RAI uptake value in normal subjects in this area was 25% +/- 8% (SD) in 1957. The iodine content of commercially baked white bread currently available in this area was found to average only 26 microgram per single slice of bread; the change in the mean 24-hour thyroid RAI uptake value that we observed between 1971 and 1975 is most likely due to a marked reduction in this source of dietary iodine.

Application of the radioiodine uptake to the clinical evaluation of thyroid disease

The radioactive iodine uptake (RAIU) merits a position of prominence in thyroid function testing. With reasonable care function testing. With reasonable care technical errors virtually can be eliminated. The routine use of precalibrated capsules (which should be counted prior to administration), and a routine precount of all patients are particularly emphasized. The availability of simple and reliable confirmatory TSH and T3 suppression tests augments the intrinsic value of the RAIU. A single RAIU value obtained any time between 15 and 30 hr after administration of the tracer usually provides all the information needed. The necessity for routine short-interval values has been overemphasized. “Normal” ranges for the RAIU should be deemphasized since almost any value is compatible with almost any state of thyroid function. The T3 suppression test is helpful for evaluating patients with suspected hyperthyroidism and marginally high values for RAIU and other tests of thyroid function. Euthyroid patients with Graves' disease in evolution, or nodular goiter, may also fail to suppress on T3. The TSH test is of value in the differential diagnosis of primary and secondary hypothyroidism. However, this test is useful more often in the evaluation of patients receiving thyroid hormone for dubious indications, or to detect impaired functional reserve capacity. RAIU values parallel thyroidal clearance of iodide. Although iodide clearance usually correlates with hormonal secretion there are exceptions, resulting either from drug ingestion or abnormal thyroid function. Correlation of RAIU values with the clinical picture is essential for proper interpretation.

T3 thyrotoxicosis. Thyrotoxicosis due to elevated serum triiodothyronine levels.

Thyrotoxicosis may be caused by elevated serum triiodothyronine (T3) in the presence of normal thyroxine (T4) concentration. Of a series of 26 selected cases, 12 have been observed in patients with toxic nodular goiter, most typically with a solitary hyperfunctioning nodule, but also with multinodular goiters. The disorder has also been observed in seven patients with classical toxic diffuse goiter (Graves' disease) including two patients with typical infiltrative ophthalmopathy. The diagnosis of T3 thyrotoxicosis should be suspected when there are clinics and laboratory evidences of hypermetabolism in the presence of normal serum T4 and the absence of thyroxine-binding globulin (TBG) abnormalities. Until T3 measurement becomes more readily available, it is advisable to employ screening with the T3 suppression test, regardless of the initial 24-hour thyroidal radioactive iodine uptake value.