Thyroid suppression and stimulation testing: The place of scanning in the evaluation of nodular thyroid disease

In the past, T3 suppression testing was often required to confirm the presence of autonomous thyroid function in patients with borderline clinical and laboratory findings suggestive of hyperthyroidism or in euthyroid patients with the stigmata of Graves' disease. Similarly, TSH stimulation testing was used to document the presence of "low thyroid reserve" in patients with borderline clinical and laboratory findings suggestive of hypothyroidism. The current availability of radioimmunoassays for triiodothyronine (T3) and thyrotorpin (TSH) plus the ability to evalate pituitary responsiveness by performing a TRH stimulation test permits a definitive diagnosis to be made in the majority of borderline situations without recourse to the more cumbersome suppression and stimulation tests. Suppression and stimulation thyroid scanning retain a unique position in the evaluation of localized areas in increased uptake of radionuclide (hot nodules), especially in patients who are euthyroid. Proof that such nodules are autonomously functioning thyroid adenomas (AFTN) greatly decreases the possibility that they represent malignant thyroid tumors. Suppression and stimulation scanning have a more limited role in the evaluation of patients with hyperthyroidism arising in a multinodular goiter, where TSH stimulation scanning may help to differentiate between toxic multinodular goiter and Graves' disease arising in a preexisting goiter.     

The role of 99mTc pertechnetate uptake in the evaluation of thyroid function

To investigate the usefulness of the 20 min 99mTc-pertechnetate uptake test, the records of 246 consecutive patients were reviewed. Of these, 192 patients (151 females, 41 males; 10 weeks to 78 years) had at least one year clinical follow-up or a confirmed diagnosis by biopsy or surgery and were included in our study. In these patients, the 99mTc pertechnetate uptake and hormonal values (T3 resin uptake, T4 RIA, T-index) were obtained. These results were then compared to the clinical diagnosis at the time of the uptake and one year later. All patients received an i.v. injection of 5 mCi of 99mTc pertechnetate. Imaging was performed using a pinhole collimator and a scintillation camera interfaced to a computer. Regions of interest for the thyroid and the background were used to calculate the 20 min 99mTc pertechnetate uptake as a percentage of the injected dose. 99mTc uptake and hormonal values were confirmatory in 158 patients (82.3%): 138 were euthyroid, 18 were hyperthyroid and 2 were hypothyroid. In 29 other patients (15.1%) the pertechnetate uptake provided useful additional information and helped to identify Hashimoto's thyroiditis (8 patients); thyroid suppression by exogenous iodide, steroids or T4 (7 patients); overtreated hyperthyroidism (1 patient); persistent hyperthyroidism (5 patients); different stages of Grave's disease (4 patients); and toxic nodular goiter (4 patients). The 99mTc uptake was misleading in 5 euthyroid patients (2.6%). We have found the 99mTc pertechnetate uptake a useful adjunct to measurement of hormonal levels in patients with suspected thyroid disease.     

Radioiodine treatment of hyperthyroidism using a simplified dosimetric approach. Clinical results

PURPOSE: To evaluate the clinical effectiveness of a simplified dosimetric approach to the iodine-131 treatment of hyperthyroidism due to Graves' disease or uninodular and multinodular toxic goiter. MATERIAL AND METHODS: We enrolled 189 patients with biochemically confirmed hyperthyroidism and performed thyroid ultrasonography and scintigraphy obtaining the diagnosis of Graves' disease in 43 patients, uninodular toxic goiter in 57 patients and multinodular toxic goiter in 89 patients. In 28 patients we found cold thyroid nodules and performed fine-needle aspiration with negative cytology for thyroid malignancy in all cases. Antithyroid drugs were stopped 5 days till radioiodine administration and, if necessary, restored 15 days after the treatment. Radioiodine uptake test was performed in all patients and therapeutic activity calculated to obtain a minimal activity of 185 MBq in the thyroid 24 hours after administration. The minimal activity was adjusted based on clinical, biochemical and imaging data to obtain a maximal activity of 370 MBq after 24 hours. RESULTS: Biochemical and clinical tests were scheduled at 3 and 12 months posttreatment and thyroxine treatment was started when hypothyroidism occurred. In Graves' disease patients a mean activity of 370 MBq (distribution 259-555 MBq) was administered. Three months after treatment and at least 15 days after methimazole discontinuation 32 of 43 (74%) patients were hypothyroid, 5 of 43 (11%) euthyroid and 6 of 43 (15%) hyperthyroid. Three of the latter were immediately submitted to a new radioiodine administration while 32 hypothyroid patients received thyroxine treatment. One year after the radioiodine treatment no patient had hyperthyroidism; 38 of 43 (89%) were on a replacement treatment while 5 (11%) remained euthyroid. In uni- and multinodular toxic goiter a mean activity of 444 MBq (distribution 259-555 MBq) was administered. Three months posttreatment 134 of 146 (92%) patients were euthyroid and 12 of 146 (8%) patients hyperthyroid. Two patients were immediately submitted to a new radioiodine administration. One year posttreatment 142 of 146 (97%) patients were euthyroid while only 4 of 146 (3%) patients showed TSH levels above the normal range. Only 2 of them required thyroxine treatment. CONCLUSIONS: The simplified dosimetric method illustrated in our paper is very effective in clinical practice because it permits to avoid resorting to sophisticated but also imprecise quantitative methods. Hypothyroidism should not be considered as a major collateral effect of radioiodine treatment, particularly in Graves' disease. In fact, the pathogenesis of the disease requires an ablative treatment with both surgery and radioidine treatment and the control of hyperthyroidism and the prevention of relapse are the major clinical targets. Vice versa, hypothyroidism was very uncommon in uni- and multinodular toxic goiter when our dosimetric approach was applied.     

Discriminant factors affecting early outcome of radioiodine treatment for Graves' disease

Pretreatment clinical, biochemical, iodine-131 (131I) scan and tracer-kinetic parameters were studied in 827 Chinese patients with Graves' disease treated with radioactive iodine. One year after 131I therapy, 56.7% were euthyroid, 33.9% were still thyrotoxic and 9.4% were hypothyroid. Discriminant analysis of all pretreatment variables identified thyroid mass, presenting free thyroxine index and 4 h 131I uptake as the three variables most helpful in discriminating the early outcome group of 131I therapy. The findings suggest that patients with large goitres and severe disease may require higher doses of 131I for treatment of Graves' disease.     

Clinical experience with sensitive thyrotropin measurements: diagnostic and therapeutic implications

A two-site immunoradiometric assay for serum thyrotropin (TSH) was modified to improve the analytical sensitivity. The sensitivity achieved (detection limit, approximately 0.1 microU/ml; lower limit of quantitative measurement, approximately 0.4 microU/ml) was comparable to that of the best competitive binding research assays, yet this assay can be performed routinely. Serum TSH was 1.82 +/- 0.69 (mean +/- s.d.) (range 0.4-3.4 microU/ml) in healthy individuals and 1.83 +/- 0.90 microU/ml (range 0.7-3.7 microU/ml) in patients with nonthyroidal disorders. By contrast, 97% of clinically hyperthyroid patients (Graves' disease, toxic nodular goiter) with high serum free T4 (FT4) and T3 had suppressed serum TSH values, i.e., less than 0.3 microU/ml. Among patients with euthyroid Graves' ophthalmopathy or nontoxic goiter those clinically suspected of mild hyperthyroidism had TSH values less than 0.3 microU/ml, while those judged euthyroid had normal values. A large proportion of thyroid patients on antithyroid drugs (poorly to well-controlled) had suppressed TSH. Of Graves' patients in remission (normal FT4 and T3), 75% had normal TSH, but individual levels changed significantly over time, suggesting that a progressive decline in TSH may be useful in predicting recurrences. In hypothyroid patients taking L-T4, serum TSH was subnormal in patients with elevated FT4, but TSH was also low in six patients clinically suspected to be thyrotoxic despite normal FT4 and T3 and in 32% of asymptomatic patients with normal thyroid hormone levels. Conversely, 23% of thyroid cancer patients who had undergone thyroidectomy were taking insufficient L-T4 to completely suppress TSH secretion. In 25 individuals who underwent thyrotropin releasing hormone (TRH) stimulation tests, the baseline serum TSH value correlated well with the peak serum TSH value post-TRH (r = 0.85). We conclude that sensitive TSH measurements could establish or confirm the diagnosis of hyperthyroidism in equivocal cases, replace most TRH-stimulation tests and be of value in optimizing L-T4 suppression therapy for thyroid cancer patients post-thyroidectomy.     

What influences early hypothyroidism after radioiodine treatment for Graves' hyperthyroidism?

OBJECTIVE: The objective of this study was to evaluate the factors influencing the occurrence of early hypothyroidism after radioiodine treatment of Graves' hyperthyroidism. MATERIAL AND METHODS: Of 147 patients with Graves' disease (GD) treated with radioactive I-131 (RAI) in our thyroid clinic between July 2003 and December 2004, 84 were followed at 2 and 4 to 5 months after treatment. The age range was 12 to 75 years and the dosage range in these patients was 7.4 to 29.9 mCi. Twenty-four were males and 60 were females. Factors possibly contributing to post-RAI hypothyroidism are: dosage of I-131, age, gender, size of the gland, initial serum free T4, free T3, thyroid-stimulating hormone (TSH) levels, pretreatment with antithyroid drugs, radioactive iodine uptake, and duration of disease. RESULTS: All patients had low TSH, elevated FT4, and elevated radioactive iodine uptake (RAIU) at 4 and/or 24 hours. Of the 84 patients followed, 46% of the males and 62% of the females became hypothyroid at 4 to 5 months (57% of the total). Twenty-one patients remained hyperthyroid and 14 patients became euthyroid. Multivariate analysis of these 84 patients showed no statistically significant single contributing factor for the development of early hypothyroidism. CONCLUSION: The early onset of hypothyroidism after RAI in GD is very common (57%) and unpredictable. Thus, after RAI treatment, all patients must be closely monitored for the development of this disorder.     

Clinical role of TSH binding inhibiting antibodies (TBIAb) assay

Anti TSH-receptor antibodies (TBIAb) were measured by a radioreceptor assay in 277 patients with Graves' disease, 101 with autoimmune thyroiditis, 43 with autonomous adenoma, 15 with subacute thyroiditis, 15 with euthyroid ophthalmopathy, 155 with euthyroid multinodular goiter, 10 with amiodarone-induced hyperthyroidism and 2 with tumoral TSH hypersecretion. TBIAb were present at high titers in 74% of patients with untreated or relapsed Graves' disease and, at lower titers, in only 10% of patients who had recovered from Graves' disease, in 8% of patients with autoimmune thyroiditis and in 4% of patients with euthyroid goiter. TBIAb were absent in normal subjects as well as in the other groups studied. These findings suggest that TBIAb represent a specific marker of Graves' disease, particularly of the untreated form. Their presence in non Graves' patients may be considered expression of inactive or inhibiting antibodies.     

Radioiodine therapy for Graves' disease: multivariate analysis of pretreatment parameters and early outcome

Twenty-one clinical, biochemical, scan and tracer-kinetic parameters were documented in 76 patients with Graves' disease who had received a standard 5-mCi therapy dose of 131I. Linear discriminant analysis was then undertaken to determine what combination of variables best predicted outcome. One year after therapy, 40 patients were euthyroid, 11 were hypothyroid, and 25 were still thyrotoxic. Linear discriminate functions combining 24-h 131I uptake, the presence or absence of thyroid eye signs and a computer-derived measurement of thyroid cell mass best discriminated the three outcome groups. The proportion of patients correctly reclassified according to outcome using these functions was, however, only just over 50%. It is concluded that no single or combination of pretreatment variables predicts early outcome with sufficient confidence to justify a rigorously 'scientific' approach to the administration of 131I therapy for Graves' disease.     

Long-term carbimazole intake does not affect success rate of radioactive 131Iodine in treatment of Graves' hyperthyroidism

OBJECTIVE: The aim of this study is to assess the effect of long-term antithyroid drug intake on the success rate of iodine-131 (131I) treatment of Graves' hyperthyroidism, and to explore other clinical/laboratory factors that may predict/affect the treatment outcome. MATERIALS AND METHODS: Fifty-eight patients with Graves' disease were referred for radioactive iodine therapy after failure of medical treatment, which was given for at least 6 months. Antithyroid drug (carbimazole) was stopped for at least 2 days before administration of a fixed dose of 370 MBq. Treatment outcome was determined at the end of 1-year follow-up after iodine administration. Treatment success was reported if the thyroid hormonal profile indicated euthyroid or hypothyroid state. RESULTS: One year after 131I administration, 19% of our patients were still hyperthyroid (treatment failure), 15.5% became euthyroid and 65.5% were hypothyroid (treatment success, 81%). No statistically significant correlation was found between treatment outcome and patient's age at the time of I administration (P=0.20); duration of medical treatment before 131I administration (P=0.22) and duration of stoppage of medical treatment before 131I intake (P=0.15). In contrast, there was significant association between treatment outcome and pretreatment Tc99m-thyroid uptake (P=0.0001), thyroid size (P=0.001) and TSH level (P=0.04). Using receiver operator characteristic curve analysis, we generated a cut-off value for thyroid uptake (18%) and thyroid weight (70 g) to predict response to 370 MBq of 131I. The 18% thyroid uptake cut-off value predicted treatment outcome with 93.6% sensitivity, 100% specificity and 94.8% accuracy, whereas the 70 g thyroid weight predicted treatment outcome with sensitivity, specificity and accuracy of 80.9, 72.7 and 79.3%, respectively. CONCLUSION: Long-term carbimazole treatment will not increase the failure rate of 131I treatment in patients with Graves' disease if the drug was discontinued for at least 2 days before iodine administration. A fixed dose of 370 MBq is efficient in patients with Tc99m-pertechnetate thyroid uptake less than 18% and gland weight less than 70 g. Patients with larger goitres and/or higher thyroid uptake level will probably need a higher dose of radioactive iodine.     

High pre-therapy [99mTc]pertechnetate thyroid uptake, thyroid size and thyrostatic drugs: predictive factors of failure in [131I]iodide therapy in Graves' disease

BACKGROUND AND OBJECTIVE: Several factors may interfere with the success rate of radioiodine therapy (RIT) in Graves' disease. Our aim was to evaluate, retrospectively, some of these factors in the outcome of RIT. METHODS: Patient gender, age at diagnosis, ophthalmopathy, disease duration, thyroid size, drug used as clinical treatment, thionamide withdrawal period during RIT preparation, FT4, TSH and [99mTc]pertechnetate thyroid uptake prior to RIT were studied as potential interference factors for RIT success. Eighty-two Graves' disease patients were submitted to RIT after thionamide treatment failure. Prior to RIT, 67 patients were receiving methimazole and 15 propylthiouracil. Thirty-three patients received thionamides during RIT; in 49 patients the medication was withdrawn for 2-30 days. [99mTc]pertechnetate thyroid uptake was determined before RIT. Fixed doses of 370 MBq of [131I]iodide were administered to all patients. RESULTS: Eleven patients became euthyroid; 40 became hypothyroid and 31 remained hyperthyroid. There was no association between outcome and age at diagnosis, gender, ophthalmopathy, pre-RIT FT4, TSH, antithyroid antibodies or thyrostatic drug. Multiple logistic regression showed higher probability of treatment success in patients with thyroid mass <53 g (odds ratio (OR)=8.9), with pre-RIT thyroid uptake <12.5% (OR=4.1) and in patients who withdrew thionamide before RIT (OR=4.9). CONCLUSIONS: Fixed doses of 370 MBq of radioiodine seem to be practical and effective for treating Graves' disease patients with [99mTc]pertechnetate uptake <12.5% and thyroid mass <53 g. This treatment is clearly not recommended for patients with large goitre. In contrast to what could be expected, patients with a high pre-RIT thyroid uptake presented a higher rate of RIT failure.     

Evaluation of the 2nd generation radio-receptional assay for anti-TSH receptor antibodies (TRAb) in autoimmune thyroid diseases. Comparison with 1st generation and anti-thyroperoxidase antibodies (AbTPO).

BACKGROUND: The detection of autoantibodies to the TSH-receptor (TRAb) by radio-receptor assays (RRA) is widely requested in clinical practice for the diagnostic workup of Graves' disease and its differentiation from diffuse thyroid autonomy. Additionally, TRAb measurement can be useful during antithyroid drug treatment of Graves' disease to evaluate the risk of relapse after therapy discontinuation. Nevertheless, some patients affected by Graves' disease are TRAb-negative when 1st generation assay is used. METHODS: In this study we evaluated the diagnostic performance of a newly developed 2nd generation TRAb assay (TRAK human DYNOtest, BRAHMS Diagnostica GmbH, Berlin, Germany) in 74 untreated patients affected by Graves' disease, 53 untreated patients affected by Hashimoto's thyroiditis and 88 patients affected by euthyroid nodular goiter. We also compared the new TRAb assay with the 1st generation test (TRAK Assay, BRAHMS Diagnostica GmbH, Berlin, Germany) and anti-thyroperoxidase assay (AbTPO DYNOtest, BRAHMS Diagnostica GmbH, Berlin). RESULTS: The 2nd generation TRAb assay showed the better diagnostic sensitivity in Graves' disease (97%) with respect to the 1st generation assay (85%) and AbTPO assay (64%). The AbTPO assay was positive in 50 of 53 (94%) patients affected by autoimmune thyroiditis. The 1st and 2nd generation TRAb assays were positive in 4 (7%) and 7 (13%) of 53 patients affected by autoimmune thyroiditis, respectively. No patients affected by nodular goiter showed positive 1st and 2nd generation TRAb assay while AbTPO levels were positive in 8 of 88 patients (specificity 91%). CONCLUSIONS: In conclusion, the 2nd generation TRAb assay is clearly more sensitive than the 1st generation test and should be used in clinical practice to minimize the incidence of TRAb-negative Graves' disease. Long term prospective studies are needed to evaluate the prognostic role of 2nd generation TRAb assay in Graves' disease. The assay of AbTPO is the best marker for autoimmune thyroiditis but is clearly less sensitive than 1st and 2nd generation TRAb assays in Graves' disease. Consequently, AbTPO assay should not be performed in Graves' disease neither alone or in association with TRAb.     

Radioiodine-treatment (RIT) of functional thyroidal autonomy

Since 1942, therapy with radioiodine (RIT) has gained a major role in the treatment of benign thyroid disorders, notably hyperthyroidism caused by Graves' disease or toxic multinodular goitre (thyroid autonomy). In iodine deficient areas thyroid autonomy accounts for 40-50% of all cases with hyperthyroidism. RIT has become a cost-effective first-line procedure in autonomy-patients with latent or overt hyperthyroidism, especially in the absence of a large goitre, after thyroid surgery and in elderly patients with associated conditions who carry a high intra- or perioperative risk. Decisions concerning the definitive treatment of thyroid autonomy should take into account previous episodes of hyperthyroidism, objective parameters of risk stratification in euthyroid patients as well as concomitant diseases and the probability of iodine exposure in the future. In Central Europe the majority of investigators prefer to estimate the therapeutic activity individually by a radioiodine test. TCTUs (global 99m-Tc-pertechnetate thyroid uptake under suppression)-based dose concepts have been proven to be highly effective in the elimination of autonomy and carry a low (< 10%) risk of post-radioiodine-therapeutic hypothyroidism. Radioiodine therapy for autonomy has been found to be both effective and safe and without major early or late side effects. The most frequent complication is hypothyroidism requiring lifelong follow-up.     

An autonomously functioning thyroid carcinoma associated with euthyroid Graves' disease.

A 39-yr-old man with an autonomously functioning thyroid carcinoma is presented. Only 17 similar cases have been reported in the literature. The patient had unilateral Graves' ophthalmopathy. He was euthyroid as reflected by normal TSH concentration, whereas the results of a T3 suppression test established the presence of autonomous thyroid function. A thyroid scan with (123)I revealed a hot nodule corresponding to the location of a papillary carcinoma and remained substantially unchanged after T3 administration. The hyperfunction of the carcinoma itself was clearly confirmed by the intense concentration of (131)I within the tumor on microautoradiograms. While a hot nodule on radioiodine scan is unlikely to be malignant, the possibility of carcinoma should not be overlooked.     

Doppler ultrasonography in predicting relapse of hyperthyroidism in Graves' disease

Purpose:
To determine whether Doppler ultrasonography could be useful in the prediction of relapse of hyperthyroidism in patients with Graves' disease.
Material and Methods:
Forty patients with Graves' disease confirmed by laboratory tests were examined for a number of blood flow parameters in the inferior thyroid artery before and after they were subjected to proper antithyroid drug treatment. Data were retrospectively reviewed and compared with findings for a control group of 16 age-matched subjects.
Results:
Significantly increased blood flow parameters were observed both in patients with active hyperthyroidism before treatment and in euthyroid patients who presented a relapse shortly after withdrawal of proper antithyroid drug treatment versus normal controls. Conversely, no significant differences were observed between patients who remained in stable remission and normal controls.
Conclusion:
Our results support the concept that Doppler ultrasonography evaluation of patients with Graves' disease may contribute to the detection of a relapsing course of hyperthyroidism.     

Iodine-131 uptake and turnover rate vary over short intervals in Graves' disease

From a Dutch questionnaire, it was apparent that nearly all institutions used percentage of radioiodine uptake for calculation of the radioiodine dose in Graves' disease. Although there is a general belief that fluctuations in radioiodine uptake may occur, with few exceptions relatively long intervals were accepted between the uptake measurement and the actual therapy dose. With the aim of optimizing the pretherapeutic work-up, we evaluated the stability of iodine uptake over time in patients with Graves' disease who were referred for 131I therapy. 131I uptake was measured in 300 consecutive patients for the calculation of the required 131I therapy dose; data were complete for 291 patients (97%). After discontinuing thyroid medication for 3 days, standardized thyroid probe measurements were performed 5 and 24 h after ingestion of a capsule containing 0.37 MBq 131I-NaI. Measurements were performed at the time of scintigraphic diagnosis (test 1), as well as immediately before 131I therapy (test 2). The time interval between test 1 and test 2 ranged from 2 to 421 (median 40) days. A relative increase or decrease greater than 10% between tests 1 and 2 occurred in 180 of 291 cases (62%) at 5 h and in 158 of 291 patients (54%) at 24 h. These changes were not related to the interval between the tests or to initial uptake values, thyroid mass, gender or age. Rapid turnover of radioiodine (5 h/24 h uptake ratio > 1) was noted in 17% of the patients during test 1 and in 15% during test 2. Rapid turnover was persistent (present in both tests 1 and 2) in only 9%. We conclude that patients with Graves' disease show considerable changes in 131I uptake over relatively short periods of time, and the turnover rate of 131I in this condition is not constant.     

The role of thyroid scanning in hyperthyroidism

Radionuclide thyroid imaging was performed in 872 consecutive patients with hyperthyroidism. Of these, 84% were found to have diffuse toxic hyperplasia (Graves' disease), while 12% had autonomously functioning nodules (Plummer's disease), 3% had Graves' disease developing in a multinodular gland, and in the remaining 1%, either a clear diagnosis could not be established or the hyperthyroidism was due to thyroiditis or the Jod-Basedow phenomenon. It was found that a thyroid scan seldom provides additional diagnostic information in patients with Graves' disease when a diffuse goitre is present. However, if patients are to be treated with radioiodine (131I), thyroid imaging with tracer quantitation can replace a 24-h 131I uptake measurement, this having the advantages that the patients are required to attend only once, and that the gland size can be measured. In addition, visual confirmation of tracer uptake by the thyroid is obtained and patients with thyroiditis will not receive inappropriate therapy. When single or multiple thyroid nodules are palpated, a thyroid scan is crucial in establishing an accurate diagnosis, as it is not otherwise possible to differentiate between Plummer's disease and Graves' disease developing in a multinodular gland. Indeed, in 20 of our 63 patients (32%) with single autonomously functioning nodules, the initial clinical assessment had been incorrect.     

Three basic patterns of changes in serum thyroid hormone levels in Graves’ disease during the one-year period after radioiodine therapy

The purpose of this study was to clarify the characteristic patterns of the thyroid hormonal changes in Graves' disease during the one-year period after 131I therapy considering that few serial hormonal data during this period are available in the literature. METHODS: The levels of serum T3, T4 and FT4 before and during one year were plotted as a function of time in 70 therapy courses of 58 patients without subsequent antithyroid or steroid therapy. RESULTS: 35 euthyroid, 6 hypothyroid and 29 hyperthyroid states were obtained during one year after therapy. Although individual patients had individual hormonal changing patterns, 3 common basic patterns were observed from baseline to one month (early) and thereafter (late), respectively. The early patterns were a decrease in 54 (77%), a minimum change in 8 (11.5%) and an increase in 8 (11.5%). The late patterns were a stable state after an initial decrease with a bottom followed by an increase (valley pattern) in 47 (67%), a stable state after an initial increase with a peak followed by a decrease with a bottom and a subsequent re-increase (mountain pattern) in 12 (17%) and a late stable state after a gradual slow decrease without an obvious bottom near or till one year (downhill pattern) in 11 (16%). The bottom level and the degree of hormonal recovery from the bottom determined the stable euthyroid, hypothyroid or hyperthyroid state in 49 (86%) of 57 with the valley or mountain pattern. Most of the bottom levels (81%) and transient abnormal changes including transient hypothyroidism (93%, 13/14), peak or hyperthyroidism (85%, 11/13) and euthyroidism (67%, 10/15) appeared within 6 months. The post-therapeutic stable euthyroid, hypothyroid or hyperthyroid state could be judged from the hormonal patterns in 57% (39/68) from 2.5 to 6 months, in 18% (12/68) from 6 to 9 months and in 25% (17/68) thereafter. CONCLUSION: Although the changes in thyroid hormones are not constant in Graves' disease during one year after 131I therapy, there are three basic patterns; valley, mountain and downhill patterns from one month after therapy. The post-therapeutic stable state can be judged by the hormonal level recovered from the bottom in most patients.     

Graves' disease: thyroid function and immunologic activity

Patients with Graves' disease were studied for two years during and after a twelve-month course of treatment. Disease activity was determined by repeated measurements of thyroidal uptake of [99mTc]pertechnetate during tri-iodothyronine administration. These in-vivo measurements of thyroid stimulation were compared with the results of in-vitro assays of Graves, immunoglobulin (TSH binding inhibitory activity--TBIA). There was no correlation between the thyroid uptake and TBIA on diagnosis. Pertechnetate uptake and TBIA both declined during the twelve months of antithyroid therapy. TBIA was detectable in sera from 19 of the 27 patients at diagnosis; in 11 of these 19 patients there was a good correlation (p less than 0.05) throughout the course of their disease between the laboratory assay of the Graves, immunoglobulin and the thyroid uptake. Probability of recurrence can be assessed but sustained remission of Graves' disease after treatment cannot be predicted from either measurement alone or in combination.     

Long-term follow-up study of I-131 therapy for Graves' disease--index associated with late-onset hypothyroidism

We have studied the follow-up of thyroid function in the patients with late-onset hypothyroidism and euthyroidism after I-131 therapy of hyperthyroidism. Thirty three patients who did not need the thyroid treatment until ten years after I-131 therapy were classified as euthyroid group. And eleven patients who needed the thyroid supplement of thyroid hormone for late-onset hypothyroidism were classified as hypothyroid group. Patients in both groups who required only a single dose of I-131 for successful treatment of hyperthyroidism had similar age, gland size, 24 hour I-131 uptake, pretreatment serum T3 uptake level and T4 concentration, and I-131 treatment dose. Subclinical hypothyroidism occurred in 28.6% of euthyroid group and 66.7% of hypothyroid group four months after I-131 therapy. The levels of T3 were recovered to higher than normal range at 6 months in euthyroid group, while the levels of T3 were kept within the normal range in the seventy percent of hypothyroid group. Patients who were still lower in the level of T3 uptake than normal range at 6 months had a higher incidence of late-onset hypothyroidism. Our observation showed no significant difference in the course of follow-up studies after I-131 therapy between the patients with late-onset hypothyroidism and euthyroidism.     

Prediction of remission in Graves' disease treated with long-term carbimazole therapy: Evaluation of technetium-99m thyroid uptake and TSH concentrations as prognostic indicators

Computerized technetium-99m thyroid uptake and thyrotropin (TSH) estimation using a sensitive immunoradiometric assay were performed at presentation and following completion of an 18-month course of antithyroid drug therapy in 45 patients with Graves' disease. All patients had increased^99mTc thyroid uptake and subnormal TSH levels before the start of treatment. Twenty-two patients developed recurrent hyperthyroidism in a 3-year follow-up period. Of these 22 patients with relapse, 20 had had a persistently increased^99mTc thyroid uptake at the end of the course of carbimazole treatment, whereas TSH had remained subnormal in 18 of the 22. All 23 patients who remained in remission until the end of the 3-year follow-up had had normal^99mTc thyroid uptake following completion of antithyroid drug treatment. TSH levels had reverted to normal in 19 cases, but remained subnormal in four cases in this group at the end of treatment. The results suggest a high likelihood of relapse in patients who have persistently increased^99mTc thyroid uptake and subnormal TSH after a full course of carbimazole treatment. Patients whose^99mTc thyroid uptake and TSH levels have reverted to normal are likely to stay in long-term remission. Assessment of^99mTc thyroid uptake and TSH levels following completion of carbimazole therapy for Graves' disease offers useful information regarding long-term prognosis.