Thyroid volume and function after 131I treatment of diffuse non-toxic goitre

OBJECTIVE Traditional treatment modalities of diffuse non-toxic goitre are thyroid hormone suppression or surgery. When treating nodular non-toxic goitre with ¹³¹I treatment a reduction in thyroid volume to about 50% has been observed. In the present study we evaluated the effect of ¹³¹I treatment of diffuse non-toxic goitre. DESIGN Retrospective study of patients treated for a diffuse non-toxic goitre and followed by evaluation of thyroid volume measured by ultrasound. PATIENTS Ten selected patients from our out-patient clinic with diffuse non-toxic goitre. MEASUREMENTS Thyroid volume was measured by ultrasound and thyroid function by serum values of T4, T3, T3 uptake ratio, TSH, TSH receptor antibodies and thyroid peroxidase antibodies (anti-TPO). Measurements were performed before and 1, 3, 6 and 12 months (and 18 months (n=7), thyroid volume measured in six patients)) after ¹³¹I treatment. RESULTS Thyroid volume declined in all patients from median 41 (range 27–160) ml to 20 (range 9–108) ml over 1 year, a reduction of 47%. One patient developed transient and one persistent hypothyroidism in the follow-up period. Both had elevated anti-TPO levels before treatment (331 and 9185 U/ml) and demonstrated titre increases of 2.5 and 30 times after 3 and 6 months, respectively. Pretreatment values were reached after 1 year. The other eight patients had normal anti-TPO levels and free T4 and T3 indices did not change during follow-up, whereas serum TSH levels demonstrated upward trends within the normal range (P<0.05). TSH receptor antibodies were normal and remained so in all patients. CONCLUSION S¹³¹I treatment of diffuse non-toxic goitre reduces thyroid volume by approximately 50% within 12–18 months. Hypothyroidism, during a limited follow-up period, developed only in patients with positive anti-TPO levels before treatment.     

Radioiodine therapy of benign non-toxic goitre. Potential role of recombinant human TSH

This review provides an update on recombinant human TSH (rh-TSH) augmented radioiodine (¹³¹I) therapy and outlines its potential role in the treatment of symptomatic benign multinodular non-toxic goitre. In some countries, ¹³¹I has been used for three decades to reduce the size of nodular goitres. The feasibility of ¹³¹I therapy depends on an adequate thyroid ¹³¹I uptake. Based on a two-fold increase in thyroid ¹³¹I uptake, superiority studies have convincingly demonstrated that the absorbed thyroid ¹³¹I dose can be increased without increasing the administered ¹³¹I activity, resulting in a 35–56% amplification of goitre reduction at one-year post radioiodine compared to conventional (without rh-TSH) ¹³¹I therapy. Although patient satisfaction is not improved at one-year, this approach facilitates tracheal decompression and is particularly promising in large goitres. The majority of multinodular non-toxic goitre patients may not require amplified goitre reduction. But as an alternative strategy, rh-TSH allows up to 80% reduction of the therapeutic ¹³¹I activity while still achieving goitre reduction comparable to that of conventional ¹³¹I therapy and maintaining high patient satisfaction. The dose-reduction (equality) strategy is attractive in terms of minimizing post-therapeutic restrictions and in reducing the potential risk of radiation-induced malignancy. Adverse effects like temporary thyroid swelling and thyroid hormone excess are to a large extent dose-dependent and generally 0.1 mg rh-TSH or less is well tolerated. Based on these results we conclude that rh-TSH augmented ¹³¹I therapy is a promising new therapeutic principle allowing the tailoring of an optimal ¹³¹I therapy on the individual level.     

Subtle changes in serum thyrotrophin (TSH) and sex-hormone-binding globulin (SHBG) levels during long-term follow-up after radioactive iodine in multinodular non-toxic goitre.

OBJECTIVE: We investigated possible changes in the pituitary-thyroid axis after radioactive iodine (RAI) treatment of multinodular non-toxic goitre. DESIGN: Consecutive patients with multinodular non-toxic goitre, who remained euthyroid after radioactive iodine (RAI) treatment. PATIENTS: Twenty-three women with multinodular non-toxic goitre were followed after treatment with RAI. MEASUREMENTS: Free T4 index (FT4I), FT3I, free T4, SHBG (immunoradiometric assay), and a third-generation TSH assay (chemiluminetric assay) TSH were measured. RESULTS: Three weeks after RAI treatment TSH had decreased and SHBG increased (P < 0.05). Only 2/18 patients actually had suppressed TSH values, while 12/18 had values in between euthyroid and toxic levels. Trend analysis from 1.5 to 24 months after RAI treatment demonstrated a progressive increase in TSH (P < 0.01) and gradual decrease in SHBG (P < 0.02). No changes in FT4I, FT3I, or free T4 were found. CONCLUSION: A third-generation TSH assay gave detailed information about changes in thyroid status when TSH was below normal values. FT4I, FT3I, and free T4 seem to be less sensitive parameters than TSH and SHBG for recording subtle changes in thyroid status after RAI treatment of nodular non-toxic goitre. We demonstrated that changes in the pituitary-thyroid axis continue for a long time after RAI treatment of multinodular non-toxic goitre. These patients should be followed up in order to detect possible late hypothyroidism.     

Diagnostic imaging work up in multi-nodular goiter

Ultrasound, scintigraphy and sonographically guided fine-needle biopsy are the cornerstones in the diagnostic work-up multinodular goitre. Subsequent decisions for adequate treatments should be based on accurate tests to avoid unnecessary intervention. Especially in areas with endemic goitre a preselection of patients for the most effective procedure e.g. surgical or medical treatment is mandatory. Autoimmune hyperthyroidism (Graves' disease), solitary hyperfunctioning thyroid nodules and toxic multinodular goitre (Plummer's disease) constitute a clear indication for radioiodine treatment in many cases. Recently, there is an emerging role for I-131 in the treatment for so called subclinical hyperthyroidism caused by either of three first entities and for patients with non-toxic goitre, in whom surgery is not an option. These patients with large non toxic goitre encompass a group of patients who are euthyroid but may benefit from diminishment of thyroid volume. We review the spectrum of diagnostic tests and provide some recommendations regarding (nuclear medicine) therapy.     

Does radioiodine therapy have an equal effect on substernal and cervical goiter volumes? Evaluation by magnetic resonance imaging.

Most often thyroidectomy is recommended in patients with large goiters. However, high-dose (131)I therapy may be used in case of contraindications to surgery. Large goiters are often partially located in the mediastinum. The aim of this study was to evaluate the impact of (131)I therapy on the cervical and the substernal goiter volume, separately. Fourteen patients (median age, 69 years; range, 52-86 years) with a large multinodular goiter (three hyperthyroid) and with a substernal extension greater than 15 mL were included. T1-weighted magnetic resonance (MR) estimates of the thyroid volume in the cervical and substernal compartments were obtained before and 1 year after high-dose (131)I therapy. The total goiter volumes ranged from 182 to 685 mL. The median substernal volume was 66 mL (fraction of total volume, 17.6%; range, 8.0%-78.9%). One year after treatment, the median substernal goiter volume was reduced by 29.2% (range, -6.1%-59.4%, mean: 26.1% +/- 6.0%), and the cervical goiter volume by 30.3% (range, 6.0%-75.4%, mean, 35.6 +/- 5.6%) compared to baseline values; p = 0.25 for difference in a regional effect. The volume reduction was unrelated to initial substernal goiter size. Likewise, deterioration of the inspiratory capacity did not correlate with the magnitude of the substernal goiter extension. In conclusion, high-dose (131)I therapy seems as effective in reducing the substernal as the cervical goiter volume. However, because the overall effect is modest, this therapy should primarily be considered for the patient with a high surgical risk.     

Appearance of thyroid stimulating antibody and Graves' disease after radioiodine therapy for toxic nodular goitre

A patient with toxic nodular goitre is described in whom radioiodine (¹³¹I) therapy paradoxically induced typical Graves' disease. This patient had a goitre with two autonomously functioning nodules suppressing uptake by the remainder of the gland. Circulating thyroid peroxidase antibody indicated the coexistence of focal lymphocytic thyroiditis. Radioiodine therapy was followed by the development of severe and persistent Graves' hyperthyroidism associated with diffuse ¹³¹I uptake by the gland. A second administration of ¹³¹I produced a further worsening of hyperthyroidism, and the appearance of ophthalmopathy. TSH-receptor antibody and thyroid stimulating antibody were undetectable before ¹³¹I, appeared after the first administration of radioiodine, and showed a further increase after the second dose of ¹³¹I. We suggest that, in a patient genetically susceptible to thyroid autoimmunity, the release of TSH-receptor antigenic components from follicular cells damaged by radioiodine therapy triggered an autoimmune response to the TSH-receptor, thus turning a toxic nodular goitre into Graves' disease.     

Radioiodine therapy for multinodular toxic goiter.

BACKGROUND: Radiolabeled iodine 131 therapy is used for treatment of multinodular toxic goiter, but long-term follow-up studies are lacking. METHODS: A prospective study of 130 consecutive patients (115 women) treated with 131I for multinodular toxic goiter and followed by evaluation of thyroid volume (determined using ultrasound) and thyroid function variables. RESULTS: The patients were observed for a median of 72 months (range, 12-180 months). Sixty-six patients received antithyroid drug pretreatment; 64 did not. Iodine 131 treatment (3.7 MBq/g thyroid tissue corrected to a 100% 24-hour 131I uptake) was given as a single dose in 81 patients, 2 doses in 38, and 3 to 5 doses in 11. One or 2 treatments cured 119 patients (92%), and 68 (52%) became euthyroid within 3 months after 131I treatment. The median 131I dose was 370 MBq (range, 93-1850 MBq). Forty-nine patients needing more than 131I dose had a reduction in median thyroid volume from 56 mL (range, 21-430 mL) to 44 mL (range, 15-108 mL), representing a 24% reduction related to the insufficient 131I dose. In all patients, the initial median thyroid volume of 44 mL (range, 16-430 mL) decreased to 25 mL (range, 8-120 mL) (P<.005), representing a median reduction of 43%, 24 months after the last 131I dose. Hypothyroidism evaluated using life-table analysis developed in 6% of patients who did not receive antithyroid pretreatment and 20% who did (P<.005) after a median of 42 months (range, 3-60 months), the total hypothyroidism frequency being 14% within 5 years of treatment. CONCLUSIONS: Ninety-two percent of patients with multinodular toxic goiter were cured with 1 or 2 treatments. The thyroid volume was reduced by 43%, with few side effects. Iodine 131 should be the choice of treatment in patients with multinodular toxic goiter.     

EFFECTS OF RADIOIODINE ON THYROTROPHIN BINDING INHIBITING IMMUNOGLOBULINS IN GRAVES''DISEASE

We have studied the effects of 131I therapy on thyrotrophin binding inhibiting immunoglobulins (TBII) in fifty-five patients with Graves' disease and five patients with toxic multinodular goitre (MNG). A group of forty patients with Graves' disease and four patients with toxic MNG were treated with drugs and acted as controls. In 78% of patients treated with 131I there was a marked increase in the serum TBII activity during the 3 months following therapy, whereas drug-treated patient showed a decrease (77%) or no change in TBII activity over the same period. TBII activity was not detectable in patients with toxic MNG before or after drug or 131I therapy. Consideration of the mechanisms involved in the changes in serum TBII activity after 131I treatment or during drug treatment provide insight into the basic defects responsible for the development of hyperthyroid Graves' disease and suggest that both the thyroid and immune system are involved.     

HUMORAL AND CELL-MEDIATED IMMUNITY IN LARGE NON-TOXIC MULTINODULAR GOITRE

Humoral and cell-mediated immunity was investigated in fourteen patients with non-toxic multinodular goitre and ten healthy controls by in vitro methods. These included determination of sheep erythrocyte and complement rosette-forming cells in the peripheral blood, immunoglobulin levels, titres of thyroglobulin and microsomal antibodies and migration inhibition test using thyroid extract and phytohemagglutinin. When compared with controls the patients showed high IgA levels and positive response to thyroid antigen in the leucocyte migration inhibition test. There was no correlation between the leucocyte migration results and the presence of auto-antibodies. These findings indicate a possible role of cell-mediated immunity in non-toxic multinodular goitre.     

Solitary adrenal gland metastasis of a follicular thyroid carcinoma presenting with hyperthyroidism.

Follicular thyroid carcinoma typically manifests under euthyroid conditions, and diagnostic scintigraphy usually identifies a cold nodule. Sometimes, such tumors can appear in the context of hyperthyroidism, which can be caused by a toxic multinodular goitre, a toxic adenoma, or even carcinoma. We report a case of follicular thyroid carcinoma discovered after surgical treatment of a toxic multinodular goiter, in which solitary adrenal gland metastasis was detected five years later. A (131)I whole body scan is the diagnostic method of choice for functioning thyroid metastasis.     

Determinants of longterm outcome of radioiodine therapy of sporadic non-toxic goitre

OBJECTIVE: Radioiodine treatment is effective in reducing the size of sporadic nontoxic goitre, albeit at the expense of a high incidence of postradiation hypothyroidism. The decrease in goitre size, however, is not observed in all subjects, and little is known about recurrent goitre growth after 131I therapy. The aim of the present study was to evaluate which factors determine the longterm outcome of 131I treatment in patients with sporadic nontoxic nodular goitre, in terms of changes in both thyroid size and thyroid function. STUDY DESIGN: Retrospective follow-up study. PATIENTS: Fifty patients with sporadic nontoxic nodular goitre were evaluated who had been treated in our institution with 131I (mean dose 4.4 MBq/g thyroid) in the period 1988-95. Nine patients received a second dose of 131I and one a third. Median follow-up time was 41 months (range 24-115). MEASUREMENTS: Thyroid function was assesed by TSH and FT4 index, and thyroid volume by ultrasound in 46 patients, by scintiscan using the Himanka formula in three and by CT-scan in one. The response to treatment was defined as a decrease in thyroid volume of greater than 13% (i.e. the mean + 2SD of the coefficient of variation of volume measurements), and recurrent goitre as an increase in thyroid volume greater than 13% after an initial response. RESULTS: Goitre size decreased from a median value of 82 ml (range 17-325) to 37 ml (range 6-204) two years after 131I treatment, a median reduction of 49%. The decrease in goitre size was directly related to the dose of 131I (r = 0.50, P = 0.0003) and indirectly to baseline goitre size (r = - 0.35, P = 0.006). Seven patients (14%) were nonresponders, and four (8%) experienced recurrent goitre growth after 3-5 years. These 11 patients (22%) when compared to the remaining 39 responders (78%) had larger goitres with more often a dominant nodule, and had received a lower 131I dose. The efficacy of a second dose of 131I (median reduction in goitre size 37%) was comparable to the first dose. Hypothyroidism occurred in 24 patients (48%), mostly in the first two years after treatment; 11 had overt and 13 subclinical hypothyroidism. Kaplan Meier statistics indicated a probability of 58% for developing hypothyroidism after 8 years. Hypothyroid patients had a smaller initial goitre size and a higher prevalence of TPO antibodies and a family history of thyroid disease than the patients who remained euthyroid; the 131I dose did not differ between the two groups. CONCLUSIONS: The size of sporadic nontoxic goitres is reduced on average by 50% after a single dose of 4.77 MBq 131I/g thyroid. Independent determinants of the relative decrease in thyroid volume are administered 131I dose and initial goitre size. Nonresponders (14%) and those with late recurrence of goitre growth (8%) have larger goitres and more often dominant nodules than responders. Determinants of postradioiodine hypothyroidism (cumulative risk 58% after 8 years) are the presence of TPO antibodies, a family history of thyroid disease and a relatively small goitre.The implications of these findings are that the efficacy of a given 131I dose can be enhanced when administered at an earlier stage when the goitre is still smaller, albeit at the expense of an increased risk for developing hypothyroidism.     

The usefulness of conventional and echo colour Doppler sonography in the differential diagnosis of toxic multinodular goitres

OBJECTIVE: To assess the potential role of conventional sonography and colour flow Doppler (CFD) sonography (CFDS) in the differential diagnosis of toxic multinodular goitres. SUBJECTS AND METHODS: We investigated 55 patients with untreated hyperthyroidism (24 with typical toxic diffuse goitre of Graves' disease (Group A); 26 with multinodular goitre (Group B); and five with single toxic adenoma (Group C); 22 euthyroid subjects (12 with non-toxic multinodular goitre (Group D) and ten normal subjects (Group E)) were included as controls. In all cases free thyroxine, free tri-iodothyronine, TSH, TSH receptor antibodies (TRAb), anti-thyroperoxidase antibody, anti-thyroglobulin antibodies and anti-thyroid microsomal antibodies were determined and a [(99m)Tc]pertechnetate thyroid scan was performed. RESULTS: Patients with toxic multinodular goitre displayed two different CFDS patterns: 18 patients (Group B-1) had nodules with normal vascularity surrounded by diffuse parenchymal hypoechogenicity with markedly increased CFD signal and maximal peak systolic velocity (PSV) (a pattern similar to Group A patients with Graves' disease); eight patients (Group B-2) had increased intra- and perinodular CFD signal and PSV with normal extranodular vascularity (a pattern similar to that found in Group C patients with single toxic adenoma). Patients of Group B-1 showed a proportion of clinically evident thyroid ophthalmopathy, positive TRAb and other thyroid autoantibodies similar to that observed in Group A patients, while no evidence of thyroid autoimmunity was found in Group B-2. Sixteen out of 18 (89%) patients from Group B-1 displayed a scintiscan pattern of diffuse uneven radionuclide distribution, while seven out of eight (87.5%) of those from Group B-2 had localized uptake in multiple discrete nodules. Taken together, these data strongly suggest that Group B-1 mostly represents patients with the multinodular variant of Graves' disease, while Group B-2 represents patients with non-autoimmune toxic multinodular goitre. CONCLUSIONS: This study shows that combined conventional sonography and CFDS may easily distinguish nodular variants of Graves' disease from non-autoimmune forms of toxic multinodular goitre and confirms the clinical usefulness of this technique in the first-line evaluation of hyperthyroid patients.     

Five-year follow-up of percutaneous ethanol injection for the treatment of hyperfunctioning thyroid nodules: a study of 117 patients

Percutaneous ethanol injection (PEI) has been suggested as an alternative to radioiodine and surgery for the treatment of autonomous thyroid nodules (ATN). OBJECTIVE In this study we have defined the long-term efficacy and safety of PEI for the treatment of ATN, and we have attempted to optimize the clinical usefulness and improve the technical approach to PEI treatment. PATIENTS One hundred and seventeen patients with ATN, 26 males and 91 females, aged 48±12.9 years (mean±SD), were offered PEI when other established treatments were refused or contraindicated. Seventy-seven patients were affected by toxic adenoma (60 with a single nodule, 17 with a multinodular goitre); 40 patients suffered from a pretoxic single nodule. METHODS Sterile 95% ethanol was administered weekly under sonographic control by a 20–22 gauge needle without anaesthesia or pharmacological sedation. During PEI treatment, 26 toxic elderly patients were treated with methimazole and propranolol. According to hormone and scintigraphic data, three possible outcomes were identified for statistical analysis: failure (persistent suppression of extra-nodular tissue uptake, along with elevated free T4 (FT4) and free T3 (FT3) and undetectable TSH levels); partial cure (normalization of FT4 and FT3 levels, with low/undetectable TSH levels; persistent suppression of extra-nodular uptake); complete cure (normal thyroid hormone and TSH levels; restored extra-nodular uptake). RESULTS The patients were followed for up to 5 years (median 2.5). PEI therapy was well tolerated by all patients. Complete cure was achieved in all pretoxic patients and in 60 (77.9%) patients with toxic adenoma, while partial cure was observed in 7 cases (9.1%) and failure in 10 (13%). PEI treatment proved similarly effective in toxic patients with a single nodule or with multinodular goitre (87 vs 88.2%, respectively). At the end of treatment, a significant shrinkage of nodule volume was observed in all patients (P=0.0001). Toxic patients with pre-treatment volume >40 ml (n=8) did not show a significant difference in treatment response rate as compared to those with volume <40 ml. Recurrence of hyperthyroidism was never observed during follow-up, independently of thyroid status before treatment. Only one patient with significant thyroid autoantibody serum levels before PEI treatment, developed subclinical hypothyroidism at 3 years. The administration of methimazole and/or propranolol did not modify PEI outcome. CONCLUSION Our data confirm the efficacy and safety of percutaneous ethanol injection for the therapy of autonomous thyroid nodules. The very low incidence of hypothyroidism along with the absence of recurrence of hyperthyroidism suggests that percutaneous ethanol injection is the treatment of choice in patients with pretoxic thyroid adenoma. Percutaneous ethanol injection appears an effective alternative procedure in toxic patients with a high surgical risk even if they have large nodules, and in younger ones in whom radioiodine is contraindicated. Patients may be submitted to anti-thyroid drug and/or β-blocker therapy if it is necessary, but this does not affect percutaneous ethanol injection treatment outcome. Finally, not only single autonomous thyroid nodules but also toxic multinodular goitre may be successfully treated by percutaneous ethanol injection.     

Clinical and biochemical changes following 131I therapy for hyperthyroidism in patients not pretreated with antithyroid drugs

BACKGROUND: Radioiodine therapy (131I) for the treatment of hyperthyroidism has been shown to be effective and safe. Despite the extensive experience with radioiodine therapy, the necessity for pretreatment with antithyroid drugs is controversial. Pretreatment is partly based on the concept that antithyroid drugs deplete the thyroidal hormonal stores, thereby reducing the risk of a radioiodine-induced aggravation of hyperthyroidism or thyroid storm. Few data are available on the frequency of clinically significant exacerbations of hyperthyroidism following 131I therapy without prior treatment with antithyroid drugs. The aim of the present study was to determine prospectively the early clinical and biochemical changes after 131I therapy in patients who were not pretreated with antithyroid drugs. METHODS: Patients with Graves' disease (n = 21), toxic multinodular goiter (n = 11) or toxic adenoma (n = 2) were studied before and after 131I therapy. Clinical and biochemical parameters of thyroid function were investigated before and 1, 2, 8, 11, 18 and 25 days after 131I treatment. Patients were given no antithyroid drugs prior to 131I therapy, all patients received beta-blocking agents for symptomatic relief. RESULTS: In 19 of 34 patients, a transient increase in thyroid hormone levels was observed, predominantly in the first week following 131I therapy. None of these patients experienced worsening of thyrotoxic symptoms. This transient increase in thyroid hormone levels was demonstrated in all patients with toxic multinodular goiter, whereas it was found in only six of 21 patients with Graves' disease. This difference could not readily be explained by differences in pretreatment thyroid hormone levels, administered dose or effectively absorbed dose of 131I. CONCLUSIONS: 131I treatment of hyperthyroidism without pretreatment with antithyroid drugs may cause a transient increase in thyroid hormone levels. Clinically significant exacerbations of hyperthyroidism were, however, not observed in our study population. Increased hormone levels following 131I therapy were more often seen in patients with toxic multinodular goiter than in patients with Graves' disease.     

TSH-receptor autoantibodies - differentiation of hyperthyroidism between Graves' disease and toxic multinodular goitre.

Previous studies indicate pre-existing subclinical Graves' disease in many patients with the scintigraphic diagnosis of toxic multinodular goitre type A, equivalent to the in Germany so-called disseminated thyroid autonomy. Furthermore, after radioiodine treatment an increase or the induction of TSH-receptor antibodies (TRAb) in patients with Graves' disease or toxic multinodular goitre has been repeatedly reported. The distinction between both hyperthyroid conditions, Graves' disease and toxic multinodular goitre type A, depends on the diagnostic power of the TSH-receptor antibody determination. Bioassays using CHO cell lines expressing the hTSH-receptor or a new TBII assay based on competitive binding to recombinant human TSH-receptor showed a higher sensitivity for the detection of TSH-receptor antibodies in patients with Graves' disease than previous assays using solubilized porcine epithelial cell membranes. In up to 50 % of patients with toxic multinodular goitre A without antithyroid drug pretreatment TSH-receptor antibodies were detectable with a high correlation between thyroid-stimulating antibodies in the bioassay and the h-TBII assay. Moreover, in a recent study the development of TSH-receptor antibodies after radioiodine treatment was detectable in 36 % of patients with toxic multinodular goitre type A, whereas TSH-receptor antibodies were not detectable in patients with toxic multinodular goitre type B or in patients with toxic adenoma. In conclusion, thyroid-stimulating antibodies in a bioassay or TSH-receptor antibodies detected with the h-TBII assay have the highest diagnostic power to differentiate Graves' disease from toxic multinodular goitre. Because of its less cumbersome assay technique the h-TBII should be performed in all patients with hyperthyroidism to differentiate Graves' disease from non-autoimmune hyperthyroidism such as toxic multinodular goitre to select the appropriate therapy for these patients.     

Influence of compensated radioiodine therapy on thyroid volume and incidence of hypothyroidism in Graves' disease

Abstract. Objectives . To investigate the long-term effect of radioactive iodine (¹³¹I) on thyroid function and size in patients with Graves' disease. Setting . Out-patient clinic in Herlev Hospital. Subjects . One hundred and seventeen consecutive patients (104 women) with Graves' disease selected for ¹³¹I treatment and followed for a minimum of 12 months (range 1–10 years, median 5 years). Interventions . ¹³¹I dose was calculated based on thyroid volume and 24-h ¹³¹I uptake. Main outcome measures . Standard thyroid function variables and ultrasonically determined thyroid volume before treatment as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated. Results . Seventy-eight patients were cured by one ¹³¹I dose and 30 by two doses, while the remaining nine patients received additional doses (range one to five doses, median one dose). Within one year, 25% developed hypothyroidism, and hereafter, hypothyroidism developed at a constant rate of 3% per year independent of antithyroid pretreatment. The cumulative 10-year risk of hypothyroidism was 60%. Initial median thyroid volume was 33 mL (range 9–106 mL). At 12 months after the last ¹³¹I dose, median thyroid volume was reduced to 14 mL (range 6–36 mL) (P < 0.00001). The median reduction being 58% (range 0–80%,), hereafter no further reduction occurred. A significant reduction in thyroid volume was also noted in patients needing subsequent ¹³¹I doses and in those developing hypothyroidism within the first year. Conclusions . ¹³¹I normalizes thyroid volume in patients with Graves' disease. Hypothyroidism seems an inevitable end result of this treatment. The present study suggests that it will be impossible to modify ¹³¹I therapy in a way to achieve both early control of hyperthyroidism and a low incidence of hypothyroidism.     

Is calculation of the dose in radioiodine therapy of hyperthyroidism worth while?

OBJECTIVE The persistent controversy as to the best approach to radioiodine dose selection in the treatment of hyperthyroldism led us to perform a study in order to compare a fixed dose regime comprising doses of 185, 370 or 555 MBq based on gland size assessment by palpation only, with a calculated ¹³¹I dose based on type of thyroid gland (diffuse, multinodular, solitary adenoma), an accurate thyroid volume measurement, and a 24-hour ¹³¹I uptake determination. DESIGN Prospective randomized study. PATIENTS Two hundred and twenty-one consecutive hyperthyroid patients referred for ¹³¹I treatment. Four patlents who dled for reasons unrelated to hyperthyroidism, 7 lost to follow-up and 47 who did not receive antithyroid drugs after treatment, were excluded. The remalnlng 163 patlents (143 women) were studied, dlvlded into subgroups accordlng to the type of gland. They all recelved antithyroid drugs prior to ¹³¹I treatment and this was resumed 7 days after treatment for a period of 3 weeks. MEASUREMENTS Thyroid function variables were determined approximately 2 weeks before ¹³¹I treatment, and again 1, 2, 3, 6, 9 and 12 months after treatment. Prior to ¹³¹I therapy the size of the thyroid gland was determined by ultrasound and a 24-hour uptake of ¹³¹I was carried out. Thyroid in 78 of the 163 patients. Twelve months after the initial ¹³¹I dose patients could be classified as euthyroid, hyperthyrold or hypothyroid. RESULT Neither in the group of 163 patients nor within the three subgroups of hyperthyroidism could any significant difference in outcome between the two treatment regimes be demonstrated. Thirty-two of 78 patients (41%) in the calculated dose group and 30 of 85 patients (35%, NS) in the fixed group were classified as hyperthroid. Seven of 78(9%) in the calculated dose group were classified as permanently hypothyroid. Finally, 39 of 78(50%) In the calculated dose group and 49 of 85(58%, NS) in the fixed group were enthyroid at 12 months after ¹³¹I treatment. One year after ¹³¹I therapy thyroid volume was deduced from 59.3 ± 9.2 (mean ± SEM) to 36.2 ± 6.6 ml (average reduction 39%) In the calculated dose group (P < 0.001). This reduction did not differ significantly from the fixed dose group where thyroid volume declined from 61.6 ± 6.1 to 41.17 ± 4.7 ml (average reduction 32%) (P < 0.001). CONCLUSIONS A semiquantitative approach is probably as good as the more elaborately calculated radiolodine dose for treatment of hyperthyroidism. It is clearly more cost effective and allows the use of predetermined standard doses.     

The effect of recombinant human tsh on the thyroid (123)i uptake in iodide treated normal subjects

Radioactive iodine therapy is often successful in the treatment of toxic or non-toxic multinodular goiter. However, when the patient has been exposed to iodine in the form of medication or radiocontrast agents prior to therapy, the thyroid radioactive iodine is often too low for successful ablation. Recently, administration of 0.9 mg of recombinant human TSH (rhTSH) has been shown to nearly double the 24-hour thyroid radioactive iodine uptake (RAIU) in euthyroid men living in the United States. In addition, 0.01 to 0.03 mg rhTSH administered 24 hours prior to (131)I in patients with a history of non-toxic multinodular goiter residing in an area of modestly low iodine intake, has also been shown to increase the 24-hour thyroid radioactive iodine uptake. We now have determined whether rhTSH administration prior to (123)I would increase the low thyroid RAIU in subjects treated with sodium iodide. Nine euthyroid men were given 15 mg iodide daily for 7 days. There was a marked increase in serum TSH values 8 and 24 hours after rhTSH administration, which induced elevated serum T4 and T3 concentrations. A 16 hour thyroid RAIU was measured at baseline, after 5 days of iodide administration, and either 8 or 32 hours after intramuscular administration of rhTSH. Administration of rhTSH 8 hours before (123)I to 4 subjects increased the 16 hour thyroid RAIU by 62% above the low post iodide thyroid RAIU. Administration of rhTSH 32 hours before (123)I administration to 5 subjects increased the 16 hour thyroid RAIU by 97% above the low iodide induced RAIU. Thus, the overall increase in the thyroid RAIU was 88% in the 9 subjects. Conclusion: Recombinant TSH moderately increased the thyroid RAIU in subjects with depressed thyroid RAIU's during iodide administration and thus may be useful in preparing patients with non-toxic or toxic goiters and low thyroid RAIU's due to excess iodine for radioactive iodine treatment. Further studies to determine the optimal protocol to enhance the effect of rhTSH will be carried out.