Role of recombinant human TSH in the management of large euthyroid multinodular goitre: a new therapeutic option? Pros and cons

Conventional 131I treatment has been used in the last 20 years for large nodular goitres when patients present high surgical risk or simply refuse surgery. 131I therapy causes a mean goitre volume reduction of about 40% after one year. However, the individual response is variable and for low radioiodine uptake and very large goitres, high 131I activities are needed in order to have a adequate 131I accumulation in the thyroid. rhTSH is approved for thyroid cancer management and has been tested off label in large goitres, in whom increases 131I uptake, thus reducing the 131I amount to be administered. The use of lower 131I activities allows to reduce the radiation burden to body and the time of social life restriction. Moreover, depending on the radiation regulations of the different countries, the 131I therapy could be carried out either as outpatients or in a shorter hospitalization period, implying a decrease of costs. The effects of rhTSH on goitre may be due not only to the 131I uptake increase, but also to a more homogeneous distribution of 131I in the gland, and to the thyroid cell activation that makes them more radiosensitive. Acute adverse effects are due to the surge of thyroid hormone in blood and to the goitre volume increase, that cause cardiac symptoms and tracheal compression, respectively. These effects are probably dose dependent and are negligible for rhTSH lower doses.     

Acute changes in thyroid volume and function following 131I therapy of multinodular goitre

OBJECTIVE Many textbooks claim that radioIodine (¹³¹I) treatment should be given with care to a goitre with substernal extension, for fear of acute swelling of the gland and thus respiratory problems. Since ¹³¹I Is used increasingly in the treatment of non-toxic as well as toxic goitre we have evaluated the acute changes in thyroid volume following ¹³¹I therapy. DESIGN Evaluation of potential acute changes in thyroid volume and function after ¹³¹I treatment in patients with non-toxic goitre treated because of compression symptoms or for cosmetic reasons, as well as In patients with toxic goitre. PATIENTS Out-patients with multinodular goitre, either non-toxic (n= 20) or toxic (n= 10). Excluded were patients with a substernal goitre. MEASUREMENTS Ultrasonically determined thyroid volume and standard thyroid function variables were Investigated before and 2, 7, 14, 21, 28 and 35 days after treatment. RESULTS In non-toxic goitres the thyroid volume did not increase significantly, the maximum increase in the median volume being 4% on day 7. Serum levels of free T3 and free T4 Indices increased by 20% (day 7) and 13% (day 14) (P= 0·002), respectively. Likewise thyroid volume in toxic nodular goitre did not change significantly after ¹³¹I treatment (maximum median increase was 2%). None of the patients presented symptoms of tracheal compression. CONCLUSIONS ¹³¹I treatment of non-toxic as well as toxic multinodular goitre does not seem to increase thyroid volume.     

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.     

Stimulation with 0.3-mg recombinant human thyrotropin prior to iodine 131 therapy to improve the size reduction of benign nontoxic nodular goiter: a prospective randomized double-blind trial

BACKGROUND: Use of recombinant human thyrotropin increases the thyroid radioiodine (iodine 131 [(131)I]) uptake and may have a role in the context of (131)I therapy of benign goiter. METHODS: In a double-blind, placebo-controlled trial, 57 patients with nodular nontoxic goiter (51 women and 6 men) were randomized to receive either 0.3 mg of recombinant human thyrotropin (n = 28) or placebo (n = 29) 24 hours before (131)I therapy. The (131)I dose was calculated based on thyroid size (measured by ultrasound), thyroid (131)I uptake, and (131)I half-life. The follow-up period was 1 year and included measurements of thyroid size and function and patient satisfaction. RESULTS: Baseline median goiter volume was 51 mL (range, 20-99 mL) in the placebo group and 59 mL (range, 25-92 mL) in the thyrotropin group (P = .75). At 12 months, the mean +/- SEM relative goiter reduction was 46.1% +/- 4.0% in the placebo group and 62.1% +/- 3.0% in the thyrotropin group (P = .002 between groups). The difference was most pronounced among patients with large goiters. Within each group, there was no significant correlation between retained thyroid (131)I dose and goiter reduction. Adverse effects were significantly more frequent in the thyrotropin group (34 vs 12 events; P<.001). Permanent hypothyroidism developed in 3 patients (11%) in the placebo group compared with 16 patients (62%) in the thyrotropin group (P<.001). Patient satisfaction was high and uninfluenced by the use of recombinant human thyrotropin. CONCLUSIONS: Stimulation with recombinant human thyrotropin prior to (131)I therapy improves thyroid size reduction by 35%, with a 5-fold higher rate of hypothyroidism. These effects are, at least partially, mediated through mechanisms other than an increase in retained (131)I thyroid dose. Further recombinant human thyrotropin dose-finding studies are warranted before routine use.     

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.     

Long-term effect of radioactive iodine on thyroid function and size in patients with solitary autonomously functioning toxic thyroid nodules

OBJECTIVE: To investigate the long-term effects of radioiodine (131I) on thyroid function and size in patients with a solitary toxic thyroid nodule. DESIGN: Prospective study of patients treated for a solitary autonomous toxic nodule, followed by evaluation of thyroid volume and function. PATIENTS: Sixty-two consecutive patients followed for a minimum of 12 months (range 12-168, median 60). Seventeen patients received antithyroid drug treatment before 131I. MEASUREMENTS: Standard thyroid function variables and ultrasonically determined thyroid volume before as well as 0.75, 1.5, 3, 6 and 12 months after treatment, and then once a year were investigated. RESULTS: 131I treatment (3.7 MBq/g thyroid tissue corrected to a 100% 24-h 131I uptake) was given as a single dose in 53 patients; six needed two doses and another three were given 3-5 131I treatments. The median initial dose was 310 MBq (140-666) and the median total dose was 332 MBq (148-1576). In patients receiving one 131I treatment (n = 53) the total thyroid volume decreased significantly from a median of 40 ml (range 19-77) to 24 ml (8-50) within 3 months. This represented a median reduction of 35%. A further significant decrease was seen after 24 months to a total reduction of 45%. In patients given more than one dose the thyroid volume was reduced from a median of 45 ml (19-104) before treatment to 30 ml (14-50) after a follow-up of 60 months (9-132) after the last 131I treatment. Patients without antithyroid pretreatment, receiving one 131I treatment (n = 39) became euthyroid after a median of 1.5 months (0.75-9) after treatment. Seventy-five per cent were euthyroid within 3 months. In patients pretreated with antithyroid drugs and treated with one dose of 131I (n = 14) euthyroidism was achieved after a median of 12 months (0.75-24) after 131I treatment. Hypothyroidism developed in five patients (8%) after a median of 36 months (6-60) after 131I treatment. CONCLUSION: A cure-rate of 75% within 3 months is seen when treating autonomous solitary toxic thyroid nodules with 131I. The thyroid volume is reduced by 35% within 3 months and 45% after 2 years. Side-effects are few and consist of hypothyroidism in less than 10% with a median follow-up of 5 years. This treatment should be regarded as the standard treatment for this condition until prospective comparisons with surgery and ethanol injection therapy have been performed.     

Long-term effects of radioiodine on thyroid function, size and patient satisfaction in non-toxic diffuse goitre

OBJECTIVE: The long-term effects of (131)I-therapy in patients with symptomatic non-toxic diffuse goitre were evaluated. DESIGN AND METHODS: In a prospective open study, 34 patients (median age: 40 yrs, range: 27-68 yrs) were enrolled who suffered from a non-toxic goitre absent of nodules on clinical examination and on ultrasonography. Treatment indication was the presence of goitre giving rise to cervical compression and/or cosmetic discomfort. The median (131)I activity was 600 MBq (200-600 MBq) administered orally on an outpatient basis. The patients were investigated by clinical examination, thyroid ultrasonography and thyroid function tests at regular intervals and for at least 12 months after the (131)I-therapy. Yearly follow-up continued until the end of the study period or if permanent hypothyroidism ensued. The severity of symptoms was evaluated by a Visual Analogue Scale (VAS) (range: 0-10). RESULTS: The median follow-up time was 36 months (12-84). Goitre volume was reduced from 67.9+/-28.5 ml to 43.4+/-18.7 ml (mean+/-S.D.) (P<0.001) 3 months after the (131)I-therapy. After 3 years of follow-up, only 28.1+/-2.0% (mean+/-S.E.) remained of the initial goitre mass (P<0.001). Goitre was no longer present in 76% of the patients at the end of follow-up. An inverse correlation was found 1 year after therapy, but not after 3 years, between the initial goitre size and the percent reduction (r=-0.44, P=0.01). Thirty-six percent had become hypothyroid after three years. Median VAS scores were reduced from an initial 7.0 (cervical compression) and 5.5 (cosmetic discomfort) to 0.0 at the end of follow-up (P<0.001). CONCLUSION: Our data justify treatment of non-toxic diffuse goitre with (131)I because goitre reduction is pronounced, along with a very high degree of patient satisfaction and few side effects. We suggest that (131)I-therapy can be used as an alternative to L-T(4) suppressive therapy and thyroidectomy in this group of patients.     

THE VALUE OF THYROID VOLUME MEASURED BY ULTRASONOGRAPHY IN THE DIAGNOSIS OF GOITRE

Thyroid volume was measured by ultrasonography in 80 euthyroid patients with sporadic nontoxic goitre and in 50 healthy adults, all residing in non-iodine deficient areas. All patients were referred because of complaints of goitre and had been diagnosed as cases of goitre by inspection and palpation. The thyroid volume in 15 patients with goitre (19%) was within the normal reference range (4.9-19.1 ml). Fourteen of the 15 patients had thyroid nodules larger (mean diameter 2.9 +/- 1.1 cm) than those detected in nine of the healthy adults (mean diameter 0.8 +/- 0.6 cm; P less than 0.001). Thyroid size as estimated by inspection and palpation (grade OA to III according to Stanbury et al., 1974) was poorly related to thyroid volume measured by ultrasonography. In conclusion: (1) a thyroid volume within the normal reference range does not rule out the presence of nodular goitre; and (2) application of thyroid volume measurement by ultrasonography may prevent overestimation of goitre prevalence in epidemiological surveys.     

A randomized trial comparing levothyroxine with radioactive iodine in the treatment of sporadic nontoxic goiter

A randomized clinical trial was performed in consecutive patients with sporadic nontoxic nodular goiter to compare efficacy and side effects of iodine-131 ((131)I) therapy with suppressive levothyroxine (L-thyroxine) treatment. Sixty-four patients were randomized after stratification for sex and menopausal age to receive (131)I (4.44 MBq/g thyroid; group A) or suppressive L-thyroxine treatment aiming at TSH values between 0.01 and 0.1 mU/L (group B). The main outcome measurements after 2 yr were goiter size by ultrasound, serum thyroid function tests, markers of bone turnover, and bone mineral density (BMD). Fifty-seven patients completed the trial. Goiter size was reduced after 2 yr by 44% in group A and by 1% in group B (P< 0.001). Nonresponders (goiter reduction <13%) were 1 of 29 patients in group A and 16 of 28 patients in group B (P = 0.00001). In responders, goiter reduction in group A (46%) was greater than in group B (22%; P< 0.005). In group A, 45% of patients developed hypothyroidism. In group B, 10 patients experienced thyrotoxic symptoms, requiring discontinuation of treatment in 2 (in 1 because of atrial fibrillation). Markers of bone formation and bone resorption increased significantly in group B, related to a mean decrease of 3.6% of BMD at the lumbar spine after 2 yr (from 1.09 +/- 0.22 to 1.05 +/- 0.23 g/cm(2); P< 0.001), both in pre- and postmenopausal women. No changes in BMD were observed in group A. In conclusion, (131)I therapy is more effective and better tolerated than L-thyroxine treatment in patients with sporadic nontoxic goiter. Suppressive L-thyroxine treatment results in significant bone loss.     

Goitre size and outcome of medical treatment of Graves' disease

One hundred and twenty-four patients with newly diagnosed hyperthyroidism received a combined thionamid-thyroxine medical therapy for approximately 2 years. According to the estimated goitre size before therapy and the type of goitre the patients were divided into 4 groups: Graves' disease no goitre (n = 19), Graves' disease small goitre (n = 57), Graves' disease medium or large goitre (n = 23), multinodular goitre (n = 25). The median follow-up period after cessation of medication was 64 (range 11-141) months. The remission rates in the different groups during follow-up were calculated using life table analysis. Graves' patients with no goitre or a small goitre had a significantly better outcome (remission % after 5 years 82.5 +/- 15.4 (SE) and 71.5 +/- 7.8, respectively) than Graves' patients with a medium size or large goitre (remission % after 5 years 37.0 +/- 11.1)(P less than 0.025). Most patients with multinodular goitre had a relapse within the first year after stop of medication (remission % after 5 years 15.5 +/- 10.1). Hence patients with Graves' disease having a small thyroid gland should be treated medically while surgery or radioiodine may be a more reasonable choice in Graves' patients with medium size or large goitres. Medically treated patients with toxic multinodular goitres have a very small chance of prolonged remission if medication is stopped.     

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.     

Iodized salt improves the effectiveness of L-thyroxine therapy after surgery for nontoxic goitre: a prospective and randomized study

OBJECTIVE: To investigate whether the addition of iodized salt to daily diet in thyroidectomized patients for nontoxic goitre could influence the effectiveness of nonsuppressive L-thyroxine (L-T4) therapy on thyroid remnant size, during 12 months' follow-up after thyroid surgery. DESIGN AND PATIENTS: A consecutive series of selected 139 patients (26 males, 113 females; median age 45 years, range 30-69 years) living in a moderate iodine-deficient area, and undergoing thyroid surgery for nontoxic multinodular goitre, was enrolled. Patients were assigned randomly to two different therapeutic regimens: 70 patients received L-T4 therapy alone (Gr. L-T4), while the remaining 69 patients took iodized salt on a daily basis in addition to L-T4 treatment (Gr. L-T4 + I). In both groups, the initial L-T4 dose was 1.5 microg/kg/day, which, in our experience, has been shown to be intermediate between suppressive and replacement doses. To avoid the risks of mild thyrotoxicosis and to limit the excessive TSH stimulation of the thyroid remnant, the L-T4 dose was adjusted in those patients with serum TSH levels outside the lowest two-thirds of the normal range (0.3-2.5 mU/l). An ultrasound evaluation of thyroid remnant size was performed after thyroid surgery and 12 months later. RESULTS: After surgery, the median thyroid remnant volume was 3.5 ml (range 0.4-13.9 ml) in Gr. L-T4 and 4.6 ml (range 0.5-12.7 ml) in Gr. L-T4 + I (P = 0.06). After 1 year of follow-up, the patients treated with L-T4 + I obtained a remnant volume reduction (-39.7%, range -87.0% to +91.2%) significantly (P = 0.006) greater than that observed in patients assuming L-T4 alone (-10.2%, range -89.4% to +85.0%). However, the percentage of patients showing an increase in remnant size in the months following surgery was higher in Gr. L-T4 than in Gr. L-T4 + I (22/60 vs. 9/66; P = 0.01). In Gr. L-T4 patients the thyroid remnant volume variation throughout 12 months of treatment was correlated significantly with the size of the thyroid remnant found at the first ultrasound evaluation (R(2) = 0.3; P < 0.001). No such correlation was found in Gr. L-T4 + I patients, for whom the therapy maintains a similar effectiveness in patients with either a large or a small postsurgery thyroid remnant. In patients treated with L-T4 alone, the remnant volume variation was correlated significantly with the median serum TSH values attained in the course of treatment (R2 = 0.4; P < 0.001). The highest reduction in remnant volume was observed only by lowering the serum TSH concentrations. In patients treated with L-T4 plus iodine, instead, the thyroid remnant volume reduction occurred independently of the plasma TSH levels attained in the course of treatment. CONCLUSIONS: Our short-term prospective and randomized study leads us to conclude that, in patients living in a moderate iodine-deficient area and undergoing thyroid surgery for nontoxic goitre: (1) the iodine prophylaxis improves the effects of postsurgery nonsuppressive L-T4 therapy on thyroid remnant size. (2) In patients treated with L-T4 alone the therapeutic effectiveness decreases in the presence of a large postsurgery thyroid remnant. With the addition of iodine, the L-T4 maintains a similar efficacy in patients with either a large or a small remnant. (3) During treatment with L-T4 alone the highest therapeutic effectiveness is attained by lowering the plasma TSH concentration. With the addition of iodized salt to the daily diet the effects of L-T4 on remnant size are relevant independently of the TSH levels.     

Use of thyroid ultrasound volume in calculating radioactive iodine dose in hyperthyroidism.

One hundred twenty-one patients treated with 131I had a thyroid ultrasound to measure thyroid volume precisely. This volume measurement was used to determine the radioactive iodine dose. The average size (+/-SEM) of the thyroid glands measured in this manner was 39.7 cm3 +/- 1.9 cc. A significant correlation was found in the estimated size of the gland by the endocrinologists and the ultrasound volume. Of the 121 patients, 89 patients had the same 131I microcurie per gram of tissue factor to determine the radioactive iodine dose. This group of patients was further evaluated in this study. The average 131I dose (+/-SEM) given was 13.2 mCi +/- 0.5 mCi. The average time until hypothyroidism was achieved 2.85 +/- 0.14 months. Ultrasound provides a safe and precise way to determine actual thyroid size when calculating 131I doses.     

Administration of a single dose of recombinant human thyrotrophin enhances the efficacy of radioiodine treatment of large compressive multinodular goitres

OBJECTIVE: Patients with very large multinodular goitres, frequently found among elderly people, often suffering from cardiovascular or other disabling disorders, may be considered as unsuitable for surgery. We have evaluated the feasibility of relatively high-dose 131I therapy in such patients. As subclinical or clinical hyperthyroidism is commonly found in these patients, associated with a low radioiodine (RAI) uptake at 24 h, we pretreated a group of patients with a single intramuscular injection of recombinant human TSH (rhTSH 0.45 mg) in order to increase the uptake of the therapeutic dose of RAI. DESIGN AND PATIENTS: Forty-one patients with large, long-standing multinodular goitres, were recruited for this study. After a careful and detailed clinical and laboratory evaluation, 34 patients (28 women, six men) were included and randomly assigned to group 1 (control, n = 17, 15 women, two men, age 63.1 +/- 11.2 years) receiving only RAI. Patients in group 2 (n = 17, 13 women, four men, age 63.6 +/- 12.3 years) received the therapeutic dose of RAI, having been pretreated (24 h) with 0.45 mg of rhTSH. Both groups of patients were submitted to a low iodine diet, 4-6 months before RAI treatment, while seven thyrotoxic patients also received methimazole (40 mg/day) until they reached euthyroidism. Ultrasonographic studies were performed for all patients and fine-needle aspiration biopsy (FNAB) were performed on one or two nodules before RAI treatment. RAI was given as a single oral dose to the hospitalized isolated patients. Blood samples for thyroid function tests and serum thyroglobulin (Tg) were collected daily during the first week following RAI treatment, and at 1, 3, 6, 9 and 12 months thereafter. MEASUREMENTS: Goitre volume was estimated by computed tomography scan. Thyroid function tests (total T3, free T4, TSH and serum Tg) were assayed with commercial kits. Urinary excretion of iodine was assayed by the Sandell-Kolthoff method. RESULTS: After the RAI therapeutic dose, serum thyroid function tests were carried out daily for the first week and then on a monthly basis (1, 3, 6, 9 and 12 months). Serum TSH levels rose to a peak level of 45.9 +/- 19.1 mU/l (24 h) in group 2 returning to normal at 72 h. Free T4 serum concentrations rose significantly to 59.35 +/- 21.61 pmol/l at 48 h (in group 2) returning to normal at 7 days. Similarly, serum TT3 also peaked above normal levels only in group 2 (6.12 +/- 1.89 nmol/l) at 24 h. Serum Tg increased in both groups (significantly higher in group 2) and remained elevated during the following 12 months. Both groups had a significant reduction in goitre volume at 12 months (group 2: 57.8%vs. group 1: 39.7%, P < 0.05). Hypothyroidism was detected after RAI treatment, respectively, in 21.4% (group 1) and 64.7% (group 2), of the patients at 12 months. CONCLUSIONS: Our results indicate that the use of hTSH increased the efficacy of the RAI therapeutic dose. This was basically due to an increased uptake of the radionuclide (as a consequence of the higher serum TSH levels) and a more extensive distribution of 131I within the nodules of the multinodular goitre. A more intense radiation effect was reflected in there being a higher output of serum Tg and thyroid hormones (group 2). As a consequence this group had a significantly higher reduction of the goitre volume. Also incidence of hypothyroidism post-RAI was significantly higher in group 2. We concluded that pretreatment with rhTSH in elderly patients with large multinodular goitres increases the uptake of the RAI therapeutic dose, thereby significantly reducing the multinodular goitre volume and relieving the compressive symptoms with relatively few side-effects.     

Long-term follow-up of treatment of thyrotoxicosis by three different methods

In view of continuing debate regarding the best definitive therapy for thyrotoxicosis, we examined the long-term outcome of radioiodine (131I) or surgical treatment of 1918 thyrotoxic patients divided into three groups: those given 131I at a dose calculated from thyroid size, 131I uptake and effective half-life to administer a fixed radioactivity dose to the thyroid; those treated with a dose of 131I (110, 185 or 370 MBq) chosen empirically; and those treated by partial thyroidectomy. A minimum 10-year follow-up was achieved for 1119 patients treated with a calculated 131I dose; a single dose resulted in control of disease in 90.5%. At 5 years, 18% were hypothyroid, the prevalence rising to 42% at 20 years. Of 504 patients treated with an empirical 131I dose and followed for at least 5 years, thyrotoxicosis was controlled by a single dose in 89.7%. The rate of hypothyroidism at 5 years (38.5%) was higher than that found in the calculated dose group. A minimum 10-year follow-up was achieved for 295 surgically treated patients; thyrotoxicosis was controlled in 89.2%. The prevalence of hypothyroidism (2% at 5 years, 27.5% at 20 years) was lower than that found after 131I, whether given by calculated or empirical dose. Each of the treatments employed resulted in an acceptable rate of cure of thyrotoxicosis. If maintenance of euthyroidism is the major objective, our findings suggest that surgery represents the treatment of choice. Furthermore, calculated dose 131I administration has advantages in terms of risk of hypothyroidism over empirical dose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

An outline concerning the potential use of recombinant human thyrotropin for improving radioiodine therapy of multinodular goiter

Radioiodine ((131)I) treatment for nontoxic and toxic multinodular goiter (MNG) is an alternative therapeutic procedure used especially for patients with contraindication for surgery. Several studies have been conducted in recent years assessing the use of recombinant human TSH (rhTSH) in increasing (131)I uptake in MNGs. This procedure also decreases the activity level of the administered (131)I, changes the distribution of (131)I in the thyroid, lowers the absorption dose, and dramatically reduces the volume of the goiter (50-75% of the baseline volume). A major disadvantage, however, is the induction of hypothyroidism in a relatively large number of patients. A transient increase in thyroid volume and tenderness was noted in the first week of treatment. Also a short period (2-4 weeks) of hyperthyroidism was observed in most patients with potential consequences particularly for the elderly. Still, there has been no evidence to date that the adverse effects outweigh the positive results of using rhTSH. The use of rhTSH in benign goiter disease has not yet been approved worldwide, but its positive activity in MNG is remarkable and promising.     

Outcome of radioiodine-131 therapy in hyperfunctioning thyroid nodules: a 20 years' retrospective study

OBJECTIVE: To investigate the risk of hypothyroidism after radioiodine (131I) treatment for hyperfunctioning thyroid nodules. DESIGN: Retrospective analysis of patients treated with 131I for hyperfunctioning thyroid nodules and followed up for a maximum of 20 years. PATIENTS: A total of 346 patients treated with 131I in the years 1975-95, for a single hyperfunctioning nodule. MEASUREMENTS: Hypothyroidism was defined as TSH levels > 3.7 mU/l. Kaplan-Meier survival analysis was used to analyse permanence of euthyroidism after 131I. A stepwise Cox proportional hazard model was used to identify factors influencing the progression to hypothyroidism. RESULTS: The cumulative incidence of hypothyroidism was 7.6% at 1 year, 28% at 5 years, 46% at 10 years and 60% at 20 years. Age (P < 0.01), 24-th 131I uptake (P < 0.05) and previous treatment with methimazole (MMI, P < 0.1) were associated with a faster progression towards hypothyroidism, while thyroid and nodule size, thyroid status at diagnosis and degree of extranodular thyroid parenchymal suppression had no influence. In hyperthyroid patients with partial parenchymal suppression, however, previous MMI treatment was the most important prognostic factor (P < 0.01). CONCLUSIONS: After 20 years of follow-up, 60% of patients treated with 131I for a single hyperfunctioning nodule are hypothyroid. Factors increasing the risk of hypothyroidism are age, 131I uptake and MMI pretreatment. The prognostic value of this last factor, however, depends on the degree of suppression of the extranodular thyroid parenchyma at the scan.     

Randomized prospective study comparing a single radioiodine dose and a single laser therapy session in autonomously functioning thyroid nodules

OBJECTIVE: To compare the efficacy of interstitial laser photocoagulation (ILP) with radioiodine in hot thyroid nodules. DESIGN: Thirty consecutive outpatients with subclinical or mild hyperthyroidism and a scintigraphically solitary hot nodule with extraglandular suppression were randomized to either one ILP session or one radioiodine ((131)I) dose. METHODS: ILP was performed under continuous ultrasound-guidance and with an output power of 2.5-3.5 W. (131)I was given as a single dose based on thyroid volume and a 24-h thyroid (131)I uptake. Thyroid function and nodule volume were evaluated at inclusion and at 1, 3 and 6 months after treatment. RESULTS: Normalization of serum TSH was achieved in 7 out of 14 patients in the ILP group and in all 15 patients in the (131)I group (P=0.0025). In the ILP group, mean thyroid nodule volume reduction was 44+/-5% (s.e.m.; P<0.001), and in the (131)I group 47+/-8% (P<0.001), within 6 months, without between-group difference (P=0.73). The mean reduction of total thyroid volume was 7+/-5% in the ILP group (P=0.20) and 26+/-8% (P=0.006) in the (131)I group (P=0.06 between-group). Two patients in the (131)I group developed hypothyroidism but no major side effects were seen. CONCLUSIONS: This first randomized study, comparing ILP with standard therapy, demonstrates that ILP and (131)I therapy approximately halves thyroid nodule volume within 6 months; but in contrast to (131)I, extranodular thyroid volume is unaffected by ILP and no patient developed hypothyroidism. Using the present design, ILP seems inferior to (131)I therapy in normalization of serum TSH. The potential value of ILP as a non-surgical alternative to (131)I needs further investigation.     

Long-term follow-up study of radioiodine treatment of hyperthyroidism

OBJECTIVE: To determine the cumulative incidence of hypothyroidism during long-term follow-up in patients treated for hyperthyroidism by radioactive iodine (131)I (RAI) therapy, the significance of clinical factors in predicting the development of hypothyroidism, and the outcome after a fixed 7 mCi (259 MBq) dose of RAI. DESIGN: Prospective cohort study of patients treated for hyperthyroidism by RAI. PATIENTS AND MEASUREMENTS: Since 1965, details on 2043 patients treated by RAI therapy in Tampere University Hospital were entered into a computerized register. Following RAI treatment, thyroid status was monitored every 1-3 months during the first year, and subsequently at 1-3-year intervals until June 2002 or until the patient died or moved out of the Tampere University Hospital district. results The cumulative incidence of hypothyroidism in patients with Graves' disease and toxic multinodular goitre at 1, 10 and 25 years was 24%vs. 4%, 59%vs. 15% and 82%vs. 32%, respectively. In a Cox regression model, previous partial thyroidectomy [risk ratio (RR) = 1.63 in patients with Graves' disease and RR = 1.59 in those with toxic multinodular goitre] and age at the first RAI treatment (RR = 0.998 and RR = 0.996 per year) were statistically significantly associated with the development of hypothyroidism both in patients with Graves' disease and in those with toxic multinodular goitre. Antithyroid medication preceding RAI therapy (RR = 0.47) decreased and female gender (RR = 1.53) increased the risk of hypothyroidism only in patients with Graves' disease. Administration of a single dose of RAI resulted in the control of hyperthyroidism in 75% of patients, while two to six RAI treatments were needed in 25% of patients to achieve either a hypothyroid or a euthyroid state in both groups. None of the clinical factors studied was associated with the remission rate either in patients with Graves' disease or in those with toxic multinodular goitre. The remission rate did not differ between the patients who received a dose of RAI calculated according to the uptake of RAI and thyroid size and those who received an empirical dose of RAI. The fixed 7 mCi (259 MBq) dose of RAI cured 80% of patients. CONCLUSION: RAI treatment is effective in treating hyperthyroidism in patients with Graves' disease, but hypothyroidism will develop in 82% of patients in 25 years. Because the development of hypothyroidism seems to be inevitable and unpredictable by any clinical factors, the objective of RAI treatment should be to minimize the persistence of hyperthyroidism with the simplest possible form of treatment. We recommend a fixed 7 mCi dose of RAI to be used as the first empirical dose in the treatment of hyperthyroidism, at least in Graves' disease.