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.     

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.     

Suppressive therapy with levothyroxinefor solitary thyroid nodules

OBJECTIVE: To evaluate the effect of treatment with TSH suppressive dose of levothyroxine in patients with benign thyroid nodules. DESIGN: Prospective randomized study. Group A (n = 20) patients received levothyroxine and group B (n = 20) patients did not. The dose of levothyroxine was adjusted to obtain an effective suppression of TSH. A clinical, analytical and morphological (with ultrasound) review was performed every 3 months. The mean +/- SD follow-up period was 10.6 +/- 2.2 months. PATIENTS: Forty euthyroid women with solitary thyroid nodule on palpation, cold on scintigraphy and cytologically benign without contraindication participated. MEASUREMENTS: At entry: biochemical and hormonal parameters, thyroid scintigraphy and thyroid ultrasonography. Every 3 months additional determinations of thyroid hormones and TSH levels were carried out, if necessary, to verify effective TSH suppression. Every 6 months thyroid ultrasound imaging was performed. RESULTS: Patients were euthyroid at entry into the study. The mean dose of levothyroxine necessary to obtain TSH suppression was 2.82 +/- 0.6 micrograms/kg/day. No significant modification in the thyroid nodule diameter (mean +/- SD 2.6 +/- 1.2 vs 2.5 +/- 1.2 cm) or in the thyroid nodule volume (10.3 +/- 11.9 vs 10.1 +/- 12.2 ml) were observed in group A. In group B the results were similar (2.8 +/- 0.9 vs 2.7 +/- 1.8 cm and 9.2 +/- 6.4 vs 9.2 +/- 9.5 ml, respectively). No differences were found in either group in the number of nodules that reduced significantly their volume (four and three, respectively). CONCLUSIONS: The suppressive therapy with levothyroxine was not effective in reducing nodule sizes in patients with solitary benign thyroid nodules.     

Effect of low- and high-dose levothyroxine on thyroid nodule volume: a crossover placebo-controlled trial

OBJECTIVE: The efficacy and the effective dose of levothyroxine suppressive therapy in the treatment of benign thyroid nodules are controversial. In this study, we aimed to determine the response of solitary thyroid nodules to low- or high-level TSH suppression in a placebo-controlled, randomized crossover trial. DESIGN: Forty-nine patients with solitary thyroid nodules on palpation were randomized to high-level and low-level TSH suppression groups. In each group, patients were further randomized to placebo and active levothyroxine subgroups. Patients in each subgroup were crossed over to placebo or active levothyroxine at the end of the first year and were then followed up for an additional year. METHODS: TSH levels were suppressed to 0.4-0.6 mIU/ml and < or = 0.01 mIU/ml in the low-level and high-level TSH suppression groups, respectively. Nodule volumes were measured at baseline and every 6 months after the desired level of TSH was reached if the patients were in the active levothyroxine treatment group or every 6 months if they were in the placebo group. RESULTS: In high-level TSH suppression groups, nodule volume decreased significantly at the end of the active treatment periods (4.99 +/- 2.02 ml vs. 3.20 +/- 1.50 ml, P < 0.01, in Group 1; and 3.72 +/- 1.79 ml to 2.05 +/- 0.64 ml, P < 0.001, in Group 2). In the low-level TSH suppression groups, nodule volume also decreased significantly at the end of the active treatment periods (4.43 +/- 1.76 ml vs. 3.04 +/- 1.32, P < 0.05, in Group 3; and 3.59 +/- 0.89 ml to 2.22 +/- 0.59 ml, P < 0.01, in Group 4). Nodule volumes regained their original volumes during the placebo treatment periods. The percentage decline in clinically relevant nodule volume reduction (> or = 50%) was similar in the low-level and high-level TSH suppression groups. CONCLUSION: Low- and high-level TSH suppression were equally effective in reducing nodule volume and thus, considering the complications of high-level TSH suppression, low-level TSH suppression should be used if one considers levothyroxine suppressive therapy to reduce thyroid nodule size.     

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.     

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.     

Autoimmunization and multinodular large toxic goiter therapy using repeated doses of 131I

The radioiodine therapy can favour and induces of autommunological reaction in thyroid gland. The aim of the study was evaluation of antithyroid autoantibodies in patients with multinodular large toxic goiter treated with repeated doses of 131I before and after therapy. Studies were conducted in 24 women (age range: 65-84 yrs) with multinodular large toxic goiters--goiter volume assessed by USG over 100 ml. Serum TSH, fT4, antithyroid antibodies (anti-TPO, anti-Tg, TSHR-Ab) levels were estimated in all patients parallel with radioiodine uptake test (after 5 and 24 hours), 131I thyroid scintigraphy and fine needle biopsy. These studies and therapy with 22 mCi 131I were repeated every 3 months. Before therapy median of thyroid volume was approximately 195 ml and during therapy gradually decreased to 110 ml after 12 months. After 12 months we found 11% of patients with hyperthyrodism, 62% of patients with euthyroidism and 27% of patients with hypothyroidism. Before radioiodine treatment aTg and aTPO presence were detected in the most of patients, but only in 5 cases above normal value. TSHRAb were detected (normal, very low values) in 16 patients. During therapy statistically significance increase of TSHRAb levels (median: from 0,27 to 0,65 after 6 months and to 0,71 IU/l after 9 months) was observed; aTPO and aTg antibodies levels showed marked tendency to rise, but without significant differences (aTPO median: from 40 IU/ml to 48 IU/ml; aTg - median: from 27 IU/ml to 46 IU/ml). During these observations we didn't find evident correlation between the levels of antithyroid antibodies, radioiodine uptake, proved reduction of goiter volume and TSH, FT4, FT3 values.     

Effects of thyroid-stimulating hormone suppression with levothyroxine in reducing the volume of solitary thyroid nodules and improving extranodular nonpalpable changes: a randomized,double-blind,placebo-controlled trial by the French Thyroid Research Group

The efficacy of suppressing TSH secretion with levothyroxine (L-T(4)) in reducing solitary thyroid nodule growth is still controversial. In this prospective multicenter, randomized, double-blind, placebo-controlled trial, 123 patients with a single palpable benign nodule were included and randomly allocated to an 18-month treatment with L-T(4) or placebo. Individual dose was adjusted to allow a serum TSH level below 0.3 mIU/liter. Clinical and ultrasonographic nodule characteristics were assessed before treatment and 3, 6, 12, and 18 months thereafter. The largest mean nodule size assessed on palpation and largest volume, assessed by ultrasonography, decreased in the L-T(4) group and increased slightly in the placebo group [size, -3.5 +/- 7 mm vs. +0.5 +/- 6 mm (P = 0.006); volume, -0.36 +/- 1.71 ml vs. +0.62 +/- 3.67 ml (P = 0.01), respectively]. The proportion of clinically relevant volume reduction (> or =50%) rose significantly in the L-T(4) group [26.6% vs. 16.9% (P = 0.04)]. The proportion of patients with a reduced number of infraclinical additional nodules was significantly higher in the L-T(4) group [9.4% vs. 0 (P = 0.04)]. It is concluded from this study that suppressive L-T(4) therapy is effective in reducing solitary thyroid nodule volume and improving infraclinical extranodular changes.     

Effect of ultrasound-guided interstitial laser photocoagulation on benign solitary solid cold thyroid nodules - a randomised study

AIM: To evaluate the efficacy of ultrasound (US)-guided interstitial laser photocoagulation (ILP) on thyroid function, nodule size and patient satisfaction in benign solitary solid cold thyroid nodules by comparing one ILP session with no treatment in a prospective randomised study. MATERIALS AND METHODS: Thirty euthyroid outpatients with a benign solitary solid and a scintigraphically cold thyroid nodule causing local discomfort were assigned to one session of ILP (n = 15) or observation (n = 15) and followed for 6 months. Thyroid nodule volume and total thyroid volume were assessed by US and thyroid function was determined by routine assays before and during follow-up. Pressure and cosmetic complaints before and at 6 months were evaluated on a visual analogue scale. ILP was performed under US guidance and with an output power of 2.5-3.5 W. RESULTS: In the ILP group, the nodule volume decreased from 8.2 ml (6.1; 11.9) (median; quartiles) to 4.8 ml (3.0; 6.6) after 6 months (P = 0.001). The overall median reduction was 44% (37; 52), which correlated with a significant decrease in pressure symptoms as well as cosmetic complaints. In the control group, a non-significant increase in median nodule volume of 7% (0; 34) after 6 months was seen. No major side-effects were seen in the ILP group. There was no correlation between thermal energy deposition and nodule volume reduction. Thyroid function was unaltered throughout. CONCLUSION: US-guided ILP, given as a single treatment, resulted in a satisfactory clinical response in the majority of patients with a benign solitary solid cold thyroid nodule, and may become a clinically relevant alternative to surgery in selected 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.     

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.     

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.     

Successful treatment of solitary toxic thyroid nodules with relatively low-dose iodine-131, with low prevalence of hypothyroidism

Forty-five patients with solitary toxic thyroid adenomas received 131I (mean dose, 10.3 mCi) for treatment of hyperthyroidism and were followed for 4.9 +/- 3.2 years (range, 0.5 to 13.5). Seventy-seven percent were euthyroid by 2 months, 91% by 6 months, and 93% by 1 year. Only 3 patients did not respond to a single dose of 131I, but all responded to multiple doses. Late recurrent hyperthyroidism occurred in 3 patients at 4.5, 6, and 10 years after treatment with a single dose of 131I. No patient developed clinical hypothyroidism, and none had a low serum thyroxine level associated with an elevated serum thyrotrophin level. Three patients developed minimal elevations in serum thyrotrophin levels: 1, 4, and 7.5 years after 131I treatment, their thyrotrophin levels were 8.4, 6.2, and 9.6 microU/mL, respectively. All 3 had normal serum thyroxine levels and were clinically euthyroid. Mean serum thyroxine concentrations of all patients were unchanged between 1 and more than 9 years of follow-up. These data suggest that solitary toxic adenomas may be treated with relatively low doses of 131I (5 to 15 mCi), and that post-treatment hypothyroidism is very unusual.     

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.     

Calculation of the radioiodine dose for the treatment of Graves' hyperthyroidism: is more than seven-thousand rad target dose necessary?

Some authors recently suggested a significant increase in the target dose of radioiodine treatment in Graves' disease. The aim of the present study was to investigate the impact of thyroid gland mass on the success rate of radioiodine treatment. For this purpose, the thyroid function of 105 consecutive Graves' patients was assessed 6 and 12 months after a 131I treatment and correlated to the gland mass. The patients were categorized according to the gland mass into small (< or = 30 g; 19 patients), medium size (31-50 g; 40 patients), and large size (> 50 g; 46 patients) groups (S, M, L groups, respectively). None of the patients received more than a 10,000-rad (100-Gy) target dose. During the calculation of administered 131I activity, late uptake measurement has also been routinely used, in addition to the usual maximal uptake parameter. The established effective half-life of 131I was highly variable (5 +/- 1.2 days; range: 2-7.6 days) and could not be predicted based on other clinical data without measuring an extended radioiodine uptake curve of the given patient. However, the correlation between the administered activity calculated from the complete set of uptake values and that of only a single late one was excellent (r = 0.99). Six months after the 131I treatment, hyperthyroidism was cured in 81% of patients with small and medium size thyroid glands, with 62% euthyroid and 19% hypothyroid ratios respectively. In the early phase of study for large goiters, the same linear mass activity function was used during calculation as in smaller glands. In these 17 patients the nonhyperthyroid result was comparable to the results of treatment of the small and medium size gland groups only after 1 year (77%), but the 6-month success rate was significantly lower (53%; p < 0.05). After obtaining these results, the usual 7000-rad target dose was increased to 8000-10,000 rad (depending on the gland mass) in another group of 29 patients with large thyroid glands that result in an acceptable 6-month success rate of 72%. In conclusion, instead of the "mCi 131I/g gland mass/maximal uptake" dose calculation, we suggest a method in which (1) the late 131I uptake measurement is taken into account and (2) for large goiters there is an additional dose adjustment, ie, increase is needed over the usual linear, size driven calculation. No overall increase of target dose over 10,000 rad is necessary if no antithyroid medication is given shortly before 131I treatment.     

Short and long term effects of radioiodine treatment on the iodine content of the thyroid gland

Thyroid iodine content (TIC) was measured in nine patients with hyperthyroid Graves' disease for 5-26 months after treatment with 131I (100-125 muCi/g tissue). In all patients, TIC decreased; in eight patients it became undetectable within 5 +/- 3 (SD) months. This fall was parallel to those of serum T3 and T4 levels and was not prevented by the administration of large doses of stable iodine. In four patients, this decrease was irreversible and they became clinically hypothyroid. In the five other patients, it was partly reversible: the secondary increase of TIC was parallel to those of serum T3 and T4 and to a decrease in TSH levels. These data suggest that during the months after 131I treatment, determination of TIC may help to distinguish transient from irreversible hypothyroidism. The late effects of 131I were studied in 38 patients who had been treated for hyperthyroid Graves' disease from 1.5-22 yr previously. The 16 patients who, at the time of examination, were euthyroid with normal serum TSH levels (less than 8 microU/ml) had a TIC [3.2 +/- 3 (SD) mg] significantly lower than that of 10 euthyroid patients previously treated only with antithyroid drug therapy (16.7 +/- 8.2 mg). A significant negative correlation was found between log basal TSH and log TIC (r = 0.61, P less than 0.001) and a positive correlation between log T4 and log TIC (r = 0.56, P less than 0.002). The T3/T4 ratio in patients with undetectable TIC (19.9 +/- 7.9) was higher than that of the other patients (14.6 +/- 3.2) (P = 0.02, Wilcoxon test). This hormonal profile was not modified by iodide supplementation, which increased TIC only transiently. The turnover of thyroid iodine was accelerated, which appeared to be the consequence of a small thyroid functional mass and of hyperstimulation by TSH.     

Low-energy interstitial laser photocoagulation for treatment of nonfunctioning thyroid nodules: therapeutic outcome in relation to pretreatment and treatment parameters.

Objective: Interstitial laser photocoagulation (ILP) is a recently proposed therapeutic procedure for the ablation of benign thyroid nodules, which has already proven to be safe and effective. However, results supporting the routine use of ILP are still limited. Design: The aim of the study was to evaluate the efficacy and safety of ILP treatment in benign nonfunctioning thyroid nodules and to establish whether the therapeutic outcome may be predicted by any clinical parameter at baseline. Twenty-three patients with either a solitary nodule or a dominant nodule within a multinodular goiter underwent ILP and were evaluated 1 and 3 months later. In order to assess the efficacy of low-energy ILP, the procedure was performed with an output power of 3 W, delivering a mean energy of 33.4 +/- 12.7 Joule/mL of nodule volume, which is much lower than previously reported. Main outcome: Nodule volume significantly decreased after ILP as assessed after 1 and 3 months (analysis of variance; F = 5.37; p = 0.007). Patients with multinodular goiter showed a greater reduction at 3 months compared with patients bearing a solitary thyroid nodule (38.6 +/- 5.3 vs. 30.9 +/- 6.5%; p < 0.01). Age, sex, ultrasound pattern (isoechogenous/hypoechogenous), pretreatment volume, number of ILP treatments, and total energy delivered did not show any significant correlation with treatment outcome. Conclusions: Our results demonstrate that ILP can produce a significant reduction of thyroid nodule volume even when a much lower energy than previously reported is delivered. ILP constitutes a minimally invasive technique, which can be carried out on an outpatient basis and could represent a valid nonsurgical alternative for thyroid nodule management. Dominant nodules within a multinodular goiter appear to be more responsive to ILP compared with solitary thyroid nodules.     

On the usefulness of levothyroxine suppressive therapy in the medical treatment of benign solitary, solid or predominantly solid, thyroid nodules

The efficacy of levothyroxine suppressive therapy in the treatment of benign solitary thyroid nodules is controversial. In order to investigate this issue further we studied 122 patients with a solitary, solid or predominantly solid, thyroid nodule. The benign (colloid) nature of all nodules was proved by fine-needle aspiration biopsy. At the pertechnetate-99m thyroid scanning 91% of the nodules were "cold" and 9% "warm". All the patients received suppressive oral doses of levothyroxine (0.1 to 0.2 mg/day). Fifty-three patients were treated with levothyroxine for 6 months, 31 for 9 months and 38 for 12 months. The size of each nodule before and after treatment was evaluated by high-resolution ultrasonography. The actual suppression of TSH secretion was monitored at 3-month intervals using an ultrasensitive immunometric assay. At the end of levothyroxine treatment, patients were classified as responders (decrease in nodule volume greater than or equal to 50%, 68/122 = 55.7%; mean percent change in nodule volume = -77.1 +/- 15.7%), partially responders (decrease in nodule volume less than 50%, 24/122 = 19.7%; mean percent change in nodule volume = -27.5 +/- 10.1%), and nonresponders, when either no change in nodule volume (16/122 = 13.1%) or an increase in nodule volume (14/122 = 11.5%) was observed. In each group serum free T4 rose significantly in response to levothyroxine therapy, whereas serum free T3 remained unchanged. TSH levels were undetectable in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

A prospective randomized trial of levothyroxine suppressive therapy for solitary thyroid nodules

OBJECTIVE We examined the effects of l -thyroxine therapy versus placebo over a 12-month period on volume of solitary thyroid nodules. DESIGN Prospective randomized clinical trial; placebo and control groups followed for one year in three centres. PATIENTS One hundred and one euthyroid patients with single palpable colloid thyroid nodules. MEASUREMENTS Serum thyroid hormones, TSH, thyroglobulin, anti-thyroglobulin and anti-thyroid peroxidase antibodies measured at the first visit and after 2, 6 and 12 months; nodule volume and contralateral thyroid lobe thickness measured by ultrasound in double blind fashion; nodule diameter measured by palpation every 6 months. RESULTS In the treatment group the nodule volume measured by ultrasound decreased progressively but not significantly; in the placebo group no changes were demonstrated. The number of nodules which decreased in size was however significantly larger in the treatment group. None of the initial parameters was predictive for the response. In the treatment group the nodule size assessed by palpation showed a significant decrease after 12 months when compared to baseline. CONCLUSIONS In non-endemic areas TSH suppression induces nodule volume reduction measured by ultrasound which, although not significant, seems to be progressive and occurring only in a subgroup of patients. Sgnificant palpatory nodule reduction is probably related to decreased thickness of the surrounding thyroid tissue still responsive to TSH.     

Recombinant human thyrotropin markedly changes the 131I kinetics during 131I therapy of patients with nodular goiter: an evaluation by a randomized double-blinded trial

The present study compares, in a randomized double-blinded design, the expected and the actual absorbed thyroid radioactive dose in response to 0.3 mg recombinant human (rh)TSH (n = 35) or placebo (n = 28) given 24 h before (131)I therapy in patients with nodular goiter (median volume, 69 ml; range, 20-440 ml). The (131)I activity calculation was based on thyroid (131)I uptake (RAIU) at 24 and 96 h after a tracer dose of 0.5 MBq (131)I. After (131)I therapy, 24- and 96-h RAIU were repeated allowing a more exact assessment of the actual absorbed thyroid dose. The median (131)I activity was 617 and 632 MBq, respectively, in the rhTSH and the placebo group. At baseline, the 24- and 96-h RAIU and the expected thyroid dose were 32.8 +/- 9.1%, 32.1 +/- 8.2%, and 96.3 +/- 16.3 Gy, respectively, in the rhTSH group and 35.7 +/- 11.8%, 35.2 +/- 11.3%, and 94.1 +/- 18.5 Gy, respectively, in the placebo group (P value not significant between groups). After (131)I therapy, the 24- and 96-h RAIU and the actual absorbed thyroid dose were 46.9 +/- 11.7%, 45.0 +/- 12.1%, and 136.7 +/- 47.9 Gy, respectively, in the rhTSH group and 33.0 +/- 11.4%, 31.0 +/- 11.3%, and 76.9 +/- 27.5 Gy, respectively, in the placebo group (P < 0.001 between groups). Comparing the expected with the actual absorbed thyroid dose, this corresponds to a mean increase of 36.4% (95% confidence interval, 21.3-53.4) in the rhTSH group and a decrease of 21.5% (95% confidence interval, -33.9 to -6.6) in the placebo group (P < 0.001), equivalent to an increase of 73.8% in the absorbed thyroid dose in the rhTSH-treated group. We have thus for the first time shown that stimulation with rhTSH before (131)I therapy not only hinders the decrease in the thyroid RAIU observed with conventional (131)I therapy but in fact also significantly enhances the absorbed thyroid dose. Whether this also leads to a significant increase in goiter size reduction needs additional study.