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.     

Approach to the patient with nontoxic multinodular goiter

Thyroid nodules are very common, and although the majority are benign, approximately 5% may harbor malignancy. The evaluation of the patient with solitary thyroid nodule is generally straightforward and will typically include measurement of serum TSH to assess thyroid function and fine-needle aspiration biopsy of the nodule, with or without ultrasound (US) guidance. The approach to the patient with nontoxic multinodular goiter represents a more difficult problem for the clinician. All patients should have serum TSH measured to assess functional thyroid status and US examination to evaluate the number, size, and sonographic features of the nodules and assist in the selection of nodules that may need fine-needle aspiration biopsy. Patients with nodules yielding malignant cytology should be referred for surgery. Given the lack of reliable markers to predict biological behavior of nodules with suspicious (indeterminate) cytology, patients with such nodules are generally advised to have surgery, unless autonomous function of these nodules can be confirmed by scintigraphy. Most of these patients, however, will ultimately prove to have benign follicular tumors. Many patients with benign but large goiters may experience clinical symptoms of pressure, such as dysphagia, choking sensation, or airway obstruction. Such patients will often require surgery for alleviation of symptoms. In the absence of malignancy, asymptomatic patients may be observed. Radioactive iodine, commonly used in many parts of Europe, is safe and effective and may be a reasonable option for many patients. Periodic follow-up with neck palpation and US exam is recommended for all patients.     

Peripheral blood levels of thyroglobulin mRNA and serum thyroglobulin concentrations after radioiodine ablation of multinodular goiter with or without pre-treatment with recombinant human thyrotropin

We investigated the effect of therapeutic doses of radioiodine (RAI) on peripheral serum messenger thyroglobulin RNA (Tg mRNA) and serum thyroglobulin (sTg) in patients with multinodular goiter (MNG) preceded or not by treatment with recombinant human TSH (rhTSH). Fourteen patients with large MNG (91-542 ml) received RAI (550-2960 MBq). Half of the patients received 0.45 mg of rhTSH prior to the treatment (RAI+rhTSH group) and half did not (RAI group). Patients' blood samples were collected before and 24, 48, and 72 h; 7 and 30 days; and 6, 9, and 12 months after RAI treatment. Serum Tg was measured by immunoradiometric assay, serum anti-Tg by radioimmunoassay, and quantification of circulating Tg mRNA was performed by real-time PCR. The shrinkage of MNG volume was documented by serial computed tomography (CT) scans before, 6 and 12 months after RAI. Peak Tg mRNA and sTg were reached earlier in the RAI+rhTSH group (24 h and 48 h) than in the RAI group (7 days). Both declined after the peak and the lowest levels were observed at 12 months. The mean reduction of the thyroid volume was 19.8% (RAI group) and 30.3% (RAI+rhTSH group) at 6 months (ns) and 32.8% RAI and 52.5% (RAI+rhTSH group) at 12 months (p<0.05). After RAI treatment there was a significant and positive correlation between goiter volume and sTg only in the RAI group (r=0.7; p=0.032). Serum anti-Tg had a transitory and relatively small elevation in 3 and 2 patients, respectively, in the RAI and RAI+rhTSH groups. We concluded that after RAI ablation of MNG there is a rapid release of Tg into the serum possibly from the colloid, which is followed by an elevation of serum Tg mRNA that may be due to an increased release of follicular cells into the blood stream. Both phenomena are enhanced by the use of rhTSH before RAI treatment as a consequence of a more effective and prolonged radiation exposure of the thyroid follicles.     

Recombinant human thyrotropin as adjuvant in the treatment of multinodular goiters with radioiodine

The use of 131I in the treatment of multinodular goiters (MNG) is well established. We evaluated the effect of 30 microCi 131I (1.11 GBq) in 18 patients with MNG with the aid of two injections of 0.1 mg recombinant human TSH (rhTSH), given on d 1 and 2. A dose of 30 microCi 131I was given on d 3. TSH, T3, free T4, and thyroglobulin were measured on d 1, 2, 3, 5, 10, 30, 60, 90, and 180, and antithyroid antibodies were measured on d 1, 30, 90, and 180. Twenty-four-hour 131I uptake measured 1-3 months before rhTSH increased from 12.3 +/- 6.2 to 53.5 +/- 10.9% (P < 0.0001), free T4 from 1.3 +/- 0.2 to peak 3.2 +/- 1.1 ng/dl levels (P < 0.0001), T3 from 113.9 +/- 35.0 to peak 332.2 +/- 123.0 ng/dl levels (P < 0.0001), TSH from 0.76 +/- 0.71 to peak 18.9 +/- 5. 3 mU/liter levels (P < 0.0001), and thyroglobulin from 280.9 +/- 370.0 to peak 1838.5 +/- 1360.7 ng/dl levels (P = 0.001). Painful thyroiditis (33%) and mild thyrotoxicosis (39%) constituted minor side effects. There were no changes in echocardiographic parameters, done before and after rhTSH administration, on d 3. Hypothyroidism developed in 65%. Mean goiter size, measured by computed tomography, decreased from 97.9 +/- 45.4 to 65.5 +/- 47.3 ml (P < 0.0001; reduction: 39 +/- 19%) after 6 months. We conclude that rhTSH is a safe and efficient therapeutic tool in the treatment of MNG allowing the use of outpatient therapeutic 131I doses.     

Pretreatment with a single,low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter

In patients with nodular goiter, radioiodine ((131)I) therapy results in a mean reduction in thyroid volume (TV) of approximately 40% after 1 yr. We have demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h radioactive iodine uptake (RAIU) in these patients. We have now studied the safety and efficacy of therapy with a reduced dose of (131)I after pretreatment with rhTSH. Twenty-two patients with nodular goiter received (131)I therapy, 24 h after im administration of 0.01 (n = 12) or 0.03 (n = 10) mg rhTSH. In preceding diagnostic studies using tracer doses of (131)I, 24-h RAIU without and with rhTSH pretreatment (either 0.01 or 0.03 mg) were compared. Therapeutic doses of (131)I were adjusted to the rhTSH-induced increases in 24-h RAIU and were aimed at 100 micro Ci/g thyroid tissue retained at 24 h. Pretreatment with rhTSH allowed dose reduction of (131)I therapy by a factor of 1.9 +/- 0.5 in the 0.01-mg and by a factor of 2.4 +/- 0.4 in the 0.03-mg rhTSH group (P < 0.05, 0.01 vs. 0.03 mg rhTSH). Before and 1 yr after therapy, TV and the smallest cross-sectional area of the tracheal lumen were measured with magnetic resonance imaging. During the year of follow-up, serum TSH, free T(4) (FT(4)), T(3), and TSH receptor antibodies were measured at regular intervals. TV before therapy was 143 +/- 54 ml in the 0.01-mg group and 103 +/- 44 ml in the 0.03-mg rhTSH group. One year after treatment, TV reduction was 35 +/- 14% (0.01 mg rhTSH) and 41 +/- 12% (0.03 mg rhTSH). In both groups, smallest cross-sectional area of the tracheal lumen increased significantly. In the 0.01-mg rhTSH group, serum FT(4) rose, after (131)I treatment, from 15.8 +/- 2.8 to 23.2 +/- 4.4 pM. In the 0.03-mg rhTSH group, serum FT(4) rose from 15.5 +/- 2.5 to 23.5 +/- 5.1 pM. Individual peak FT(4) levels, reached between 1 and 28 d after (131)I treatment, were above the normal range in 12 patients. TSH receptor antibodies were negative in all patients before therapy and became positive in 4 patients. Hyperthyroidism developed in 3 of these 4 patients between 23 and 25 wk after therapy. In conclusion, in patients with nodular goiter pretreatment with a single, low dose of rhTSH allowed approximately 50-60% reduction of the therapeutic dose of radioiodine without compromising the efficacy of TV reduction.     

Cardiovascular assessment of hyperthyroid patients with multinodular goiter before and after radioiodine treatment preceded by stimulation with recombinant human TSH

Treatment of large multinodular goiter (MNG) with radioiodine preceded by recombinant human thyrotropin (0.1 mg rhTSH) has been shown to be a safe alternative for patients with comorbidities that preclude surgery. However, the increase in serum thyroid hormones that follows both treatments may be harmful for some patients, particularly those with underlying cardiovascular disease. In this study, we evaluated cardiac parameters (clinical, ECG, 24-h Holter, Doppler echocardiogram, treadmill stress test) in 27 of 42 patients (ages 42–80 years) with large MNGs who were treated with rhTSH before receiving 30 mCi radioiodine therapy. At baseline, 18 patients had subclinical and six patients had overt iodine-induced hyperthyroidism. All patients had a transient surge in serum levels of free T4 and total T3 into the hyperthyroid range after therapy. However, repeated cardiac evaluation did not show significant changes as compared with baseline evaluation. In conclusion, rhTSH stimulated RAI treatment of MNG did not affect structural and functional parameters of the heart, despite transient high-serum levels of thyroid hormones.     

Use of recombinant human thyrotropin before radioiodine therapy in patients with advanced differentiated thyroid carcinoma

The use of 131I for radioablative therapy in patients with differentiated thyroid cancer (DTC) requires a sufficient serum concentration of TSH for efficient thyroid tissue uptake of iodine. We describe the use of recombinant human TSH (rhTSH) in conjunction with ablative radioiodine therapy (RIT) in 11 patients (16 total treatments) with advanced and/or recurrent DTC (5 papillary, 6 follicular) for whom withdrawal of thyroid hormone suppression therapy (THST), the standard method to increase serum TSH, was not an option. Indications for rhTSH use in these patients included inability to tolerate withdrawal of thyroid hormones due to very poor physical condition or inability to achieve sufficient serum TSH levels after THST withdrawal. Ten patients had undergone thyroidectomy, and most (9 of 11) had received prior ablative RIT after THST withdrawal. Baseline thyroglobulin levels ranged from 25 to nearly 30,000 ng/mL, reflecting the heterogeneity of the patient population. In 7 cases (5 patients), posttherapy thyroglobulin levels assessed at a mean of 4.3 months (range, 2-10 months) after 131I therapy were decreased by at least 30% compared to pretherapy levels. In follow-up visits, an additional 3 patients showed marked clinical improvement or decreased or stabilized tumor burden in whole body scans compared to pretherapy scans. Three patients died of progressive disease within 2 months of therapy before follow-up assessments occurred. No adverse events were reported among the 8 surviving patients. The results suggest that rhTSH offers a promising alternative to THST withdrawal to allow ablative RIT after effective TSH stimulation in patients with advanced recurrent DTC who would not otherwise be able to receive this treatment. This therapeutic indication extends the clinical potential of this new agent, already demonstrated to be effective for use with 131I for diagnostic purposes.     

Management of the nontoxic multinodular goiter: a North American survey.

To assess approaches to the diagnosis and therapy of patients with nontoxic multinodular goiter, a questionnaire was circulated to all members of the American Thyroid Association (ATA). An index case report was presented (42-yr-old woman with an irregular, nontender, bilaterally enlarged thyroid of 50-80 g and no clinical suspicion of malignancy or thyroid dysfunction), and 11 variations were proposed to evaluate how each alteration would affect management. One hundred and forty responses were retained (approximately 50% of clinically active ATA members). For the index case, a TSH determination was the routine choice of 100%, and serum thyroid autoantibodies were measured by 74%. Simultaneous use of serum TSH, a thyroid hormone assay, and antithyroid peroxidase was employed by 49%. Only 4% included a calcitonin assay. The median number of blood tests ordered was 3 (range, 1-7). Ultrasound was used by 59%, thyroid scintigraphy by 24%, and both imaging modalities by 11%. Fine needle aspiration biopsy (FNAB) was performed by 74%. If scintigraphy showed inhomogeneous tracer distribution or a dominant hypofunctioning region, FNAB was performed by 15% and 97%, respectively. L-T4 treatment was preferred by 56%, radioiodine by 1%, surgery by 6%, and 36% would recommend no treatment. A large goiter, a history of external radiation, or rapid growth increased the preference for surgery. In case of a suppressed serum TSH level, radioiodine was used by 56%. In conclusion, in the work-up of patients with nontoxic multinodular goiter, ATA clinicians employ determinations of TSH often combined with a T4 and/or T3 assay and antithyroid peroxidase antibodies. Thyroid imaging, primarily ultrasound, is performed by more than two thirds, and FNAB by three fourths. This diagnostic evaluation is significantly less extensive than that of the European Thyroid Association members, but the distribution of treatment choices is quite similar. In accordance with their European colleagues, the majority of ATA members prefer the use of L-T4 therapy. There is, however, still a wide variation in the perceived optimal management of this condition among members of both organizations.     

Administration of a single low dose of recombinant human thyrotropin significantly enhances thyroid radioiodide uptake in nontoxic nodular goiter

Radioiodine (131I) is increasingly used as treatment for volume reduction of nontoxic, nodular goiter. A high dose of 131I is often needed because of low thyroid radioiodide uptake (RAIU). We investigated whether pretreatment with a single, low dose of recombinant human TSH (rhTSH; Thyrogen, Genzyme Transgenics Corp.) enhances RAIU in 15 patients with nontoxic, nodular goiter (14 women and 1 man; aged 61+/-11 yr). Four patients were studied twice, and 1 patient was studied 3 times. RAIU was measured both under basal conditions and after pretreatment (im) with rhTSH, given either 2 h (0.01 mg; n = 7) or 24 h [0.01 mg (n = 7) or 0.03 mg (n = 7)] before 131I administration (20-40 microCi). Serum levels of TSH, free T4 (FT4), and total T3 were measured at 2, 5, 8, 24, 48, 72, 96, and 192 h after rhTSH administration. After administration of 0.01 mg rhTSH, serum TSH rose from 0.7+/-0.5 to a peaklevel of 4.4+/-1.1 mU/L (P < 0.0001), FT4 rose from 16.0+/-2.6 to 18.5+/-3.7 pmol/L (P < 0.0001), and T3 rose from 2.10+/-0.41 to 2.63 - 0.66 nmol/L (P < 0.0001). After administration of 0.03 mg rhTSH, TSH rose from 0.6+/-0.4 to 15.8+/-2.3 mU/L (P < 0.0001), FT4 rose from 15.2+/-1.5 to 21.7+/-2.9 pmol/L (P < 0.0001), and T3 rose from 1.90+/-0.43 to 3.19+/-0.61 nmol/L (P < 0.0001). Peak TSH levels were reached at 5-8 h and peak FT4 and T3 levels at 8-96 h after rhTSH administration. Administration of 0.01 mg rhTSH 2 h before 131I increased 24-h RAIU from 30+/-11% to 42+/-10% (P < 0.02), 0.01 mg rhTSH administered 24 h before 131I increased 24-h RAIU from 29+/-10% to 51+/-10% (P < 0.0001), and 0.03 mg rhTSH administered 24 h before 131I increased 24-h RAIU from 33+/-11% to 63+/-9% (P < 0.0001). After administration of 0.01 mg rhTSH 2 h before 131I, 24-h RAIU did not increase in 1 patient, whereas the increase in 24-h RAIU was less than 10% in 2 other patients. In contrast, administration of rhTSH 24 h before 131I increased 24-h RAIU by more than 10% in all 14 patients (by >20% in 10 and by >30% in 6). In conclusion, pretreatment with a single, low dose of rhTSH in patients with nontoxic, nodular goiter increased RAIU considerably. Our observations hold promise that administration of rhTSH before 131I therapy for nontoxic, nodular goiter will allow treatment with lower doses of 131I in these patients.     

Incidence of radioiodine induced Graves' disease in patients with multinodular toxic goiter.

In this study, we assessed the incidence of Graves' disease (GD) following radioiodine therapy (RIT) in a large cohort of well characterized patients with autonomy in comparison to the clinical course of control patients with thyroidal autonomy not definitively treated with (131)I or surgery. 622 consecutive patients were treated with (131)I for autonomy (unifocal: n = 321; multifocal: n = 199; disseminated: n = 102) and followed up for at least 6 months post RIT. 108 consecutive patients with autonomy not definitively treated (unifocal: n = 49; multifocal: n = 42; disseminated: n = 11) followed up for at least 6 months served as controls. Initial evaluation and follow-up included determination of FT3, FT4, TSH, autoantibodies against the thyroid peroxidase (anti-TPO) and TSH-receptor antibodies (TRAb) by highly sensitive radio receptor-assay, quantitative thyroid scintigraphy and sonography. After 6 months, GD was newly diagnosed in 1/321 patients with unifocal autonomy, in 1/199 patients with multifocal autonomy and in 0/108 control patients. In patients with disseminated autonomy (group C), GD was diagnosed significantly more often compared to the other groups (5/102 patients; 4,1 %; p < 0.05). In conclusion, RIT may induce Graves' disease in a few cases with toxic multinodular goiter. The incidence in this population is small. Compared with patients suffering from uni- or multifocal autonomy, subjects with disseminated autonomy have a more than tenfold higher risk for the development of GD.     

Transient goiter enlargement after administration of 0.3 mg of recombinant human thyrotropin in patients with benign nontoxic nodular goiter: a randomized, double-blind, crossover trial

BACKGROUND: Recombinant human (rh) TSH, in doses from 0.01 to 0.9 mg, has been used to augment the effect of radioiodine ((131)I) therapy in patients with a benign nontoxic nodular goiter. Transient thyroid enlargement and thyrotoxicosis may be seen following (131)I therapy. AIM: The aim of the study was to investigate whether rhTSH per se causes goiter enlargement, until now an issue evaluated only in healthy nongoitrous subjects. METHODS: In random order, 10 patients with nontoxic nodular goiter [mean 39.8 +/- 20.5 (sd) ml] received either 0.3 mg rhTSH or isotonic saline in a double-blinded crossover design. Thyroid volume (by ultrasound) and function were closely monitored during the following 28 d. RESULTS: Saline injection did not affect thyroid function or size. After rhTSH, median serum TSH increased from baseline 0.97 mU/liter (range 0.39-1.56) to 37.0 mU/liter (range 18.5-55.0) at 24 h (P < 0.01), with a subsequent decline to subnormal levels at d 7. Mean free T(4) and free T(3) increased significantly from baseline to a maximum at 48 h. Twenty-four hours after rhTSH, the mean goiter volume was significantly increased by 9.8 +/- 2.3% (sem) (P = 0.01) and after 48 h by 24.0 +/- 5.1% (P = 0.002). The goiter enlargement had reverted at d 7. Nine patients had symptoms of hyperthyroidism and/or cervical compression after rhTSH, as opposed to one during placebo treatment (P < 0.02). CONCLUSIONS: A transient average goiter enlargement of up to 24% is seen after 0.3 mg rhTSH. This may lead to a significant cervical compression when used for augmentation of (131)I therapy in patients with goiter. The use of lower doses of rhTSH needs to be explored.     

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.     

Low-dose recombinant human thyrotropin-aided radioiodine treatment of large, multinodular goiters in elderly patients

OBJECTIVE: We aimed to assess low-dose recombinant human thyroid-stimulating hormone (rhTSH)-aided, fixed-activity radioiodine therapy of large, multinodular goiters (MNGs) in elderly patients with comorbidities. DESIGN: This was a short-term, observational study. METHODS: We measured 24-h thyroid radioiodine uptake (RAIU) of 2 microCi 131-iodine at baseline and 24 h after intramuscular injection of 0.03 mg rhTSH in 17 patients (aged 60-86 years, 12 women), who subsequently received 30 mCi 131-iodine 24 h after an identical rhTSH injection. TSH and free thyroxine (FT4) were measured at baseline and days 10, 30 and 90 after therapy. Thyroid volume was assessed by computed tomography at baseline and day 180. RESULTS: rhTSH, 0.03 mg, significantly increased mean 24-h thyroid RAIU from 25.8% +/- 10.3% to 43.3% +/- 8.4% (68% relative increase; t(16) = -8.43, P < 0.001). The proportion of patients overtly or subclinically hyperthyroid (TSH < 0.5 mU/l) decreased from 71% (12/17) at baseline to 19% (3/16) at 3 months. Mean serum FT4 peaked at slightly above normal range, 25.9 +/- 7.7 pmol/l (46% over baseline) and was 21% under baseline levels at 3 months. Mean estimated thyroid volume fell 34% from baseline to 6 months (170.0 +/- 112.8 to 113.1 +/- 97.5 ml; P < 0.01). Symptomatic relief, improved well-being, and/or reduction or elimination of antihyperthyroid medication were seen in 76% of patients. Three (18%) patients had transient neck pain or tenderness, or palpitations; one had transient asymptomatic thyroid enlargement; and three (18%) became hypothyroid by 3 months. CONCLUSIONS: Intramuscular rhTSH, 0.03 mg, followed 24 h later by 30 mCi 131-iodine, is a safe, effective and convenient treatment for MNG in elderly patients with comorbidities.     

Recurrence of hyperthyroidism in multinodular goiter after long-term drug therapy: a comparison with Graves' disease.

The chance of permanent remission after prolonged drug therapy was investigated in 41 patients with toxic multinodular goiter. For purposes of comparison a group of 41 patients with Graves' disease was also studied. After euthyroidism was achieved all patients received a combination of thionamide and thyroxine for at least 12 months. The minimum follow-up period was 2 yr. Relapse of thyrotoxicosis occurred in 95.1% of patients with toxic multinodular goiter and 34.1% of patients with Graves' disease (p < 0.001). It is concluded that for patients with toxic multinodular goiter early radioiodine therapy or surgery is preferred since prolonged drug therapy seldom produces permanent remission.     

Clinical comparison of whole-body radioiodine scan and serum thyroglobulin after stimulation with recombinant human thyrotropin.

Sensitive monitoring for thyroid cancer recurrence or persistence includes whole-body radioiodine scanning (WBS) and measurement of serum thyroglobulin (Tg) after endogenous or exogenous thyrotropin (TSH) stimulation. We reviewed our experience using recombinant human thyrotropin (rhTSH) in 83 patients to compare the clinical relevance of a positive WBS and/or Tg. Ten patients had a positive WBS; eight of these patients had activity limited to the thyroid bed. rhTSH-stimulated Tg was 2 ng/mL or more in 25 and 5 ng/mL or more in 13 patients. Of the patients with a negative WBS, 11 of 20 patients with a Tg 2 ng/mL or more and 7 of 9 patients with a Tg 5 ng/mL or more received therapy or further evaluation based on the Tg alone. Conversely, only 1 of 5 patients with a serum Tg less than 2 ng/mL received therapy or further evaluation based on a positive WBS alone. Three of the patients who did not receive therapy or further evaluation, had subsequent negative WBS 10-12 months later, suggesting lack of clinically significant disease. Twenty patients had a negative WBS and serum Tg 2 ng/mL or more. Eleven of 20 patients had a Tg less than 5 ng/mL and 4 of these patients had further evaluation with a neck ultrasound. One patient had a biopsy-proven recurrence (rhTSH-stimulated Tg 4 ng/mL). Subsequent evaluations (> or = 6 months later) have been negative for 8 patients. Of the nine patients with a Tg 5 ng/mL or more and a negative WBS, 7 had further evaluation and 6 of 7 had identified disease. In summary, rhTSH-stimulated WBS and Tg are complementary, but Tg is a more sensitive indicator of disease recurrence or persistence. In our practice, an rhTSH-stimulated Tg greater than 4-5 ng/mL often resulted in further evaluation, while a Tg less than 4 ng/mL rarely resulted in further immediate evaluation.     

Improvement of goiter volume reduction after 0.3 mg recombinant human thyrotropin-stimulated radioiodine therapy in patients with a very large goiter: a double-blinded, randomized trial

INTRODUCTION: The effect of (131)I therapy amplification by recombinant human (rh) TSH prestimulation in very large goiters has not been evaluated in a double-blinded, placebo-controlled study. METHODS: Twenty-nine patients (22 females; age range 37-87 yr) with a large multinodular goiter (median 160 ml, range 99-440 ml) were randomized to receive placebo (n = 15) or 0.3 mg rhTSH (n = 14) 24 h before (131)I administration. Goiter volume was monitored by magnetic resonance imaging. RESULTS: On average, the goiter volume was unchanged 1 wk after therapy in both groups, but the largest deviations from baseline were observed in the rhTSH group. After 12 months the median goiter volume was reduced from 170 to 121 ml in the placebo group and from 151 to 72 ml in the rhTSH group, respectively (within group: P = 0.001; between group: P = 0.019). This corresponds to reductions of 34.1 +/- 3.2 and 53.3 +/- 3.3%, respectively (between group: P < 0.001). In the placebo group, the goiter reduction correlated positively with the retained thyroid (131)I dose, whereas such a relationship was absent in the rhTSH group. Adverse effects, mainly related to thyroid pain and cervical compression, were more frequent in the rhTSH group. At 12 months, goiter-related complaints were significantly reduced in both groups without any between-group difference. One and three patients in the placebo and the rhTSH group, respectively, developed hypothyroidism. CONCLUSION: rhTSH-stimulated (131)I therapy improves the reduction of very large goiters by more than 50%, compared with (131)I therapy alone, but at the expense of more adverse effects after therapy. Our data suggest that rhTSH stimulation may work through mechanisms that go beyond the increase in thyroid (131)I uptake.