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Departments of Nuclear Medicine (W.-A.N., D.A.H.) and Radiology (H.C.v.d.B.), Catharina Hospital, 5602 ZA Eindhoven, The Netherlands; and Departments of Endocrinology (W.-A.N., A.R.H.), Chemical Endocrinology (C.G.S., H.A.R.), and Nuclear Medicine (F.H.C.), University Medical Center Nijmegen, 6500 HB Nijmegen, The Netherlands
Address all correspondence and requests for reprints to: W.-A. Nieuwlaat, M.D., Department of Endocrinology, University Medical Center Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: w.nieuwlaat{at}endo.umcn.nl.
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Abstract |
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Twenty-two patients with nodular goiter received 131I 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 131I, 24-h RAIU without and with rhTSH pretreatment (either 0.01 or 0.03 mg) were compared. Therapeutic doses of 131I were adjusted to the rhTSH-induced increases in 24-h RAIU and were aimed at 100 µCi/g thyroid tissue retained at 24 h. Pretreatment with rhTSH allowed dose reduction of 131I 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 T4 (FT4), T3, 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 FT4 rose, after 131I treatment, from 15.8 ± 2.8 to 23.2 ± 4.4 pM. In the 0.03-mg rhTSH group, serum FT4 rose from 15.5 ± 2.5 to 23.5 ± 5.1 pM. Individual peak FT4 levels, reached between 1 and 28 d after 131I 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.
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Introduction |
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In the reported studies, a single dose of approximately 100 µCi (3.7 MBq) of 131I per gram of thyroid tissue, corrected for radioactive iodine uptake (RAIU) at 24 h, was given. In patients with nontoxic, nodular goiter, RAIU is usually rather low. As a result, high doses of 131I are often needed, causing a relatively high radiation burden to extrathyroidal tissues (11). One of the causes of a low RAIU in these patients is a low-normal or below-normal serum level of TSH.
Recently, we reported that, in patients with nodular goiter, administration of a single, low dose of 0.01 or 0.03 mg recombinant human TSH (rhTSH) doubled 24-h RAIU (12). We also described that pretreatment with rhTSH caused a more homogeneous distribution of radioiodine on the thyroid scintigrams of nodular goiters (13). These observations suggest that administration of rhTSH before 131I therapy for volume reduction of nontoxic, nodular goiter may allow treatment with lower doses of 131I in these patients without diminishing the radiation-absorbed dose in the thyroid.
Before rhTSH can be advised as an adjunct to 131I therapy in patients with nontoxic, nodular goiter, the safety of the administration of a therapeutic dose of 131I after pretreatment with rhTSH has to be investigated. First, it has to be ascertained that pretreatment with rhTSH does not exacerbate the increases in serum thyroid hormone levels commonly seen in the first weeks after 131I treatment of nontoxic, nodular goiter. Second, it has to be determined that this therapy does not cause acute enlargement of the goiter, compressing the trachea further (14). Therefore, the first aim of this study was to determine the short-term safety of the administration of a therapeutic dose of 131I after pretreatment with a single, low dose (0.01 or 0.03 mg) of rhTSH. In this study, the therapeutic dose of 131I was adjusted to the rhTSH-induced increase in 24-h RAIU, as determined in a diagnostic study using a tracer dose of 131I. The second aim was to determine the efficacy of this therapy in terms of TV reduction and increase of the smallest cross-sectional area of the tracheal lumen (SCAT) after 1 yr.
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Patients and Methods |
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Twenty-two patients with nodular goiter (18 females and 4 males; 60 ± 9 yr old; mean ± SD; range, 45–73 yr), who were referred for 131I therapy to reduce TV, participated in this study. All patients had a negative test result (<1 IU/liter) for serum levels of TSH receptor antibodies (TRAbs) (DYNOtest TRAK human; Brahms Diagnostica GmbH, Hennigsdorf, Germany). All patients had normal serum levels of free T4 (FT4) (chemiluminescent immunoassay, ACS:180 FrT4; Chiron Corp., Fernwald, Germany; normal values, 9.0–22.3 pM) and total T3 (chemiluminescent immunoassay, ACS T3; Ciba Diagnostics Corp., Medfield, MA; normal values, 1.0–3.0 nM), whereas the serum TSH level (2-site chemiluminometric immunoassay, ACS TSH-3; Ciba Diagnostics Corp.; normal values, 0.2–5.5 mU/liter) was normal (19 patients) or below normal (3 patients). Based on the results of careful palpation of the thyroid, followed by fine-needle aspiration biopsy of dominant nodules and of those that had a different consistency from other nodules within the gland, there was no suspicion of thyroid malignancy in any of the patients. None of the patients had a recent history of taking any medication known to affect thyroid function or RAIU. Patients had not received iodine-containing agents in the last 6 months. Twenty-four-hour iodide excretion was 169 ± 71 µg (range, 80–330 µg). An electrocardiogram, complete blood count, liver enzyme determinations, plasma creatinine and glucose measurements, and screening urinalysis did not show abnormalities in any of the patients. The institutional human research committee approved the study, and written informed consent was obtained from all patients.
Diagnostic investigations
A diagnostic dose of 20 µCi (0.8 MBq) sodium (131I) iodide was administered as an oral solution, together with 1 mCi (40 MBq) sodium (123I) iodide for thyroid scintigraphy. RAIU as a percentage of the administered dose of 131I, corrected for physical decay, was measured at 24 h using a 3 x 3-in. NaI(Tl) detector. Deadtime corrections were made using standard software. The use of the net area under the 364-kiloelectron volts peak of 131I was checked to prohibit any interference of the low-energy photons of 123I with RAIU measurements. Thyroid scintigraphy in the 159-kiloelectron volts window of 123I was performed 24 h after radioiodide administration. All thyroid scintigrams showed a heterogeneous uptake.
The influence of rhTSH on RAIU was investigated in each patient at least 2 wk after radioiodine administration for the baseline RAIU. After reconstitution of freeze-dried rhTSH (ampoules containing 0.9 mg rhTSH, Thyrogen; Genzyme Transgenics Corp., Cambridge, MA) with 1.2 ml sterile water, part of the obtained solution was diluted with saline to a final concentration of 0.05 mg/ml. Immediately after dilution, 0.01 mg (0.2 ml; n = 12) or 0.03 mg (0.6 ml; n = 10) rhTSH was injected in the quadriceps muscle. A diagnostic dose of 20–40 µCi (0.8–1.6 MBq) sodium 131I was administered as an oral solution [together with 1 mCi (40 MBq) sodium 123I for thyroid scintigraphy] 24 h after the administration of rhTSH. RAIU as a percentage of the administered dose of 131I, corrected for background activity from the radioiodine from the baseline investigation and for physical decay, was measured at 24 h. Thyroid scintigraphy was performed 24 h after radioiodine administration (results not included in the present report).
Radioiodine therapy
Thirty-five ± 21 d (range, 13–84 d) after the diagnostic rhTSH study, patients received a second injection of rhTSH in the quadriceps muscle, using the same rhTSH dose as was given for the diagnostic study. Twenty-four hours later, radioiodine was given as a single oral dose on an inpatient basis. The therapeutic dose of 131I was adjusted to the rhTSH-induced increase in 24-h RAIU, as determined for each individual patient in the preceding diagnostic study, and was aimed at delivering 100 µCi (3.7 MBq) 131I/g of thyroid tissue retained at 24 h, according to the following formula: administered activity (GBq) = [thyroid weight (g) x 0.37]/24-h thyroid RAIU (%) (15). For calculation of the therapeutic dose of radioiodine, we estimated thyroid weight from the planimetric surface on the baseline scintigram, using the formula of Doering and Kramer (16): thyroid weight (g) = 0.326 x (surface in cm2)3/2. Mean thyroid weight, as estimated from the planar thyroid scintigraphies, was 148 ± 62 g (range, 70–265 g).
Follow-up investigations
Symptoms and signs of thyrotoxicosis, thyroiditis, or tracheal compression and vital signs (blood pressure, pulse rate, and body temperature) were recorded immediately before and 2, 5, and 8 h after rhTSH pretreatment, as well as immediately before and 1, 2, 3, 7, 10, 14, 21, 28, 56, and 84 d after 131I therapy.
Before and 1 wk and 1 yr after radioiodine treatment, TV and the SCAT were measured. TV was measured by magnetic resonance imaging (MRI) (MRI Intera software release 8.1.3; Philips Medical Systems, Best, The Netherlands) operating at a field strength of 1.5 tesla. Transversal, sagittal, and coronal T1-weighted images [TR (repetition time) = 600 ms; echo time = 14 ms] were obtained by using a standard quadrature neck coil. The slices had a thickness of 4 mm (with an interslice gap of 0.4 mm) in the transversal plane and 3 mm (with an interslice gap of 0.3 mm) in the coronal and sagittal planes and covered the entire thyroid gland. The thyroid outline was drawn manually on each slice, and the surface of the traced areas was calculated (Easy Vision software; Philips Medical Systems). To calculate the TV, we multiplied the sum of the traced surfaces in each plane by the sum of the slice thickness and interslice gap. TV, as used hereafter, is the mean of the measurements in the three imaging planes. The precision of TV measurement by MRI is high. The intraobserver coefficient of variation is 2.2% ± 2.0%, and the interobserver coefficient of variation is 4.1% ± 2.2% (17). SCAT, a measure of tracheal compression (18), was determined by manually drawing a line along the outer contour of the trachea in the transversal T1-weighted images. All measurements were done blinded.
Serum TSH, FT4, and T3 levels were measured immediately before rhTSH pretreatment and 2, 5, and 8 h after rhTSH administration, as well as immediately before and 1, 2, 3, 7, 10, 14, 21, 28, and 56 d and 3, 6, 9, and 12 months after 131I treatment. Serum levels of C-reactive protein (CRP) (BNII hs-CRP; Dade Behring, Deerfield, IL; normal value < 12.5 mg/liter) was measured immediately before and 7, 10, 14, 21, 28, 42, and 56 d and 3 months after 131I treatment. Serum levels of TRAbs (DYNOtest TRAK human; Brahms Diagnostica GmbH; negative value < 1 IU/liter and positive value > 1.5 IU/liter) and of anti-TPO antibodies (DYNOtest anti-TPOn; Brahms Diagnostica GmbH; negative value < 60 U/ml) were measured before and 3, 6, 9, and 12 months after 131I therapy.
Statistical analyses
The mean ± SD values are given. Statistical analyses were done using the Mann-Whitney U test for unpaired observations (P values denoted as P), the Wilcoxon sign-rank test for paired observations (P values denoted as P*), and Spearman’s test for nonparametric correlations (P values denoted as P**). The level of significance was 0.05.
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Results |
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Effect of rhTSH administration on RAIU (Table 1
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In the diagnostic studies, using a tracer dose of 131I, administration of 0.01 mg rhTSH, 24 h before 131I, increased 24-h RAIU from 27 ± 8% to 50 ± 11% (P* < 0.005). Administration of 0.03 mg rhTSH, 24 h before 131I, increased 24-h RAIU from 22 ± 4% to 54 ± 9% (P* < 0.01). The ratio between 24-h RAIU after rhTSH and baseline 24-h RAIU (RAIU ratio) was significantly higher (P < 0.05) in patients who received 0.03 mg rhTSH (2.4 ± 0.4) than in those who received 0.01 mg rhTSH (1.9 ± 0.5).
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, Fig. 1).
In each patient, the therapeutic dose of 131I was reduced according to the calculated RAIU ratio in that patient. This resulted in a dose reduction with a factor of 1.9 ± 0.5 (range, 1.2–2.6) in the 0.01-mg rhTSH group and of 2.4 ± 0.4 (range, 2.0–3.1) in the 0.03-mg rhTSH group (P < 0.05). 131I doses were reduced from 68.9 ± 28.1 mCi (2550 ± 1041 MBq) to 39.4 ± 16.8 mCi (1457 ± 621 MBq) in the 0.01-mg rhTSH group and from 52.1 ± 33.3 mCi (1927 ± 1233 MBq) to 22.8 ± 5.7 mCi (843 ± 210 MBq) in the 0.03-mg rhTSH group.
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Effect of rhTSH administration on serum TSH levels (Fig. 2).
After administration of 0.01 mg rhTSH, serum TSH rose from 0.68 ± 0.50 mU/liter (range, <0.03–1.70 mU/liter) to a peak of 4.49 ± 2.03 mU/liter (range, 2.20–9.80 mU/liter; P* < 0.005). After administration of 0.03 mg rhTSH, serum TSH rose from 0.53 ± 0.54 mU/liter (range, <0.03–1.80 mU/liter) to a peak of 11.10 ± 2.59 mU/liter (range, 7.00–15.10 mU/liter; P* < 0.01). Peak levels of serum TSH were significantly higher (P < 0.0001) after administration of 0.03 mg rhTSH than after administration of 0.01 mg rhTSH. In both groups, peak levels of serum TSH were reached at 5–8 h after administration of rhTSH. Thereafter, serum TSH declined rapidly; and, in all patients, a decrease in serum TSH below the baseline level was observed.
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Serum FT4 and T3 levels after rhTSH administration followed by 131I therapy (Table 2).
In the 0.01-mg rhTSH group, serum FT4 rose from 15.8 ± 2.8 pM (range, 11.4–20.7 pM) before rhTSH administration, to 17.7 ± 3.1 pM (range, 13.2-22.9 pM) immediately before 131I therapy, i.e. 24 h after rhTSH administration (P* < 0.005). Serum FT4 levels at 2, 5, and 8 h after rhTSH administration were 15.8 ± 3.2 pM, 16.3 ± 3.1 pM, and 17.5 ± 2.9 pM, respectively. After 131I administration, serum FT4 levels increased further, to a peak level of 23.2 ± 4.4 pM (range, 16.2–32.4 pM; P* < 0.005 vs. FT4 levels immediately before 131I administration; Fig. 2). Serum T3 rose from 2.22 ± 0.38 nM (range, 1.80–2.90 nM) before rhTSH administration to 2.63 ± 0.42 nM (range, 1.90-3.40 nM) immediately before 131I therapy (P* < 0.005). Serum T3 levels at 2, 5, and 8 h after rhTSH administration were 2.33 ± 0.49, 2.59 ± 0.45, and 2.73 ± 0.43 nM, respectively. After 131I administration, serum T3 increased further, to a peak level of 3.12 ± 0.58 nM (range, 2.60–4.60 nM; P* < 0.005 vs. T3 levels immediately before 131I administration).
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Individual peak FT4 and T3 levels were reached between 1 and 28 d after 131I administration and were above the normal range in 12 (0.01-mg rhTSH group, n = 7; and 0.03-mg rhTSH group, n = 5) and 11 (0.01-mg rh TSH group, n = 5; and 0.03-mg rhTSH group, n = 6) patients, respectively.
TV and SCAT, 1 wk after 131I therapy (Table 2).
Before 131I therapy, TV (as measured with MRI) was 143 ± 54 ml (range, 70–209 ml) in the 0.01-mg rhTSH group and 103 ± 44 ml (range, 44–172 ml) in the 0.03-mg rhTSH group [P = NS (not significant), 0.01 mg rhTSH vs. 0.03 mg rhTSH]. SCAT was 1.18 ± 0.42 cm2 (range, 0.55–2.12 cm2) in the 0.01-mg rhTSH group and 1.07 ± 0.52 cm2 (range, 0.16–1.91 cm2) in the 0.03-mg rhTSH group (P = NS, 0.01 mg rhTSH vs. 0.03 mg rhTSH).
One week after 131I therapy, TV was 151 ± 61 ml (range, 74–240 ml) in the 0.01-mg rhTSH group and 114 ± 44 ml (range, 47–179 ml) in the 0.03-mg rhTSH group. Compared with the pretreatment TV, the increase of TV was 5% ± 8% (range, -6%–15%) in the 0.01-mg rhTSH group (P* = NS) and 5% ± 6% (range, -4%–17%) in the 0.03-mg rhTSH group (P* < 0.05). SCAT was 1.23 ± 0.50 cm2 (range, 0.61–2.53 cm2) in the 0.01-mg rhTSH group and 1.07 ± 0.58 cm2 (range, 0.14–1.88 cm2) in the 0.03-mg rhTSH group. In both groups, SCAT did not change significantly after 1 wk. Compared with the pretreatment SCAT, change of SCAT was 3% ± 8% (range, -13%–19%) in the 0.01-mg rhTSH group (P* = NS) and 0% ± 9% (range, -11%–19%) in the 0.03-mg rhTSH group (P* = NS).
Serum hs-CRP levels after rhTSH administration followed by 131I therapy. In most patients, serum hs-CRP levels were undetectable both before and after 131I therapy. Only in 1 patient in the 0.01-mg rhTSH group and in 1 patient in the 0.03-mg rhTSH group did hs-CRP levels exceed the upper level of the normal range after 131I therapy (peak levels were 33.2 mg/liter at 7 d and 20.3 mg/liter at 10 d after 131I therapy, respectively).
TV and SCAT, 1 yr after 131I therapy (Table 1, Fig. 3).
One year after 131I treatment, TV was 91 ± 41 ml (range, 50–170 ml) in the 0.01-mg rhTSH group and 62 ± 35 ml (range, 23–127 ml) in the 0.03-mg rhTSH group. Compared with pretreatment TV, TV 1 yr after 131I therapy was lower in all patients. Volume reduction after 1 yr was 35% ± 14% (range, 13%–68%) in the 0.01-mg rhTSH group (P* < 0.005) and 41% ± 12% (range, 26%–61%) in the 0.03-mg rhTSH group (P* < 0.01). TV reduction was not significantly different between the two groups.
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In the total group of 22 patients, there was no correlation between TV reduction and increase of SCAT (correlation coefficient = 0.12, P** = NS). TV reduction achieved 1 yr after 131I therapy was not significantly correlated with baseline TV (correlation coefficient = 0.09, P** = NS).
Thyroid function after 131I therapy. Serum levels of TRAbs became positive (>1.5 IU/liter) in four patients (0.01-mg rhTSH group, n = 3; and 0.03-mg rhTSH group, n = 1) 6 months after 131I therapy. The individual peak levels were 2.8, 15.5, 4.1, and 2.2 IU/liter. Three of them (all in the 0.01-mg rhTSH group) developed symptoms and signs of hyperthyroidism between 23 and 25 wk after 131I therapy. At the time of diagnosis of hyperthyroidism, serum TSH levels were less than 0.03 mU/liter, and serum FT4 levels were 52.5, 58.0, and 35.7 pM.
In the year after 131I therapy, L-thyroxine therapy was started in 8 patients (0.01-mg rhTSH group, n = 4; and 0.03-mg rhTSH group, n = 4) because, during follow-up, an elevated serum TSH level was measured. Pretreatment serum TSH levels were significantly (P < 0.05) higher in these 8 patients (0.99 ± 0.56 mU/liter; range 0.27–1.80 mU/liter) than in the other 14 patients (0.39 ± 0.31 mU/liter; range, <0.03–1.30 mU/liter). There was no significant difference in pretreatment TVs between the two groups. TV reduction tended to be higher (P = 0.05) in the patients in whom the serum TSH level became elevated during follow-up. Before therapy, anti-TPO antibodies were positive (>60 U/ml) in 3 patients of the total group. One year after therapy, anti-TPO antibodies were still positive in these 3 patients and had become positive in one other patient. There was no significant relation between the presence of anti-TPO antibodies and the development of an elevated serum TSH level: anti-TPO antibodies were positive both before and 1 yr after 131I therapy in 2 of the 8 patients, who started with L-thyroxine during the first year after 131I therapy. In the other 6 patients in whom the serum TSH level became elevated during follow-up, anti-TPO antibodies were negative both before and 1 yr after therapy.
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Discussion |
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Our results are in line with those in earlier studies on TV reduction by radioiodine therapy in patients with nodular goiter, showing that radioiodine treatment results in a reduction of goiter volume by approximately 40% after 1 yr (3, 6, 7). In these studies, like in our study, single doses of approximately 100 µCi (3.7 MBq) 131I per gram of thyroid tissue, corrected for the percentage uptake of radioiodine in the thyroid at 24 h, were given. However, an important difference between the present study and the earlier reports is that, in our study, pretreatment with rhTSH allowed reduction of the therapeutic dose of radioiodine by a factor of 1.9 (on average) in the group pretreated with 0.01 mg rhTSH and of 2.4 (on average) in the group pretreated with 0.03 mg rhTSH.
The radiation burden of radioiodine therapy to extrathyroidal organs is directly related to the dose of radioiodine administered (11). In our study, pretreatment with rhTSH allowed approximately 50–60% reduction of the therapeutic dose of radioiodine. Such a dose reduction may have important practical consequences. Until now, most clinicians have restricted radioiodine therapy for nontoxic, nodular goiter to elderly patients, especially those who have a high operative risk or refuse surgery. In these patients, the benefits of noninvasive radioiodine treatment outweigh the lifetime risk of this mode of therapy. However, because pretreatment with rhTSH may substantially lower the dose of radioiodine to be administered, this therapy may become more attractive for younger patients.
A main goal of the present study was to investigate the safety of the administration of a therapeutic dose of 131I after pretreatment with rhTSH. We investigated whether pretreatment with a low dose of rhTSH did not exacerbate the mild increases in serum thyroid hormone levels and TV commonly seen after radioiodine treatment of nodular goiter (14). This proved to be not the case: only mild increases in serum FT4 and T3 were observed, and no symptoms and signs of thyrotoxicosis occurred. Therefore, in our opinion, routine ß blockade is not necessary.
In the 0.03-mg rhTSH group, a small increase in TV was observed 1 wk after 131I therapy, but this was not accompanied by further narrowing of the tracheal lumen. We observed no symptoms or signs of thyroiditis in our patients, and serum CRP levels after radioiodine therapy did exceed the normal range in only 2 of the 22 patients. From our data, it seems that, in patients with nontoxic, nodular goiter, 131I therapy after pretreatment with a low dose of rhTSH is safe.
In our study, three patients developed hyperthyroidism between 23 and 25 wk after 131I therapy, which was accompanied by the presence of positive serum levels of TRAbs. Autoimmune hyperthyroidism may occur several months after radioiodine therapy for nontoxic, nodular goiter in approximately 5% of patients (20). It is of note that all three cases of autoimmune hyperthyroidism occurred in the group pretreated with the lowest dose of rhTSH, making a relationship with rhTSH pretreatment less likely.
In the year after 131I therapy, L-thyroxine was started in eight patients, because, during follow-up, an elevated serum TSH level was measured. Reported incidences of posttreatment hypothyroidism after radioiodine therapy for nontoxic, nodular goiter in literature vary from 8–100% (1, 2, 4, 5, 6, 7, 19, 21). Nygaard et al. (2), using the life table method, calculated a cumulative risk of hypothyroidism of 22% at 5 yr after radioiodine treatment for small nontoxic goiters. However, in more recent studies, higher incidences were found, e.g. 22% after 1 yr (6) and 45% after 2 yr (7). Posttreatment hypothyroidism seems to be more common in patients with small goiters and in those with high pretreatment serum anti-TPO antibody concentrations (19). In our study, there was no correlation between the presence of anti-TPO antibodies before radioiodine treatment and the development of an elevated serum TSH level during follow-up, and there was no significant difference in pretreatment TV between patients who developed an elevated TSH level during follow-up and those who did not.
Our study has a number of limitations. First, it is an observational study, not a randomized trial comparing the safety and efficacy of 131I therapy after pretreatment with different doses of rhTSH with that of standard 131I therapy, i.e. without pretreatment with rhTSH. For this reason, our finding that a dose of 0.03 mg rhTSH resulted in a significantly higher increase in 24-h RAIU than a dose of 0.01 mg rhTSH has to be confirmed in a randomized setting. Second, it was not investigated whether doses of rhTSH higher than 0.03 mg rhTSH resulted in even higher increases of 24 h RAIU and whether pretreatment with such higher doses of rhTSH before radioiodine therapy is safe and more effective than pretreatment with the doses used in our study. Third, this study was performed in an area with sufficient iodide intake. We cannot exclude that the effect of rhTSH pretreatment may be greater in areas with a higher iodide intake than in The Netherlands. Fourth, our study cannot answer the question of whether radioiodine therapy after pretreatment with rhTSH, but without diminishing the dose of 131I according to the rhTSH-induced increase in 24-h RAIU, resulting in a higher radiation dose to the thyroid, may improve the effect of radioiodine therapy with respect to TV reduction.
In conclusion, pretreatment with a single, low dose of rhTSH in patients with nodular goiter allows a 50–60% reduction of the therapeutic dose of radioiodine without compromising the efficacy of TV reduction. Further studies are needed to assess whether treatment with larger doses of rhTSH and/or 131I results in larger TV reduction in these patients.
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Footnotes |
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Abbreviations: CRP, C-reactive protein; FT4, free T4; NS, not significant; MRI, magnetic resonance imaging; RAIU, radioactive iodine uptake; rhTSH, recombinant human TSH; SCAT, smallest cross-sectional area of the tracheal lumen; TRAb, TSH receptor antibody; TV, thyroid volume.
Received October 14, 2002.
Accepted March 17, 2003.
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S. Pena, S. Arum, M. Cross, B. Magnani, E. N. Pearce, M. E. Oates, and L. E. Braverman 123I Thyroid Uptake and Thyroid Size at 24, 48, and 72 Hours after the Administration of Recombinant Human Thyroid-Stimulating Hormone to Normal Volunteers J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 506 - 510. [Abstract] [Full Text] [PDF]
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C. C. Albino, C. O. Mesa Jr., M. Olandoski, C. E. Ueda, L. C. Woellner, C. A. Goedert, A. M. Souza, and H. Graf Recombinant Human Thyrotropin as Adjuvant in the Treatment of Multinodular Goiters with Radioiodine J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2775 - 2780. [Abstract] [Full Text] [PDF]
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V. E. Nielsen, S. J. Bonnema, H. Boel-Jorgensen, A. Veje, and L. Hegedus Recombinant Human Thyrotropin Markedly Changes the 131I Kinetics during 131I Therapy of Patients with Nodular Goiter: An Evaluation by a Randomized Double-Blinded Trial J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 79 - 83. [Abstract] [Full Text] [PDF]
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L. A. Diehl, V. Garcia, S. J. Bonnema, L. Hegedus, C. C. Albino, H. Graf, and for the Latin American Thyroid Society Management of the Nontoxic Multinodular Goiter in Latin America: Comparison with North America and Europe, an Electronic Survey J. Clin. Endocrinol. Metab., January 1, 2005; 90(1): 117 - 123. [Abstract] [Full Text] [PDF]
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V. E. Nielsen, S. J. Bonnema, and L. Hegedus Effects of 0.9 mg Recombinant Human Thyrotropin on Thyroid Size and Function in Normal Subjects: A Randomized, Double-Blind, Cross-Over Trial J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2242 - 2247. [Abstract] [Full Text] [PDF]
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W.-A. Nieuwlaat, A. R. Hermus, H. A. Ross, W. C. Buijs, M. A. Edelbroek, J. W. Bus, F. H. Corstens, and D. A. Huysmans Dosimetry of Radioiodine Therapy in Patients with Nodular Goiter After Pretreatment with a Single, Low Dose of Recombinant Human Thyroid-Stimulating Hormone J. Nucl. Med., April 1, 2004; 45(4): 626 - 633. [Abstract] [Full Text] [PDF]
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S. J. Bonnema, V. E. Nielsen, and L. Hegedus Pretreatment with a Single, Low Dose of Recombinant Human Thyrotropin Allows Dose Reduction of Radioiodine Therapy in Patients with Nodular Goiter J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6113 - 6114. [Full Text] [PDF]
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W.-A. Nieuwlaat, D. A. Huysmans, and A. R. Hermus Authors' Response: Pretreatment with a Single, Low Dose of Recombinant Human Thyrotropin Allows Dose Reduction of Radioiodine Therapy in Patients with Nodular Goiter J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 6114 - 6115. [Full Text] [PDF]
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) or 0.03 mg rhTSH (patients 13–22, 
). In each patient, the therapeutic dose of 131I was reduced according to the calculated RAIU ratio in that patient (RAIU ratio = ratio between 24-h RAIU after rhTSH and baseline 24-h RAIU, as determined before in diagnostic studies using tracer doses of 131I).
